Sample records for beta peptide-induced inflammation

  1. PARP-1 modulates amyloid beta peptide-induced neuronal damage.

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    Sara Martire

    Full Text Available Amyloid beta peptide (Aβ causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose polymerase (PARP-1. To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma cells were treated with Aβ25-35 fragment in the presence or absence of MC2050, a new PARP-1 inhibitor. Aβ25-35 induces an enhancement of PARP activity which is prevented by cell pre-treatment with MC2050. These data were confirmed by measuring PARP-1 activity in CHO cells transfected with amylod precursor protein and in vivo in brains specimens of TgCRND8 transgenic mice overproducing the amyloid peptide. Following Aβ25-35 exposure a significant increase in intracellular ROS was observed. These data were supported by the finding that Aβ25-35 induces DNA damage which in turn activates PARP-1. Challenge with Aβ25-35 is also able to activate NF-kB via PARP-1, as demonstrated by NF-kB impairment upon MC2050 treatment. Moreover, Aβ25-35 via PARP-1 induces a significant increase in the p53 protein level and a parallel decrease in the anti-apoptotic Bcl-2 protein. These overall data support the hypothesis of PARP-1 involvment in cellular responses induced by Aβ and hence a possible rationale for the implication of PARP-1 in neurodegeneration is discussed.

  2. Ethyl ether fraction of Gastrodia elata Blume protects amyloid beta peptide-induced cell death. (United States)

    Kim, Hyeon-Ju; Moon, Kwang-Deog; Lee, Dong-Seok; Lee, Sang-Han


    Alzheimer's disease is the most common cause of dementia in the elderly. Recently, it has been reported that Alzheimer's disease is associated with cell death in neuronal cells including the hippocampus. Amyloid beta-peptide stimulates neuronal cell death, but the underlying signaling pathways are poorly understood. In order to develop anti-dementia agents with potential therapeutic value, we examined the effect of the herbal compound Gastrodia elata Blume (GEB) on neuronal cell death induced by amyloid beta-peptide in IMR-32 neuroblastoma cells. The fractionation of GEB was carried out in various solvents. The hydroxyl radical scavenging effect of the ethyl ether fraction was more potent than any other fractions. In cells treated with amyloid beta-peptide, the neuroprotective effect of the ethyl ether, chloroform, and butanol fractions was 92, 44, and 39%, respectively, compared with control. Taken together, these results suggest that the ethyl ether fraction of GEB contains one or more compounds that dramatically reduce amyloid beta-peptide induced neuronal cell death in vitro.

  3. DCP-LA neutralizes mutant amyloid beta peptide-induced impairment of long-term potentiation and spatial learning. (United States)

    Nagata, Tetsu; Tomiyama, Takami; Tominaga, Takemi; Mori, Hiroshi; Yaguchi, Takahiro; Nishizaki, Tomoyuki


    Long-term potentiation (LTP) was monitored from the CA1 region of the intact rat hippocampus by delivering high frequency stimulation (HFS) to the Schaffer collateral commissural pathway. Intraventricular injection with mutant amyloid beta(1-42) peptide lacking glutamate-22 (Abeta(1-42)E22Delta), favoring oligomerization, 10 min prior to HFS, inhibited expression of LTP, with the potency more than wild-type amyloid beta(1-42) peptide. Intraperitoneal injection with the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) 70 min prior to HFS neutralized mutant Abeta(1-42)E22Delta peptide-induced LTP inhibition. In the water maze test, continuous intraventricular injection with mutant Abeta(1-42)E22Delta peptide for 14 days prolonged the acquisition latency as compared with that for control, with the potency similar to wild-type Abeta(1-42) peptide, and intraperitoneal injection with DCP-LA shortened the prolonged latency to control levels. The results of the present study indicate that DCP-LA neutralizes mutant Abeta(1-42)E22Delta peptide-induced impairment of LTP and spatial learning.

  4. Topical Cathelicidin (LL-37) an Innate Immune Peptide Induces Acute Olfactory Epithelium Inflammation in a Mouse Model (United States)

    Alt, Jeremiah A.; Qin, Xuan; Pulsipher, Abigail; Orb, Quinn; Orlandi, Richard R.; Zhang, Jianxing; Schults, Austin; Jia, Wanjian; Presson, Angela P.; Prestwich, Glenn; Oottamasathien, Siam


    Background Cathelicidin (LL-37) is an endogenous innate immune peptide that is elevated in patients with chronic rhinosinusitis (CRS). The role of LL-37 in olfactory epithelium (OE) inflammation remains unknown. We hypothesized that 1) LL-37 topically delivered would elicit profound OE inflammation, and 2) LL-37 induced inflammation is associated with increased infiltration of neutrophils and mast cells. Methods To test our hypothesis we challenged C57BL/6 mice intranasally with increasing concentrations of LL-37. At 24 hours tissues were examined histologically and scored for inflammatory cell infiltrate, edema, and secretory hyperplasia. In separate experiments, fluorescently conjugated LL-37 was instilled and tissues were examined at 0.5 and 24 hours. To test our last hypothesis, we performed tissue myeloperoxidase (MPO) assays for neutrophil activity and immunohistochemistry for tryptase to determine the mean number of mast cells per mm2. Results LL-37 caused increased inflammatory cell infiltrate, edema, and secretory cell hyperplasia of the sinonasal mucosa with higher LL-37 concentrations yielding significantly more inflammatory changes (p < 0.01). Fluorescent LL-37 demonstrated global sinonasal epithelial binding and tissue distribution. Further, higher concentrations of LL-37 led to significantly greater MPO levels with dose-dependent increases in mast cell infiltration (p < 0.01). Conclusions LL-37 has dramatic inflammatory effects in the OE mucosa that is dose-dependent. The observed inflammatory changes in the olfactory mucosa were associated with the infiltration of both neutrophils and mast cells. Our biologic model represents a new model to further investigate the role of LL-37 in OE inflammation. PMID:26346056

  5. Inhibitory effect of oatmeal extract oligomer on vasoactive intestinal peptide-induced inflammation in surviving human skin. (United States)

    Boisnic, S; Branchet-Gumila, M C; Coutanceau, C


    The aim of this study was to evaluate the antiinflammatory effect of oatmeal extract oligomer on skin fragments stimulated by a neuromediator, vasoactive intestinal peptide (VIP). Skin fragments (from plastic surgery) were maintained in survival conditions for 6 h. To induce inflammation, VIP was placed in contact with dermis by culture medium. Histological analysis was then performed on hematoxylin- and eosin-stained slides. Edema was evaluated with semiquantitative scores. Vasodilation was studied by quantifying the percentage of dilated vessels according to scores and by measuring their surface by morphometrical image analysis. TNF-alpha dosage was made on culture supernatants. Vasodilation was significantly increased after application of VIP. After treatment with oatmeal extract oligomer, the mean surface of dilated vessels and edema were significantly decreased compared with VIP-treated skin. Moreover, treatment with this extract decreased TNF-alpha.

  6. Effects of Capsule Yi -Zhi on learning and memory disorder and beta-amyloid peptide induced neurotoxicity in rats

    Institute of Scientific and Technical Information of China (English)

    XUJiang-Ping; WUHang-Yu; LILin


    AIM To investigate the effects of Capsule Yi-Zhi (CYZ) on learning and memory disorder and beta-amyloid protein induced neurotoxieity in rats. Methods Various doses of CYZ were administered to Sprague-Dawley (SD) rats for 8 days, twice a day. Then scopolamine hydrobromide (Sco) intraperitoneal injection was performed on each rat and the

  7. Inhibition of cytosolic Phospholipase A2 prevents prion peptide-induced neuronal damage and co-localisation with Beta III Tubulin

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    Last Victoria


    Full Text Available Abstract Background Activation of phospholipase A2 (PLA2 and the subsequent metabolism of arachidonic acid (AA to prostaglandins have been shown to play an important role in neuronal death in neurodegenerative disease. Here we report the effects of the prion peptide fragment HuPrP106-126 on the PLA2 cascade in primary cortical neurons and translocation of cPLA2 to neurites. Results Exposure of primary cortical neurons to HuPrP106-126 increased the levels of phosphorylated cPLA2 and caused phosphorylated cPLA2 to relocate from the cell body to the cellular neurite in a PrP-dependent manner, a previously unreported observation. HuPrP106-126 also induced significant AA release, an indicator of cPLA2 activation; this preceded synapse damage and subsequent cellular death. The novel translocation of p-cPLA2 postulated the potential for exposure to HuPrP106-126 to result in a re-arrangement of the cellular cytoskeleton. However p-cPLA2 did not colocalise significantly with F-actin, intermediate filaments, or microtubule-associated proteins. Conversely, p-cPLA2 did significantly colocalise with the cytoskeletal protein beta III tubulin. Pre-treatment with the PLA2 inhibitor, palmitoyl trifluoromethyl ketone (PACOCF3 reduced cPLA2 activation, AA release and damage to the neuronal synapse. Furthermore, PACOCF3 reduced expression of p-cPLA2 in neurites and inhibited colocalisation with beta III tubulin, resulting in protection against PrP-induced cell death. Conclusions Collectively, these findings suggest that cPLA2 plays a vital role in the action of HuPrP106-126 and that the colocalisation of p-cPLA2 with beta III tubulin could be central to the progress of neurodegeneration caused by prion peptides. Further work is needed to define exactly how PLA2 inhibitors protect neurons from peptide-induced toxicity and how this relates to intracellular structural changes occurring in neurodegeneration.

  8. 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR attenuates the expression of LPS- and Aβ peptide-induced inflammatory mediators in astroglia

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    Giri Shailendra


    Full Text Available Abstract Background Alzheimer's disease (AD pathology shows characteristic 'plaques' rich in amyloid beta (Aβ peptide deposits. Inflammatory process-related proteins such as pro-inflammatory cytokines have been detected in AD brain suggesting that an inflammatory immune reaction also plays a role in the pathogenesis of AD. Glial cells in culture respond to LPS and Aβ stimuli by upregulating the expression of cytokines TNF-α, IL-1β, and IL-6, and also the expression of proinflammatory genes iNOS and COX-2. We have earlier reported that LPS/Aβ stimulation-induced ceramide and ROS generation leads to iNOS expression and nitric oxide production in glial cells. The present study was undertaken to investigate the neuroprotective function of AICAR (a potent activator of AMP-activated protein kinase in blocking the pro-oxidant/proinflammatory responses induced in primary glial cultures treated with LPS and Aβ peptide. Methods To test the anti-inflammatory/anti-oxidant functions of AICAR, we tested its inhibitory potential in blocking the expression of pro-inflammatory cytokines and iNOS, expression of COX-2, generation of ROS, and associated signaling following treatment of glial cells with LPS and Aβ peptide. We also investigated the neuroprotective effects of AICAR against the effects of cytokines and inflammatory mediators (released by the glia, in blocking neurite outgrowth inhibition, and in nerve growth factor-(NGF induced neurite extension by PC-12 cells. Results AICAR blocked LPS/Aβ-induced inflammatory processes by blocking the expression of proinflammatory cytokine, iNOS, COX-2 and MnSOD genes, and by inhibition of ROS generation and depletion of glutathione in astroglial cells. AICAR also inhibited down-stream signaling leading to the regulation of transcriptional factors such as NFκB and C/EBP which are critical for the expression of iNOS, COX-2, MnSOD and cytokines (TNF-α/IL-1β and IL-6. AICAR promoted NGF-induced neurite growth

  9. Blockade of PKC-beta protects HUVEC from advanced glycation end products induced inflammation. (United States)

    Xu, Youhua; Wang, Shanshan; Feng, Liang; Zhu, Quan; Xiang, Ping; He, Bao


    Advanced glycation end products (AGEs) have been recognized as a pivotal inducer in diabetes and kinds of aging-related vasculopathy. Endothelial dysfunction and inflammatory cells adhesion to endothelium have been regarded as important and early factors in the pathogenesis of vascular complications in diabetic patients. Owing to the key role of PKC-beta in AGEs-induced vascular dysfunction, we investigated effects of blocking PKC-beta by LY333531 on macrophage adhesion to HUVEC and the related mechanism. Transwell HUVEC-macrophage co-culture system was established to evaluate macrophage migration and adhesion ability. Immunocytochemistry was applied to examine TGF-beta1, ICAM-1 and RAGE protein expressions by SABC or SABC-AP method; mRNA expression of TGF-beta1, ICAM-1 and RAGE was determined by real-time RT-PCR. SOD and MDA levels in culture supernatant were detected. We found that LY333531 significantly reduced AGEs-induced macrophage adhesion to HUVEC. Blockade of PKC-beta strikingly decreased HUVEC TGF-beta1 and ICAM-1 expression in both protein and mRNA levels, RAGE protein level was also down-regulated. Furthermore, the anti-oxidative stress index, SOD/MDA was dramatically elevated on LY333531 application. Therefore we conclude that LY333531 can reduce AGEs-induced macrophage adhesion to endothelial cells and relieve the local inflammation, this was realized by its effect on decreasing inflammatory cytokines' expression and increasing cell anti-oxidative ability.

  10. Non-redundant properties of IL-1alpha and IL-1beta during acute colon inflammation in mice

    NARCIS (Netherlands)

    Bersudsky, M.; Luski, L.; Fishman, D.; White, R.M.; Ziv-Sokolovskaya, N.; Dotan, S.; Rider, P.; Kaplanov, I.; Aychek, T.; Dinarello, C.A.; Apte, R.N.; Voronov, E.


    OBJECTIVE: The differential role of the IL-1 agonists, IL-1alpha, which is mainly cell-associated versus IL-1beta, which is mostly secreted, was studied in colon inflammation. DESIGN: Dextran sodium sulfate (DSS) colitis was induced in mice globally deficient in either IL-1alpha or IL-1beta, and in

  11. Interrelation of inflammation and APP in sIBM: IL-1 beta induces accumulation of beta-amyloid in skeletal muscle. (United States)

    Schmidt, Jens; Barthel, Konstanze; Wrede, Arne; Salajegheh, Mohammad; Bähr, Mathias; Dalakas, Marinos C


    Distinct interrelationships between inflammation and beta-amyloid-associated degeneration, the two major hallmarks of the skeletal muscle pathology in sporadic inclusion body myositis (sIBM), have remained elusive. Expression of markers relevant for these pathomechanisms were analysed in biopsies of sIBM, polymyositis (PM), dermatomyositis (DM), dystrophic and non-myopathic muscle as controls, and cultured human myotubes. By quantitative PCR, a higher upregulation was noted for the mRNA-expression of CXCL-9, CCL-3, CCL-4, IFN-gamma, TNF-alpha and IL-1 beta in sIBM muscle compared to PM, DM and controls. All inflammatory myopathies displayed overexpression of degeneration-associated markers, yet only in sIBM, expression of the mRNA of amyloid precursor protein (APP) significantly and consistently correlated with inflammation in the muscle and mRNA-levels of chemokines and IFN-gamma. Only in sIBM, immunohistochemical analysis revealed that inflammatory mediators including IL-1 beta co-localized to beta-amyloid depositions within myofibres. In human myotubes, exposure to IL-1 beta caused upregulation of APP with subsequent intracellular aggregation of beta-amyloid. Our data suggest that, in sIBM muscle, production of high amounts of pro-inflammatory mediators specifically induces beta-amyloid-associated degeneration. The observations may help to design targeted treatment strategies for chronic inflammatory disorders of the skeletal muscle.

  12. Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation

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    Oh Ki


    Full Text Available Abstract Background Alzheimer's disease (AD is characterized by extensive loss of neurons in the brain of AD patients. Intracellular accumulation of beta-amyloid peptide (Aβ has also shown to occur in AD. Neuro-inflammation has been known to play a role in the pathogenesis of AD. Methods In this study, we investigated neuro-inflammation and amyloidogenesis and memory impairment following the systemic inflammation generated by lipopolysaccharide (LPS using immunohistochemistry, ELISA, behavioral tests and Western blotting. Results Intraperitoneal injection of LPS, (250 μg/kg induced memory impairment determined by passive avoidance and water maze tests in mice. Repeated injection of LPS (250 μg/kg, 3 or 7 times resulted in an accumulation of Aβ1–42 in the hippocampus and cerebralcortex of mice brains through increased β- and γ-secretase activities accompanied with the increased expression of amyloid precursor protein (APP, 99-residue carboxy-terminal fragment of APP (C99 and generation of Aβ1–42 as well as activation of astrocytes in vivo. 3 weeks of pretreatment of sulindac sulfide (3.75 and 7.5 mg/kg, orally, an anti-inflammatory agent, suppressed the LPS-induced amyloidogenesis, memory dysfunction as well as neuronal cell death in vivo. Sulindac sulfide (12.5–50 μM also suppressed LPS (1 μg/ml-induced amyloidogenesis in cultured neurons and astrocytes in vitro. Conclusion This study suggests that neuro-inflammatory reaction could contribute to AD pathology, and anti-inflammatory agent could be useful for the prevention of AD.

  13. Inflammation

    DEFF Research Database (Denmark)

    Holst-Hansen, Thomas

    Inflammation is an intricate response relying on the activation and response of both the innate immune system and the infected tissue to remove a threat. The pro-inflammatory NF-kappaB pathway has been studied extensively, among others because of its key role in regulation of inflammation. However...

  14. Mice Lacking beta2-Integrin Function Remain Glucose Tolerant in Spite of Insulin Resistance, Neutrophil Infiltration and Inflammation. (United States)

    Meakin, Paul J; Morrison, Vicky L; Sneddon, Claire C; Savinko, Terhi; Uotila, Liisa; Jalicy, Susan M; Gabriel, Jennie L; Kang, Li; Ashford, Michael L J; Fagerholm, Susanna C


    Beta2-integrins are important in leukocyte trafficking and function, and are regulated through the binding of cytoplasmic proteins, such as kindlin-3, to their intracellular domain. Here, we investigate the involvement of beta2-integrins in the regulation of metabolic disease using mice where the kindlin-3 binding site in the beta2-integrin cytoplasmic tail has been mutated (TTT/AAA-beta2-integrin knock-in (KI) mice), leading to expressed but dysfunctional beta2-integrins and significant neutrophilia in vivo. Beta2-integrin KI mice fed on a high fat diet showed normal weight gain, and normal accumulation of macrophages and lymphocytes in white adipose tissue (WAT) and liver, but increased neutrophil numbers especially in WAT. In addition, beta2-integrin KI mice fed on a high fat diet showed significantly increased peripheral insulin resistance in response to high-fat feeding. However, this was associated with improved glucose disposal following glucose load. Interestingly, beta2-integrin KI neutrophils produced more elastase in vitro, in response to stimulation. Beta2-integrin KI mice displayed variability of tissue inflammatory status, with liver and WAT exhibiting little or no difference in inflammation compared to high fat fed controls, whereas skeletal muscle demonstrated a raised inflammatory profile in association with higher elastase levels and diminished signalling through the IRS1-PKB pathway. In conclusion, although expression of dysfunctional beta2-integrins increased neutrophil production and infiltration into tissue, skeletal muscle was the most affected tissue exhibiting evidence of higher neutrophil activity and insulin resistance. Thus, beta2-integrins modulate glucose homeostasis during high fat feeding predominantly through actions on skeletal muscle to affect metabolic phenotype in vivo.

  15. Mice Lacking beta2-Integrin Function Remain Glucose Tolerant in Spite of Insulin Resistance, Neutrophil Infiltration and Inflammation.

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    Paul J Meakin

    Full Text Available Beta2-integrins are important in leukocyte trafficking and function, and are regulated through the binding of cytoplasmic proteins, such as kindlin-3, to their intracellular domain. Here, we investigate the involvement of beta2-integrins in the regulation of metabolic disease using mice where the kindlin-3 binding site in the beta2-integrin cytoplasmic tail has been mutated (TTT/AAA-beta2-integrin knock-in (KI mice, leading to expressed but dysfunctional beta2-integrins and significant neutrophilia in vivo. Beta2-integrin KI mice fed on a high fat diet showed normal weight gain, and normal accumulation of macrophages and lymphocytes in white adipose tissue (WAT and liver, but increased neutrophil numbers especially in WAT. In addition, beta2-integrin KI mice fed on a high fat diet showed significantly increased peripheral insulin resistance in response to high-fat feeding. However, this was associated with improved glucose disposal following glucose load. Interestingly, beta2-integrin KI neutrophils produced more elastase in vitro, in response to stimulation. Beta2-integrin KI mice displayed variability of tissue inflammatory status, with liver and WAT exhibiting little or no difference in inflammation compared to high fat fed controls, whereas skeletal muscle demonstrated a raised inflammatory profile in association with higher elastase levels and diminished signalling through the IRS1-PKB pathway. In conclusion, although expression of dysfunctional beta2-integrins increased neutrophil production and infiltration into tissue, skeletal muscle was the most affected tissue exhibiting evidence of higher neutrophil activity and insulin resistance. Thus, beta2-integrins modulate glucose homeostasis during high fat feeding predominantly through actions on skeletal muscle to affect metabolic phenotype in vivo.

  16. Metabolically induced liver inflammation leads to NASH and differs from LPS- or IL-1 beta-induced chronic inflammation

    NARCIS (Netherlands)

    Liang, Wen; Lindeman, Jan H.; Menke, Aswin L.; Koonen, Debby P.; Morrison, Martine; Havekes, Louis M.; van den Hoek, Anita M.; Kleemann, Robert


    The nature of the chronic inflammatory component that drives the development of non-alcoholic steatohepatitis (NASH) is unclear and possible inflammatory triggers have not been investigated systematically. We examined the effect of non-metabolic triggers (lipopolysaccharide (LPS), interleukin-1 beta

  17. Beta-endorphin 1-31 biotransformation and cAMP modulation in inflammation.

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    Naghmeh Hajarol Asvadi

    Full Text Available A large body of evidence now exists for the immune cell expression, production, and the release of beta-endorphin (BE 1-31 within inflamed tissue. The inflammatory milieu is characterised by increased acidity, temperature and metabolic activity. Within these harsh conditions BE 1-31 is even more susceptible to increased enzymatic degradation over that of plasma or other non-injured tissue. To elucidate the biotransformation pathways of BE 1-31 and provide an insight to the impact of inflamed tissue environments, BE 1-31 and three of its major N-terminal fragments (BE 1-11, BE 1-13 and BE 1-17 were incubated in inflamed tissue homogenates at pH 5.5 for 2 hrs. In addition, the potency of BE 1-31 and five main N--terminal fragments (BE 1-9, BE 1-11, BE 1-13, BE 1-17, BE 1-20 was assessed at mu-opioid receptors (MOR, delta-opioid receptors (DOR, and kappa-opioid receptors (KOR. Opioid receptor potency was investigated by examining the modulation of forskolin induced cAMP accumulation. The majority of the N-terminal fragment of BE 1-31 had similar efficacy to BE 1-31 at MOR. The shortest of the major N-terminal fragments (BE 1-9, had partial agonist activity at MOR but possessed the highest potency of all tested peptides at DOR. There was limited effect for BE 1-31 and the biotransformed peptides at KOR. Major N-terminal fragments produced within inflamed tissue have increased presence within inflamed tissue over that of the parent molecule BE 1-31 and may therefore contribute to BE 1-31 efficacy within disease states that involve inflammation.

  18. A clinical perspective of IL-1beta as the gatekeeper of inflammation.

    NARCIS (Netherlands)

    Dinarello, C.A.


    An expanding spectrum of acute and chronic non-infectious inflammatory diseases is uniquely responsive to IL-1beta neutralization. IL-1beta-mediated diseases are often called "auto-inflammatory" and the dominant finding is the release of the active form of IL-1beta driven by endogenous molecules act

  19. 1,8-cineole (eucalyptol) mitigates inflammation in amyloid Beta toxicated PC12 cells: relevance to Alzheimer's disease. (United States)

    Khan, Andleeb; Vaibhav, Kumar; Javed, Hayate; Tabassum, Rizwana; Ahmed, Md Ejaz; Khan, Mohd Moshahid; Khan, M Badruzzaman; Shrivastava, Pallavi; Islam, Farah; Siddiqui, M Saeed; Safhi, M M; Islam, Fakhrul


    Inflammatory process has a fundamental role in the pathogenesis of Alzheimer's disease and insoluble amyloid beta deposits and neurofibrillary tangles provide the obvious stimuli for inflammation. The present study demonstrate the effect of pretreatment of 1,8-cineole (Cin) on inflammation induced by Aβ(25-35) in differentiated PC12 cells. The cells were treated with Cin at different doses for 24 h and then replaced by media containing Aβ(25-35) for another 24 h. The cell viability was decreased in Aβ(25-35) treated cells which was significantly restored by Cin pretreatment. Cin successfully reduced the mitochondrial membrane potential, ROS and NO levels in Aβ(25-35) treated cells. Cin also lowered the levels of proinflammatory cytokines TNF-α, IL-1β and IL-6 in Aβ(25-35) treated cells. Moreover, Cin also succeeded in lowering the expression of NOS-2, COX-2 and NF-κB. This study suggests the protective effects of Cin on inflammation and provides additional evidence for its potential beneficial use in therapy as an anti-inflammatory agent in neurodegenerative disease.

  20. [The effect of a simulated inflammation procedure in simulated body fluid on bone-like apatite formation on porous HA/beta-TCP bioceramics]. (United States)

    Ji, Jingou; Ran, Junguo; Gou, Li; Wang, Fangfu; Sun, Luwei


    The formation of bone-like apatite on porous HA/beta-TCP bioceramics in dynamic simulated body fluid (SBF) undergoing a simulated inflammation procedure (pH = 6.5) was investigated in order to study the mechanism of osteoinduction and build a new method to choose biomaterials with better bioactivity. The results showed that the surface of porous HA/beta-TCP bioceramics which underwent a simulated inflammation procedure in dynamic SBF was more smooth. The light acidity in the simulated inflammation procedure would dissolve the fine grains and the parts possessing smaller curvature radius on the surface of porous HA/beta-TCP bioceramics, which would reduce the bioceramics solubility. Followed in normal SBF (pH = 7.4), the amount of bone-like apatite formed on the porous HA/beta-TCP bioceramics was less than that of porous HA/beta-TCP bioceramics incubation in normal SBF all along. The results also showed that the amount of bone-like apatite formed on the porous HA/beta-TCP bioceramics sintered by a microwave plasma was more than that of porous HA/beta-TCP bioceramics sintered by a conventional furnace.

  1. Reversal of new-onset diabetes through modulating inflammation and stimulating beta-cell replication in nonobese diabetic mice by a dipeptidyl peptidase IV inhibitor. (United States)

    Tian, Lei; Gao, Jie; Hao, Jianqiang; Zhang, Yu; Yi, Huimin; O'Brien, Timothy D; Sorenson, Robert; Luo, Jian; Guo, Zhiguang


    Inhibition of dipeptidyl peptidase IV (DPP-IV) activity by NVP-DPP728, a DPP-IV inhibitor, improves the therapeutic efficacy of glucagon-like peptide-1 (GLP-1). CD26 is a membrane-associated glycoprotein with DPP-IV activity and is expressed on lymphocytes. We investigated the effect of NVP-DPP728 on reversing new-onset diabetes in nonobese diabetic (NOD) mice and modulating the inflammatory response and stimulating beta-cell regeneration. New-onset diabetic NOD mice were treated with NVP-DPP728 for 2, 4, and 6 wk. Blood glucose level was monitored. Regulatory T cells in thymus and secondary lymph nodes, TGF-beta1 and GLP-1 in plasma, and the insulin content in the pancreas were measured. Immunostaining for insulin and bromodeoxyuridine (BrdU) were performed. The correlation of beta-cell replication with inflammation was determined. In NVP-DPP728-treated NOD mice, diabetes could be reversed in 57, 74, and 73% of mice after 2, 4, and 6 wk treatment, respectively. Insulitis was reduced and the percentage of CD4(+)CD25(+)FoxP3(+) regulatory T cells was increased in treated NOD mice with remission. Plasma TGF-beta1 and GLP-1, the insulin content, and both insulin(+) and BrdU(+) beta-cells in pancreas were also significantly increased. No significant correlations were found between numbers of both insulin(+) and BrdU(+) beta-cells in islets and beta-cell area or islets with different insulitis score in NOD mice with remission of diabetes. In conclusion, NVP-DPP728 treatment can reverse new-onset diabetes in NOD mice by reducing insulitis, increasing CD4(+)CD25(+)FoxP3(+) regulatory T cells, and stimulating beta-cell replication. beta-Cell replication is not associated with the degree of inflammation in NVP-DPP728-treated NOD mice.

  2. Type 1 Diabetes Candidate Genes Linked to Pancreatic Islet Cell Inflammation and Beta-Cell Apoptosis (United States)

    Størling, Joachim; Pociot, Flemming


    Type 1 diabetes (T1D) is a chronic immune-mediated disease resulting from the selective destruction of the insulin-producing pancreatic islet β-cells. Susceptibility to the disease is the result of complex interactions between environmental and genetic risk factors. Genome-wide association studies (GWAS) have identified more than 50 genetic regions that affect the risk of developing T1D. Most of these susceptibility loci, however, harbor several genes, and the causal variant(s) and gene(s) for most of the loci remain to be established. A significant part of the genes located in the T1D susceptibility loci are expressed in human islets and β cells and mounting evidence suggests that some of these genes modulate the β-cell response to the immune system and viral infection and regulate apoptotic β-cell death. Here, we discuss the current status of T1D susceptibility loci and candidate genes with focus on pancreatic islet cell inflammation and β-cell apoptosis. PMID:28212332

  3. Type 1 Diabetes Candidate Genes Linked to Pancreatic Islet Cell Inflammation and Beta-Cell Apoptosis. (United States)

    Størling, Joachim; Pociot, Flemming


    Type 1 diabetes (T1D) is a chronic immune-mediated disease resulting from the selective destruction of the insulin-producing pancreatic islet β-cells. Susceptibility to the disease is the result of complex interactions between environmental and genetic risk factors. Genome-wide association studies (GWAS) have identified more than 50 genetic regions that affect the risk of developing T1D. Most of these susceptibility loci, however, harbor several genes, and the causal variant(s) and gene(s) for most of the loci remain to be established. A significant part of the genes located in the T1D susceptibility loci are expressed in human islets and β cells and mounting evidence suggests that some of these genes modulate the β-cell response to the immune system and viral infection and regulate apoptotic β-cell death. Here, we discuss the current status of T1D susceptibility loci and candidate genes with focus on pancreatic islet cell inflammation and β-cell apoptosis.

  4. Induction and effector phase of allergic lung inflammation is independent of CCL21/CCL19 and LT-beta

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    Corinne Ploix, Riaz I. Zuberi, Fu-Tong Liu, Monica J. Carson, David D. Lo


    Full Text Available The chemokines CCL21 and CCL19, and cell bound TNF family ligand lymphotoxin beta (LTβ, have been associated with numerous chronic inflammatory diseases. A general role in chronic inflammatory diseases cannot be assumed however; in the case of allergic inflammatory disease, CCL21/CCL19 and LTβ have not been associated with the induction, recruitment, or effector function of Th2 cells nor dendritic cells to the lung. We have examined the induction of allergic inflammatory lung disease in mice deficient in CCL21/CCL19 or LTβ and found that both kinds of mice can develop allergic lung inflammation. To control for effects of priming differences in knockout mice, adoptive transfers of Th2 cells were also performed, and they showed that such effector cells had equivalent effects on airway hyper-responsiveness in both knockout background recipients. Moreover, class II positive antigen presenting cells (B cells and CD11c+ dendritic cells showed normal recruitment to the peribronchial spaces along with CD4 T cells. Thus, the induction of allergic responses and recruitment of both effector Th2 cells and antigen presenting cells to lung peribronchial spaces can develop independently of CCL21/CCL19 and LTβ.

  5. Beetroot (Beta vulgaris L. Extract Ameliorates Gentamicin-Induced Nephrotoxicity Associated Oxidative Stress, Inflammation, and Apoptosis in Rodent Model

    Directory of Open Access Journals (Sweden)

    Ali A. El Gamal


    Full Text Available The present investigation was designed to investigate the protective effect of (Beta vulgaris L. beat root ethanolic extract (BVEE on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific kidney function parameters (urea, uric acid, total protein, creatinine, and histopathology of kidney tissue were evaluated to access gentamicin-induced nephrotoxicity. The oxidative/nitrosative stress (Lipid peroxidation, MDA, NP-SH, Catalase, and nitric oxide levels was assessed. The inflammatory response (TNF-α, IL-6, MPO, NF-κB (p65, and NF-κB (p65 DNA binding and apoptotic marker (Caspase-3, Bax, and Bcl-2 were also evaluated. BVEE (250 and 500 mg/kg treatment along with gentamicin restored/increased the renal endogenous antioxidant status. Gentamicin-induced increased renal inflammatory cytokines (TNF-α and IL-6, nuclear protein expression of NF-κB (p65, NF-κB-DNA binding activity, myeloperoxidase (MPO activity, and nitric oxide level were significantly down regulated upon BVEE treatment. In addition, BVEE treatment significantly reduced the amount of cleaved caspase 3 and Bax, protein expression and increased the Bcl-2 protein expression. BVEE treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. These findings suggest that BVEE treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, inflammation, and apoptosis in the kidney.

  6. Soy peptide-induced stem cell proliferation: involvement of ERK and TGF-β1. (United States)

    Lee, Jienny; Roh, Kyung-Baeg; Kim, Sang-Cheol; Lee, Jongsung; Park, Deokhoon


    This study was conducted to investigate the proliferative effect of vegetable soy peptides on adult stem cells (ASCs) in the absence of serum and their possible mechanisms of action. The proliferation of human adipose tissue-derived mesenchymal stem cells (ADSCs) and cord blood-derived mesenchymal stem cells (CB-MSCs) treated with soy peptides was found to increase significantly upon 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Click-iT 5-ethynyl-2'-deoxyuridine flow cytometry assay. In addition, soy peptides led to stepwise phosphorylation of the p44/42 MAPK (ERK), mammalian target of rapamycin (mTOR), p70 S6 kinase, S6 ribosomal protein (S6RP) and eukaryotic initiation factor 4E (eIF4E) in ADSCs. Furthermore, quantitative analysis of the cytokines revealed that the production of transforming growth factor-beta1 (TGF-β1), vascular endothelial growth factor and interleukin-6 increased significantly in response to treatment with soy peptides in both ADSCs and CB-MSCs. Similarly, soy peptide-induced phosphorylation of the ERK/mTOR/S6RP/eIF4E pathway was blocked in response to pretreatment with PD98059, a specific ERK inhibitor. Moreover, inhibition of TGF-β1 through PD98059 pretreatment and a consecutive decrease in ADSC proliferation revealed that TGF-β1 induces the phosphorylation of mTOR/S6RP/eIF4E. Collectively, the results of this study indicate that ERK-dependent production of TGF-β1 plays a crucial role in the soy peptide-induced proliferation of ADSCs under serum-free conditions.

  7. Comparative assessment of effectiveness of ketoprofen and ketoprofen/beta-cyclodextrin complex in two experimental models of inflammation in rats. (United States)

    Grecu, Mariana; Năstasă, Valentin; Ilie, Cornelia; Miron, Liviu; Mareş, Mihai


    Oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) can lead to adverse effects such as gastrointestinal distress. The complexation of different groups of active substances with β-cyclodextrin (β-CD) has drawn considerable interest over recent years. The purpose of this study was to analyze the ketoprofen/β-cyclodextrin (K/β-CD) conjugate complex as well as to assess its anti-inflammatory effect after oral administration (doses of 30 mg/m(2) and 15 mg/m(2) of body surface), compared with ketoprofen. The studies were done on two models of experimentally-induced acute inflammation in rats (n = 48, 6/group), by means of intraplantar administration of a 10% aqueous kaolin suspension and intraperitoneal administration of a 1% sodium thioglycolate solution. The dynamics of the acute inflammatory process and the anti-inflammatory effects were monitored using plethysmometric determinations after 3, 6, 9, 12, 24 and 48 h (plantar inflammation), and the absorbance of the exudates (spectrophotometrically read) and nucleated cell counts after 24 h (peritoneal inflammation). The coupling of ketoprofen with β-CD resulted in increased solubility (100% in 60 min) of the newly-formed product, which further resulted in a higher bioavailability compared with ketoprofen (ketoprofen.

  8. The Evaluation of the Role of Beta-Hydroxy Fatty Acids on Chronic Inflammation and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    A. S. Soydan


    Full Text Available β-hydroxy fatty acids are a major component of lipid A moiety of lipopolysaccaride. We aimed to investigate the role of free β-hydroxy fatty acids on inflammation, as well as to evaluate their effects on cytokine release from human blood cells, and whether they exist in plasma of patients with chronic inflammatory diseases with/without insulin resistance. Peripheral venous blood was incubated with β-hydroxy lauric and β-hydroxy myristic acids (each 100 ng, 1 μg, 10 μg/mL up to 24 hours. Cytokines were measured from culture media and plasma. Free fatty acids and biochemical parameters were also measured from patients' plasma. Only β-hydroxy lauric acid significantly stimulated interleukin-6 production at 10 μg/mL compared to control (533.9±218.1 versus 438.3±219.6 pg/mL, P<.05. However, free β-hydroxy lauric and myristic acids were not found in patients' plasma. Therefore, free β-hydroxy lauric and myristic acids do not seem to have a role on sterile inflammation in chronic inflammatory diseases associated with insulin resistance.

  9. Applying fluorescence correlation spectroscopy to investigate peptide-induced membrane disruption

    DEFF Research Database (Denmark)

    Kristensen, Kasper; Henriksen, Jonas Rosager; Andresen, Thomas Lars


    to quantify leakage of fluorescent molecules of different sizes from large unilamellar lipid vesicles, thereby providing a tool for estimating the size of peptide-induced membrane disruptions. If fluorescently labeled lipids are incorporated into the membranes of the vesicles, FCS can also be used to obtain...

  10. Icariside II, a Broad-Spectrum Anti-cancer Agent, Reverses Beta-Amyloid-Induced Cognitive Impairment through Reducing Inflammation and Apoptosis in Rats (United States)

    Deng, Yuanyuan; Long, Long; Wang, Keke; Zhou, Jiayin; Zeng, Lingrong; He, Lianzi; Gong, Qihai


    Beta-amyloid (Aβ) deposition, associated neuronal apoptosis and neuroinflammation are considered as the important factors which lead to cognitive deficits in Alzheimer’s disease (AD). Icariside II (ICS II), an active flavonoid compound derived from Epimedium brevicornum Maxim, has been extensively used to treat erectile dysfunction, osteoporosis and dementia in traditional Chinese medicine. Recently, ICS II attracts great interest due to its broad-spectrum anti-cancer property. ICS II shows an anti-inflammatory potential both in cancer treatment and cerebral ischemia-reperfusion. It is not yet clear whether the anti-inflammatory effect of ICS II could delay progression of AD. Therefore, the current study aimed to investigate the effects of ICS II on the behavioral deficits, Aβ levels, neuroinflammatory responses and apoptosis in Aβ25-35-treated rats. We found that bilateral hippocampal injection of Aβ25-35 induced cognitive impairment, neuronal damage, along with increase of Aβ, inflammation and apoptosis in hippocampus of rats. However, treatment with ICS II 20 mg/kg could improve the cognitive deficits, ameliorate neuronal death, and reduce the levels of Aβ in the hippocampus. Furthermore, ICS II could suppress microglial and astrocytic activation, inhibit expression of IL-1β, TNF-α, COX-2, and iNOS mRNA and protein, and attenuate the Aβ induced Bax/Bcl-2 ratio elevation and caspase-3 activation. In conclusion, these results showed that ICS II could reverse Aβ-induced cognitive deficits, possibly via the inhibition of neuroinflammation and apoptosis, which suggested a potential protective effect of ICS II on AD. PMID:28210222

  11. Local therapy with CpG motifs in a murine model of allergic airway inflammation in IFN-beta knock-out mice

    DEFF Research Database (Denmark)

    Matheu, Victor; Treschow, Alexandra; Teige, Ingrid;


    of CpG-ODN is not known. OBJECTIVE: Here, we aimed to elucidate the role of IFN-beta in the anti-allergic effect of CpG motifs. METHODS: We assessed the immune response in OVA-primed/OVA-challenged IFN-beta knockout (-/-) mice compared to wild type (WT) control, after intranasal and systemic treatment...

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

    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 ...

  13. Fibrils from designed non-amyloid-related synthetic peptides induce AA-amyloidosis during inflammation in an animal model.

    Directory of Open Access Journals (Sweden)

    Per Westermark

    Full Text Available BACKGROUND: Mouse AA-amyloidosis is a transmissible disease by a prion-like mechanism where amyloid fibrils act by seeding. Synthetic peptides with no amyloid relationship can assemble into amyloid-like fibrils and these may have seeding capacity for amyloid proteins. PRINCIPAL FINDINGS: Several synthetic peptides, designed for nanotechnology, have been examined for their ability to produce fibrils with Congo red affinity and concomitant green birefringence, affinity for thioflavin S and to accelerate AA-amyloidosis in mice. It is shown that some amphiphilic fibril-forming peptides not only produced Congo red birefringence and showed affinity for thioflavin S, but they also shortened the lag phase for systemic AA-amyloidosis in mice when they were given intravenously at the time of inflammatory induction with silver nitride. Peptides, not forming amyloid-like fibrils, did not have such properties. CONCLUSIONS: These observations should caution researchers and those who work with synthetic peptides and their derivatives to be aware of the potential health concerns.

  14. Treatment with non-selective beta blockers is associated with reduced severity of systemic inflammation and improved survival of patients with acute-on-chronic liver failure

    DEFF Research Database (Denmark)

    Mookerjee, Rajeshwar P; Pavesi, Marco; Thomsen, Karen Louise


    BACKGROUND AND AIMS: Non-selective beta-blockers (NSBBs) have been shown to have deleterious outcomes in patients with refractory ascites, alcoholic hepatitis and spontaneous bacterial peritonitis leading many physicians to stop the drug in these cases. Acute on chronic liver failure (ACLF...

  15. Retroperitoneal inflammation (United States)

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

  16. Improvement of hypertension, endothelial function and systemic inflammation following short-term supplementation with red beet (Beta vulgaris L.) juice: a randomized crossover pilot study. (United States)

    Asgary, S; Afshani, M R; Sahebkar, A; Keshvari, M; Taheri, M; Jahanian, E; Rafieian-Kopaei, M; Malekian, F; Sarrafzadegan, N


    Hypertension is a major risk factor for cardiovascular disease and has a prevalence of about one billion people worldwide. It has been shown that adherence to a diet rich in fruits and vegetables helps in decreasing blood pressure (BP). This study aimed to investigate the effect of raw beet juice (RBJ) and cooked beet (CB) on BP of hypertensive subjects. In this randomized crossover study, 24 hypertensive subjects aged 25-68 years old were divided into two groups. One group took RBJ for 2 weeks and the other group took CB. After 2 weeks of treatment, both groups had a washout for 2 weeks then switched to the alternate treatment. Each participant consumed 250 ml day(-1) of RBJ or 250 g day(-1) of CB each for a period of 2 weeks. Body weight, BP, flow-mediated dilation (FMD), lipid profile and inflammatory parameters were measured at baseline and after each period. According to the results, high-sensitivity C-reactive protein (hs-CRP) and tumour necrosis factor alpha (TNF-α) were significantly lower and FMD was significantly higher after treatment with RBJ compared with CB (P<0.05). FMD was significantly (P<0.05) increased, but systolic and diastolic BP, intracellular adhesion molecule-1 (ICAM-1), vascular endothelial adhesion molecule-1 (VCAM-1), hs-CRP, interleukin-6, E-selectin and TNF-α were significantly (P<0.05) decreased with RBJ or CB. Total antioxidant capacity was increased and non-high-density lipoprotein (HDL), low-density lipoprotein (LDL) and total cholesterol (TC) were decreased with RBJ but not with CB. Although both forms of beetroot were effective in improving BP, endothelial function and systemic inflammation, the raw beetroot juice had greater antihypertensive effects. Also more improvement was observed in endothelial function and systemic inflammation with RBJ compared with CB.

  17. Hydrogen sulfide inhibits beta-amyloid peptide-induced apoptosis in PC12 cells and the underlying mechanisms

    Institute of Scientific and Technical Information of China (English)

    Xiuqin Chen; Jingtian Li; Jinhui Zou; Bailing Li; Meng Wang


    BACKGROUND: Studies have demonstrated that hydrogen sulfide (H2S) levels are 55% lower in brains of Alzheimer's disease (AD) patients than in age-matched normal individuals, which suggests that H2S might be involved in some aspects of AD pathogenesis.OBJECTIVE: To observe the protective mechanisms of varied concentrations of H2S against β -amyloid-peptide (A β) induced apoptosis in pheochromoytoma (PC12) cells, and to analyze the pathway of action.DESIGN, TIME AND SETTING: A controlled, observational, in vitro experiment was performed at Nenrophysiology Laboratory in Zhougshan Medical School, Sun Yat-sen University between July 2006 and May 2007.MATERIALS: PC12 cells were provided by the Animal Experimental Center of Medical School of Sun Yat-sen University. Glybenclamide, rhodamine123, and dihydrorhodamine123 were purchased from Sigma (USA).METHODS: PCI2 cells were incubated at 37℃ in a 5% CO2-enriched incubator with RPMI-1640 medium, supplemented with 5% horse-serum and 10% fetal bovine serum. Cells in logarithmic growth curves received different treatment: The PC12 cells were maintains at 37℃ with the original medium, then incubated in A β 25-35, sodium hydrosulfide (NariS), glybenclamide, NailS+ A β 25-35, or pretreated with glybenelamide 30 minutes prior to administration of and A β 25-35, respectively. MAIN OUTCOME MEASURES: (1) The survival rate of PC12 cells was detected by MTT assay and Hoechst staining. (2) The apoptosis rate of PC12 cells was detected utilizing flow cytometry with propidium iodide staining, and morphological changes of apoptotic cells were observed. (3) The mitochondrial membrane potential was detected by Rhodamine 123-combined flow cytometry. (4) The intracellular reactive oxygen species content was detected by dihydrorhodamine123-combined flow cytometry. RESULTS: A β 25-35 induced significantly decreased viability and increased percentage of apoptosis in PC 12 cells, as well as dissipated mitochondrial membrane potential expression and an overproduction of reactive oxygen species. When PC12 cells were co-treated with Nails and A β 25-35, the decreased cell viability induced by 20 μ mol/L A β 25-35 was concentration-dependently blocked by NariS (50, 100, and 200 p mol/L). NaHS (100 μ mol/L) obviously reduced the percentage of apoptotic PCI2 cells induced by 20 μ mol/L A β 25-35. In addition, 100 μ mol/L NariS inhibited mitochondrial membrane potential dissipation and reactive oxygen species overproduction. When the ATP-sensitive K channel (KATP) inhibitor, glybenclamide, was administered 30 minutes prior to NailS and A β 25-35 treatment, the NariS-dependent cellular protection was partly blocked. This resulted in reduced PC12 cell viability and increased the percentage of apoptosis, as well as significantly blocked mitochondrial membrane potential preservation and inhibited reactive oxygen species overproduction due to Naris treatment.CONCLUSION: NaHS protected PC 12 cells against A β 25-35-induced damage. NariS-dependent cellular protection was associated with mitochondrial membrane potential preservation and inhibition of reactive oxygen species overproduction. The KATP channel inhibitor, glybenclamide, significantly blocked the cellular protective effects of NariS, indicating that KATP channel activation plays an important role in NariS-induced protection of PC 12 cells to A β 25 35-induced damage.

  18. Role of oxidative stress, inflammation, nitric oxide and transforming growth factor-beta in the protective effect of diosgenin in monocrotaline-induced pulmonary hypertension in rats. (United States)

    Ahmed, Lamiaa A; Obaid, Al Arqam Z; Zaki, Hala F; Agha, Azza M


    Pulmonary hypertension is a progressive disease of various origins that is associated with right ventricular dysfunction. In the present study, the protective effect of diosgenin was investigated in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60 mg/kg). Diosgenin (100 mg/kg) was given by oral administration once daily for 3 weeks. At the end of the experiment, mean arterial blood pressure, electrocardiography and echocardiography were recorded. Rats were then sacrificed and serum was separated for determination of total nitrate/nitrite level. Right ventricles and lungs were isolated for estimation of oxidative stress markers, tumor necrosis factor-alpha, total nitrate/nitrite and transforming growth factor-beta contents. Myeloperoxidase and caspase-3 activities in addition to endothelial and inducible nitric oxide synthase protein expression were also determined. Moreover, histological analysis of pulmonary arteries and cardiomyocyte cross-sectional area was performed. Diosgenin treatment provided a significant improvement toward preserving hemodynamic changes and alleviating oxidative stress, inflammatory and apoptotic markers induced by monocrotaline in rats. Furthermore, diosgenin therapy prevented monocrotaline-induced changes in nitric oxide production, endothelial and inducible nitric oxide synthase protein expression as well as histological analysis. These findings support the beneficial effect of diosgenin in pulmonary hypertension induced by monocrotaline in rats.

  19. Traumatic Brain Injury, Microglia, and Beta Amyloid


    Mannix, Rebekah C.; Whalen, Michael J


    Recently, there has been growing interest in the association between traumatic brain injury (TBI) and Alzheimer's Disease (AD). TBI and AD share many pathologic features including chronic inflammation and the accumulation of beta amyloid (A\\(\\beta\\)). Data from both AD and TBI studies suggest that microglia play a central role in A\\(\\beta\\) accumulation after TBI. This paper focuses on the current research on the role of microglia response to A\\(\\beta\\) after TBI.

  20. Beta Thalassemia (United States)

    Beta thalassemia is found in people of Mediterranean, Middle Eastern, African, South Asian (Indian, Pakistani, etc.), Southeast Asian and Chinese descent. 1 Beta Thalassemia ßß Normal beta globin genes found on chromosomes ...

  1. Role of IL-1beta in type 2 diabetes

    DEFF Research Database (Denmark)

    Dinarello, Charles A; Donath, Marc Y; Mandrup-Poulsen, Thomas


    To understand the role of inflammation as the fundamental cause of type 2 diabetes and specifically to examine the contribution of IL-1beta.......To understand the role of inflammation as the fundamental cause of type 2 diabetes and specifically to examine the contribution of IL-1beta....

  2. Amyloid β Peptide-Induced Changes in Prefrontal Cortex Activity and Its Response to Hippocampal Input (United States)

    Flores-Martínez, Ernesto


    Alterations in prefrontal cortex (PFC) function and abnormalities in its interactions with other brain areas (i.e., the hippocampus) have been related to Alzheimer Disease (AD). Considering that these malfunctions correlate with the increase in the brain's amyloid beta (Aβ) peptide production, here we looked for a causal relationship between these pathognomonic signs of AD. Thus, we tested whether or not Aβ affects the activity of the PFC network and the activation of this cortex by hippocampal input stimulation in vitro. We found that Aβ application to brain slices inhibits PFC spontaneous network activity as well as PFC activation, both at the population and at the single-cell level, when the hippocampal input is stimulated. Our data suggest that Aβ can contribute to AD by disrupting PFC activity and its long-range interactions throughout the brain. PMID:28127312

  3. NADPH oxidase mediates β-amyloid peptide-induced activation of ERK in hippocampal organotypic cultures (United States)

    Serrano, Faridis; Chang, Angela; Hernandez, Caterina; Pautler, Robia G; Sweatt, J David; Klann, Eric


    Background Previous studies have shown that beta amyloid (Aβ) peptide triggers the activation of several signal transduction cascades in the hippocampus, including the extracellular signal-regulated kinase (ERK) cascade. In this study we sought to characterize the cellular localization of phosphorylated, active ERK in organotypic hippocampal cultures after acute exposure to either Aβ (1-42) or nicotine. Results We observed that Aβ and nicotine increased the levels of active ERK in distinct cellular localizations. We also examined whether phospho-ERK was regulated by redox signaling mechanisms and found that increases in active ERK induced by Aβ and nicotine were blocked by inhibitors of NADPH oxidase. Conclusion Our findings indicate that NADPH oxidase-dependent redox signaling is required for Aβ-induced activation of ERK, and suggest a similar mechanism may occur during early stages of Alzheimer's disease. PMID:19804648

  4. Amyloid β Peptide-Induced Changes in Prefrontal Cortex Activity and Its Response to Hippocampal Input

    Directory of Open Access Journals (Sweden)

    Ernesto Flores-Martínez


    Full Text Available Alterations in prefrontal cortex (PFC function and abnormalities in its interactions with other brain areas (i.e., the hippocampus have been related to Alzheimer Disease (AD. Considering that these malfunctions correlate with the increase in the brain’s amyloid beta (Aβ peptide production, here we looked for a causal relationship between these pathognomonic signs of AD. Thus, we tested whether or not Aβ affects the activity of the PFC network and the activation of this cortex by hippocampal input stimulation in vitro. We found that Aβ application to brain slices inhibits PFC spontaneous network activity as well as PFC activation, both at the population and at the single-cell level, when the hippocampal input is stimulated. Our data suggest that Aβ can contribute to AD by disrupting PFC activity and its long-range interactions throughout the brain.

  5. Vasoactive intestinal peptide induces cyclooxygenase-2 expression through nuclear factor-κB in human prostate cell lines. Differential time-dependent responses in cancer progression


    Fernández-Martínez, Ana B.; Collado, Beatriz; Bajo, Ana M.; Sánchez-Chapado, Manuel; Prieto,Juan C.; Carmena, María J.


    Vasoactive intestinal peptide induces cyclooxygenase-2 expression through nuclear factor-?B in human prostate cell lines. Differential time-dependent responses in cancer progression SPAIN (Fernandez-Martinez, Ana B.) SPAIN Received: 2006-09-11 Revised: 2007-01-11 Accepted: 2007-01-11

  6. The comparative effectiveness of demineralized bone matrix, beta-tricalcium phosphate, and bovine-derived anorganic bone matrix on inflammation and bone formation using a paired calvarial defect model in rats

    Directory of Open Access Journals (Sweden)

    Khoshzaban A


    Full Text Available Ahad Khoshzaban1,2,3, Shahram Mehrzad1, Vida Tavakoli2, Saeed Heidari Keshel2, Gholam Reza Behrouzi2, Maryam Bashtar2 1Iranian Tissue Bank Research and Preparation Center, Imam Khomeini Hospital Complex, 2Stem Cells Preparation Unit, Eye Research Center, Farabi Hospital, Tehran University of Medical Science, 3Dental Bio Material Department, Tehran University of Medical Science, Faculty of Dentistry, Tehran, Iran Background: In this study, the effectiveness of Iranian Tissue Bank–produced demineralized bone matrix (ITB-DBM, beta-tricalcium phosphate (ßTCP, and Bio-Oss® (Geistlich Pharma AG, Wolhusen, Switzerland were evaluated and compared with double controls. The main goal was to measure the amount of new bone formation in the center of defects created in rat calvaria. Another goal was to compare the controls and evaluate the effects of each treatment material on their adjacent untreated (control defects. Methods: In this study, 40 male Wistar rats were selected and divided into four groups, In each group, there were ten rats with two defects in their calvarias; one of them is considered as control and the other one was treated with ITB-DBM (group 1, BIO-OSS (group2, and ßTCP (group 3, respectively. But in group 4, both defects were considered as control. The amount of inflammation and new bone formation were evaluated at 4 and 10 weeks. In the first group, one defect was filled with ITB-DBM; in the second group, one defect was filled with Bio-Oss; in the third group, one defect was filled with ßTCP; and in the fourth group, both defects were left unfilled. Zeiss microscope (Carl Zeiss AG, Oberkochen, Germany and Image Tool® (version 3.0; University of Texas Health Science Center at San Antonio, San Antonio, TX software were used for evaluation. SPSS Statistics (IBM Corp, Somers, NY was used for statistical analysis. Results: Maximum bone formation at 4 and 10 weeks were observed in the ITB-DBM group (46.960% ± 4.366%, 94.970% ± 0

  7. Inflammation and Heart Disease (United States)

    ... Disease Venous Thromboembolism Aortic Aneurysm More Inflammation and Heart Disease Updated:Oct 12,2016 Understand the risks of ... inflammation causes cardiovascular disease, inflammation is common for heart disease and stroke patients and is thought to be ...

  8. The chalcone derivative Chana 1 protects against amyloid β peptide-induced oxidative stress and cognitive impairment. (United States)

    Kwak, Jieun; Kim, Mi-Jeong; Choi, Kyung-Chul; Choi, Hyo-Kyung; Jun, Woojin; Park, Hyun-Jin; Lee, Yoo-Hyun; Yoon, Ho-Geun


    Alzheimer's disease (AD) is the most common neurodegenerative disease to cause dementia in the elderly. Amyloid β (Aβ)-peptide induced oxidative stress causes the initiation and progression of AD. Recently, new chalcone derivatives termed the Chana series were synthesized. Among them, Chana 1 showed high free radical scavenging activity (72.5%), as measured by a DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. In this study, we investigated the effect of Chana 1 against Aβ-induced cytotoxicity and cognitive deficits. Additionally, we sought to estimate the lethal dose, 50% (LD50) of Chana 1 in mice using an acute oral toxicity test. We found that Chana 1 significantly protected against Aβ-induced neuronal cell death in PC12 cells. Oral administration of Chana 1 at a dose of 50 mg/kg body weight/day significantly improved Aβ-induced learning and memory impairment in mice, as measured in Y-maze and passive avoidance tests. In acute toxicity tests, the LD50 in mice was determined to be 520.44 mg/kg body weight. The data are valuable for future studies and suggest that Chana 1 has therapeutic potential for the management of neurodegenerative disease.

  9. Endocrine expression of the active form of TGF-beta1 in the TGF-beta1 null mice fails to ameliorate lethal phenotype. (United States)

    Longenecker, Glenn; Thyagarajan, Tamizchelvi; Nagineni, Chandrasekharam N; Flanders, Kathleen C; Factor, Valentina; Miller, Georgina; Ward, Jerrold M; Nalca, Aysegul; Rangnekar, Vivek M; Thorgeirsson, Snorri; Kulkarni, Ashok B


    TGF-beta1 null mice die by 3 to 4 weeks of age due to a severe autoimmune-mediated multifocal inflammation resulting in multi-organ failure. To assess the therapeutic potential of circulating levels of active TGF-beta1, we generated mice with endocrine expression of active TGF-beta1 on a TGF-beta1 null background (TGF-beta1 (-/-/TG)) by crossing TGF-beta1(+/-) mice with transgenic mice (TG) that express recombinant TGF-beta1 specifically in the liver and secrete it in the blood. The TGF-beta1 (-/-/TG) mice exhibit a survival profile similar to the TGF-beta1 (-/-) mice indicating a failure to rescue the lethal phenotype. However, serum TGF-beta1 levels in the TGF-beta1 (-/-/TG) mice were restored to near normal levels with expression in all the tissues, notably in the kidney and spleen. Histopathology showed reduced inflammation in the target tissues, especially in the heart. Interestingly, unlike TGF-beta1 (-/-) mice, the TGF-beta1 (-/-/TG) mice have glomerulonephritis in their kidneys similar to the TG mice. Thus, the phenotype of TGF-beta1 (-/-/TG) animal model indicates the potential role of circulating active-TGF-beta1 in reducing inflammation, but its failure to rescue lethality in TGF-beta1 null mice indicates a critical autocrine role of TGF-beta1.

  10. Gliadin peptides induce tissue transglutaminase activation and ER-stress through Ca2+ mobilization in Caco-2 cells.

    Directory of Open Access Journals (Sweden)

    Ivana Caputo

    Full Text Available BACKGROUND: Celiac disease (CD is an intestinal inflammatory condition that develops in genetically susceptible individuals after exposure to dietary wheat gliadin. The role of post-translational modifications of gliadin catalyzed by tissue transglutaminase (tTG seems to play a crucial role in CD. However, it remains to be established how and where tTG is activated in vivo. We have investigated whether gliadin peptides modulate intracellular Ca(2+ homeostasis and tTG activity. METHODS/PRINCIPAL FINDINGS: We studied Ca(2+ homeostasis in Caco-2 cells by single cell microfluorimetry. Under our conditions, A-gliadin peptides 31-43 and 57-68 rapidly mobilized Ca(2+ from intracellular stores. Specifically, peptide 31-43 mobilized Ca(2+ from the endoplasmic reticulum (ER and mitochondria, whereas peptide 57-68 mobilized Ca(2+ only from mitochondria. We also found that gliadin peptide-induced Ca(2+ mobilization activates the enzymatic function of intracellular tTG as revealed by in situ tTG activity using the tTG substrate pentylamine-biotin. Moreover, we demonstrate that peptide 31-43, but not peptide 57-68, induces an increase of tTG expression. Finally, we monitored the expression of glucose-regulated protein-78 and of CCAAT/enhancer binding protein-homologous protein, which are two biochemical markers of ER-stress, by real-time RT-PCR and western blot. We found that chronic administration of peptide 31-43, but not of peptide 57-68, induces the expression of both genes. CONCLUSIONS: By inducing Ca(2+ mobilization from the ER, peptide 31-43 could promote an ER-stress pathway that may be relevant in CD pathogenesis. Furthermore, peptides 31-43 and 57-68, by activating intracellular tTG, could alter inflammatory key regulators, and induce deamidation of immunogenic peptides and gliadin-tTG crosslinking in enterocytes and specialized antigen-presenting cells.

  11. Inflammation links excess fat to insulin resistance: the role of the interleukin-1 family

    NARCIS (Netherlands)

    Tack, C.J.; Stienstra, R.; Joosten, L.A.B.; Netea, M.G.


    A growing body of evidence suggests that cytokines of the interleukin-1 (IL-1) family, particularly IL-1 beta but also IL-1Ra and IL-18, are involved in obesity-associated inflammation. IL-1 beta is produced via cleavage of pro-IL-1 beta by caspase-1, which in turn is activated by a multiprotein com

  12. Inflammation links excess fat to insulin resistance: the role of the interleukin-1 family.

    NARCIS (Netherlands)

    Tack, C.J.J.; Stienstra, R.; Joosten, L.A.B.; Netea, M.G.


    A growing body of evidence suggests that cytokines of the interleukin-1 (IL-1) family, particularly IL-1beta but also IL-1Ra and IL-18, are involved in obesity-associated inflammation. IL-1beta is produced via cleavage of pro-IL-1beta by caspase-1, which in turn is activated by a multiprotein comple

  13. Inflammation of the Penis (United States)

    ... CDC's HPV Vaccine Guidelines Additional Content Medical News Inflammation of the Penis (Balanitis; Posthitis; Balanoposthitis) By Patrick ... Penile and Testicular Disorders Epididymitis and Epididymo-orchitis Inflammation of the Penis Orchitis Peyronie Disease Phimosis and ...

  14. Inflammation of the Orbit (United States)

    ... Boomers Additional Content Medical News Inflammation of the Orbit (Inflammatory Orbital Pseudotumor) By James Garrity, MD, Mayo ... Socket Disorders Cavernous Sinus Thrombosis Inflammation of the Orbit Orbital Cellulitis Preseptal Cellulitis Tumors of the Orbit ...

  15. FGF23 and inflammation (United States)

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


    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

  16. Beta-glucuronidase in physiology and disease. (United States)

    Basińska, Agnieszka; Floriańczyk, Bolesław


    beta-glucoronidase (EC is a lysosomal enzyme catylysing the decomposition of beta-D-glucoronides--compounds arising as a result of the combination of beta-D-glucoronic acid and a number of compounds both exo- and endogenous, containing hydroxylic, carboxylic, amine, imine or thiol groups. The most common test evaluating the activity of the enzyme is that using phenolphtalein glucoronide as a biosynthetic substrate. The freed aglycons are colorimetrically assayed. The activity of beta-glucoronidase increases in many pathological conditions: liver infammations, cirrhosis of the liver, inflammations of other organs, cholestatic jaundice, tuberculosis, sarcoidosis and also in neoplasms. Many authors point to beta-glucoronidase as a sensitive indicator signalling cell damage.

  17. TAT-mediated intracellular delivery of NPM-derived peptide induces apoptosis in leukemic cells and suppresses leukemogenesis in mice. (United States)

    Zhou, Yun; Du, Wei; Koretsky, Tara; Bagby, Grover C; Pang, Qishen


    Nucleophosmin (NPM) is frequently overexpressed in leukemias and other tumors. NPM has been reported to suppress oncogene-induced senescence and apoptosis and may represent a therapeutic target for cancer. We fused a NPM-derived peptide to the HIV-TAT (TAT-NPMDeltaC) and found that the fusion peptide inhibited proliferation and induced apoptotic death of primary fibroblasts and preleukemic stem cells. TAT-NPMDeltaC down-regulated several NF-kappaB-controlled survival and inflammatory proteins and suppressed NF-kappaB-driven reporter gene activities. Using an inflammation-associated leukemia model, we demonstrate that TAT-NPMDeltaC induced proliferative suppression and apoptosis of preleukemic stem cells and significantly delayed leukemic development in mice. Mechanistically, TAT-NPMDeltaC associated with wild-type NPM proteins and formed complexes with endogenous NPM and p65 at promoters of several antiapoptotic and inflammatory genes and abrogated their transactivation by NF-kappaB in leu-kemic cells. Thus, TAT-delivered NPM peptide may provide a novel therapy for inflammation-associated tumors that require NF-kappaB signaling for survival.

  18. Inflammation Aggravates Disease Severity in Marfan Syndrome Patients

    NARCIS (Netherlands)

    Radonic, Teodora; de Witte, Piet; Groenink, Maarten; de Waard, Vivian; Lutter, Rene; van Eijk, Marco; Jansen, Marnix; Timmermans, Janneke; Kempers, Marlies; Scholte, Arthur J.; Hilhorst-Hofstee, Yvonne; van den Berg, Maarten P.; van Tintelen, J. Peter; Pals, Gerard; Baars, Marieke J. H.; Mulder, Barbara J. M.; Zwinderman, Aeilko H.


    Background: Marfan syndrome (MFS) is a pleiotropic genetic disorder with major features in cardiovascular, ocular and skeletal systems, associated with large clinical variability. Numerous studies reveal an involvement of TGF-beta signaling. However, the contribution of tissue inflammation is not ad

  19. Targeting inflammation in diabetes: Newer therapeutic options

    Institute of Scientific and Technical Information of China (English)

    Neeraj; Kumar; Agrawal; Saket; Kant


    Inflammation has been recognised to both decrease beta cell insulin secretion and increase insulin resis-tance. Circulating cytokines can affect beta cell function directly leading to secretory dysfunction and increased apoptosis. These cytokines can also indirectly affect beta cell function by increasing adipocyte inflamma-tion.The resulting glucotoxicity and lipotoxicity further enhance the inflammatory process resulting in a vicious cycle. Weight reduction and drugs such as metformin have been shown to decrease the levels of C-Reactive Protein by 31% and 13%, respectively. Pioglitazone, insulin and statins have anti-inflammatory effects. In-terleukin 1 and tumor necrosis factor-α antagonists are in trials and NSAIDs such as salsalate have shown an improvement in insulin sensitivity. Inhibition of 12-lipo-oxygenase, histone de-acetylases, and activation of sirtuin-1 are upcoming molecular targets to reduce in-flammation. These therapies have also been shown to decrease the conversion of pre-diabetes state to diabe-tes. Drugs like glicazide, troglitazone, N-acetylcysteine and selective COX-2 inhibitors have shown benefit in diabetic neuropathy by decreasing inflammatory mark-ers. Retinopathy drugs are used to target vascular en-dothelial growth factor, angiopoietin-2, various protein-ases and chemokines. Drugs targeting the proteinases and various chemokines are pentoxifylline, inhibitors of nuclear factor-kappa B and mammalian target of rapa-mycin and are in clinical trials for diabetic nephropathy. Commonly used drugs such as insulin, metformin, per-oxisome proliferator-activated receptors, glucagon like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors also decrease inflammation. Anti-inflammatory thera-pies represent a potential approach for the therapy of diabetes and its complications.

  20. Estrogens, inflammation and cognition. (United States)

    Au, April; Feher, Anita; McPhee, Lucy; Jessa, Ailya; Oh, Soojin; Einstein, Gillian


    The effects of estrogens are pleiotropic, affecting multiple bodily systems. Changes from the body's natural fluctuating levels of estrogens, through surgical removal of the ovaries, natural menopause, or the administration of exogenous estrogens to menopausal women have been independently linked to an altered immune profile, and changes to cognitive processes. Here, we propose that inflammation may mediate the relationship between low levels of estrogens and cognitive decline. In order to determine what is known about this connection, we review the literature on the cognitive effects of decreased estrogens due to oophorectomy or natural menopause, decreased estrogens' role on inflammation--both peripherally and in the brain--and the relationship between inflammation and cognition. While this review demonstrates that much is unknown about the intersection between estrogens, cognition, inflammation, we propose that there is an important interaction between these literatures.

  1. Orbital inflammation: Corticosteroids first. (United States)

    Dagi Glass, Lora R; Freitag, Suzanne K


    Orbital inflammation is common, and may affect all ages and both genders. By combining a thorough history and physical examination, targeted ancillary laboratory testing and imaging, a presumptive diagnosis can often be made. Nearly all orbital inflammatory pathology can be empirically treated with corticosteroids, thus obviating the need for histopathologic diagnosis prior to initiation of therapy. In addition, corticosteroids may be effective in treating concurrent systemic disease. Unless orbital inflammation responds atypically or incompletely, patients can be spared biopsy.

  2. Interferon-beta attenuates lung inflammation following experimental subarachnoid hemorrhage

    NARCIS (Netherlands)

    Cobelens, P.M.; Tiebosch, I.A.C.W.; Dijkhuizen, R.M.; van der Meide, P.H.; Zwartbol, R.; Heijnen, C.J.; Kesecioglu, J.; van den Bergh, W.M.


    Introduction: Aneurysmal subarachnoid hemorrhage (SAH) affects relatively young people and carries a poor prognosis with a case fatality rate of 35%. One of the major systemic complications associated with SAH is acute lung injury (ALI) which occurs in up to one-third of the patients and is associat

  3. [Connective tissue and inflammation]. (United States)

    Jakab, Lajos


    The author summarizes the structure of the connective tissues, the increasing motion of the constituents, which determine the role in establishing the structure and function of that. The structure and function of the connective tissue are related to each other in the resting as well as inflammatory states. It is emphasized that cellular events in the connective tissue are part of the defence of the organism, the localisation of the damage and, if possible, the maintenance of restitutio ad integrum. The organism responds to damage with inflammation, the non specific immune response, as well as specific, adaptive immunity. These processes are located in the connective tissue. Sterile and pathogenic inflammation are relatively similar processes, but inevitable differences are present, too. Sialic acids and glycoproteins containing sialic acids have important roles, and the role of Siglecs is also highlighted. Also, similarities and differences in damages caused by pathogens and sterile agents are briefly summarized. In addition, the roles of adhesion molecules linked to each other, and the whole event of inflammatory processes are presented. When considering practical consequences it is stressed that the structure (building up) of the organism and the defending function of inflammation both have fundamental importance. Inflammation has a crucial role in maintaining the integrity and the unimpaired somato-psychological state of the organism. Thus, inflammation serves as a tool of organism identical with the natural immune response, inseparably connected with the specific, adaptive immune response. The main events of the inflammatory processes take place in the connective tissue.

  4. Unfolding, aggregation, and seeded amyloid formation of lysine-58-cleaved beta(2)-microglobulin

    DEFF Research Database (Denmark)

    Heegaard, N.H.H.; Jørgensen, T.J.D.; Rozlosnik, N.;


    beta(2)-Microglobulin (beta(2)m) is the amyloidogenic protein in dialysis-related amyloidosis, but the mechanisms underlying beta(2)m fibrillogenesis in vivo are largely unknown. We study a structural variant of beta(2)M that has been linked to cancer and inflammation and may be present in the ci......beta(2)-Microglobulin (beta(2)m) is the amyloidogenic protein in dialysis-related amyloidosis, but the mechanisms underlying beta(2)m fibrillogenesis in vivo are largely unknown. We study a structural variant of beta(2)M that has been linked to cancer and inflammation and may be present...... in the circulation of dialysis patients. This beta(2)M variant, Delta K58-beta(2)m, is a disulfide-linked two-chain molecule consisting of amino acid residues 1-57 and 59-99 of intact beta(2)m, and we here demonstrate and characterize its decreased conformational stability as compared to wild-type (wt) beta(2)M......, and at 37 degrees C the half-time for unfolding is more than 170-fold faster than at 15 degrees C. Conformational changes are also reflected by a very prominent Congo red binding of Delta K58-beta(2)m at 37 degrees C, by the evolution of thioflavin T fluorescence, and by changes in intrinsic fluorescence...

  5. Inflammation and colon cancer. (United States)

    Terzić, Janos; Grivennikov, Sergei; Karin, Eliad; Karin, Michael


    The connection between inflammation and tumorigenesis is well-established and in the last decade has received a great deal of supporting evidence from genetic, pharmacological, and epidemiological data. Inflammatory bowel disease is an important risk factor for the development of colon cancer. Inflammation is also likely to be involved with other forms of sporadic as well as heritable colon cancer. The molecular mechanisms by which inflammation promotes cancer development are still being uncovered and could differ between colitis-associated and other forms of colorectal cancer. Recent work has elucidated the role of distinct immune cells, cytokines, and other immune mediators in virtually all steps of colon tumorigenesis, including initiation, promotion, progression, and metastasis. These mechanisms, as well as new approaches to prevention and therapy, are discussed in this review.

  6. Sinonasal inflammation in COPD

    DEFF Research Database (Denmark)

    Håkansson, Kåre; Konge, Lars; Thomsen, Sf


    In this review we demonstrate that patients with chronic obstructive pulmonary disease (COPD) frequently report sinonasal symptoms. Furthermore, we present evidence that smoking on its own can cause nasal disease, and that in COPD patients, nasal inflammation mimics that of the bronchi. All...... this evidence suggests that COPD related sinonasal disease does exist and that smoking on its own rather than systemic inflammation triggers the condition. However, COPD related sinonasal disease remains to be characterized in terms of symptoms and endoscopic findings. In addition, more studies are needed...... to quantify the negative impact of sinonasal symptoms on the quality of life in COPD patients....

  7. Quercetin, Inflammation and Immunity. (United States)

    Li, Yao; Yao, Jiaying; Han, Chunyan; Yang, Jiaxin; Chaudhry, Maria Tabassum; Wang, Shengnan; Liu, Hongnan; Yin, Yulong


    In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity.

  8. Effects of Yizhi Capsule (益智胶囊) on Learning and Memory Disorder and β-amyloid Peptide Induced Neurotoxicity in Rats

    Institute of Scientific and Technical Information of China (English)

    WU Hang-yu; XU Jiang-ping; LI Lin; ZHU Bai-hua


    Objective: To explore the effects of Yizhi Capsule (益智胶囊, YZC) on learning and memory disorder and β-amyloid peptide induced neurotoxicity in rats. Methods: Various doses of YZC were administered to Sprague-Dawley (SD) rats for 8 consecutive days, twice a day. On the 8th day of the experiment,scopolamine hydrobromide was intraperitoneally injected to every rat and Morris water maze test and shuttle dark avoidance test were carried out respectively to explore the changes of learning and memory capacities in the rats. Besides, after the cerebral cortical neurons of newborn SD rats aged within 3 days were cultured in vitro for 7 days, drug serum containing YZC was added to the cultured neurons before or after β amyloid peptide25-35 (Aβ25-35) intoxication to observe the protective effect of YZC on neurotoxicity by MTT assay and to determine the LDH content in the supernatant. Results: Compared with those untreated with YZC, the rats having received YZC treatment got superiority in shorter time of platform seeking in Morris water maze test,as well as elongated latent period and less times of error in shuttle dark avoidance test. On the cultured neurons, YZC drug serum could effectively increase the survival rate of Aβ25-35 intoxicated neurons and reduce the LDH contents in cultured supernatant. Conclusion: YZC has an action of improving learning and memory disorder, and good protective effect on Aβ25-35 induced neurotoxicity in SD rats.

  9. Immunsystemet ved kronisk inflammation

    DEFF Research Database (Denmark)

    Bendtzen, Klaus


    Innate and adaptive immunity has evolved as a defence against infections and as an important repair mechanism after physical injury. If elimination of microbes and healing is not achieved, or if the immune system is dysregulated, chronic inflammation ensues. Immune cells become engaged in prolonged...

  10. Ion channels in inflammation. (United States)

    Eisenhut, Michael; Wallace, Helen


    Most physical illness in vertebrates involves inflammation. Inflammation causes disease by fluid shifts across cell membranes and cell layers, changes in muscle function and generation of pain. These disease processes can be explained by changes in numbers or function of ion channels. Changes in ion channels have been detected in diarrhoeal illnesses, pyelonephritis, allergy, acute lung injury and systemic inflammatory response syndromes involving septic shock. The key role played by changes in ion transport is directly evident in inflammation-induced pain. Expression or function of all major categories of ion channels like sodium, chloride, calcium, potassium, transient receptor potential, purinergic receptor and acid-sensing ion channels can be influenced by cyto- and chemokines, prostaglandins, leukotrienes, histamine, ATP, reactive oxygen species and protons released in inflammation. Key pathways in this interaction are cyclic nucleotide, phosphoinositide and mitogen-activated protein kinase-mediated signalling, direct modification by reactive oxygen species like nitric oxide, ATP or protons and disruption of the cytoskeleton. Therapeutic interventions to modulate the adverse and overlapping effects of the numerous different inflammatory mediators on each ion transport system need to target adversely affected ion transport systems directly and locally.

  11. The glycosylated flavonoids vitexin, isovitexin, and quercetrin isolated from Serjania erecta Radlk (Sapindaceae) leaves protect PC12 cells against amyloid-β25-35 peptide-induced toxicity. (United States)

    Guimarães, Camila Carla; Oliveira, Denise Dias; Valdevite, Mayara; Saltoratto, Ana Lúcia Fachin; Pereira, Sarazete Izidia Vaz; França, Suzelei de Castro; Pereira, Ana Maria Soares; Pereira, Paulo Sérgio


    The Aβ peptide-mediated toxicity participates in the neuronal death that occurs in Alzheimer's disease. The present study aims to isolate the major compounds of Serjania erecta Radlk leaves and assess whether these compounds protect PC12 cells from Aβ25-35 peptide-induced toxicity. We isolated three flavonoid glycosides with high purity: quercetrin, vitexin, and isovitexin. The Aβ25-35 peptide alone decreased the PC12 cell viability in a concentration-dependent manner, as evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. We selected the Aβ25-35 peptide concentration of 50 µM for the experiments. Treatment of PC12 cells with the flavonoids before exposure to the Aβ25-35 peptide increased cell viability, i.e., these compounds protected the cells against Aβ25-35 peptide-induced toxicity. Vitexin promoted higher protection levels than quercetrin and isovitexin, and reduced the lactate dehydrogenase release and NO production in Aβ25-35 peptide-treated PC12 cells. Therefore, the glycosylated flavonoids that exist in S. erecta leaves, especially vitexin, protect PC12 cells from Aβ25-35 peptide-induced toxicity.

  12. COPD exacerbations, inflammation and treatment

    NARCIS (Netherlands)

    Bathoorn, Derk


    This thesis describes investigations into the inflammation in COPD, and its treatment. Inflammation in COPD is a central factor in the onset of the disease and its progression. During acute deteriorations of the disease, exacerbations, the inflammation is more severe, and depending on the cause of t

  13. S4(13)-PV cell-penetrating peptide induces physical and morphological changes in membrane-mimetic lipid systems and cell membranes: implications for cell internalization. (United States)

    Cardoso, Ana M S; Trabulo, Sara; Cardoso, Ana L; Lorents, Annely; Morais, Catarina M; Gomes, Paula; Nunes, Cláudia; Lúcio, Marlene; Reis, Salette; Padari, Kärt; Pooga, Margus; Pedroso de Lima, Maria C; Jurado, Amália S


    The present work aims to gain insights into the role of peptide-lipid interactions in the mechanisms of cellular internalization and endosomal escape of the S4(13)-PV cell-penetrating peptide, which has been successfully used in our laboratory as a nucleic acid delivery system. A S4(13)-PV analogue, S4(13)-PVscr, displaying a scrambled amino acid sequence, deficient cell internalization and drug delivery inability, was used in this study for comparative purposes. Differential scanning calorimetry, fluorescence polarization and X-ray diffraction at small and wide angles techniques showed that both peptides interacted with anionic membranes composed of phosphatidylglycerol or a mixture of this lipid with phosphatidylethanolamine, increasing the lipid order, shifting the phase transition to higher temperatures and raising the correlation length between the bilayers. However, S4(13)-PVscr, in contrast to the wild-type peptide, did not promote lipid domain segregation and induced the formation of an inverted hexagonal lipid phase instead of a cubic phase in the lipid systems assayed. Electron microscopy showed that, as opposed to S4(13)-PVscr, the wild-type peptide induced the formation of a non-lamellar organization in membranes of HeLa cells. We concluded that lateral phase separation and destabilization of membrane lamellar structure without compromising membrane integrity are on the basis of the lipid-driven and receptor-independent mechanism of cell entry of S4(13)-PV peptide. Overall, our results can contribute to a better understanding of the role of peptide-lipid interactions in the mechanisms of cell-penetrating peptide membrane translocation, helping in the future design of more efficient cell-penetrating peptide-based drug delivery systems.

  14. Gut Microbiota and Inflammation

    Directory of Open Access Journals (Sweden)

    Goran Molin


    Full Text Available Systemic and local inflammation in relation to the resident microbiota of the human gastro-intestinal (GI tract and administration of probiotics are the main themes of the present review. The dominating taxa of the human GI tract and their potential for aggravating or suppressing inflammation are described. The review focuses on human trials with probiotics and does not include in vitro studies and animal experimental models. The applications of probiotics considered are systemic immune-modulation, the metabolic syndrome, liver injury, inflammatory bowel disease, colorectal cancer and radiation-induced enteritis. When the major genomic differences between different types of probiotics are taken into account, it is to be expected that the human body can respond differently to the different species and strains of probiotics. This fact is often neglected in discussions of the outcome of clinical trials with probiotics.

  15. Nanoparticles and Inflammation

    Directory of Open Access Journals (Sweden)

    Ross Stevenson


    Full Text Available The development of nanoscale molecular probes capable of diagnosis, characterization, and clinical treatment of disease is leading to a new generation of imaging technologies. Such probes are particularly relevant to inflammation, where the detection of subclinical, early disease states could facilitate speedier detection that could yield enhanced, tailored therapies. Nanoparticles offer robust platforms capable of sensitive detection, and early research has indicated their suitability for the detection of vascular activation and cellular recruitment at subclinical levels. This suggests that nanoparticle techniques may provide excellent biomarkers for the diagnosis and progression of inflammatory diseases with magnetic resonance imaging (MRI, fluorescent quantum dots (QDs, and surface enhanced Raman scattering (SERS probes being just some of the new methodologies employed. Development of these techniques could lead to a range of sensitive probes capable of ultrasensitive, localized detection of inflammation. This article will discuss the merits of each approach, with a general overview to their applicability in inflammatory diseases.

  16. Beta-carotene (United States)

    ... patches on the tongue and mouth called oral leukoplakia. Taking beta-carotene by mouth for up to 12 months seems to decrease symptoms of oral leukoplakia. Osteoarthritis. Beta-carotene taken by mouth may prevent ...

  17. Inflammation and Incretins

    Directory of Open Access Journals (Sweden)

    Amitabh Hatwal


    Full Text Available Nutrient excess results in systemic inflammation in diabetes contributing to insulin resistance, dyslipidaemia and increased cardiovascular risk. GLP-1 agonists and DPP-4 inhibitors, which are now well accepted therapies for diabetes may play a unique role in modulating this inflammatory process. Incretin based therapies have shown beneficial anti-inflammatory effects on surrogate markers but cardiovascular outcome data is still lacking.

  18. Peritoneal dialysis and inflammation. (United States)

    Velloso, Marina Souza Silva; Otoni, Alba; de Paula Sabino, Adriano; de Castro, Whocely Victor; Pinto, Sérgio Wyton Lima; Marinho, Maria Aparecida Silva; Rios, Danyelle Romana Alves


    Peritoneal dialysis (PD) is a kidney replacement therapy for end stage renal disease (ESRD) patients. Despite being a lifesaving treatment, the rate of mortality in patients under PD is elevated, mainly due to the chronic peritoneal dysfunction which is characterized by inflammation, peritoneal fibrosis and neoangiogenesis. The inflammatory process is trigged and modulated by the type of the peritoneal dialysis solutions (PDSs) used during PD. Currently, different PDSs are commercially available: (i) the conventional solutions; (ii) solutions of neutral pH containing low concentration of glucose degradation products (GDPs); (iii) solutions with icodextrin; and (iv) solutions containing taurine. Therefore, the aim of this review is to describe the different types of peritoneal dialysis solutions used during PD and their relationship with systemic and intraperitoneal inflammation. Some studies suggested that solutions of neutral pH containing low concentration of GDPs, icodextrin and taurine have better biocompatibility and lower influence on the inflammatory process compared to the conventional one. On the other hand, the studies, in general, were performed with a small population and for a short period of time. Therefore, further well-designed and -controlled clinical trials with larger number of individuals are required in order to better understand the role of different peritoneal dialysis solution types in the development of inflammation in patients with chronic peritoneal dialysis. Accordingly, studies that are more well-designed, well-controlled and with a larger number of patients are needed to explain and define the role of different types of PDS in the inflammation development in patients with chronic peritoneal dialysis.

  19. TWEAK Promotes Peritoneal Inflammation (United States)

    Sanz, Ana Belen; Aroeira, Luiz Stark; Bellon, Teresa; del Peso, Gloria; Jimenez-Heffernan, Jose; Santamaria, Beatriz; Sanchez-Niño, Maria Dolores; Blanco-Colio, Luis Miguel; Lopez-Cabrera, Manuel; Ruiz-Ortega, Marta; Egido, Jesus; Selgas, Rafael; Ortiz, Alberto


    Peritoneal dialysis (PD) is complicated by peritonitis episodes that cause loss of mesothelium and eventually sclerosing peritonitis. An improved understanding of the molecular contributors to peritoneal injury and defense may increase the therapeutic armamentarium to optimize peritoneal defenses while minimizing peritoneal injury. There is no information on the expression and function of the cytokine TWEAK and its receptor Fn14 during peritoneal injury. Fn14 expression and soluble TWEAK levels were measured in human PD peritoneal effluent cells or fluids with or without peritonitis. Fn14 expression was also analyzed in peritoneal biopsies from PD patients. Actions of intraperitoneal TWEAK were studied in mice in vivo. sTWEAK levels were increased in peritoneal effluent in PD peritonitis. Effluent sTWEAK levels correlated with the number of peritoneal macrophages (r = 0.491, p = 0.002). Potential TWEAK targets that express the receptor Fn14 include mesothelial cells and macrophages, as demonstrated by flow cytometry of peritoneal effluents and by analysis of peritoneal biopsies. Peritoneal biopsy Fn14 correlated with mesothelial injury, fibrosis and inflammation, suggesting a potential deleterious effect of TWEAK/Fn14. In this regard, intraperitoneal TWEAK administration to mice promoted peritoneal inflammation characterized by increased peritoneal effluent MCP-1, Fn14 and Gr1+ macrophages, increased mesothelial Fn14, MCP-1 and CCL21 expression and submesothelial tissue macrophage recruitment. Taken together these data suggest that the TWEAK/Fn14 system may promote inflammation and tissue injury during peritonitis and PD. PMID:24599047

  20. Inflammation and pulmonary hypertension. (United States)

    Mathew, Rajamma


    Pulmonary hypertension (PH) is a serious disorder with high morbidity and mortality rate. Evidence is accumulating to suggest that inflammation plays a significant role in the pathogenesis of PH. Endothelial cells play an important role in inflammation and immune reactions, and inflammatory cytokines cause endothelial dysfunction. Endothelial dysfunction is a hallmark of PH, consisting of reduced availability of vasodilators and antiproliferative factors and increased production of vasoconstrictors and vascular proliferative factors. Up-regulation of inflammatory cytokines and perivascular inflammatory cell infiltration have been detected in the lungs of patients with idiopathic PH. Prevalence of PH in patients with systemic inflammatory diseases is well documented. Interestingly, a significant loss of endothelial caveolin-1, a potent immunomodulator and an inhibitor of cell proliferation, has been reported in human and experimental forms of PH. Reduction in the expression of caveolin-1 is known to result in the removal of antiproliferative activities, thus, leading to deregulated vascular cell proliferation. This article summarizes the roles of inflammation and endothelial caveolin-1 and their possible interrelationship in PH.

  1. Forward-Looking Betas

    DEFF Research Database (Denmark)

    Christoffersen, Peter; Jacobs, Kris; Vainberg, Gregory

    Few issues are more important for finance practice than the computation of market betas. Existing approaches compute market betas using historical data. While these approaches differ in terms of statistical sophistication and the modeling of the time-variation in the betas, they are all backward......-looking. This paper introduces a radically different approach to estimating market betas. Using the tools in Bakshi and Madan (2000) and Bakshi, Kapadia and Madan (2003) we employ the information embedded in the prices of individual stock options and index options to compute our forward-looking market beta...

  2. Eicosanoids in skin inflammation. (United States)

    Nicolaou, Anna


    Eicosanoids play an integral part in homeostatic mechanisms related to skin health and structural integrity. They also mediate inflammatory events developed in response to environmental factors, such as exposure to ultraviolet radiation, and inflammatory and allergic disorders, including psoriasis and atopic dermatitis. This review article discusses biochemical aspects related to cutaneous eicosanoid metabolism, the contribution of these potent autacoids to skin inflammation and related conditions, and considers the importance of nutritional supplementation with bioactives such as omega-3 and omega-6 polyunsaturated fatty acids and plant-derived antioxidants as means of addressing skin health issues.

  3. Interleukin-1 beta (IL-1 beta) induces thrombocytosis in mice: Possible implication of IL-6

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, H.; Ishibashi, T.; Shikama, Y.; Okano, A.; Akiyama, Y.; Uchida, T.; Maruyama, Y. (Fukushima Medical College (Japan))


    We administered recombinant human interleukin-1 beta (IL-1 beta), the common mediator of inflammation process, to C57B1/6 male mice (0.5 microgram, every 12 hours over five times) intraperitoneally and consequently induced a remarkable thrombocytosis. Day 1 was designated as the following day of the last injection in the morning. A significant thrombocytosis was observed on days 1 through 5 with a peak on day 2 (162 +/- 9 x 10(4)/mm3) compared with the control mice injected with heated IL-1 beta (101 +/- 11 x 10(4)/mm3). A striking increase in mean size of marrow megakaryocytes was noted on days 1 and 2. The incorporation of 75Se-selenomethionine into circulating platelets as a measure of platelet production was about 2.3 times higher in IL-1 beta-treated mice than in control mice. To determine which factor(s) is responsible for elicited thrombocytosis, the in vitro studies and bioassays for several hematopoietic factors were performed. IL-1 beta by itself did not stimulate megakaryocytopoiesis in vitro, suggesting that the thrombocytosis is attributed to other factor(s) via IL-1 beta stimulation. Serum colony-stimulating factor (CSF) activity after a single IL-1 beta (0.5 microgram) injection, monitored by colony assay with 10% tested serum, peaked at 3 hours. Formed colonies were mostly granulocyte (G) and granulocyte-macrophage (GM)-types, and studies using rabbit anti-mouse GM-CSF serum or using human marrow as target cells showed that the CSF activity of the tested serum consisted of, at least, GM-CSF and G-CSF. Addition of IL-3 concomitantly with the tested serum gave rise to a greater number of megakaryocytic colonies. Serum IL-3, monitored by IL-3-dependent cell line 32D clone 5, and erythropoietin activities were not detected at serum level in IL-1 beta-treated mice.

  4. Probiotics as regulators of inflammation: A review

    Directory of Open Access Journals (Sweden)

    David W. Lescheid


    Full Text Available A substantial and increasing body of clinical evidence supports the role of specific strains and mixtures of probiotics in the prevention and treatment of certain diseases. Several general mechanisms of action have been proposed, including supporting repair of hyperpermeable epithelial barriers, interfering with infection by pathogens, and restoring a healthful balance of commensal microbes to affect metabolism. Emerging evidence supports an additional role of probiotics as important modulators of immune system responses, including inflammation, at mucosal surfaces. In particular, by preventing or repairing ‘leaky’ epithelial barriers, probiotics can indirectly affect the inflammatory response by negating the source of pro-inflammatory stimuli associated with low-grade endotoxemia. They also enhance production of short chain fatty acids with anti-inflammatory properties (e.g. butyrate as well as increase synthesis of antimicrobial peptides that influence inflammation resolution pathways in the mucosa. Furthermore, probiotics and some of their secreted metabolic products can act as ligands for innate immune system receptors, directly influencing key pro-inflammatory pathways. They also stimulate the differentiation and activity of important immune cells (e.g., dendritic cells, T cells, and subsequently increase production of important regulatory cytokines, including interleukin-10 (IL-10 and transforming growth factor-beta (TGF-. Finally, there are limited but increasing animal studies and clinical trials demonstrating probiotics do affect common biomarkers of inflammation, including C-reactive protein, as well as signs and symptoms of the associated diseases suggesting they can have therapeutic benefit in the treatment of chronic inflammatory disease

  5. Betting against Beta

    DEFF Research Database (Denmark)

    Frazzini, Andrea; Heje Pedersen, Lasse


    We present a model with leverage and margin constraints that vary across investors and time. We find evidence consistent with each of the model's five central predictions: (1) Because constrained investors bid up high-beta assets, high beta is associated with low alpha, as we find empirically for......, the return of the BAB factor is low. (4) Increased funding liquidity risk compresses betas toward one. (5) More constrained investors hold riskier assets....... for US equities, 20 international equity markets, Treasury bonds, corporate bonds, and futures. (2) A betting against beta (BAB) factor, which is long leveraged low-beta assets and short high-beta assets, produces significant positive risk-adjusted returns. (3) When funding constraints tighten...

  6. Betting Against Beta

    DEFF Research Database (Denmark)

    Frazzini, Andrea; Heje Pedersen, Lasse

    We present a model with leverage and margin constraints that vary across investors and time. We find evidence consistent with each of the model’s five central predictions: (1) Since constrained investors bid up high-beta assets, high beta is associated with low alpha, as we find empirically for U...... of the BAB factor is low; (4) Increased funding liquidity risk compresses betas toward one; (5) More constrained investors hold riskier assets........S. equities, 20 international equity markets, Treasury bonds, corporate bonds, and futures; (2) A betting-against-beta (BAB) factor, which is long leveraged low beta assets and short high-beta assets, produces significant positive risk-adjusted returns; (3) When funding constraints tighten, the return...

  7. The effect of inflammation and its reduction on brain plasticity in multiple sclerosis: MRI evidence (United States)

    d'Ambrosio, Alessandro; Petsas, Nikolaos; Wise, Richard G.; Sbardella, Emilia; Allen, Marek; Tona, Francesca; Fanelli, Fulvia; Foster, Catherine; Carnì, Marco; Gallo, Antonio; Pantano, Patrizia; Pozzilli, Carlo


    Abstract Brain plasticity is the basis for systems‐level functional reorganization that promotes recovery in multiple sclerosis (MS). As inflammation interferes with plasticity, its pharmacological modulation may restore plasticity by promoting desired patterns of functional reorganization. Here, we tested the hypothesis that brain plasticity probed by a visuomotor adaptation task is impaired with MS inflammation and that pharmacological reduction of inflammation facilitates its restoration. MS patients were assessed twice before (sessions 1 and 2) and once after (session 3) the beginning of Interferon beta (IFN beta), using behavioural and structural MRI measures. During each session, 2 functional MRI runs of a visuomotor task, separated by 25‐minutes of task practice, were performed. Within‐session between‐run change in task‐related functional signal was our imaging marker of plasticity. During session 1, patients were compared with healthy controls. Comparison of patients' sessions 2 and 3 tested the effect of reduced inflammation on our imaging marker of plasticity. The proportion of patients with gadolinium‐enhancing lesions reduced significantly during IFN beta. In session 1, patients demonstrated a greater between‐run difference in functional MRI activity of secondary visual areas and cerebellum than controls. This abnormally large practice‐induced signal change in visual areas, and in functionally connected posterior parietal and motor cortices, was reduced in patients in session 3 compared with 2. Our results suggest that MS inflammation alters short‐term plasticity underlying motor practice. Reduction of inflammation with IFN beta is associated with a restoration of this plasticity, suggesting that modulation of inflammation may enhance recovery‐oriented strategies that rely on patients' brain plasticity. Hum Brain Mapp 37:2431–2445, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:26991559

  8. Imperfect World of $\\beta\\beta$-decay Nuclear Data Sets

    CERN Document Server

    Pritychenko, B


    The precision of double-beta ($\\beta\\beta$) decay experimental half lives and their uncertainties is reanalyzed. The method of Benford's distributions has been applied to nuclear reaction, structure and decay data sets. First-digit distribution trend for $\\beta\\beta$-decay T$_{1/2}^{2\

  9. Thrown off balance: the effect of antenatal inflammation on the developing lung and immune system. (United States)

    Kunzmann, Steffen; Collins, Jennifer J P; Kuypers, Elke; Kramer, Boris W


    In recent years, translational research with various animal models has been helpful to answer basic questions about the effect of antenatal inflammation on maturation and development of the fetal lung and immune system. The fetal lung and immune systems are very plastic and their development can be conditioned and influenced by both endogenous and/or exogenous factors. Antenatal inflammation can induce pulmonary inflammation, leading to lung injury and remodeling in the fetal lung. Exposure to antenatal inflammation can induce interleukin-1α production, which enhances surfactant protein and lipid synthesis thereby promoting lung maturation. Interleukin-1α is therefore a candidate for the link between lung inflammation and lung maturation, preventing respiratory distress syndrome in preterm infants. Antenatal inflammation can, however, cause structural changes in the fetal lung and affect the expression of growth factors, such as transforming growth factor-beta, connective tissue growth factor, fibroblast growth factor-10, or bone morphogenetic protein-4, which are essential for branching morphogenesis. These alterations cause alveolar and microvascular simplification resembling the histology of bronchopulmonary dysplasia. Antenatal inflammation may also affect neonatal outcome by modulating the responsiveness of the immune system. Lipopolysaccharide-tolerance (endotoxin hyporesponsiveness/immunoparalysis), induced by exposure to inflammation in utero, may prevent fetal lung damage, but increases susceptibility to postnatal infections. Moreover, prenatal exposure to inflammation appears to be a predisposition for the development of adverse neonatal outcomes, like bronchopulmonary dysplasia, if the preterm infant is exposed to a second postnatal hit, such as mechanical ventilation oxygen exposure, infections, or steroids.

  10. Activation of Sirt1 by resveratrol inhibits TNF-α induced inflammation in fibroblasts.

    Directory of Open Access Journals (Sweden)

    Xiaoxia Zhu

    Full Text Available Inflammation is one of main mechanisms of autoimmune disorders and a common feature of most diseases. Appropriate suppression of inflammation is a key resolution to treat the diseases. Sirtuin1 (Sirt1 has been shown to play a role in regulation of inflammation. Resveratrol, a potent Sirt1 activator, has anti-inflammation property. However, the detailed mechanism is not fully understood. In this study, we investigated the anti-inflammation role of Sirt1 in NIH/3T3 fibroblast cell line. Upregulation of matrix metalloproteinases 9 (MMP-9, interleukin-1beta (IL-1β, IL-6 and inducible nitric oxide synthase (iNOS were induced by tumor necrosis factor alpha (TNF-α in 3T3 cells and resveratrol suppressed overexpression of these pro-inflammatory molecules in a dose-dependent manner. Knockdown of Sirt1 by RNA interference caused 3T3 cells susceptible to TNF-α stimulation and diminished anti-inflammatory effect of resveratrol. We also explored potential anti-inflammatory mechanisms of resveratrol. Resveratrol reduced NF-κB subunit RelA/p65 acetylation, which is notably Sirt1 dependent. Resveratrol also attenuated phosphorylation of mammalian target of rapamycin (mTOR and S6 ribosomal protein (S6RP while ameliorating inflammation. Our data demonstrate that resveratrol inhibits TNF-α-induced inflammation via Sirt1. It suggests that Sirt1 is an efficient target for regulation of inflammation. This study provides insight on treatment of inflammation-related diseases.

  11. SOCS, inflammation and autoimmunity

    Directory of Open Access Journals (Sweden)

    Akihiko eYoshimura


    Full Text Available Cytokines play essential roles in innate and adaptive immunity. However, excess cytokines or dysregulation of cytokine signaling can cause a variety of diseases, including allergies, autoimmune diseases, inflammation, and cancer. Most cytokines utilize the so-called Janus kinase-signal transducers and activators of transcription (JAK-STAT pathway. This pathway is negatively regulated by various mechanisms including suppressors of cytokine signaling (SOCS proteins. SOCS proteins bind to JAK or cytokine receptors, thereby suppressing further signaling events. Especially, SOCS1 and SOCS3 are strong inhibitors of JAK, because these two contain kinase inhibitory region (KIR at the N-terminus. Studies using conditional knockout mice have shown that SOCS proteins are key physiological as well as pathological regulators of immune homeostasis. Recent studies have also demonstrated that SOCS1 and SOCS3 are important regulators of helper T cell differentiation and functions.

  12. Synovial tissue hypoxia and inflammation in vivo.

    LENUS (Irish Health Repository)

    Ng, C T


    INTRODUCTION: Hypoxia is a microenvironmental feature in the inflamed joint, which promotes survival advantage for cells. The aim of this study was to examine the relationship of partial oxygen pressure in the synovial tissue (tPO(2)) in patients with inflammatory arthritis with macroscopic\\/microscopic inflammation and local levels of proinflammatory mediators. METHODS: Patients with inflammatory arthritis underwent full clinical assessment and video arthroscopy to quantify macroscopic synovitis and measure synovial tPO(2) under direct visualisation. Cell specific markers (CD3 (T cells), CD68 (macrophages), Ki67 (cell proliferation) and terminal deoxynucleotidyl transferase dUTP nick end labelling (cell apoptosis)) were quantified by immunohistology. In vitro migration was assessed in primary and normal synoviocytes (synovial fibroblast cells (SFCs)) using a wound repair scratch assay. Levels of tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), interferon gamma (IFNgamma), IL6, macrophage inflammatory protein 3alpha (MIP3alpha) and IL8 were quantified, in matched serum and synovial fluid, by multiplex cytokine assay and ELISA. RESULTS: The tPO(2) was 22.5 (range 3.2-54.1) mm Hg and correlated inversely with macroscopic synovitis (r=-0.421, p=0.02), sublining CD3 cells (-0.611, p<0.01) and sublining CD68 cells (r=-0.615, p<0.001). No relationship with cell proliferation or apoptosis was found. Primary and normal SFCs exposed to 1% and 3% oxygen (reflecting the median tPO(2) in vivo) induced cell migration. This was coupled with significantly higher levels of synovial fluid tumour necrosis factor alpha (TNFalpha), IL1beta, IFNgamma and MIP3alpha in patients with tPO(2) <20 mm Hg (all p values <0.05). CONCLUSIONS: This is the first study to show a direct in vivo correlation between synovial tPO(2), inflammation and cell migration, thus it is proposed that hypoxia is a possible primary driver of inflammatory processes in the arthritic joint.

  13. Regulation of stem cell factor expression in inflammation and asthma

    Directory of Open Access Journals (Sweden)

    Carla A Da Silva


    Full Text Available Stem cell factor (SCF is a major mast cell growth factor, which could be involved in the local increase of mast cell number in the asthmatic airways. In vivo, SCF expression increases in asthmatic patients and this is reversed after treatment with glucocorticoids. In vitro in human lung fibroblasts in culture, IL-1beta, a pro-inflammatory cytokine, confirms this increased SCF mRNA and protein expression implying the MAP kinases p38 and ERK1/2 very early post-treatment, and glucocorticoids confirm this decrease. Surprisingly, glucocorticoids potentiate the IL-1beta-enhanced SCF expression at short term treatment, implying increased SCF mRNA stability and SCF gene transcription rate. This potentiation involves p38 and ERK1/2. Transfection experiments with the SCF promoter including intron1 also confirm this increase and decrease of SCF expression by IL-1beta and glucocorticoids, and the potentiation by glucocorticoids of the IL-1beta-induced SCF expression. Deletion of the GRE or kappaB sites abolishes this potentiation, and the effect of IL-1beta or glucocorticoids alone. DNA binding of GR and NF-kappaB are also demonstrated for these effects. In conclusion, this review concerns new mechanisms of regulation of SCF expression in inflammation that could lead to potential therapeutic strategy allowing to control mast cell number in the asthmatic airways.

  14. Study on MCP-1 related to inflammation induced by biomaterials

    Energy Technology Data Exchange (ETDEWEB)

    Ding Tingting [Ninth People' s Hospital, School of Medicine, Shanghai Jiao Tong University/Shanghai Biomaterials Research and Testing Center, Shanghai 200023 (China); Sun Jiao [Shanghai Key Laboratory of Stomatology, Shanghai 200023 (China); Zhang Ping, E-mail: [School of Life Science, East China Normal University, Shanghai 200062 (China)


    The study of inflammation is important for understanding the reaction between biomaterials and the human body, in particular, the interaction between biomaterials and immune system. In the current study, rat macrophages were induced by multiple biomaterials with different biocompatibilities, including polyvinyl chloride (PVC) containing 8% of organic tin, a positive control material with cellular toxicity. Human umbilical vein endothelial cells (ECV-304), cultured with PRMI-1640, were detached from cells cultured with the supernatant of macrophages containing TNF-alpha and IL-1beta because of stimulation by biomaterials. The cells were then treated with different biomaterials. Then both TNF-alpha and IL-1beta in macrophages were detected by ELISA. Levels of monocyte chemoattractant protein-1 (MCP-1) were measured by RT-PCR. The results suggested that the expression of TNF-alpha and IL-1beta was elevated by polytetrafluoroethylene (PTFE), polylactic-co-glycolic acid (PLGA) and American NPG alloy (p < 0.001). The level of MCP-1 cultured in supernatant of macrophages was higher than in PRMI-1640 with the same biomaterials. And the exposure to PTFE, PLGA and NPG resulted in the high expression of MCP-1 (p < 0.001) following cytokine stimulation. MCP-1 was also significantly expressed in beta-tricalcium phosphate (beta-TCP) and calcium phosphate cement samples (CPC) (p < 0.01). Thus, TNF-alpha, IL-1beta and MCP-1 had played an important role in the immune reaction induced by biomaterials and there was a close relationship between the expression of cytokines and biomcompatibility of biomaterials. Furthermore, these data suggested that MCP-1 was regulated by TNF-alpha and IL-1beta, and activated by both cytokines and biomaterials. The data further suggested that the expression of MCP-1 could be used as a marker to indicate the degree of immune reaction induced by biomaterials.

  15. [Corticosteroid hormones and angiotensin-converting enzyme in the dynamics of chronic granulomatous inflammation]. (United States)

    Cherkasova, A P; Selyatitskaya, V G


    It was studied the contents of corticosteroid hormones in the adrenal gland, plasma and 11beta-hydroxysteroid dehydrogenase activity (11betaHSD) in the liver and kidneys, as well as the activity of angiotensin-converting enzyme (ACE) in blood plasma, lung, renal cortex and liver of male rats in the dynamics of SiO2-induced inflammation. The study showed that chronic granulomatous inflammation in rats was accompanied by an initial short-term reaction to the activation of synthesis of the main glucocorticoid hormone, followed by specific inhibition of synthesis of this hormone as well as 11betaHSD activity in the adrenal gland. Inflammation caused less pronounced changes in the functional state of the renin-angiotensin system, however, inhibition of ACE activity observed in plasma, liver and kidneys during the initial period of inflammation. Factor analysis revealed a violation of intersystem relations of hypothalamic-pituitary-adrenocortical and renin-angiotensin systems in inflammation due, probably, to the modulating influence of cytokines.

  16. Negative Beta Encoder

    CERN Document Server

    Kohda, Tohru; Aihara, Kazuyuki


    A new class of analog-digital (A/D), digital-analog (D/A) converters as an alternative to conventional ones, called $\\beta$-encoder, has been shown to have exponential accuracy in the bit rates while possessing self-correction property for fluctuations of amplifier factor $\\beta$ and quantizer threshold $\

  17. Double beta decay experiments

    CERN Document Server

    Barabash, A S


    The present status of double beta decay experiments is reviewed. The results of the most sensitive experiments are discussed. Proposals for future double beta decay experiments with a sensitivity to the $$ at the level of (0.01--0.1) eV are considered.

  18. Thymosin {beta}4 promotes the migration of endothelial cells without intracellular Ca{sup 2+} elevation

    Energy Technology Data Exchange (ETDEWEB)

    Selmi, Anna [Department of Molecular and Medical Biophysics, Medical University of Lodz, 92-215 Lodz (Poland); Malinowski, Mariusz [Institute of Medical Biology, Polish Academy of Sciences, Lodz (Poland); Brutkowski, Wojciech [Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw (Poland); Bednarek, Radoslaw [Department of Molecular and Medical Biophysics, Medical University of Lodz, 92-215 Lodz (Poland); Cierniewski, Czeslaw S., E-mail: [Department of Molecular and Medical Biophysics, Medical University of Lodz, 92-215 Lodz (Poland); Institute of Medical Biology, Polish Academy of Sciences, Lodz (Poland)


    Numerous studies have demonstrated the effects of T{beta}4 on cell migration, proliferation, apoptosis and inflammation after exogenous treatment, but the mechanism by which T{beta}4 functions is still unclear. Previously, we demonstrated that incubation of endothelial cells with T{beta}4 induced synthesis and secretion of various proteins, including plasminogen activator inhibitor type 1 and matrix metaloproteinases. We also showed that T{beta}4 interacts with Ku80, which may operate as a novel receptor for T{beta}4 and mediates its intracellular activity. In this paper, we provide evidence that T{beta}4 induces cellular processes without changes in the intracellular Ca{sup 2+} concentration. External treatment of HUVECs with T{beta}4 and its mutants deprived of the N-terminal tetrapeptide AcSDKP (T{beta}4{sub AcSDKPT/4A}) or the actin-binding sequence KLKKTET (T{beta}4{sub KLKKTET/7A}) resulted in enhanced cell migration and formation of tubular structures in Matrigel. Surprisingly, the increased cell motility caused by T{beta}4 was not associated with the intracellular Ca{sup 2+} elevation monitored with Fluo-4 NW or Fura-2 AM. Therefore, it is unlikely that externally added T{beta}4 induces HUVEC migration via the surface membrane receptors known to generate Ca{sup 2+} influx. Our data confirm the concept that externally added T{beta}4 must be internalized to induce intracellular mechanisms supporting endothelial cell migration.

  19. Genetics Home Reference: beta thalassemia (United States)

    ... Understand Genetics Home Health Conditions beta thalassemia beta thalassemia Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Beta thalassemia is a blood disorder that reduces the production ...

  20. Rapid synthesis of beta zeolites (United States)

    Fan, Wei; Chang, Chun -Chih; Dornath, Paul; Wang, Zhuopeng


    The invention provides methods for rapidly synthesizing heteroatom containing zeolites including Sn-Beta, Si-Beta, Ti-Beta, Zr-Beta and Fe-Beta. The methods for synthesizing heteroatom zeolites include using well-crystalline zeolite crystals as seeds and using a fluoride-free, caustic medium in a seeded dry-gel conversion method. The Beta zeolite catalysts made by the methods of the invention catalyze both isomerization and dehydration reactions.

  1. Thermography in ocular inflammation (United States)

    Kawali, Ankush A


    Background and Objectives: The purpose of this study was to evaluate ocular inflammatory and non-inflammatory conditions using commercially available thermal camera. Materials and Methods: A non-contact thermographic camera (FLIR P 620) was used to take thermal pictures of seven cases of ocular inflammation, two cases of non-inflammatory ocular pathology, and one healthy subject with mild refractive error only. Ocular inflammatory cases included five cases of scleritis, one case of postoperative anterior uveitis, and a case of meibomian gland dysfunction with keratitis (MGD-keratitis). Non-inflammatory conditions included a case of conjunctival benign reactive lymphoid hyperplasia (BRLH) and a case of central serous chorio-retinopathy. Thermal and non-thermal photographs were taken, and using analyzing software, the ocular surface temperature was calculated. Results: Patient with fresh episode of scleritis revealed high temperature. Eyes with MGD-keratitis depicted lower temperature in clinically more affected eye. Conjunctival BRLH showed a cold lesion on thermography at the site of involvement, in contrast to cases of scleritis with similar clinical presentation. Conclusion: Ocular thermal imaging is an underutilized diagnostic tool which can be used to distinguish inflammatory ocular conditions from non-inflammatory conditions. It can also be utilized in the evaluation of tear film in dry eye syndrome. Its applications should be further explored in uveitis and other ocular disorders. Dedicated “ocular thermographic” camera is today's need of the hour. PMID:24347863

  2. Leptospira and Inflammation

    Directory of Open Access Journals (Sweden)

    C. F. Gonçalves-de-Albuquerque


    Full Text Available Leptospirosis is an important zoonosis and has a worldwide impact on public health. This paper will discuss both the role of immunogenic and pathogenic molecules during leptospirosis infection and possible new targets for immunotherapy against leptospira components. Leptospira, possess a wide variety of mechanisms that allow them to evade the host immune system and cause infection. Many molecules contribute to the ability of Leptospira to adhere, invade, and colonize. The recent sequencing of the Leptospira genome has increased our knowledge about this pathogen. Although the virulence factors, molecular targets, mechanisms of inflammation, and signaling pathways triggered by leptospiral antigens have been studied, some questions are still unanswered. Toll-like receptors (TLRs are the primary sensors of invading pathogens. TLRs recognize conserved microbial pattern molecules and activate signaling pathways that are pivotal to innate and adaptive immune responses. Recently, a new molecular target has emerged—the Na/K-ATPase—which may contribute to inflammatory and metabolic alteration in this syndrome. Na/K-ATPase is a target for specific fatty acids of host origin and for bacterial components such as the glycolipoprotein fraction (GLP that may lead to inflammasome activation. We propose that in addition to TLRs, Na/K-ATPase may play a role in the innate response to leptospirosis infection.

  3. Apoptosis and inflammation

    Directory of Open Access Journals (Sweden)

    C. Haanen


    Full Text Available During the last few decades it has been recognized that cell death is not the consequence of accidental injury, but is the expression of a cell suicide programme. Kerr et al. (1972 introduced the term apoptosis. This form of cell death is under the influence of hormones, growth factors and cytokines, which depending upon the receptors present on the target cells, may activate a genetically controlled cell elimination process. During apoptosis the cell membrane remains intact and the cell breaks into apoptotic bodies, which are phagocytosed. Apoptosis, in contrast to necrosis, is not harmful to the host and does not induce any inflammatory reaction. The principal event that leads to inflammatory disease is cell damage, induced by chemical/physical injury, anoxia or starvation. Cell damage means leakage of cell contents into the adjacent tissues, resulting in the capillary transmigration of granulocytes to the injured tissue. The accumulation of neutrophils and release of enzymes and oxygen radicals enhances the inflammatory reaction. Until now there has been little research into the factors controlling the accumulation and the tissue load of granulocytes and their histotoxic products in inflammatory processes. Neutrophil apoptosis may represent an important event in the control of intlamtnation. It has been assumed that granulocytes disintegrate to apoptotic bodies before their fragments are removed by local macrophages. Removal of neutrophils from the inflammatory site without release of granule contents is of paramount importance for cessation of inflammation. In conclusion, apoptotic cell death plays an important role in inflammatory processes and in the resolution of inflammatory reactions. The facts known at present should stimulate further research into the role of neutrophil, eosinophil and macrophage apoptosis in inflammatory diseases.

  4. [Inflammation of the parathyroid glands]. (United States)

    Ting, S; Synoracki, S; Sheu, S-Y; Schmid, K W


    Inflammation of the parathyroid glands is rare when compared to other endocrine organs. This leads to the use of descriptive terms as well as the lack of a generally accepted classification for inflammatory disorders of the parathyroid glands. This review article proposes that parathyroid inflammation be subdivided morphologically into (a) non-specific lymphocytic infiltration, which is more an expression of damage to small vessels, due to e. g. severe systemic inflammation or myocardial infarction, (b) autoimmunogenic lymphocytic parathyroiditis, (c) nonimmunogenic inflammation caused by granulomatous diseases or infections and (d) invasive sclerosing (peri) parathyroiditis. As only parathyroid glands removed due to hyperparathyroidism and normal parathyroid glands incidentally removed during thyroid surgery are seen almost exclusively in routine histopathology, virtually no information about the morphological correlate of hypoparathyroidism is available.

  5. Osteoprotegerin and biomarkers of vascular inflammation in type 2 diabetes.

    LENUS (Irish Health Repository)

    O'Sullivan, Eoin P


    Osteoprotegerin (OPG), receptor activator for nuclear factor kappa beta ligand (RANKL) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) are newly discovered members of the tumour necrosis factor-alpha receptor superfamily. While their role in bone metabolism is well described, their function within the vasculature is poorly understood. OPG inhibits vascular calcification in vitro and high serum levels have been demonstrated in type 2 diabetes, but serum RANKL and TRAIL and their potential correlation with well-established biomarkers of subclinical vascular inflammation such as high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) have not been described.

  6. A beta2-microglobulin cleavage variant fibrillates at near-physiological pH

    DEFF Research Database (Denmark)

    Corlin, Dorthe B; Johnsen, Christina K; Nissen, Mogens H


    Beta2-microglobulin (beta2m) deposits as amyloid in dialysis-related amyloidosis (DRA), predominantly in joints. The molecular mechanisms underlying the amyloidogenicity of beta2m are still largely unknown. In vitro, acidic conditions, pH ... several days. Here, we show that amyloid fibrils are generated in less than an hour when a cleavage variant of beta2m--found in the circulation of many dialysis patients--is exposed to pH levels (pH 6.6) occurring in joints during inflammation. Aggregation and fibrillation, including seeding effects...... with intact, native beta2m were studied by Thioflavin T fluorescence spectroscopy, turbidimetry, capillary electrophoresis, and electron microscopy. We conclude that a biologically relevant variant of beta2m is amyloidogenic at slightly acidic pH. Also, only a very small amount of preformed fibrils...

  7. Age-Related Macular Degeneration in the Aspect of Chronic Low-Grade Inflammation (Pathophysiological ParaInflammation

    Directory of Open Access Journals (Sweden)

    Małgorzata Nita


    Full Text Available The products of oxidative stress trigger chronic low-grade inflammation (pathophysiological parainflammation process in AMD patients. In early AMD, soft drusen contain many mediators of chronic low-grade inflammation such as C-reactive protein, adducts of the carboxyethylpyrrole protein, immunoglobulins, and acute phase molecules, as well as the complement-related proteins C3a, C5a, C5, C5b-9, CFH, CD35, and CD46. The complement system, mainly alternative pathway, mediates chronic autologous pathophysiological parainflammation in dry and exudative AMD, especially in the Y402H gene polymorphism, which causes hypofunction/lack of the protective complement factor H (CFH and facilitates chronic inflammation mediated by C-reactive protein (CRP. Microglial activation induces photoreceptor cells injury and leads to the development of dry AMD. Many autoantibodies (antibodies against alpha beta crystallin, alpha-actinin, amyloid, C1q, chondroitin, collagen I, collagen III, collagen IV, elastin, fibronectin, heparan sulfate, histone H2A, histone H2B, hyaluronic acid, laminin, proteoglycan, vimentin, vitronectin, and aldolase C and pyruvate kinase M2 and overexpression of Fcc receptors play role in immune-mediated inflammation in AMD patients and in animal model. Macrophages infiltration of retinal/choroidal interface acts as protective factor in early AMD (M2 phenotype macrophages; however it acts as proinflammatory and proangiogenic factor in advanced AMD (M1 and M2 phenotype macrophages.

  8. Can non-selective beta-blockers prevent hepatocellular carcinoma in patients with cirrhosis?

    DEFF Research Database (Denmark)

    Thiele, Maja; Wiest, Reiner; Gluud, Lise Lotte


    Hepatocellular carcinoma is the main liver-related cause of death in patients with compensated cirrhosis. The early phases are asymptomatic and the prognosis is poor, which makes prevention essential. We propose that non-selective beta-blockers decrease the incidence and growth of hepatocellular...... carcinoma via a reduction of the inflammatory load from the gut to the liver and inhibition of angiogenesis. Due to their effect on the portal pressure, non-selective beta-blockers are used for prevention of esophageal variceal bleeding. Recently, non-hemodynamic effects of beta-blockers have received...... reduce hepatic inflammation. Blockage of β-adrenoceptors also decrease angiogenesis by inhibition of vascular endothelial growth factors. Because gut-derived inflammation and neo-angiogenesis are important in hepatic carcinogenesis, non-selective beta-blockers can potentially reduce the development...

  9. Alveolar inflammation in cystic fibrosis

    DEFF Research Database (Denmark)

    Ulrich, Martina; Worlitzsch, Dieter; Viglio, Simona


    BACKGROUND: In infected lungs of the cystic fibrosis (CF) patients, opportunistic pathogens and mutated cystic fibrosis transmembrane conductance regulator protein (CFTR) contribute to chronic airway inflammation that is characterized by neutrophil/macrophage infiltration, cytokine release...... accumulated in type II alveolar epithelial cells, lacking CFTR. P. aeruginosa organisms were rarely present in inflamed alveoli. CONCLUSIONS: Chronic inflammation and remodeling is present in alveolar tissues of the CF lung and needs to be addressed by anti-inflammatory therapies....

  10. Incisional wound healing in transforming growth factor-beta1 null mice. (United States)

    Koch, R M; Roche, N S; Parks, W T; Ashcroft, G S; Letterio, J J; Roberts, A B


    Expression of endogenous transforming growth factor-beta1 is reduced in many animal models of impaired wound healing, and addition of exogenous transforming growth factor-beta has been shown to improve healing. To test the hypothesis that endogenous transforming growth factor-beta1 is essential for normal wound repair, we have studied wound healing in mice in which the transforming growth factor-beta1 gene has been deleted by homologous recombination. No perceptible differences were observed in wounds made in 3-10-day-old neonatal transforming growth factor-beta1 null mice compared to wild-type littermates. To preclude interference from maternally transferred transforming growth factor-beta1, cutaneous wounds were also made on the backs of 30-day-old transforming growth factor-beta1 null and littermate control mice treated with rapamycin, which extends their lifetime and suppresses the inflammatory response characteristic of the transforming growth factor-beta1 null mice. Again, no impairment in healing was seen in transforming growth factor-beta1 null mice. Instead these wounds showed an overall reduction in the amount of granulation tissue and an increased rate of epithelialization compared to littermate controls. Our data suggest that release of transforming growth factor-beta1 from degranulating platelets or secretion by infiltrating macrophages and fibroblasts is not critical to initiation or progression of tissue repair and that endogenous transforming growth factor-beta1 may actually function to increase inflammation and retard wound closure.

  11. Thymosin Beta 4 and Thymosin Beta 10 Expression in Hepatocellular Carcinoma (United States)

    Theunissen, W.; Fanni, D.; Nemolato, S.; Di Felice, E.; Cabras, T.; Gerosa, C.; Van Eyken, P.; Messana, I.; Castagnola, M.; Faa, G.


    Thymosin beta 4 (Tβ4) and thymosin beta 10 (Tβ10) are two members of the beta-thymosin family involved in many cellular processes such as cellular motility, angiogenesis, inflammation, cell survival and wound healing. Recently, a role for beta-thymosins has been proposed in the process of carcinogenesis as both peptides were detected in several types of cancer. The aim of the present study was to investigate the expression pattern of Tβ4 and Tβ10 in hepatocellular carcinoma (HCC). To this end, the expression pattern of both peptides was analyzed in liver samples obtained from 23 subjects diagnosed with HCC. Routinely formalin-fixed and paraffin-embedded liver samples were immunostained by indirect immunohistochemistry with polyclonal antibodies to Tβ4 and Tβ10. Immunoreactivity for Tβ4 and Tβ10 was detected in the liver parenchyma of the surrounding tumor area. Both peptides showed an increase in granular reactivity from the periportal to the periterminal hepatocytes. Regarding HCC, Tβ4 reactivity was detected in 7/23 cases (30%) and Tβ10 reactivity in 22/23 (96%) cases analyzed, adding HCC to human cancers that express these beta-thymosins. Intriguing finding was seen looking at the reactivity of both peptides in tumor cells infiltrating the surrounding liver. Where Tβ10 showed a strong homogeneous expression, was Tβ4 completely absent in cells undergoing stromal invasion. The current study shows expression of both beta-thymosins in HCC with marked differences in their degree of expression and frequency of immunoreactivity. The higher incidence of Tβ10 expression and its higher reactivity in tumor cells involved in stromal invasion indicate a possible major role for Tβ10 in HCC progression. PMID:24704991

  12. Thymosin beta 4 and thymosin beta 10 expression in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    W. Theunissen


    Full Text Available Thymosin beta 4 (Tβ4 and thymosin beta 10 (Tβ10 are two members of the beta-thymosin family involved in many cellular processes such as cellular motility, angiogenesis, inflammation, cell survival and wound healing. Recently, a role for beta-thymosins has been proposed in the process of carcinogenesis as both peptides were detected in several types of cancer. The aim of the present study was to investigate the expression pattern of Tβ4 and Tβ10 in hepatocellular carcinoma (HCC. To this end, the expression pattern of both peptides was analyzed in liver samples obtained from 23 subjects diagnosed with HCC. Routinely formalin-fixed and paraffin-embedded liver samples were immunostained by indirect immunohistochemistry with polyclonal antibodies to Tβ4 and Tβ10. Immunoreactivity for Tβ4 and Tβ10 was detected in the liver parenchyma of the surrounding tumor area. Both peptides showed an increase in granular reactivity from the periportal to the periterminal hepatocytes. Regarding HCC, Tβ4 reactivity was detected in 7/23 cases (30% and Tβ10 reactivity in 22/23 (97% cases analyzed, adding HCC to human cancers that express these beta-thymosins. Intriguing finding was seen looking at the reactivity of both peptides in tumor cells infiltrating the surrounding liver. Where Tβ10 showed a strong homogeneous expression, was Tβ4 completely absent in cells undergoing stromal invasion. The current study shows expression of both beta-thymosins in HCC with marked differences in their degree of expression and frequency of immunoreactivity. The higher incidence of Tβ10 expression and its higher reactivity in tumor cells involved in stromal invasion indicate a possible major role for Tβ10 in HCC progression.

  13. Neutrinoless double beta decay

    Indian Academy of Sciences (India)

    Kai Zuber


    The physics potential of neutrinoless double beta decay is discussed. Furthermore, experimental considerations as well as the current status of experiments are presented. Finally, an outlook towards the future, work on nuclear matrix elements and alternative processes is given.

  14. Alpha and Beta Determinations

    CERN Document Server

    Dunietz, Isard


    Because the Bd -> J/psi Ks asymmetry determines only sin(2 beta), a discrete ambiguity in the true value of beta remains. This note reviews how the ambiguity can be removed. Extractions of the CKM angle alpha are discussed next. Some of the methods require very large data samples and will not be feasible in the near future. In the near future, semi-inclusive CP-violating searches could be undertaken, which are reviewed last.

  15. {beta} - amyloid imaging probes

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jae Min [Seoul National University College of Medicine, Seoul (Korea, Republic of)


    Imaging distribution of {beta} - amyloid plaques in Alzheimer's disease is very important for early and accurate diagnosis. Early trial of the {beta} -amyloid plaques includes using radiolabeled peptides which can be only applied for peripheral {beta} - amyloid plaques due to limited penetration through the blood brain barrier (BBB). Congo red or Chrysamine G derivatives were labeled with Tc-99m for imaging {beta} - amyloid plaques of Alzheimer patient's brain without success due to problem with BBB penetration. Thioflavin T derivatives gave breakthrough for {beta} - amyloid imaging in vivo, and a benzothiazole derivative [C-11]6-OH-BTA-1 brought a great success. Many other benzothiazole, benzoxazole, benzofuran, imidazopyridine, and styrylbenzene derivatives have been labeled with F-18 and I-123 to improve the imaging quality. However, [C-11]6-OH-BTA-1 still remains as the best. However, short half-life of C-11 is a limitation of wide distribution of this agent. So, it is still required to develop an Tc-99m, F-18 or I-123 labeled agent for {beta} - amyloid imaging agent.

  16. Beta cell dynamics: beta cell replenishment, beta cell compensation and diabetes. (United States)

    Cerf, Marlon E


    Type 2 diabetes, characterized by persistent hyperglycemia, arises mostly from beta cell dysfunction and insulin resistance and remains a highly complex metabolic disease due to various stages in its pathogenesis. Glucose homeostasis is primarily regulated by insulin secretion from the beta cells in response to prevailing glycemia. Beta cell populations are dynamic as they respond to fluctuating insulin demand. Beta cell replenishment and death primarily regulate beta cell populations. Beta cells, pancreatic cells, and extra-pancreatic cells represent the three tiers for replenishing beta cells. In rodents, beta cell self-replenishment appears to be the dominant source for new beta cells supported by pancreatic cells (non-beta islet cells, acinar cells, and duct cells) and extra-pancreatic cells (liver, neural, and stem/progenitor cells). In humans, beta cell neogenesis from non-beta cells appears to be the dominant source of beta cell replenishment as limited beta cell self-replenishment occurs particularly in adulthood. Metabolic states of increased insulin demand trigger increased insulin synthesis and secretion from beta cells. Beta cells, therefore, adapt to support their physiology. Maintaining physiological beta cell populations is a strategy for targeting metabolic states of persistently increased insulin demand as in diabetes.

  17. Role of Resistin in Inflammation and Inflammation-Related Diseases

    Institute of Scientific and Technical Information of China (English)

    Shanshan Pang; Yingying Le


    Resistin is a newly identified adipocyte secreted hormone belonging to a cysteine-rich protein family. It is expressed in white adipose tissues in rodents and has also been found in several other tissues in human. Insulin, glucose,many cytokines and anti-diabetic thiazolidinediones are regulators of resistin gene expression. Resistin was firstly proposed to be involved in insulin resistance and type 2 diabetes. Recently, it was found to be relevant to inflammation and inflammation-related diseases like atherosclerosis and arthritis.

  18. Sirtuins Link Inflammation and Metabolism

    Directory of Open Access Journals (Sweden)

    Vidula T. Vachharajani


    Full Text Available Sirtuins (SIRT, first discovered in yeast as NAD+ dependent epigenetic and metabolic regulators, have comparable activities in human physiology and disease. Mounting evidence supports that the seven-member mammalian sirtuin family (SIRT1–7 guard homeostasis by sensing bioenergy needs and responding by making alterations in the cell nutrients. Sirtuins play a critical role in restoring homeostasis during stress responses. Inflammation is designed to “defend and mend” against the invading organisms. Emerging evidence supports that metabolism and bioenergy reprogramming direct the sequential course of inflammation; failure of homeostasis retrieval results in many chronic and acute inflammatory diseases. Anabolic glycolysis quickly induced (compared to oxidative phosphorylation for ROS and ATP generation is needed for immune activation to “defend” against invading microorganisms. Lipolysis/fatty acid oxidation, essential for cellular protection/hibernation and cell survival in order to “mend,” leads to immune repression. Acute/chronic inflammations are linked to altered glycolysis and fatty acid oxidation, at least in part, by NAD+ dependent function of sirtuins. Therapeutically targeting sirtuins may provide a new class of inflammation and immune regulators. This review discusses how sirtuins integrate metabolism, bioenergetics, and immunity during inflammation and how sirtuin-directed treatment improves outcome in chronic inflammatory diseases and in the extreme stress response of sepsis.

  19. Endogenous Receptor Agonists: Resolving Inflammation

    Directory of Open Access Journals (Sweden)

    Gerhard Bannenberg


    Full Text Available Controlled resolution or the physiologic resolution of a well-orchestrated inflammatory response at the tissue level is essential to return to homeostasis. A comprehensive understanding of the cellular and molecular events that control the termination of acute inflammation is needed in molecular terms given the widely held view that aberrant inflammation underlies many common diseases. This review focuses on recent advances in the understanding of the role of arachidonic acid and ω-3 polyunsaturated fatty acids (PUFA–derived lipid mediators in regulating the resolution of inflammation. Using a functional lipidomic approach employing LC-MS-MS–based informatics, recent studies, reviewed herein, uncovered new families of local-acting chemical mediators actively biosynthesized during the resolution phase from the essential fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. These new families of local chemical mediators are generated endogenously in exudates collected during the resolution phase, and were coined resolvins and protectins because specific members of these novel chemical families control both the duration and magnitude of inflammation in animal models of complex diseases. Recent advances on the biosynthesis, receptors, and actions of these novel anti-inflammatory and proresolving lipid mediators are reviewed with the aim to bring to attention the important role of specific lipid mediators as endogenous agonists in inflammation resolution.

  20. Boosted beta regression.

    Directory of Open Access Journals (Sweden)

    Matthias Schmid

    Full Text Available Regression analysis with a bounded outcome is a common problem in applied statistics. Typical examples include regression models for percentage outcomes and the analysis of ratings that are measured on a bounded scale. In this paper, we consider beta regression, which is a generalization of logit models to situations where the response is continuous on the interval (0,1. Consequently, beta regression is a convenient tool for analyzing percentage responses. The classical approach to fit a beta regression model is to use maximum likelihood estimation with subsequent AIC-based variable selection. As an alternative to this established - yet unstable - approach, we propose a new estimation technique called boosted beta regression. With boosted beta regression estimation and variable selection can be carried out simultaneously in a highly efficient way. Additionally, both the mean and the variance of a percentage response can be modeled using flexible nonlinear covariate effects. As a consequence, the new method accounts for common problems such as overdispersion and non-binomial variance structures.

  1. Paeonol attenuates inflammation-mediated neurotoxicity and microglial activation

    Institute of Scientific and Technical Information of China (English)

    Kyong Nyon Nam; Byung-Cheol Woo; Sang-Kwan Moon; Seong-Uk Park; Joo-young Park; Jae-Woong Hwang; Hyung-Sup Bae; Chang-Nam Ko; Eunjoo Hwang Lee


    Chronic activation of microglial cells endangers neuronal survival through the release of various proinflammatory and neurotoxic factors. The root of Paeonia lactiflora Pall has been considered useful for the treatment of various disorders in traditional oriental medicine. Paeonol, found in the root of Paeonia lactiflora Pall, has a wide range of pharmacological functions, including anti-oxidative, anti-inflammatory and neuroprotective activities. The objective of this study was to examine the efficacy of paeonol in the repression of inflammation-induced neurotoxicity and microglial cell activation. Organotypic hippocampal slice cultures and primary microglial cells from rat brain were stimulated with bacterial lipopolysaccharide. Paeonol pretreatment was performed for 30 minutes prior to lipopolysaccharide addition. Cell viability and nitrite (the production of nitric oxide), tumor necrosis factor-alpha and interleukin-1beta products were measured after lipopolysaccharide treatment. In organotypic hippocampal slice cultures, paeonol blocked lipopolysaccharide-related hippocampal cell death and inhibited the release of nitrite and interleukin-1beta. Paeonol was effective in inhibiting nitric oxide release from primary microglial cells. It also reduced the lipopolysaccharide-stimulated release of tumor necrosis factor-alpha and interleukin-1β from microglial cells. Paeonol possesses neuroprotective activity in a model of inflammation-induced neurotoxicity and reduces the release of neurotoxic and proinflammatory factors in activated microglial cells.

  2. Lung inflammation caused by inhaled toxicants: a review

    Directory of Open Access Journals (Sweden)

    Wong J


    Full Text Available John Wong, Bruce E Magun, Lisa J Wood School of Nursing, MGH Institute of Health Professions, Boston, MA, USA Abstract: Exposure of the lungs to airborne toxicants from different sources in the environment may lead to acute and chronic pulmonary or even systemic inflammation. Cigarette smoke is the leading cause of chronic obstructive pulmonary disease, although wood smoke in urban areas of underdeveloped countries is now recognized as a leading cause of respiratory disease. Mycotoxins from fungal spores pose an occupational risk for respiratory illness and also present a health hazard to those living in damp buildings. Microscopic airborne particulates of asbestos and silica (from building materials and those of heavy metals (from paint are additional sources of indoor air pollution that contributes to respiratory illness and is known to cause respiratory illness in experimental animals. Ricin in aerosolized form is a potential bioweapon that is extremely toxic yet relatively easy to produce. Although the aforementioned agents belong to different classes of toxic chemicals, their pathogenicity is similar. They induce the recruitment and activation of macrophages, activation of mitogen-activated protein kinases, inhibition of protein synthesis, and production of interleukin-1 beta. Targeting either macrophages (using nanoparticles or the production of interleukin-1 beta (using inhibitors against protein kinases, NOD-like receptor protein-3, or P2X7 may potentially be employed to treat these types of lung inflammation without affecting the natural immune response to bacterial infections. Keywords: cigarette, mycotoxin, trichothecene, ricin, inflammasome, macrophage, inhibitors

  3. Granulomatous inflammation in Acanthamoeba sclerokeratitis

    Directory of Open Access Journals (Sweden)

    Samrat Chatterjee


    Full Text Available This report describes the histopathological findings in a patient with Acanthamoeba sclerokeratitis (ASK. A 58-year-old patient with ASK underwent enucleation and sections of the cornea and sclera were subjected to histopathology and immunohistochemistry with monoclonal mouse antihuman antibodies against T cell CD3 and B cell CD20 antigens. Hematoxylin and Eosin stained sections of the cornea revealed epithelial ulceration, Bowman′s membrane destruction, stromal vascularization, infiltration with lymphocytes, plasma cells, and granulomatous inflammation with multinucleated giant cells (MNGC. The areas of scleritis showed complete disruption of sclera collagen, necrosis and infiltration with neutrophils, macrophages, lymphocytes, and granulomatous inflammation with MNGC. No cyst or trophozoites of Acanthamoeba were seen in the cornea or sclera. Immunophenotyping revealed that the population of lymphocytes was predominantly of T cells. Granulomatous inflammation in ASK is probably responsible for the continuance and progression of the scleritis and management protocols should include immunosuppressive agents alongside amoebicidal drugs.

  4. Parkinson's Disease and Systemic Inflammation (United States)

    Ferrari, Carina C.; Tarelli, Rodolfo


    Peripheral inflammation triggers exacerbation in the central brain's ongoing damage in several neurodegenerative diseases. Systemic inflammatory stimulus induce a general response known as sickness behaviour, indicating that a peripheral stimulus can induce the synthesis of cytokines in the brain. In Parkinson's disease (PD), inflammation was mainly associated with microglia activation that can underlie the neurodegeneration of neurons in the substantia nigra (SN). Peripheral inflammation can transform the “primed” microglia into an “active” state, which can trigger stronger responses dealing with neurodegenerative processes. Numerous evidences show that systemic inflammatory processes exacerbate ongoing neurodegeneration in PD patient and animal models. Anti-inflammatory treatment in PD patients exerts a neuroprotective effect. In the present paper, we analyse the effect of peripheral infections in the etiology and progression in PD patients and animal models, suggesting that these peripheral immune challenges can exacerbate the symptoms in the disease. PMID:21403862

  5. Points of control in inflammation (United States)

    Nathan, Carl


    Inflammation is a complex set of interactions among soluble factors and cells that can arise in any tissue in response to traumatic, infectious, post-ischaemic, toxic or autoimmune injury. The process normally leads to recovery from infection and to healing, However, if targeted destruction and assisted repair are not properly phased, inflammation can lead to persistent tissue damage by leukocytes, lymphocytes or collagen. Inflammation may be considered in terms of its checkpoints, where binary or higher-order signals drive each commitment to escalate, go signals trigger stop signals, and molecules responsible for mediating the inflammatory response also suppress it, depending on timing and context. The non-inflammatory state does not arise passively from an absence of inflammatory stimuli; rather, maintenance of health requires the positive actions of specific gene products to suppress reactions to potentially inflammatory stimuli that do not warrant a full response.

  6. Oral inflammation in small animals. (United States)

    Lommer, Milinda J


    The oral cavity can be affected by a wide variety of disorders characterized by inflammation of the gingiva and/or oral mucosa. In dogs and cats, differential diagnoses for generalized oral inflammatory disorders include plaque-reactive mucositis, chronic gingivostomatitis, eosinophilic granuloma complex, pemphigus and pemphigoid disorders, erythema multiforme, and systemic lupus erythematosus. In addition, endodontic or periodontal abscesses, infectious conditions, reactive lesions, and neoplastic conditions may initially present with localized or generalized inflammation of the oral mucosa. Determination of the underlying cause of an oral inflammatory condition relies on a thorough history, complete physical and oral examination, and incisional biopsy and histopathologic examination of lesions.

  7. Beta and Gamma Gradients

    DEFF Research Database (Denmark)

    Løvborg, Leif; Gaffney, C. F.; Clark, P. A.;


    Experimental and/or theoretical estimates are presented concerning, (i) attenuation within the sample of beta and gamma radiation from the soil, (ii) the gamma dose within the sample due to its own radioactivity, and (iii) the soil gamma dose in the proximity of boundaries between regions...... of differing radioactivity. It is confirmed that removal of the outer 2 mm of sample is adequate to remove influence from soil beta dose and estimates are made of the error introduced by non-removal. Other evaluations include variation of the soil gamma dose near the ground surface and it appears...

  8. Genetic models for CNS inflammation

    DEFF Research Database (Denmark)

    Owens, T; Wekerle, H; Antel, J


    The use of transgenic technology to over-express or prevent expression of genes encoding molecules related to inflammation has allowed direct examination of their role in experimental disease. This article reviews transgenic and knockout models of CNS demyelinating disease, focusing primarily...

  9. Purinergic Receptors in Ocular Inflammation

    Directory of Open Access Journals (Sweden)

    Ana Guzman-Aranguez


    Full Text Available Inflammation is a complex process that implies the interaction between cells and molecular mediators, which, when not properly “tuned,” can lead to disease. When inflammation affects the eye, it can produce severe disorders affecting the superficial and internal parts of the visual organ. The nucleoside adenosine and nucleotides including adenine mononucleotides like ADP and ATP and dinucleotides such as P1,P4-diadenosine tetraphosphate (Ap4A, and P1,P5-diadenosine pentaphosphate (Ap5A are present in different ocular locations and therefore they may contribute/modulate inflammatory processes. Adenosine receptors, in particular A2A adenosine receptors, present anti-inflammatory action in acute and chronic retinal inflammation. Regarding the A3 receptor, selective agonists like N6-(3-iodobenzyl-5′-N-methylcarboxamidoadenosine (CF101 have been used for the treatment of inflammatory ophthalmic diseases such as dry eye and uveoretinitis. Sideways, diverse stimuli (sensory stimulation, large intraocular pressure increases can produce a release of ATP from ocular sensory innervation or after injury to ocular tissues. Then, ATP will activate purinergic P2 receptors present in sensory nerve endings, the iris, the ciliary body, or other tissues surrounding the anterior chamber of the eye to produce uveitis/endophthalmitis. In summary, adenosine and nucleotides can activate receptors in ocular structures susceptible to suffer from inflammatory processes. This involvement suggests the possible use of purinergic agonists and antagonists as therapeutic targets for ocular inflammation.

  10. Natural products to target inflammation

    NARCIS (Netherlands)

    Allijn, Iris Eva


    Chapter 1 Most Western lifestyle diseases such as type 2 diabetes mellitus, cardiovascular disease and cancer have a chronic inflammatory process at its base. Therefore, inflammation is an important therapeutic target. Due to their potency, steroidal drugs dominate the current treatment of inflammat

  11. Platelets in inflammation and infection. (United States)

    Jenne, Craig N; Kubes, Paul


    Although platelets are traditionally recognized for their central role in hemostasis, many lines of research clearly demonstrate these rather ubiquitous blood components are potent immune modulators and effectors. Platelets have been shown to directly recognize, sequester and kill pathogens, to activated and recruit leukocytes to sites of infection and inflammation, and to modulate leukocyte behavior, enhancing their ability to phagocytose and kill pathogens and inducing unique effector functions, such as the production of Neutrophil Extracellular Traps (NETs). This multifaceted response to infection and inflammation is due, in part, to the huge array of soluble mediators and cell surface molecules expressed by platelets. From their earliest origins as primordial hemocytes in invertebrates to their current form as megakaryocyte-derived cytoplasts, platelets have evolved to be one of the key regulators of host intravascular immunity and inflammation. In this review, we present the diverse roles platelets play in immunity and inflammation associated with autoimmune diseases and infection. Additionally, we highlight recent advances in our understanding of platelet behavior made possible through the use of advanced imaging techniques that allow us to visualize platelets and their interactions, in real-time, within the intact blood vessels of a living host.

  12. IFN-beta gene deletion leads to augmented and chronic demyelinating experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Teige, Ingrid; Treschow, Alexandra; Teige, Anna;


    Since the basic mechanisms behind the beneficial effects of IFN-beta in multiple sclerosis (MS) patients are still obscure, here we have investigated the effects of IFN-beta gene disruption on the commonly used animal model for MS, experimental autoimmune encephalomyelitis (EAE). We show that IFN......-beta knockout (KO) mice are more susceptible to EAE than their wild-type (wt) littermates; they develop more severe and chronic neurological symptoms with more extensive CNS inflammation and demyelination. However, there was no discrepancy observed between wt and KO mice regarding the capacity of T cells...... to proliferate or produce IFN-gamma in response to recall Ag. Consequently, we addressed the effect of IFN-beta on encephalitogenic T cell development and the disease initiation phase by passive transfer of autoreactive T cells from KO or wt littermates to both groups of mice. Interestingly, IFN-beta KO mice...

  13. Dipotassium Glycyrrhizate Inhibits HMGB1-Dependent Inflammation and Ameliorates Colitis in Mice.

    Directory of Open Access Journals (Sweden)

    Roberta Vitali

    Full Text Available High mobility group box-1 (HMGB1 is a DNA-binding protein that is released from injured cells during inflammation. Advances in targeting HMGB1 represent a major challenge to improve the treatment of acute/chronic inflammation.This study is aimed at verifying whether the inhibition of HMGB1 through dipotassium glycyrrhizate (DPG is a good strategy to reduce intestinal inflammation.Human colon adenocarcinoma cell line, HT29, human epithelial colorectal adenocarcinoma, Caco2, and murine macrophage cell line, RAW 264.7, were cultured to investigate the effect of DPG on the secretion of HMGB1. Acute colitis was induced in C57BL/6 mice through administration of 3% dextran sodium sulphate (DSS; a combined treatment with DSS and 3 or 8 mg/kg/day DPG was used to investigate the effects of DPG on intestinal inflammation. Animals were euthanized at seventh day and colonic samples underwent molecular and histological analyses.DPG significantly reduces in vitro the release of HMGB1 in the extracellular matrix as well as expression levels of pro-inflammatory cytokines, TNF-alpha, IL-1beta and IL-6, by inhibiting HMGB1. Moreover, DPG significantly decreases the severity of DSS-induced colitis in mice. Murine colonic samples show decreased mRNA levels of pro-inflammatory cytokines TNF-alpha, IL-1beta and IL-6, as well as HMGB1 receptors, RAGE and TLR4. Finally, HMGB1, abundantly present in the feces of mice with DSS-induced colitis, is strongly reduced by DPG.HMGB1 is an early pro-inflammatory cytokine and an active protagonist of mucosal gut inflammation. DPG exerts inhibitory effects against HMGB1 activity, significantly reducing intestinal inflammation. Thus, we reason that DPG could represent an innovative tool for the management of human intestinal inflammation.

  14. Dipotassium Glycyrrhizate Inhibits HMGB1-Dependent Inflammation and Ameliorates Colitis in Mice (United States)

    Vitali, Roberta; Palone, Francesca; Cucchiara, Salvatore; Negroni, Anna; Cavone, Leonardo; Costanzo, Manuela; Aloi, Marina; Dilillo, Anna; Stronati, Laura


    Background High mobility group box-1 (HMGB1) is a DNA-binding protein that is released from injured cells during inflammation. Advances in targeting HMGB1 represent a major challenge to improve the treatment of acute/chronic inflammation. Aim This study is aimed at verifying whether the inhibition of HMGB1 through dipotassium glycyrrhizate (DPG) is a good strategy to reduce intestinal inflammation. Methods Human colon adenocarcinoma cell line, HT29, human epithelial colorectal adenocarcinoma, Caco2, and murine macrophage cell line, RAW 264.7, were cultured to investigate the effect of DPG on the secretion of HMGB1. Acute colitis was induced in C57BL/6 mice through administration of 3% dextran sodium sulphate (DSS); a combined treatment with DSS and 3 or 8 mg/kg/day DPG was used to investigate the effects of DPG on intestinal inflammation. Animals were euthanized at seventh day and colonic samples underwent molecular and histological analyses. Results DPG significantly reduces in vitro the release of HMGB1 in the extracellular matrix as well as expression levels of pro-inflammatory cytokines, TNF-alpha, IL-1beta and IL-6, by inhibiting HMGB1. Moreover, DPG significantly decreases the severity of DSS-induced colitis in mice. Murine colonic samples show decreased mRNA levels of pro-inflammatory cytokines TNF-alpha, IL-1beta and IL-6, as well as HMGB1 receptors, RAGE and TLR4. Finally, HMGB1, abundantly present in the feces of mice with DSS-induced colitis, is strongly reduced by DPG. Conclusions HMGB1 is an early pro-inflammatory cytokine and an active protagonist of mucosal gut inflammation. DPG exerts inhibitory effects against HMGB1 activity, significantly reducing intestinal inflammation. Thus, we reason that DPG could represent an innovative tool for the management of human intestinal inflammation. PMID:23840500

  15. Applied Beta Dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Rich, B.L.


    Measurements of beta and/or nonpenetrating exposure results is complicated and past techniques and capabilities have resulted in significant inaccuracies in recorded results. Current developments have resulted in increased capabilities which make the results more accurate and should result in less total exposure to the work force. Continued development of works in progress should provide equivalent future improvements.

  16. Beta Thalassemia (For Parents) (United States)

    ... had their spleens removed. Slower growth rates. The anemia resulting from beta thalassemia can cause children to grow more slowly and also can lead ... boost production of new red blood cells. Some children with moderate anemia may require an occasional blood transfusion , particularly after ...

  17. Trichoderma .beta.-glucosidase (United States)

    Dunn-Coleman, Nigel; Goedegebuur, Frits; Ward, Michael; Yao, Jian


    The present invention provides a novel .beta.-glucosidase nucleic acid sequence, designated bgl3, and the corresponding BGL3 amino acid sequence. The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding BGL3, recombinant BGL3 proteins and methods for producing the same.

  18. Roughing up Beta

    DEFF Research Database (Denmark)

    Bollerslev, Tim; Li, Sophia Zhengzi; Todorov, Viktor

    Motivated by the implications from a stylized equilibrium pricing framework, we investigate empirically how individual equity prices respond to continuous, or \\smooth," and jumpy, or \\rough," market price moves, and how these different market price risks, or betas, are priced in the cross-section...

  19. Microbial deprivation, inflammation and cancer. (United States)

    von Hertzen, Leena C; Joensuu, H; Haahtela, T


    Dysregulated immune function is involved in the pathogenesis of many common human diseases. Living in urban, microbe-poor environment may have a profound influence on the immune function and eventually also on carcinogenesis. Unfortunately, few studies have thus far addressed the role of exposure to the environmental microbiota on the risk of cancer. Which mechanisms are broken in individuals prone to develop chronic inflammation in response to exposure that does not cause harm in others? Recent work in immunology has revealed that Th17 cells, a third subset of Th cells, and inflammatory cytokines, particularly IL-23, are closely linked with tumour-associated inflammation. Albeit the precise role of Th17 cells in cancer is still unclear and a matter of debate, accumulating evidence shows that Th17 cells are enriched in a wide range of human tumours, and that these tumour-derived Th17 cells may promote angiogenesis, tumour growth and inflammation. Regulatory T cells, in turn, appear to have counter-regulatory effects on Th17 cells and can inhibit their function. Thus, the regulatory network, induced and strengthened by continuous exposure to environmental microbiota, may play an important role in tumour immunobiology in preventing the establishment of chronic inflammation in its early phases. In addition, the discovery of the Toll-like receptor (TLR) system has brought micro-organisms to new light; continuous signalling via these TLRs and other receptors that sense microbial components is necessary for epithelial cell integrity, tissue repair, and recovery from injury. In this communication, we summarise the epidemiological data of living in environments with diverse microbial exposures and the risk of cancer, and discuss the related immunological mechanisms, focusing on the links between environmental microbiota, the Th17/IL-23 axis and cancer-associated inflammation.

  20. Targeting inflammation in metabolic syndrome. (United States)

    Welty, Francine K; Alfaddagh, Abdulhamied; Elajami, Tarec K


    The metabolic syndrome (MetS) is comprised of a cluster of closely related risk factors, including visceral adiposity, insulin resistance, hypertension, high triglyceride, and low high-density lipoprotein cholesterol; all of which increase the risk for the development of type 2 diabetes and cardiovascular disease. A chronic state of inflammation appears to be a central mechanism underlying the pathophysiology of insulin resistance and MetS. In this review, we summarize recent research which has provided insight into the mechanisms by which inflammation underlies the pathophysiology of the individual components of MetS including visceral adiposity, hyperglycemia and insulin resistance, dyslipidemia, and hypertension. On the basis of these mechanisms, we summarize therapeutic modalities to target inflammation in the MetS and its individual components. Current therapeutic modalities can modulate the individual components of MetS and have a direct anti-inflammatory effect. Lifestyle modifications including exercise, weight loss, and diets high in fruits, vegetables, fiber, whole grains, and low-fat dairy and low in saturated fat and glucose are recommended as a first line therapy. The Mediterranean and dietary approaches to stop hypertension diets are especially beneficial and have been shown to prevent development of MetS. Moreover, the Mediterranean diet has been associated with reductions in total and cardiovascular mortality. Omega-3 fatty acids and peroxisome proliferator-activated receptor α agonists lower high levels of triglyceride; their role in targeting inflammation is reviewed. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone blockers comprise pharmacologic therapies for hypertension but also target other aspects of MetS including inflammation. Statin drugs target many of the underlying inflammatory pathways involved in MetS.

  1. Prenatal Inflammation Linked to Autism Risk (United States)

    ... Thursday, January 24, 2013 Prenatal inflammation linked to autism risk Maternal inflammation during early pregnancy may be related to an increased risk of autism in children, according to new findings supported by ...

  2. Aetiological factors behind adipose tissue inflammation

    DEFF Research Database (Denmark)

    von Scholten, Bernt J; Andresen, Erik N; Sørensen, Thorkild I A


    Despite extensive research into the biological mechanisms behind obesity-related inflammation, knowledge of environmental and genetic factors triggering such mechanisms is limited. In the present narrative review we present potential determinants of adipose tissue inflammation and suggest ways...

  3. TGF-beta and osteoarthritis.

    NARCIS (Netherlands)

    Blaney Davidson, E.N.; Kraan, P.M. van der; Berg, W.B. van den


    OBJECTIVE: Cartilage damage is a major problem in osteoarthritis (OA). Growth factors like transforming growth factor-beta (TGF-beta) have great potential in cartilage repair. In this review, we will focus on the potential therapeutic intervention in OA with TGF-beta, application of the growth facto

  4. Pramipexole reduces inflammation in the experimental animal models of inflammation. (United States)

    Sadeghi, Heibatollah; Parishani, Mohammad; Akbartabar Touri, Mehdi; Ghavamzadeh, Mehdi; Jafari Barmak, Mehrzad; Zarezade, Vahid; Delaviz, Hamdollah; Sadeghi, Hossein


    Pramipexole is a dopamine (DA) agonist (D2 subfamily receptors) that widely use in the treatment of Parkinson's diseases. Some epidemiological and genetic studies propose a role of inflammation in the pathophysiology of Parkinson's disease. To our knowledge, there is no study regarding the anti-inflammatory activity of pramipexol. Therefore, the aim of the study was to investigate anti-inflammatory effect of pramipexol. Anti-inflammatory effects of pramipexole were studied in three well-characterized animal models of inflammation, including carrageenan- or formalin-induced paw inflammation in rats, and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema in mice. The animals received pramipexol (0.25, 0.5 and 1 mg/kg, I.P.) 30 min before subplantar injection of carrageenan or formalin. Pramipexol (0.5 and 1 mg/kg) was also injected 30 min before topical application of TPA on the ear mice. Serum malondialdehyde (MDA) levels were evaluated in the carrageenan test. Finally, pathological examination of the inflamed tissues was carried out. Pramipexole significantly inhibited paw inflammation 1, 2, 3 and 4 h after carrageenan challenge compared with the control group (p Pramipexol also showed considerable anti-inflammatory activity against formalin-evoked paw edema over a period of 24 h (p pramipexol (p pramipexole reduced tissue injury, neutrophil infiltration, and subcutaneous edema. Pramipexole did not alter the increased serum levels of MDA due to carrageenan injection. These data clearly indicate that pramipexol possesses significant anti-inflammatory activity. It seems that its antioxidants do not play an important role in these effects.

  5. Two chromogranin a-derived peptides induce calcium entry in human neutrophils by calmodulin-regulated calcium independent phospholipase A2.

    Directory of Open Access Journals (Sweden)

    Dan Zhang

    Full Text Available BACKGROUND: Antimicrobial peptides derived from the natural processing of chromogranin A (CgA are co-secreted with catecholamines upon stimulation of chromaffin cells. Since PMNs play a central role in innate immunity, we examine responses by PMNs following stimulation by two antimicrobial CgA-derived peptides. METHODOLOGY/PRINCIPAL FINDINGS: PMNs were treated with different concentrations of CgA-derived peptides in presence of several drugs. Calcium mobilization was observed by using flow cytometry and calcium imaging experiments. Immunocytochemistry and confocal microscopy have shown the intracellular localization of the peptides. The calmodulin-binding and iPLA2 activating properties of the peptides were shown by Surface Plasmon Resonance and iPLA2 activity assays. Finally, a proteomic analysis of the material released after PMNs treatment with CgA-derived peptides was performed by using HPLC and Nano-LC MS-MS. By using flow cytometry we first observed that after 15 s, in presence of extracellular calcium, Chromofungin (CHR or Catestatin (CAT induce a concentration-dependent transient increase of intracellular calcium. In contrast, in absence of extra cellular calcium the peptides are unable to induce calcium depletion from the stores after 10 minutes exposure. Treatment with 2-APB (2-aminoethoxydiphenyl borate, a store operated channels (SOCs blocker, inhibits completely the calcium entry, as shown by calcium imaging. We also showed that they activate iPLA2 as the two CaM-binding factors (W7 and CMZ and that the two sequences can be aligned with the two CaM-binding domains reported for iPLA2. We finally analyzed by HPLC and Nano-LC MS-MS the material released by PMNs following stimulation by CHR and CAT. We characterized several factors important for inflammation and innate immunity. CONCLUSIONS/SIGNIFICANCE: For the first time, we demonstrate that CHR and CAT, penetrate into PMNs, inducing extracellular calcium entry by a CaM-regulated i

  6. Gulf War Illness Inflammation Reduction Trial (United States)


    1 AWARD NUMBER: W81XWH-14-1-0477 TITLE: Gulf War Illness Inflammation Reduction Trial PRINCIPAL INVESTIGATOR: Ronald R. Bach, Ph.D...5a. CONTRACT NUMBER Gulf War Illness Inflammation Reduction Trial 5b. GRANT NUMBER W81XWH-14-1-0477 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...GWI). Elevated biomarkers of inflammation were observed in our pilot observational study of GWI. Thus, chronic inflammation appears to be part of

  7. Scutellaria baicalensis stem-leaf total flavonoid reduces neuronal apoptosis induced by amyloid beta-peptide (25-35)

    Institute of Scientific and Technical Information of China (English)

    Ruiting Wang; Xingbin Shen; Enhong Xing; Lihua Guan; Lisheng Xin


    Scutellaria baicalensis stem-leaf total flavonoid might attenuate learning/memory impairment and neuronal loss in rats induced by amyloid beta-peptide. This study aimed to explore the effects of Scutellaria baicalensis stem-leaf total flavonoid on amyloid beta-peptide-induced neuronal apoptosis and the expression of apoptosis-related proteins in the rat hippocampus. Male Wistar rats were given intragastric administration of Scutellaria baicalensis stem-leaf total flavonoid, 50 or 100 mg/kg, once per day. On day 8 after administration, 10 μg amyloid beta-peptide (25–35) was injected into the bilateral hippocampus of rats to induce neuronal apoptosis. On day 20, hippocampal tissue was harvested and probed with the terminal deoxyribonucleotidyl transferase-mediated biotin-16-dUTP nick-end labeling assay. Scutellaria baicalensis stem-leaf total flavonoid at 50 and 100 mg/kg reduced neuronal apoptosis induced by amyloid beta-peptide (25–35) in the rat hippocampus. Immunohistochemistry and western blot assay revealed that expression of the pro-apoptotic protein Bax, cytochrome c and caspase-3 was significantly diminished by 50 and 100 mg/kg Scutellaria baicalensis stem-leaf total flavonoid, while expression of the anti-apoptotic protein Bcl-2 was increased. Moreover, 100 mg/kg Scutellaria baicalensis stem-leaf total flavonoid had a more dramatic effect than the lower dosage. These experimental findings indicate that Scutellaria baicalensis stem-leaf total flavonoid dose-dependently attenuates neuronal apoptosis induced by amyloid beta-peptide in the hippocampus, and it might mediate this by regulating the expression of Bax, cytochrome c, caspase-3 and Bcl-2.

  8. Autonomic fiber sprouting in the skin in chronic inflammation

    Directory of Open Access Journals (Sweden)

    Longo Geraldine


    Full Text Available Abstract Pain is a major symptom associated with chronic inflammation. In previous work from our laboratory, we have shown that in animal models of neuropathic pain there is a sprouting of sympathetic fibers into the upper dermis, a territory normally devoid of them. However, it is not known whether such sympathetic spouting, which is likely trophic factor mediated, also occurs in chronic inflammation and arthritis. In the present study, we used a rat model of chronic inflammation in which a small single dose of complete Freund's adjuvant (CFA was injected subcutaneously, unilaterally, into the plantar surface of the hindpaw. This led to a localized long-term skin inflammation and arthritis in all joints of the hindpaw. Animals were perfused with histological fixatives at 1, 2, 3 or 4 weeks after the injection. Experimental animals treated with CFA were compared to saline-injected animals. We then investigated the changes in the pattern of peripheral innervation of the peptidergic nociceptors and sympathetic fibers in rat glabrous hindpaw skin. Antibodies directed towards calcitonin gene-related peptide (CGRP and dopamine beta-hydroxylase (DBH were used for the staining of peptidergic and sympathetic fibers, respectively. Immunofluorescence was then used to analyze the different nerve fiber populations of the upper dermis. At 4 weeks following CFA treatment, DBH-immunoreactive (IR fibers were found to sprout into the upper dermis, in a pattern similar to the one we had observed in animals with a chronic constriction injury of the sciatic nerve in a previous publication. There was also a significant increase in the density of CGRP-IR fibers in the upper dermis in CFA treated animals at 2, 3 and 4 weeks post-injection. The increased peptidergic fiber innervation and the ectopic autonomic fibers found in the upper dermis may have a role in the pain-related behavior displayed by these animals.

  9. Differential regulation of chemoattractant-stimulated beta 2, beta 3, and beta 7 integrin activity. (United States)

    Sadhu, C; Masinovsky, B; Staunton, D E


    Leukocyte adhesion to endothelium and extravasation are dynamic processes that require activation of integrins. Chemoattractants such as IL-8 and FMLP are potent activators of leukocyte integrins. To compare the chemoattractant-stimulated activation of three integrins, alpha 4 beta 7, alpha L beta 2, and alpha V beta 3, in the same cellular context, we expressed an IL-8 receptor (IL-8RA) and FMLP receptor (FPR) in the lymphoid cell line JY. Chemoattractants induced a rapid increase in alpha L beta 2- and alpha V beta 3-dependent JY adhesion within 5 min, and it was sustained for 30 min. In contrast, stimulation of alpha 4 beta 7-dependent adhesion was transient, returning to basal levels by 30 min. The activation profiles of the integrins were similar regardless of whether IL-8 or FMLP was used for induction. We also demonstrate that alpha 4 beta 7-dependent adhesion was uniquely responsive to the F actin-disrupting agent cytochalasin D and the protein kinase C (PKC) inhibitor chelerythrin. While alpha V beta 3- and alpha L beta 2-mediated cell adhesion was significantly reduced by cytochalasin D, alpha 4 beta 7-mediated adhesion was enhanced. Chelerythrin inhibited both the IL-8 and PMA activation of alpha L beta 2 and alpha V beta 3. In contrast, inducible alpha 4 beta 7 activity was unaffected, and basal activity was increased. These findings demonstrate that the mechanism of alpha 4 beta 7 regulation by chemoattractants is different from that of alpha L beta 2 and alpha V beta 3 and that it appears to involve distinct cytoskeletal and PKC dependencies. In addition, PKC activity may be a positive or negative regulator of integrin-dependent adhesion.

  10. Platelets in inflammation and immunity. (United States)

    Herter, J M; Rossaint, J; Zarbock, A


    The paradigm of platelets as mere mediators of hemostasis has long since been replaced by a dual role: hemostasis and inflammation. Now recognized as key players in innate and adaptive immune responses, platelets have the capacity to interact with almost all known immune cells. These platelet-immune cell interactions represent a hallmark of immunity, as they can potently enhance immune cell functions and, in some cases, even constitute a prerequisite for host defense mechanisms such as NETosis. In addition, recent studies have revealed a new role for platelets in immunity: They are ubiquitous sentinels and rapid first-line immune responders, as platelet-pathogen interactions within the vasculature appear to precede all other host defense mechanisms. Here, we discuss recent advances in our understanding of platelets as inflammatory cells, and provide an exemplary review of their role in acute inflammation.

  11. Obesity, inflammation, and liver cancer. (United States)

    Sun, Beicheng; Karin, Michael


    Obesity has become a universal and major public health problem with increasing prevalence in both adults and children in the 21st century, even in developing countries. Extensive epidemiological studies reveal a strong link between obesity and development and progression of various types of cancers. The connection between obesity and liver cancer is particularly strong and obesity often results in liver diseases such as non-alcoholic fatty liver disease (NAFLD) and the more severe non-alcoholic steatohepatitis (NASH). NASH is characterized by fatty liver inflammation and is believed to cause fibrosis and cirrhosis. The latter is a known liver cancer risk factor. In fact due to its much higher prevalence obesity may be a more substantial contributor to overall hepatocellular carcinoma burden than infection with hepatitis viruses. Here we review and discuss recent advances in elucidation of cellular and molecular alterations and signaling pathways associated with obesity and liver inflammation and their contribution to hepatocarcinogenesis.

  12. Beta-thalassemia

    Directory of Open Access Journals (Sweden)

    Origa Raffaella


    Full Text Available Abstract Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands, dilated myocardiopathy, liver fibrosis and cirrhosis. Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes, gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely

  13. Beta-thalassemia. (United States)

    Galanello, Renzo; Origa, Raffaella


    Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC) transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands), dilated myocardiopathy, liver fibrosis and cirrhosis). Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes), gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely, deletions in the beta

  14. Beta and muon decays

    Energy Technology Data Exchange (ETDEWEB)

    Galindo, A.; Pascual, P.


    These notes represent a series of lectures delivered by the authors in the Junta de Energia Nuclear, during the Spring term of 1965. They were devoted to graduate students interested in the Theory of Elementary Particles. Special emphasis was focussed into the computational problems. Chapter I is a review of basic principles (Dirac equation, transition probabilities, final state interactions.) which will be needed later. In Chapter II the four-fermion punctual Interaction is discussed, Chapter III is devoted to the study of beta-decay; the main emphasis is given to the deduction of the formulae corresponding to electron-antineutrino correlation, electron energy spectrum, lifetimes, asymmetry of electrons emitted from polarized nuclei, electron and neutrino polarization and time reversal invariance in beta decay. In Chapter IV we deal with the decay of polarized muons with radiative corrections. Chapter V is devoted to an introduction to C.V.C. theory. (Author)

  15. Realized Beta GARCH

    DEFF Research Database (Denmark)

    Hansen, Peter Reinhard; Lunde, Asger; Voev, Valeri Radkov


    We introduce a multivariate generalized autoregressive conditional heteroskedasticity (GARCH) model that incorporates realized measures of variances and covariances. Realized measures extract information about the current levels of volatilities and correlations from high-frequency data, which...... is particularly useful for modeling financial returns during periods of rapid changes in the underlying covariance structure. When applied to market returns in conjunction with returns on an individual asset, the model yields a dynamic model specification of the conditional regression coefficient that is known...... as the beta. We apply the model to a large set of assets and find the conditional betas to be far more variable than usually found with rolling-window regressions based exclusively on daily returns. In the empirical part of the paper, we examine the cross-sectional as well as the time variation...

  16. Regulating Inflammation in the Heart


    Fairweather, DeLisa


    Cardiovascular disease is the leading cause of death in the United States and estimated to be the leading cause of death worldwide by the year 2020. Many pathogens including bacteria, protozoa, and viruses are associated with inflammatory heart disease in patients, and can induce similar disease in animal models. Recognition of pathogens by the innate immune system leads to the release of proinflammatory cytokines that both reduce infection and increase inflammation in the heart. Signaling pa...

  17. Coroutine Sequencing in BETA

    DEFF Research Database (Denmark)

    Kristensen, Bent Bruun; Madsen, Ole Lehrmann; Møller-Pedersen, Birger;

    In object-oriented programming, a program execution is viewed as a physical model of some real or imaginary part of the world. A language supporting object-oriented programming must therefore contain comprehensive facilities for modeling phenomena and concepts form the application domain. Many ap...... applications in the real world consist of objects carrying out sequential processes. Coroutines may be used for modeling objects that alternate between a number of sequential processes. The authors describe coroutines in BETA...

  18. Magic Baseline Beta Beam

    CERN Document Server

    Agarwalla, Sanjib Kumar; Raychaudhuri, Amitava


    We study the physics reach of an experiment where neutrinos produced in a beta-beam facility at CERN are observed in a large magnetized iron calorimeter (ICAL) at the India-based Neutrino Observatory (INO). The CERN-INO distance is close to the so-called "magic" baseline which helps evade some of the parameter degeneracies and allows for a better measurement of the neutrino mass hierarchy and $\\theta_{13}$.

  19. Beta cell adaptation in pregnancy

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis


    Pregnancy is associated with a compensatory increase in beta cell mass. It is well established that somatolactogenic hormones contribute to the expansion both indirectly by their insulin antagonistic effects and directly by their mitogenic effects on the beta cells via receptors for prolactin...... and growth hormone expressed in rodent beta cells. However, the beta cell expansion in human pregnancy seems to occur by neogenesis of beta cells from putative progenitor cells rather than by proliferation of existing beta cells. Claes Hellerström has pioneered the research on beta cell growth for decades......, but the mechanisms involved are still not clarified. In this review the information obtained in previous studies is recapitulated together with some of the current attempts to resolve the controversy in the field: identification of the putative progenitor cells, identification of the factors involved...

  20. Regulation of beta cell replication

    DEFF Research Database (Denmark)

    Lee, Ying C; Nielsen, Jens Høiriis


    Beta cell mass, at any given time, is governed by cell differentiation, neogenesis, increased or decreased cell size (cell hypertrophy or atrophy), cell death (apoptosis), and beta cell proliferation. Nutrients, hormones and growth factors coupled with their signalling intermediates have been...... suggested to play a role in beta cell mass regulation. In addition, genetic mouse model studies have indicated that cyclins and cyclin-dependent kinases that determine cell cycle progression are involved in beta cell replication, and more recently, menin in association with cyclin-dependent kinase...... inhibitors has been demonstrated to be important in beta cell growth. In this review, we consider and highlight some aspects of cell cycle regulation in relation to beta cell replication. The role of cell cycle regulation in beta cell replication is mostly from studies in rodent models, but whether...

  1. Inflammation in coronary artery diseases

    Institute of Scientific and Technical Information of China (English)

    LI Jian-jun


    The concept that atherosclerosis is an inflammation has been increasingly recognized,and subsequently resulted in great interest in revealing the inflammatory nature of the atherosclerotic process.More recently,a large body of evidence has supported the idea that inflammatory mechanisms play a pivotal role throughout all phases of atherogenesis,from endothelial dysfunction and the formation of fatty streaks to plaque destabilization and the acute coronary events due to vulnerable plaque rupture.Indeed,although triggers and pathways of inflammation are probably multiple and vary in different clinical entities of atherosclerotic disorders,an imbalance between anti-inflammatory mechanisms and pro-inflammatory factors will result in an atherosclerotic progression.Vascular endothelial dysfunction and lipoprotein retention into the arterial intima have been reported as the earliest events in atherogenesis with which inflammation is linked.Inflammatory has also been extended to the disorders of coronary microvasculature,and associated with special subsets of coronary artery disease such as silent myocardial ischemia,myocardial ischemia-reperfusion,cardiac syndrome X,variant angina,coronary artery ectasia,coronary calcification and in-stent restenosis.Inflammatory biomarkers,originally studied to better understand the pathophysiology of atherosclerosis,have generated increasing interest among researches and clinicians.The identification of inflammatory biomarkers and cellular/molecular pathways in atherosclerotic disease represent important goals in cardiovascular disease research,in particular with respect of the development of therapeutic strategies to prevent or reverse atherosclerotic diseases.

  2. LHCb: $2\\beta_s$ measurement at LHCb

    CERN Multimedia

    Conti, G


    A measurement of $2\\beta_s$, the phase of the $B_s-\\bar{B_s}$ oscillation amplitude with respect to that of the ${\\rm b} \\rightarrow {\\rm c^{+}}{\\rm W^{-}}$ tree decay amplitude, is one of the key goals of the LHCb experiment with first data. In the Standard Model (SM), $2\\beta_s$ is predicted to be $0.0360^{+0.0020}_{-0.0016} \\rm rad$. The current constraints from the Tevatron are: $2\\beta_{s}\\in[0.32 ; 2.82]$ at 68$\\%$CL from the CDF experiment and $2\\beta_{s}=0.57^{+0.24}_{-0.30}$ from the D$\\oslash$ experiment. Although the statistical uncertainties are large, these results hint at the possible contribution of New Physics in the $B_s-\\bar{B_s}$ box diagram. After one year of data taking at LHCb at an average luminosity of $\\mathcal{L}\\sim2\\cdot10^{32}\\rm cm^{-2} \\rm s^{-1}$ (integrated luminosity $\\mathcal{L}_{\\rm int}\\sim 2 \\rm fb^{-1}$), the expected statistical uncertainty on the measurement is $\\sigma(2\\beta_s)\\simeq 0.03$. This uncertainty is similar to the $2\\beta_s$ value predicted by the SM.

  3. Essential role of TGF-beta/Smad pathway on statin dependent vascular smooth muscle cell regulation.

    Directory of Open Access Journals (Sweden)

    Juan Rodríguez-Vita

    Full Text Available BACKGROUND: The 3-hydroxy-3-methylglutaryl CoA reductase inhibitors (also called statins exert proven beneficial effects on cardiovascular diseases. Recent data suggest a protective role for Transforming Growth Factor-beta (TGF-beta in atherosclerosis by regulating the balance between inflammation and extracellular matrix accumulation. However, there are no studies about the effect of statins on TGF-beta/Smad pathway in atherosclerosis and vascular cells. METHODOLOGY: In cultured vascular smooth muscle cells (VSMCs statins enhanced Smad pathway activation caused by TGF-beta. In addition, statins upregulated TGF-beta receptor type II (TRII, and increased TGF-beta synthesis and TGF-beta/Smad-dependent actions. In this sense, statins, through Smad activation, render VSMCs more susceptible to TGF-beta induced apoptosis and increased TGF-beta-mediated ECM production. It is well documented that high doses of statins induce apoptosis in cultured VSMC in the presence of serum; however the precise mechanism of this effect remains to be elucidated. We have found that statins-induced apoptosis was mediated by TGF-beta/Smad pathway. Finally, we have described that RhoA inhibition is a common intracellular mechanisms involved in statins effects. The in vivo relevance of these findings was assessed in an experimental model of atherosclerosis in apolipoprotein E deficient mice: Treatment with Atorvastatin increased Smad3 phosphorylation and TRII overexpression, associated to elevated ECM deposition in the VSMCs within atheroma plaques, while apoptosis was not detected. CONCLUSIONS: Statins enhance TGF-beta/Smad pathway, regulating ligand levels, receptor, main signaling pathway and cellular responses of VSMC, including apoptosis and ECM accumulation. Our findings show that TGF-beta/Smad pathway is essential for statins-dependent actions in VSMCs.

  4. Andrographolide inhibits NF-kappaBeta activation and attenuates neointimal hyperplasia in arterial restenosis. (United States)

    Wang, Yu-Jiu; Wang, Jin-Tao; Fan, Quan-Xin; Geng, Jian-Guo


    The NF-kappaBeta transcription factors modulate the expression of tissue factor (TF), E-selectin (CD62E) and vascular cell adhesion molecule-1 (VCAM-1), which are essential for thrombosis and inflammation. We have previously shown that andrographolide (Andro) covalently modifies the reduced cysteine(62) of p50 - a major subunit of NF-kappaBeta transcription factors, thus blocking the binding of NF-kappaBeta transcription factors to the promoters of their target genes, preventing NF-kappaBeta activation and inhibiting inflammation in vitro and in vivo. Here we report that Andro, but not its inactive structural analog 4H-Andro, significantly suppressed the proliferation of arterial neointima ( approximately 60% reduction) in a murine model of arterial restenosis. Consistently, p50(-/-) mice manifested attenuated neointimal hyperplasia upon arterial ligation. Notably, the same dosage of Andro did not further reduce neointimal formation in p50(-/-) mice, which implicates the specificity of Andro on p50 for treating experimental arterial restenosis. The upregulation of NF-kappaBeta target genes, including TF, E-selectin and VCAM-1, and the increased deposition of leukocytes (mainly CD68+ macrophages) were clearly detected within the injured arterial walls, all of which were significantly abolished by treatment with Andro or genetic deletion of p50. The expression of TF, E-selectin and VCAM-1 was also markedly upregulated in the patient sample of thrombotic vasculitis, indicating the clinical relevance of NF-kappaBeta activation in the pathogeneses of occlusive arterial diseases. Our data thus indicate that, by the downregulation of the NF-kappaBeta target genes that are critical in thrombosis and inflammation, specific inhibitors of p50, such as Andro, may be therapeutically valuable for preventing and treating thrombotic arterial diseases, including neointimal hyperplasia in arterial restenosis.

  5. Cloning and characterization of exodus, a novel beta-chemokine. (United States)

    Hromas, R; Gray, P W; Chantry, D; Godiska, R; Krathwohl, M; Fife, K; Bell, G I; Takeda, J; Aronica, S; Gordon, M; Cooper, S; Broxmeyer, H E; Klemsz, M J


    Chemokines are a family of related proteins that regulate leukocyte infiltration into inflamed tissue. Some chemokines such as MIP-1 alpha also inhibit hematopoietic progenitor cell proliferation. Recently, three chemokines, MIP-1 alpha, MIP-1 beta, and RANTES, have been found to significantly decrease human immunodeficiency virus production from infected T cells. We report here the cloning and characterization of a novel human chemokine termed Exodus for its chemotactic properties. This novel chemokine is distantly related to other chemokines (28% homology with MIP-1 alpha) and shares several biological activities. Exodus is expressed preferentially in lymphocytes and monocytes, and its expression is markedly upregulated by mediators of inflammation such as tumor necrosis factor or lipopolysaccharide. Purified synthetic Exodus was found to inhibit proliferation of myeloid progenitors in colony formation assays. Exodus also stimulated chemotaxis of peripheral blood mononuclear cells. The sequence homology, expression, and biological activity indicate that Exodus represents a novel divergent beta-chemokine.

  6. Beta-blockers and heart failure. (United States)

    Cruickshank, John M


    The life-time risk of developing HF is about 20% (40% if hypertension present). With increasing longevity in the developed world the burden of HF (hospitalisation) is set to increase over the next 10-20 years. CAD and hypertension are the two main causes of HF; CAD (and obesity) in the case of systolic HF and hypertension in the case of diastolic HF (mainly in the elderly). BB have become the corner-stone (alongside ACE-inhibitors) in the treatment of systolic HF. Bisoprolol, metoprolol and carvedilol (on an ACE-inhibitor background) have reduced all-cause death by 34-5%. The presence of intrinsic sympathomemetic activity (xamoterol, bucindolol, nebivolol) diminishes efficacy in the treatment of systolic HF. First-line bisoprolol has proved "non-inferior" to first-line enalapril in reducing all-cause death and is probably superior in reducing sudden death. The main mode of action of BB in treating systolic HF is inhibition of chronic beta-1 stimulation-induced myocardial apoptosis/necrosis/inflammation. The combination of pure beta-1 blockade (low-dose bisoprolol) and pure beta-2 blockade (clenbuterol) may prove invaluable in the treatment of end-stage systolic HF (thus avoiding cardiac transplantation). The appropriate treatment of diastolic HF has yet to be determined. Beta-blockade is effective in the prevention of HF i) in the post-MI period and ii) as first-line agents in the treatment of young/middle-aged hypertension and as second-line agents (to first-line diuretics) in the treatment of elderly systolic hypertension. BB are highly effective in reversing LVH in young/middle-aged hypertensives (LVH pre-disposes to HF in young/middle-aged hypertension) and are (bisoprolol) at least as good as ACE-inhibitors. Choice of BB is important as benefit is not a class-effect. ISA (xamoterol, bucindolol, nebivolol) markedly diminishes efficacy. The choice is between bisoprolol, metoprolol succinate and carvedilol for optimal efficacy. Adverse reactions are associated

  7. Inflammation and cancer stem cells. (United States)

    Shigdar, Sarah; Li, Yong; Bhattacharya, Santanu; O'Connor, Michael; Pu, Chunwen; Lin, Jia; Wang, Tao; Xiang, Dongxi; Kong, Lingxue; Wei, Ming Q; Zhu, Yimin; Zhou, Shufeng; Duan, Wei


    Cancer stem cells are becoming recognised as being responsible for metastasis and treatment resistance. The complex cellular and molecular network that regulates cancer stem cells and the role that inflammation plays in cancer progression are slowly being elucidated. Cytokines, secreted by tumour associated immune cells, activate the necessary pathways required by cancer stem cells to facilitate cancer stem cells progressing through the epithelial-mesenchymal transition and migrating to distant sites. Once in situ, these cancer stem cells can secrete their own attractants, thus providing an environment whereby these cells can continue to propagate the tumour in a secondary niche.

  8. Intestinal inflammation and pain management. (United States)

    Basso, Lilian; Bourreille, Arnaud; Dietrich, Gilles


    Intestinal inflammation results in the production of inflammatory pain-inducing mediators that may directly activate colon sensory neurons. Endogenous opioids produced by mucosal effector CD4(+) T lymphocytes identified as colitogenic may paradoxically counterbalance the local pro-algesic effect of inflammatory mediators by acting on opioid receptors expressed on sensory nerve endings. The review will focus on the endogenous immune-mediated regulation of visceral inflammatory pain, current pain treatments in inflammatory bowel diseases and prospectives on new opioid therapeutic opportunities to alleviate pain but avoiding common centrally-mediated side effects.

  9. Chemokines in cancer related inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Allavena, Paola; Germano, Giovanni; Marchesi, Federica [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089, Rozzano, Milan (Italy); Mantovani, Alberto, E-mail: [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089, Rozzano, Milan (Italy); Department of Translational Medicine, University of Milan (Italy)


    Chemokines are key players of the cancer-related inflammation. Chemokine ligands and receptors are downstream of genetic events that cause neoplastic transformation and are abundantly expressed in chronic inflammatory conditions which predispose to cancer. Components of the chemokine system affect multiple pathways of tumor progression including: leukocyte recruitment, neo-angiogenesis, tumor cell proliferation and survival, invasion and metastasis. Evidence in pre-clinical and clinical settings suggests that the chemokine system represents a valuable target for the development of innovative therapeutic strategies.

  10. The linkage between inflammation and immune tolerance: interfering with inflammation in cancer. (United States)

    Rogovskii, Vladimir Stanislavovich


    Inflammation is linked to immune tolerance. In pregnancy and in immune privileged organs constitutive low-grade inflammation is required for maintaining immunological tolerance. Apart from immune tolerance in normality, there is the phenomenon of immune tolerance in cancer which mediates tumor escape from the immune system. It is widely accepted that, in many situations, chronic inflammation critically contributes to cancer. Like other types of immune tolerance, tumor-induced tolerance is also mediated by inflammation. In this review, the main mechanisms that link inflammation and tolerance are considered. We discuss drug targets that are in use to interfere with inflammation in cancer.

  11. Simultaneous beta and gamma spectroscopy (United States)

    Farsoni, Abdollah T.; Hamby, David M.


    A phoswich radiation detector for simultaneous spectroscopy of beta rays and gamma rays includes three scintillators with different decay time characteristics. Two of the three scintillators are used for beta detection and the third scintillator is used for gamma detection. A pulse induced by an interaction of radiation with the detector is digitally analyzed to classify the type of event as beta, gamma, or unknown. A pulse is classified as a beta event if the pulse originated from just the first scintillator alone or from just the first and the second scintillator. A pulse from just the third scintillator is recorded as gamma event. Other pulses are rejected as unknown events.

  12. Brain beta-amyloid accumulation in transgenic mice expressing mutant superoxide dismutase 1. (United States)

    Turner, Bradley J; Li, Qiao-Xin; Laughton, Katrina M; Masters, Colin L; Lopes, Elizabeth C; Atkin, Julie D; Cheema, Surindar S


    Oxidative stress is implicated in both the deposition and pathogenesis of beta-amyloid (Abeta) protein in Alzheimer's disease (AD). Accordingly, overexpression of the antioxidant enzyme superoxide dismutase 1 (SOD1) in neuronal cells and transgenic AD mice reduces Abeta toxicity and accumulation. In contrast, mutations in SOD1 associated with amyotrophic lateral sclerosis (ALS) confer enhanced pro-oxidative enzyme activities. We therefore examined whether ALS-linked mutant SOD1 overexpression in motor neuronal cells or transgenic ALS mice modulates Abeta toxicity or its accumulation in the brain. Aggregated, but not freshly solubilised, substrate-bound Abeta peptides induced degenerative morphology and cytotoxicity in motor neuron-like NSC-34 cells. Transfection of NSC-34 cells with human wild-type SOD1 attenuated Abeta-induced toxicity, however this neuroprotective effect was also observed for ALS-linked mutant SOD1. Analysis of the cerebral cortex, brainstem, cerebellum and olfactory bulb from transgenic SOD1G93A mice using enzyme-linked immunosorbent assay of acid-guanidine extracts revealed age-dependent elevations in Abeta levels, although not significantly different from wild-type mouse brain. In addition, brain amyloid protein precursor (APP) levels remained unaltered as a consequence of mutant SOD1 expression. We therefore conclude that mutant SOD1 overexpression promotes neither Abeta toxicity nor brain accumulation in these ALS models.

  13. Growth hormone, inflammation and aging

    Directory of Open Access Journals (Sweden)

    Michal M. Masternak


    Full Text Available Mutant animals characterized by extended longevity provide valuable tools to study the mechanisms of aging. Growth hormone and insulin-like growth factor-1 (IGF-1 constitute one of the well-established pathways involved in the regulation of aging and lifespan. Ames and Snell dwarf mice characterized by GH deficiency as well as growth hormone receptor/growth hormone binding protein knockout (GHRKO mice characterized by GH resistance live significantly longer than genetically normal animals. During normal aging of rodents and humans there is increased insulin resistance, disruption of metabolic activities and decline of the function of the immune system. All of these age related processes promote inflammatory activity, causing long term tissue damage and systemic chronic inflammation. However, studies of long living mutants and calorie restricted animals show decreased pro-inflammatory activity with increased levels of anti-inflammatory adipokines such as adiponectin. At the same time, these animals have improved insulin signaling and carbohydrate homeostasis that relate to alterations in the secretory profile of adipose tissue including increased production and release of anti-inflammatory adipokines. This suggests that reduced inflammation promoting healthy metabolism may represent one of the major mechanisms of extended longevity in long-lived mutant mice and likely also in the human.

  14. Factor V Leiden and Inflammation

    Directory of Open Access Journals (Sweden)

    Silvia Perez-Pujol


    Full Text Available Factor V Leiden, is a variant of human factor V (FV, also known as proaccelerin, which leads to a hypercoagulable state. Along these years, factor V Leiden (FVL has been studied from the pathophysiologic point of view, and research has been focused on finding clinical approaches for the management of the FVL associated to a trombophilic state. Less attention has been paid about the possible role of FVL in inflammatory conditions known to be present in different disorders such as uremia, cirrhosis, liver transplantation, depression as well as sepsis, infection or, inflammatory bowel disease (IBD. Whether platelet FVL will increase the activation of coagulation and/or in which proportion is able to determine the final outcome in the previously mentioned inflammatory conditions is a subject that remains uncertain. This paper will review the association of FVL with inflammation. Specifically, it will analyze the important role of the endothelium and the contribution of other inflammatory components involved at both the immune and vascular levels. This paper will also try to emphasize the importance of being a FVL carrier in associations to diseases where a chronic inflammation occurs, and how this condition may be determinant in the progression and outcome of a specific clinic situation.

  15. Focal brain inflammation and autism. (United States)

    Theoharides, Theoharis C; Asadi, Shahrzad; Patel, Arti B


    Increasing evidence indicates that brain inflammation is involved in the pathogenesis of neuropsychiatric diseases. Autism spectrum disorders (ASD) are characterized by social and learning disabilities that affect as many as 1/80 children in the USA. There is still no definitive pathogenesis or reliable biomarkers for ASD, thus significantly curtailing the development of effective therapies. Many children with ASD regress at about age 3 years, often after a specific event such as reaction to vaccination, infection, stress or trauma implying some epigenetic triggers, and may constitute a distinct phenotype. ASD children respond disproportionally to stress and are also affected by food and skin allergies. Corticotropin-releasing hormone (CRH) is secreted under stress and together with neurotensin (NT) stimulates mast cells and microglia resulting in focal brain inflammation and neurotoxicity. NT is significantly increased in serum of ASD children along with mitochondrial DNA (mtDNA). NT stimulates mast cell secretion of mtDNA that is misconstrued as an innate pathogen triggering an auto-inflammatory response. The phosphatase and tensin homolog (PTEN) gene mutation, associated with the higher risk of ASD, which leads to hyper-active mammalian target of rapamycin (mTOR) signalling that is crucial for cellular homeostasis. CRH, NT and environmental triggers could hyperstimulate the already activated mTOR, as well as stimulate mast cell and microglia activation and proliferation. The natural flavonoid luteolin inhibits mTOR, mast cells and microglia and could have a significant benefit in ASD.

  16. Obstructive sleep apnea and inflammation.

    LENUS (Irish Health Repository)

    McNicholas, Walter T


    The pathogenesis of cardiovascular complications in obstructive sleep apnea syndrome (OSAS) is not fully understood but is likely multifactorial in origin. Inflammatory processes play an important role in the pathogenesis of atherosclerosis, and circulating levels of several markers of inflammation have been associated with future cardiovascular risk. These include cell adhesion molecules such as intercellular adhesion molecule-1 and selectins, cytokines such as tumour necrosis factor alpha and interleukin 6, chemokines such as interleukin 8, and C-reactive protein. There is also increasing evidence that inflammatory processes play an important role in the cardiovascular pathophysiology of OSAS and many of the inflammatory markers associated with cardiovascular risk have been reported as elevated in patients with OSAS. Furthermore, animal and cell culture studies have demonstrated preferential activation of inflammatory pathways by intermittent hypoxia, which is an integral feature of OSAS. The precise role of inflammation in the development of cardiovascular disease in OSAS requires further study, particularly the relationship with oxidative stress, metabolic dysfunction, and obesity.

  17. Lymphocyte 'homing' and chronic inflammation. (United States)

    Sakai, Yasuhiro; Kobayashi, Motohiro


    Chronic inflammation is a response to prolonged exposure to injurious stimuli that harm and destroy tissues and promote lymphocyte infiltration into inflamed sites. Following progressive accumulation of lymphocytes, the histology of inflamed tissue begins to resemble that of peripheral lymphoid organs, which can be referred to as lymphoid neogenesis or formation of tertiary lymphoid tissues. Lymphocyte recruitment to inflamed tissues is also reminiscent of lymphocyte homing to peripheral lymphoid organs. In the latter, under physiological conditions, homing receptors expressed on lymphocytes adhere to vascular addressin expressed on high endothelial venules (HEVs), initiating a lymphocyte migration process composed of sequential adhesive interactions. Intriguingly, in chronic inflammation, HEV-like vessels are induced de novo, despite the fact that the inflamed site is not originally lymphoid tissue, and these vessels contribute to lymphocyte recruitment in a manner similar to physiological lymphocyte homing. In this review, we first describe physiological lymphocyte homing mechanisms focusing on vascular addressins. We then describe HEV-like vessel-mediated pathogenesis seen in various chronic inflammatory disorders such as Helicobacter pylori gastritis, inflammatory bowel disease (IBD), autoimmune pancreatitis and sclerosing sialadenitis, as well as chronic inflammatory cell neoplasm MALT lymphoma, with reference to our work and that of others.

  18. Hyperglycemia, tumorigenesis, and chronic inflammation. (United States)

    Chang, Shu-Chun; Yang, Wei-Chung Vivian


    Hyperglycemia is the most prominent sign that characterizes diabetes. Hyperglycemia favors malignant cell growth by providing energy to cancer cells. Clinical studies also showed an increased risk of diabetes being associated with different types of cancers. In addition, poorly regulated glucose metabolism in diabetic patients is often found with increased levels of chronic inflammatory markers, e.g., interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, and emerging evidence has highlighted activation of the immune response in the progression and development of cancer cells. Therefore, uncontrolled proinflammatory responses could conceivably create a chronic inflammatory state, promoting a tumor-favorable microenvironment and potentially triggering immune overactivation and cancer growth. To further understand how hyperglycemia contributes to immune overactivation, the tumor microenvironment and the development of chronic inflammation-associated tumors may provide insights into tumor biology and immunology. This paper provides a brief introduction to hyperglycemia-associated diseases, followed by a comprehensive overview of the current findings of regulatory molecular mechanisms of glycosylation on proteoglycans in the extracellular matrix under hyperglycemic conditions. Then, the authors discuss the role of hyperglycemia in tumorigenesis (particularly in prostate, liver, colorectal, and pancreatic cancers), as well as the contribution of hyperglycemia to chronic inflammation. The authors end with a brief discussion on the future perspectives of hyperglycemia/tumorigenesis and potential applications of alternative/effective therapeutic strategies for hyperglycemia-associated cancers.

  19. Beta section Beta: biogeographical patterns of variation and taxonomy.

    NARCIS (Netherlands)

    Letschert, J.P.W.


    In Chapter 1 an account is given of the historical subdivision of the genus Beta and its sections, and the relations of the sections are discussed. Emphasis is given to the taxonomic treatment of wild section Beta by various authors. The Linnaean names B. vulgaris L. and B. maritima L. are lectotypi

  20. Role of Inflammation and Oxidative Stress Mediators in Gliomas

    Directory of Open Access Journals (Sweden)

    Alfredo Conti


    Full Text Available Gliomas are the most common primary brain tumors of the central nervous system. Despite relevant progress in conventional treatments, the prognosis of such tumors remains almost invariably dismal. The genesis of gliomas is a complex, multistep process that includes cellular neoplastic transformation, resistance to apoptosis, loss of control of the cell cycle, angiogenesis, and the acquisition of invasive properties. Among a number of different biomolecular events, the existence of molecular connections between inflammation and oxidative stress pathways and the development of this cancer has been demonstrated. In particular, the tumor microenvironment, which is largely orchestrated by inflammatory molecules, is an indispensable participant in the neoplastic process, promoting proliferation, survival and migration of such tumors. Proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, as well as chemokines and prostaglandins, are synthesized by resident brain cells and lymphocytes invading the affected brain tissue. Key mediators of cancer progression include nuclear factor-kappaB, reactive oxygen and nitrogen species, and specific microRNAs. The collective activity of these mediators is largely responsible for a pro-tumorigenic response through changes in cell proliferation, cell death, cellular senescence, DNA mutation rates, DNA methylation and angiogenesis. We provide a general overview of the connection between specific inflammation and oxidative stress pathway molecules and gliomas. The elucidation of specific effects and interactions of these factors may provide the opportunity for the identification of new target molecules leading to improved diagnosis and treatment.

  1. Modulation of brain dead induced inflammation by vagus nerve stimulation. (United States)

    Hoeger, S; Bergstraesser, C; Selhorst, J; Fontana, J; Birck, R; Waldherr, R; Beck, G; Sticht, C; Seelen, M A; van Son, W J; Leuvenink, H; Ploeg, R; Schnuelle, P; Yard, B A


    Because the vagus nerve is implicated in control of inflammation, we investigated if brain death (BD) causes impairment of the parasympathetic nervous system, thereby contributing to inflammation. BD was induced in rats. Anaesthetised ventilated rats (NBD) served as control. Heart rate variability (HRV) was assessed by ECG. The vagus nerve was electrically stimulated (BD + STIM) during BD. Intestine, kidney, heart and liver were recovered after 6 hours. Affymetrix chip-analysis was performed on intestinal RNA. Quantitative PCR was performed on all organs. Serum was collected to assess TNFalpha concentrations. Renal transplantations were performed to address the influence of vagus nerve stimulation on graft outcome. HRV was significantly lower in BD animals. Vagus nerve stimulation inhibited the increase in serum TNFalpha concentrations and resulted in down-regulation of a multiplicity of pro-inflammatory genes in intestinal tissue. In renal tissue vagal stimulation significantly decreased the expression of E-selectin, IL1beta and ITGA6. Renal function was significantly better in recipients that received a graft from a BD + STIM donor. Our study demonstrates impairment of the parasympathetic nervous system during BD and inhibition of serum TNFalpha through vagal stimulation. Vagus nerve stimulation variably affected gene expression in donor organs and improved renal function in recipients.

  2. Protein expression analysis of inflammation-related colon carcinogenesis

    Directory of Open Access Journals (Sweden)

    Yasui Yumiko


    Full Text Available Background: Chronic inflammation is a risk factor for colorectal cancer (CRC development. The aim of this study was to determine the differences in protein expression between CRC and the surrounding nontumorous colonic tissues in the mice that received azoxymethane (AOM and dextran sodium sulfate (DSS using a proteomic analysis. Materials and Methods: Male ICR mice were given a single intraperitoneal injection of AOM (10 mg/kg body weight, followed by 2% (w/v DSS in their drinking water for seven days, starting one week after the AOM injection. Colonic adenocarcinoma developed after 20 weeks and a proteomics analysis based on two-dimensional gel electrophoresis and ultraflex TOF/TOF mass spectrometry was conducted in the cancerous and nontumorous tissue specimens. Results: The proteomic analysis revealed 21 differentially expressed proteins in the cancerous tissues in comparison to the nontumorous tissues. There were five markedly increased proteins (beta-tropomyosin, tropomyosin 1 alpha isoform b, S100 calcium binding protein A9, and an unknown protein and 16 markedly decreased proteins (Car1 proteins, selenium-binding protein 1, HMG-CoA synthase, thioredoxin 1, 1 Cys peroxiredoxin protein 2, Fcgbp protein, Cytochrome c oxidase, subunit Va, ETHE1 protein, and 7 unknown proteins. Conclusions: There were 21 differentially expressed proteins in the cancerous tissues of the mice that received AOM and DSS. Their functions include metabolism, the antioxidant system, oxidative stress, mucin production, and inflammation. These findings may provide new insights into the mechanisms of inflammation-related colon carcinogenesis and the establishment of novel therapies and preventative strategies to treat carcinogenesis in the inflamed colon.

  3. Cyclic modular beta-sheets. (United States)

    Woods, R Jeremy; Brower, Justin O; Castellanos, Elena; Hashemzadeh, Mehrnoosh; Khakshoor, Omid; Russu, Wade A; Nowick, James S


    The development of peptide beta-hairpins is problematic, because folding depends on the amino acid sequence and changes to the sequence can significantly decrease folding. Robust beta-hairpins that can tolerate such changes are attractive tools for studying interactions involving protein beta-sheets and developing inhibitors of these interactions. This paper introduces a new class of peptide models of protein beta-sheets that addresses the problem of separating folding from the sequence. These model beta-sheets are macrocyclic peptides that fold in water to present a pentapeptide beta-strand along one edge; the other edge contains the tripeptide beta-strand mimic Hao [JACS 2000, 122, 7654] and two additional amino acids. The pentapeptide and Hao-containing peptide strands are connected by two delta-linked ornithine (deltaOrn) turns [JACS 2003, 125, 876]. Each deltaOrn turn contains a free alpha-amino group that permits the linking of individual modules to form divalent beta-sheets. These "cyclic modular beta-sheets" are synthesized by standard solid-phase peptide synthesis of a linear precursor followed by solution-phase cyclization. Eight cyclic modular beta-sheets 1a-1h containing sequences based on beta-amyloid and macrophage inflammatory protein 2 were synthesized and characterized by 1H NMR. Linked cyclic modular beta-sheet 2, which contains two modules of 1b, was also synthesized and characterized. 1H NMR studies show downfield alpha-proton chemical shifts, deltaOrn delta-proton magnetic anisotropy, and NOE cross-peaks that establish all compounds but 1c and 1g to be moderately or well folded into a conformation that resembles a beta-sheet. Pulsed-field gradient NMR diffusion experiments show little or no self-association at low (

  4. Resolution of inflammation: a new therapeutic frontier. (United States)

    Fullerton, James N; Gilroy, Derek W


    Dysregulated inflammation is a central pathological process in diverse disease states. Traditionally, therapeutic approaches have sought to modulate the pro- or anti-inflammatory limbs of inflammation, with mixed success. However, insight into the pathways by which inflammation is resolved has highlighted novel opportunities to pharmacologically manipulate these processes - a strategy that might represent a complementary (and perhaps even superior) therapeutic approach. This Review discusses the state of the art in the biology of resolution of inflammation, highlighting the opportunities and challenges for translational research in this field.

  5. Inflammation, Infection, and Future Cardiovascular Risk (United States)


    Cardiovascular Diseases; Coronary Disease; Cerebrovascular Accident; Myocardial Infarction; Venous Thromboembolism; Heart Diseases; Infection; Chlamydia Infections; Cytomegalovirus Infections; Helicobacter Infections; Herpesviridae Infections; Inflammation

  6. Integration of BETA with Eclipse

    DEFF Research Database (Denmark)

    Andersen, Peter; Madsen, Ole Lehrmann; Enevoldsen, Mads Brøgger


    This paper presents language interoperability issues appearing in order to implement support for the BETA language in the Java-based Eclipse integrated development environment. One of the challenges is to implement plug-ins in BETA and be able to load them in Eclipse. In order to do this, some form...

  7. Measurements of sin 2 $\\beta$

    CERN Document Server

    Tricomi, A


    A review of the most recent measurements of the CP violating parameter sin 2 beta from LEP and CDF is reported. These yield an average value of sin 2 beta =0.91+or-0.35, giving a confidence level that CP violation in the B system has been observed of almost 99%. (10 refs).

  8. Beta decay of Cu-56

    NARCIS (Netherlands)

    Borcea, R; Aysto, J; Caurier, E; Dendooven, P; Doring, J; Gierlik, M; Gorska, M; Grawe, H; Hellstrom, M; Janas, Z; Jokinen, A; Karny, M; Kirchner, R; La Commara, M; Langanke, K; Martinez-Pinedo, G; Mayet, P; Nieminen, A; Nowacki, F; Penttila, H; Plochocki, A; Rejmund, M; Roeckl, E; Schlegel, C; Schmidt, K; Schwengner, R; Sawicka, M


    The proton-rich isotope Cu-56 was produced at the GSI On-Line Mass Separator by means of the Si-28(S-32, p3n) fusion-evaporation reaction. Its beta -decay properties were studied by detecting beta -delayed gamma rays and protons. A half-Life of 93 +/- 3 ms was determined for Cu-56. Compared to the p

  9. Beta Function and Anomalous Dimensions

    DEFF Research Database (Denmark)

    Pica, Claudio; Sannino, Francesco


    We demonstrate that it is possible to determine the coefficients of an all-order beta function linear in the anomalous dimensions using as data the two-loop coefficients together with the first one of the anomalous dimensions which are universal. The beta function allows to determine the anomalou...

  10. Beta-conglycinin and gut histology of sunshine bass fed diets with new varieties of non-GM soybeans (United States)

    It is reported that the soybean protein (Beta-conglycinin) might cause inflammation of the distal intestine and stimulate endogenous cholecystokinin release that suppresses food intake in fish. We are studying the effects of meals made from new strains of non-GMO soybeans with high protein and redu...

  11. Interleukin-1beta inhibits paw oedema induced by local administration of latex of Calotropis procera extracts. (United States)

    Arya, Soneera; Kumar, Vijay L


    Interleukin-1beta (IL-1beta), a pro-inflammatory cytokine, has been reported to exhibit anti-inflammatory properties in the carrageenan-induced paw oedema model. In the present study, we have evaluated the anti-inflammatory activity of IL-1beta against inflammation induced by local administration of the methanol extract of dried latex of Calotropis procera (MeDL) and compared it with that against carrageenan. The anti-inflammatory activity of standard anti-inflammatory drugs, phenylbutazone (PBZ) and dexamethasone (DEX), was also evaluated against both inflammagens. Injection of an aqueous solution of dried latex and MeDL into the sub-plantar surface of the rat paw produced intense inflammation with a peak response occurring within 2 h, while the peak inflammatory response with carrageenan was obtained at 3 h. Subcutaneous injection of IL-1beta was found to be more effective against the inflammatory response elicited by carrageenan (70% inhibition) as compared to MeDL (50% inhibition) at 20microg/kg dose. On the other hand, PBZ effectively inhibited the inflammatory response elicited by both MeDL and carrageenan, while DEX was more effective against carrageenan. Thus, our study indicates that the difference in the anti-inflammatory effect of IL-1beta against latex of C. procera extract and carrageenan is due to the release of different mediators released by these inflammagens.

  12. RAVEN Beta Release

    Energy Technology Data Exchange (ETDEWEB)

    Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Alfonsi, Andrea [Idaho National Lab. (INL), Idaho Falls, ID (United States); Cogliati, Joshua Joseph [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mandelli, Diego [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kinoshita, Robert Arthur [Idaho National Lab. (INL), Idaho Falls, ID (United States); Wang, Congjian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Maljovec, Daniel Patrick [Idaho National Lab. (INL), Idaho Falls, ID (United States); Talbot, Paul William [Idaho National Lab. (INL), Idaho Falls, ID (United States)


    This documents the release of the Risk Analysis Virtual Environment (RAVEN) code. A description of the RAVEN code is provided, and discussion of the release process for the M2LW-16IN0704045 milestone. The RAVEN code is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. RAVEN is capable of investigating the system response as well as the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. RAVEN has now increased in maturity enough for the Beta 1.0 release.

  13. Polyphenols, inflammation, and cardiovascular disease. (United States)

    Tangney, Christy C; Rasmussen, Heather E


    Polyphenols are compounds found in foods such as tea, coffee, cocoa, olive oil, and red wine and have been studied to determine if their intake may modify cardiovascular disease (CVD) risk. Historically, biologic actions of polyphenols have been attributed to antioxidant activities, but recent evidence suggests that immunomodulatory and vasodilatory properties of polyphenols may also contribute to CVD risk reduction. These properties will be discussed, and recent epidemiological evidence and intervention trials will be reviewed. Further identification of polyphenols in foods and accurate assessment of exposures through measurement of biomarkers (i.e., polyphenol metabolites) could provide the needed impetus to examine the impact of polyphenol-rich foods on CVD intermediate outcomes (especially those signifying chronic inflammation) and hard endpoints among high risk patients. Although we have mechanistic insight into how polyphenols may function in CVD risk reduction, further research is needed before definitive recommendations for consumption can be made.

  14. Postischemic Inflammation in Acute Stroke (United States)

    Consoli, Arturo; Arnaboldi, Marco; Consoli, Domenico


    Cerebral ischemia is caused by arterial occlusion due to a thrombus or an embolus. Such occlusion induces multiple and concomitant pathophysiological processes that involve bioenergetic failure, acidosis, loss of cell homeostasis, excitotoxicity, and disruption of the blood-brain barrier. All of these mechanisms contribute to neuronal death, mainly via apoptosis or necrosis. The immune system is involved in this process in the early phases after brain injury, which contributes to potential enlargement of the infarct size and involves the penumbra area. Whereas inflammation and the immune system both exert deleterious effects, they also contribute to brain protection by stimulating a preconditioning status and to the concomitant repair of the injured parenchyma. This review describes the main phases of the inflammatory process occurring after arterial cerebral occlusion, with an emphasis on the role of single mediators. PMID:28079313

  15. Microbes, intestinal inflammation and probiotics. (United States)

    Khan, Mohammad W; Kale, Amod A; Bere, Praveen; Vajjala, Sriharsha; Gounaris, Elias; Pakanati, Krishna Chaitanya


    Inflammatory bowel disease (IBD) is known for causing disturbed homeostatic balance among the intestinal immune compartment, epithelium and microbiota. Owing to the emergence of IBD as a major cause of morbidity and mortality, great efforts have been put into understanding the sequence of intestinal inflammatory events. Intestinal macrophages and dendritic cells act in a synergistic fashion with intestinal epithelial cells and microbiota to initiate the triad that governs the intestinal immune responses (whether inflammatory or regulatory). In this review, we will discuss the interplay of intestinal epithelial cells, bacteria and the innate immune component. Moreover, whether or not genetic intervention of probiotic bacteria is a valid approach for attenuating/mitigating exaggerated inflammation and IBD will also be discussed.

  16. [Serum beta 2 microglobulin (beta 2M) following renal transplantation]. (United States)

    Pacheco-Silva, A; Nishida, S K; Silva, M S; Ramos, O L; Azjen, H; Pereira, A B


    Although there was an important improvement in graft and patient survival the last 10 years, graft rejection continues to be a major barrier to the success of renal transplantation. Identification of a laboratory test that could help to diagnose graft rejection would facilitate the management of renal transplanted patients. PURPOSE--To evaluate the utility of monitoring serum beta 2M in recently transplanted patients. METHODS--We daily determined serum beta 2M levels in 20 receptors of renal grafts (10 from living related and 10 from cadaveric donors) and compared them to their clinical and laboratory evolution. RESULTS--Eight patients who presented immediate good renal function following grafting and did not have rejection had a mean serum beta 2M of 3.7 mg/L on the 4th day post transplant. The sensitivity of the test for the diagnosis of acute rejection was 87.5%, but the specificity was only 46%. Patients who presented acute tubular necrosis (ATN) without rejection had a progressive decrease in their serum levels of beta 2M, while their serum creatinine changed as they were dialyzed. In contrast, patients with ATN and concomitance of acute rejection or CSA nephrotoxicity presented elevated beta 2M and creatinine serum levels. CONCLUSION--Daily monitoring of serum beta 2M does not improve the ability to diagnose acute rejection in patients with good renal function. However, serum beta 2M levels seemed to be useful in diagnosing acute rejection or CSA nephrotoxicity in patients with ATN.

  17. Modulation of interleukin-1beta mediated inflammatory response in human astrocytes by flavonoids: implications in neuroprotection. (United States)

    Sharma, Vivek; Mishra, Mamata; Ghosh, Soumya; Tewari, Richa; Basu, Anirban; Seth, Pankaj; Sen, Ellora


    The proinflammatory cytokine interleukin-1beta (IL-1beta) contributes to inflammation and neuronal death in CNS injuries and neurodegenerative pathologies, and astrocytes have been implicated as the primary mediators of IL-1beta induced neuronal death. As astrocytes play an important role in supporting the survival and functions of neurons, we investigated the effect of plant flavonoids quercetin and luteolin, with known anti-inflammatory properties in modulating the response of human astrocytes to IL-1beta for therapeutic intervention. Flavonoids significantly decreased the release of reactive oxygen species (ROS) from astrocytes stimulated with IL-1beta. This decrease was accompanied by an increase in expression of superoxide dismutase (SOD-1) and thioredoxin (TRX1)-mediators associated with protection against oxidative stress. Flavonoids not only modulated the expression of astrocytes specific molecules such as glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), and ceruloplasmin (CP) both in the presence and absence of IL-1beta but also decreased the elevated levels of proinflammatory cytokine interleukin-6 (IL-6) and chemokines interleukin-8 (IL-8), interferon-inducible protein (IP-10), monocyte-chemoattractant protein-1 (MCP-1), and RANTES from IL-1beta activated astrocytes. Significant decrease in neuronal apoptosis was observed in neurons cultured in conditioned medium obtained from astrocytes treated with a combination of IL-1beta and flavonoids as compared to that treated with IL-1beta alone. Our result suggests that by (i) enhancing the potential of activated astrocytes to detoxify free radical, (ii) reducing the expression of proinflammatory cytokines and chemokines, and (iii) modulating expression of mediators associated with enhanced physiological activity of astrocyte in response to injury, flavonoids confer (iv) protection against IL-1beta induced astrocyte mediated neuronal damage.

  18. Pain related inflammation analysis using infrared images (United States)

    Bhowmik, Mrinal Kanti; Bardhan, Shawli; Das, Kakali; Bhattacharjee, Debotosh; Nath, Satyabrata


    Medical Infrared Thermography (MIT) offers a potential non-invasive, non-contact and radiation free imaging modality for assessment of abnormal inflammation having pain in the human body. The assessment of inflammation mainly depends on the emission of heat from the skin surface. Arthritis is a disease of joint damage that generates inflammation in one or more anatomical joints of the body. Osteoarthritis (OA) is the most frequent appearing form of arthritis, and rheumatoid arthritis (RA) is the most threatening form of them. In this study, the inflammatory analysis has been performed on the infrared images of patients suffering from RA and OA. For the analysis, a dataset of 30 bilateral knee thermograms has been captured from the patient of RA and OA by following a thermogram acquisition standard. The thermograms are pre-processed, and areas of interest are extracted for further processing. The investigation of the spread of inflammation is performed along with the statistical analysis of the pre-processed thermograms. The objectives of the study include: i) Generation of a novel thermogram acquisition standard for inflammatory pain disease ii) Analysis of the spread of the inflammation related to RA and OA using K-means clustering. iii) First and second order statistical analysis of pre-processed thermograms. The conclusion reflects that, in most of the cases, RA oriented inflammation affects bilateral knees whereas inflammation related to OA present in the unilateral knee. Also due to the spread of inflammation in OA, contralateral asymmetries are detected through the statistical analysis.

  19. Dual role of neutrophils in inflammation

    NARCIS (Netherlands)

    Pillay, J.


    Systemic inflammation is a hallmark of trauma, sepsis and various severe infectious diseases. Severe systemic inflammation can lead to inflammatory complications. The Acute Respiratory Distress Syndrome (ARDS) and Multiple Organ Dysfunction Syndrome (MODS) are seen after trauma and in sepsis and are

  20. Neurogenic inflammation in human and rodent skin

    DEFF Research Database (Denmark)

    Schmelz, M; Petersen, Lars Jelstrup


    The combination of vasodilation and protein extravasation following activation of nociceptors has been termed "neurogenic inflammation." In contrast to rodents, no neurogenic protein extravasation can be elicited in healthy human skin. Dermal microdialysis has considerably increased our knowledge...... about neurogenic inflammation in human skin, including the involvement of mast cells....

  1. Radiopharmaceuticals for imaging chronic lymphocytic inflammation

    NARCIS (Netherlands)

    Malviya, Gaurav; De Vries, Erik F. J.; Dierckx, Rudi A.; Signore, Alberto


    In the last few decades, a number of radiopharmaceuticals for imaging inflammation have been proposed that differ in their specificity and mechanism of uptake in inflamed foci as compared to the traditional inflammation imaging agents. Radiolabelled cytokines represent a reliable tool for the precli

  2. Inflammation and its echo in atherosclerosis

    NARCIS (Netherlands)

    van Leuven, S.I.


    Inflammation plays a major role during all phases of atherogenesis from plaque initiation up to plaque rupture. In this thesis the role of inflammation in the pathophysiology of atherosclerosis is examined from different angles. In part I the effect of various pro-inflammatory mediators is examined

  3. Susceptibility to chronic inflammation: an update. (United States)

    Nasef, Noha Ahmed; Mehta, Sunali; Ferguson, Lynnette R


    Chronic inflammation is defined by the persistence of inflammatory processes beyond their physiological function, resulting in tissue destruction. Chronic inflammation is implicated in the progression of many chronic diseases and plays a central role in chronic inflammatory and autoimmune disease. As such, this review aims to collate some of the latest research in relation to genetic and environmental susceptibilities to chronic inflammation. In the genetic section, we discuss some of the updates in cytokine research and current treatments that are being developed. We also discuss newly identified canonical and non-canonical genes associated with chronic inflammation. In the environmental section, we highlight some of the latest updates and evidence in relation to the role that infection, diet and stress play in promoting inflammation. The aim of this review is to provide an overview of the latest research to build on our current understanding of chronic inflammation. It highlights the complexity associated with chronic inflammation, as well as provides insights into potential new targets for therapies that could be used to treat chronic inflammation and consequently prevent disease progression.

  4. Reparative inflammation takes charge of tissue regeneration

    NARCIS (Netherlands)

    Karin, Michael; Clevers, Hans


    Inflammation underlies many chronic and degenerative diseases, but it also mitigates infections, clears damaged cells and initiates tissue repair. Many of the mechanisms that link inflammation to damage repair and regeneration in mammals are conserved in lower organisms, indicating that it is an evo

  5. Innate Immune Responses to Engineered Nanomaterials During Allergic Airway Inflammation (United States)

    Shipkowski, Kelly Anne

    The field of nanotechnology is continually advancing, and increasing amounts of consumer goods are being produced using engineered nanomaterials (ENMs). The health risks of occupational and/or consumer exposure to ENMs are not completely understood, although significant research indicates that pulmonary exposure to nanomaterials induces toxic effects in the lungs of exposed animals. Multi-walled carbon nanotubes (MWCNTs) are a specific category of ENMs and consist of sheets of graphene rolled into cylinders that are multiple layers thick in order to strengthen their rigidity. MWCNTs have a fiber-like shape, similar to that of asbestos, which allows for a high aspect ratio and makes them difficult to clear from the lung. Studies with rodent models have demonstrated that pulmonary exposure to ENMs, in particular MWCNTs, results in acute lung inflammation and the subsequent development of chronic fibrosis, suggesting a potential human health risk to individuals involved in the manufacturing of products utilizing these nanomaterials. Induction of IL-1beta secretion via activation of the inflammasome is a prime mechanism of MWCNT-induced inflammation. The inflammasome is a multi-protein scaffold found in a variety of cell types that forms in response to a variety of immune signals, including particulates. Sensitization with allergens, such as house dust mite (HDM), increases levels of the T helper 2 (Th2) cytokines IL-4 and IL-13 in mice and in humans, and there is particular cause for concern in cases of MWCNT exposure in individuals with pre-existing allergic airway disease, such as asthma. MWCNT exposure exacerbates airway inflammation and fibrosis in animal models of pre-existing allergic asthma, suggesting that individuals suffering from asthma are more susceptible to the toxic pulmonary effects of MWCNT exposure. Asthma is an exceptionally prominent human disease, and therefore the goal of this research was to better understand how pre-existing allergic airway

  6. Treating dyslipidemias: is inflammation the missing link? (United States)

    Papoutsidakis, Nikolaos; Deftereos, Spyridon; Giannopoulos, Georgios; Panagopoulou, Vasiliki; Manolis, Antonis S; Bouras, Georgios


    Low-grade chronic inflammation is now being held as an important process in the development of atherosclerosis, with new links between dyslipidemia and inflammation being constantly found. While most studies aim to discover inflammatory pathways leading from dyslipidemia to atherogenesis, there is evidence that inflammation can also act in reverse, altering lipid metabolism in unfavorable ways, possibly creating a vicious cycle of inflammationdyslipidemia- inflammation. This is highly relevant for the search of novel therapeutic targets. In this review, after a brief account of the inflammatory mechanisms leading from dyslipidemia to atherogenesis, we focus on what is currently known about the ways inflammation can impair lipid metabolism and whether anti-inflammatory therapies could have a role in dyslipidemia management.

  7. CART peptide induces neuroregeneration in stroke rats. (United States)

    Luo, Yu; Shen, Hui; Liu, Hua-Shan; Yu, Seong-Jin; Reiner, David J; Harvey, Brandon K; Hoffer, Barry J; Yang, Yihong; Wang, Yun


    Utilizing a classic stroke model in rodents, middle cerebral artery occlusion (MCAo), we describe a novel neuroregenerative approach using the repeated intranasal administration of cocaine- and amphetamine-regulated transcript (CART) peptide starting from day 3 poststroke for enhancing the functional recovery of injured brain. Adult rats were separated into two groups with similar infarction sizes, measured by magnetic resonance imaging on day 2 after MCAo, and were treated with CART or vehicle. The CART treatment increased CART level in the brain, improved behavioral recovery, and reduced neurological scores. In the subventricular zone (SVZ), CART enhanced immunolabeling of bromodeoxyuridine, a neural progenitor cell marker Musashi-1, and the proliferating cell nuclear antigen, as well as upregulated brain-derived neurotrophic factor (BDNF) mRNA. AAV-GFP was locally applied to the SVZ to examine migration of SVZ cells. The CART enhanced migration of GFP(+) cells from SVZ toward the ischemic cortex. In SVZ culture, CART increased the size of neurospheres. The CART-mediated cell migration from SVZ explants was reduced by anti-BDNF blocking antibody. Using (1)H-MRS (proton magnetic resonance spectroscopy), increases in N-acetylaspartate levels were found in the lesioned cortex after CART treatment in stroke brain. Cocaine- and amphetamine-regulated transcript increased the expression of GAP43 and fluoro-ruby fluorescence in the lesioned cortex. In conclusion, our data suggest that intranasal CART treatment facilitates neuroregeneration in stroke brain.


    Directory of Open Access Journals (Sweden)

    Olena eLykhmus


    Full Text Available Neuro-inflammation, one of the pathogenic causes of neurodegenerative diseases, is regulated through the cholinergic anti-inflammatory pathway via the 7 nicotinic acetylcholine receptor (7 nAChR. We previously showed that either bacterial lipopolysaccharide (LPS or immunization with the 7(1-208 nAChR fragment decrease 7 nAChRs density in the mouse brain, exacerbating chronic inflammation, beta-amyloid accumulation and episodic memory decline, which mimic the early stages of Alzheimer’s disease. To study the molecular mechanisms underlying the LPS and antibody effects in the brain, we employed an in vivo model of acute LPS-induced inflammation and an in vitro model of cultured glioblastoma U373 cells. Here, we report that LPS challenge decreased the levels of 7 nAChR RNA and protein and of acetylcholinesterase (AChE RNA and activity in distinct mouse brain regions, sensitized brain mitochondria to the apoptogenic effect of Ca2+ and modified brain microRNA profiles, including the cholinergic-regulatory CholinomiRs-132/212, in favor of anti-inflammatory and pro-apoptotic ones. Adding 7(1-208-specific antibodies to the LPS challenge prevented elevation of both the anti-inflammatory and pro-apoptotic miRNAs while supporting the resistance of brain mitochondria to Ca2+ and maintaining 7 nAChR/AChE decreases. In U373 cells, 7-specific antibodies and LPS both stimulated interleukin-6 production through the p38/Src-dependent pathway. Our findings demonstrate that acute LPS-induced inflammation induces the cholinergic anti-inflammatory pathway in the brain, that 7 nAChR down-regulation limits this pathway, and that 7-specific antibodies aggravate neuroinflammation by inducing the pro-inflammatory interleukin-6 and dampening anti-inflammatory miRNAs; however, these antibodies may protect brain mitochondria and decrease the levels of pro-apoptotic miRNAs, preventing LPS-induced neurodegeneration.

  9. Molecular Mechanisms Regulating LPS-Induced Inflammation in the Brain (United States)

    Lykhmus, Olena; Mishra, Nibha; Koval, Lyudmyla; Kalashnyk, Olena; Gergalova, Galyna; Uspenska, Kateryna; Komisarenko, Serghiy; Soreq, Hermona; Skok, Maryna


    Neuro-inflammation, one of the pathogenic causes of neurodegenerative diseases, is regulated through the cholinergic anti-inflammatory pathway via the α7 nicotinic acetylcholine receptor (α7 nAChR). We previously showed that either bacterial lipopolysaccharide (LPS) or immunization with the α7(1–208) nAChR fragment decrease α7 nAChRs density in the mouse brain, exacerbating chronic inflammation, beta-amyloid accumulation and episodic memory decline, which mimic the early stages of Alzheimer’s disease (AD). To study the molecular mechanisms underlying the LPS and antibody effects in the brain, we employed an in vivo model of acute LPS-induced inflammation and an in vitro model of cultured glioblastoma U373 cells. Here, we report that LPS challenge decreased the levels of α7 nAChR RNA and protein and of acetylcholinesterase (AChE) RNA and activity in distinct mouse brain regions, sensitized brain mitochondria to the apoptogenic effect of Ca2+ and modified brain microRNA profiles, including the cholinergic-regulatory CholinomiRs-132/212, in favor of anti-inflammatory and pro-apoptotic ones. Adding α7(1–208)-specific antibodies to the LPS challenge prevented elevation of both the anti-inflammatory and pro-apoptotic miRNAs while supporting the resistance of brain mitochondria to Ca2+ and maintaining α7 nAChR/AChE decreases. In U373 cells, α7-specific antibodies and LPS both stimulated interleukin-6 production through the p38/Src-dependent pathway. Our findings demonstrate that acute LPS-induced inflammation induces the cholinergic anti-inflammatory pathway in the brain, that α7 nAChR down-regulation limits this pathway, and that α7-specific antibodies aggravate neuroinflammation by inducing the pro-inflammatory interleukin-6 and dampening anti-inflammatory miRNAs; however, these antibodies may protect brain mitochondria and decrease the levels of pro-apoptotic miRNAs, preventing LPS-induced neurodegeneration. PMID:27013966

  10. Experiments on double beta decay

    Energy Technology Data Exchange (ETDEWEB)

    Busto, J. [Neuchatel Univ. (Switzerland). Inst. de Physique


    The Double Beta Decay, and especially ({beta}{beta}){sub 0{nu}} mode, is an excellent test of Standard Model as well as of neutrino physics. From experimental point of view, a very large number of different techniques are or have been used increasing the sensitivity of this experiments quite a lot (the factor of 10{sup 4} in the last 20 years). In future, in spite of several difficulties, the sensitivity would be increased further, keeping the interest of this very important process. (author) 4 figs., 5 tabs., 21 refs.

  11. Dosimetry of {beta} extensive sources; Dosimetria de fuentes {beta} extensas

    Energy Technology Data Exchange (ETDEWEB)

    Rojas C, E.L.; Lallena R, A.M. [Departamento de Fisica Moderna, Universidad de Granada, E-18071 Granada (Spain)


    In this work, we have been studied, making use of the Penelope Monte Carlo simulation code, the dosimetry of {beta} extensive sources in situations of spherical geometry including interfaces. These configurations are of interest in the treatment of the called cranealfaringyomes of some synovia leisure of knee and other problems of interest in medical physics. Therefore, its application can be extended toward problems of another areas with similar geometric situation and beta sources. (Author)

  12. Copernicus revisited: amyloid beta in Alzheimer's disease. (United States)

    Joseph, J; Shukitt-Hale, B; Denisova, N A; Martin, A; Perry, G; Smith, M A


    The beta-amyloid hypothesis of Alzheimer's Disease (AD) has dominated the thinking and research in this area for over a decade and a half. While there has been a great deal of effort in attempting to prove its centrality in this devastating disease, and while an enormous amount has been learned about its properties (e.g., putative toxicity, processing and signaling), Abeta has not proven to be both necessary and sufficient for the development, neurotoxicity, and cognitive deficits associated with this disease. Instead, the few treatments that are available have emerged from aging research and are primarily directed toward modification of acetylcholine levels. Clearly, it is time to rethink this position and to propose instead that future approaches should focus upon altering the age-related sensitivity of the neuronal environment to insults involving such factors as inflammation and oxidative stress. In other words "solve the problems of aging and by extension those of AD will also be reduced." This review is being submitted as a rather Lutherian attempt to "nail an alternative thesis" to the gate of the Church of the Holy Amyloid to open its doors to the idea that aging is the most pervasive element in this disease and Abeta is merely one of the planets.

  13. Assessment of in situ adipose tissue inflammation by microdialysis

    DEFF Research Database (Denmark)

    Langkilde, Anne; Andersen, Ove; Henriksen, Jens H;


    Inflammation, and specifically adipose tissue (AT) inflammation, is part of the pathophysiology of obesity and HIV-associated lipodystrophy. Local AT protein assessment methods are limited, and AT inflammation studies have therefore primarily examined inflammatory gene expression. We therefore...

  14. Genetic variation in estrogen receptor, C-reactive protein and fibrinogen does not predict the plasma levels of inflammation markers after longterm hormone replacement therapy

    DEFF Research Database (Denmark)

    de Maat, Moniek P M; Madsen, Jonna Skov; Langdahl, Bente Lomholt;


    Markers of inflammation, such as C-reactive protein (CRP) and fibrinogen, are associated with the risk of atherothrombosis. Plasma levels of these markers of inflammation are affected by hormone replacement therapy (HRT) and modulated by smoking. We studied whether genetic variation in the estrogen...... receptor- 1 (ESR1), CRP and fibrinogen-beta genes influences the plasma levels of inflammation markers after HRT. Plasma CRP and fibrinogen were measured after five years follow-up in healthy postmenopausal women (per-protocol group) who were randomised to hormone therapy (n=187) or no treatment (n=249......). The effect of HRT, smoking and genetic variations in ESR1 (PvuII and XbaI), CRP (1444C/T) and fibrinogen-beta (FGB, -455G/A) were determined. The plasma concentration of CRP was higher in the HRT group than in the control group (2.03 mg/l and 1.41 mg/l, respectively; p

  15. Evolution of outer membrane beta-barrels from an ancestral beta beta hairpin. (United States)

    Remmert, M; Biegert, A; Linke, D; Lupas, A N; Söding, J


    Outer membrane beta-barrels (OMBBs) are the major class of outer membrane proteins from Gram-negative bacteria, mitochondria, and plastids. Their transmembrane domains consist of 8-24 beta-strands forming a closed, barrel-shaped beta-sheet around a central pore. Despite their obvious structural regularity, evidence for an origin by duplication or for a common ancestry has not been found. We use three complementary approaches to show that all OMBBs from Gram-negative bacteria evolved from a single, ancestral beta beta hairpin. First, we link almost all families of known single-chain bacterial OMBBs with each other through transitive profile searches. Second, we identify a clear repeat signature in the sequences of many OMBBs in which the repeating sequence unit coincides with the structural beta beta hairpin repeat. Third, we show that the observed sequence similarity between OMBB hairpins cannot be explained by structural or membrane constraints on their sequences. The third approach addresses a longstanding problem in protein evolution: how to distinguish between a very remotely homologous relationship and the opposing scenario of "sequence convergence." The origin of a diverse group of proteins from a single hairpin module supports the hypothesis that, around the time of transition from the RNA to the protein world, proteins arose by amplification and recombination of short peptide modules that had previously evolved as cofactors of RNAs.

  16. Platelets, inflammation and tissue regeneration. (United States)

    Nurden, Alan T


    Blood platelets have long been recognised to bring about primary haemostasis with deficiencies in platelet production and function manifesting in bleeding while upregulated function favourises arterial thrombosis. Yet increasing evidence indicates that platelets fulfil a much wider role in health and disease. First, they store and release a wide range of biologically active substances including the panoply of growth factors, chemokines and cytokines released from a-granules. Membrane budding gives rise to microparticles (MPs), another active participant within the blood stream. Platelets are essential for the innate immune response and combat infection (viruses, bacteria, micro-organisms). They help maintain and modulate inflammation and are a major source of pro-inflammatory molecules (e.g. P-selectin, tissue factor, CD40L, metalloproteinases). As well as promoting coagulation, they are active in fibrinolysis; wound healing, angiogenesis and bone formation as well as in maternal tissue and foetal vascular remodelling. Activated platelets and MPs intervene in the propagation of major diseases. They are major players in atherosclerosis and related diseases, pathologies of the central nervous system (Alzheimers disease, multiple sclerosis), cancer and tumour growth. They participate in other tissue-related acquired pathologies such as skin diseases and allergy, rheumatoid arthritis, liver disease; while, paradoxically, autologous platelet-rich plasma and platelet releasate are being used as an aid to promote tissue repair and cellular growth. The above mentioned roles of platelets are now discussed.

  17. Fruit polyphenols, immunity and inflammation. (United States)

    González-Gallego, Javier; García-Mediavilla, M Victoria; Sánchez-Campos, Sonia; Tuñón, María J


    Flavonoids are a large class of naturally occurring compounds widely present in fruits, vegetables and beverages derived from plants. These molecules have been reported to possess a wide range of activities in the prevention of common diseases, including CHD, cancer, neurodegenerative diseases, gastrointestinal disorders and others. The effects appear to be related to the various biological/pharmacological activities of flavonoids. A large number of publications suggest immunomodulatory and anti-inflammatory properties of these compounds. However, almost all studies are in vitro studies with limited research on animal models and scarce data from human studies. The majority of in vitro research has been carried out with single flavonoids, generally aglycones, at rather supraphysiological concentrations. Few studies have investigated the anti-inflammatory effects of physiologically attainable flavonoid concentrations in healthy subjects, and more epidemiological studies and prospective randomised trials are still required. This review summarises evidence for the effects of fruit and tea flavonoids and their metabolites in inflammation and immunity. Mechanisms of effect are discussed, including those on enzyme function and regulation of gene and protein expression. Animal work is included, and evidence from epidemiological studies and human intervention trials is reviewed. Biological relevance and functional benefits of the reported effects, such as resistance to infection or exercise performance, are also discussed.

  18. Red cell DAMPs and inflammation. (United States)

    Mendonça, Rafaela; Silveira, Angélica A A; Conran, Nicola


    Intravascular hemolysis, or the destruction of red blood cells in the circulation, can occur in numerous diseases, including the acquired hemolytic anemias, sickle cell disease and β-thalassemia, as well as during some transfusion reactions, preeclampsia and infections, such as those caused by malaria or Clostridium perfringens. Hemolysis results in the release of large quantities of red cell damage-associated molecular patterns (DAMPs) into the circulation, which, if not neutralized by innate protective mechanisms, have the potential to activate multiple inflammatory pathways. One of the major red cell DAMPs, heme, is able to activate converging inflammatory pathways, such as toll-like receptor signaling, neutrophil extracellular trap formation and inflammasome formation, suggesting that this DAMP both activates and amplifies inflammation. Other potent DAMPs that may be released by the erythrocytes upon their rupture include heat shock proteins (Hsp), such as Hsp70, interleukin-33 and Adenosine 5' triphosphate. As such, hemolysis represents a major inflammatory mechanism that potentially contributes to the clinical manifestations that have been associated with the hemolytic diseases, such as pulmonary hypertension and leg ulcers, and likely plays a role in specific complications of sickle cell disease such as endothelial activation, vaso-occlusive processes and tissue injury.

  19. Metal Dyshomeostasis and Inflammation in Alzheimer’s and Parkinson’s Diseases: Possible Impact of Environmental Exposures


    Oddvar Myhre; Hans Utkilen; Nur Duale; Gunnar Brunborg; Tim Hofer


    A dysregulated metal homeostasis is associated with both Alzheimer's (AD) and Parkinson's (PD) diseases; AD patients have decreased cortex and elevated serum copper levels along with extracellular amyloid-beta plaques containing copper, iron, and zinc. For AD, a putative hepcidin-mediated lowering of cortex copper mechanism is suggested. An age-related mild chronic inflammation and/or elevated intracellular iron can trigger hepcidin production followed by its binding to ferroportin which is t...

  20. Questions Students Ask: Beta Decay. (United States)

    Koss, Jordan; Hartt, Kenneth


    Answers a student's question about the emission of a positron from a nucleus. Discusses the problem from the aspects of the uncertainty principle, beta decay, the Fermi Theory, and modern physics. (YP)

  1. Beta Function and Anomalous Dimensions

    CERN Document Server

    Pica, Claudio


    We demonstrate that it is possible to determine the coefficients of an all-order beta function linear in the anomalous dimensions using as data the two-loop coefficients together with the first one of the anomalous dimensions which are universal. The beta function allows to determine the anomalous dimension of the fermion masses at the infrared fixed point, and the resulting values compare well with the lattice determinations.

  2. Cholinergic Regulation of Airway Inflammation and Remodelling

    Directory of Open Access Journals (Sweden)

    Saeed Kolahian


    Full Text Available Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway diseases. Moreover, it has become apparent that acetylcholine is synthesized by nonneuronal cells and tissues, including inflammatory cells and structural cells. In this paper, we will discuss the regulatory role of acetylcholine in inflammation and remodelling in which we will focus on the role of the airway smooth muscle cell as a target cell for acetylcholine that modulates inflammation and remodelling during respiratory diseases such as asthma and COPD.

  3. Polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase activity and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Morant, Marc


    The present invention relates to isolated polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  4. The role of Toll-like receptor 2 in inflammation and fibrosis during progressive renal injury.

    Directory of Open Access Journals (Sweden)

    Jaklien C Leemans

    Full Text Available Tissue fibrosis and chronic inflammation are common causes of progressive organ damage, including progressive renal disease, leading to loss of physiological functions. Recently, it was shown that Toll-like receptor 2 (TLR2 is expressed in the kidney and activated by endogenous danger signals. The expression and function of TLR2 during renal fibrosis and chronic inflammation has however not yet been elucidated. Therefore, we studied TLR2 expression in human and murine progressive renal diseases and explored its role by inducing obstructive nephropathy in TLR2(-/- or TLR2(+/+ mice. We found that TLR2 is markedly upregulated on tubular and tubulointerstitial cells in patients with chronic renal injury. In mice with obstructive nephropathy, renal injury was associated with a marked upregulation and change in distribution of TLR2 and upregulation of murine TLR2 danger ligands Gp96, biglycan, and HMGB1. Notably, TLR2 enhanced inflammation as reflected by a significantly reduced influx of neutrophils and production of chemokines and TGF-beta in kidneys of TLR2(-/- mice compared with TLR2(+/+ animals. Although, the obstructed kidneys of TLR2(-/- mice had less interstitial myofibroblasts in the later phase of obstructive nephropathy, tubular injury and renal matrix accumulation was similar in both mouse strains. Together, these data demonstrate that TLR2 can initiate renal inflammation during progressive renal injury and that the absence of TLR2 does not affect the development of chronic renal injury and fibrosis.

  5. Fibrosis and inflammation are greater in muscles of beta-sarcoglycan-null mouse than mdx mouse. (United States)

    Gibertini, Sara; Zanotti, Simona; Savadori, Paolo; Curcio, Maurizio; Saredi, Simona; Salerno, Franco; Andreetta, Francesca; Bernasconi, Pia; Mantegazza, Renato; Mora, Marina


    The Sgcb-null mouse, with knocked-down β-sarcoglycan, develops severe muscular dystrophy as in type 2E human limb girdle muscular dystrophy. The mdx mouse, lacking dystrophin, is the most used model for Duchenne muscular dystrophy (DMD). Unlike DMD, the mdx mouse has mild clinical features and shows little fibrosis in limb muscles. To characterize ECM protein deposition and the progression of muscle fibrosis, we evaluated protein and transcript levels of collagens I, III and VI, decorin, and TGF-β1, in quadriceps and diaphragm, at 2, 4, 8, 12, 26, and 52 weeks in Sgcb-null mice, and protein levels at 12, 26, and 52 weeks in mdx mice. In Sgcb-null mice, severe morphological disruption was present from 4 weeks in both quadriceps and diaphragm, and included conspicuous deposition of extracellular matrix components. Histopathological features of Sgcb-null mouse muscles were similar to those of age-matched mdx muscles at all ages examined, but, in the Sgcb-null mouse, the extent of connective tissue deposition was generally greater than mdx. Furthermore, in the Sgcb-null mouse, the amount of all three collagen isoforms increased steadily, while, in the mdx, they remained stable. We also found that, at 12 weeks, macrophages were significantly more numerous in mildly inflamed areas of Sgcb-null quadriceps compared to mdx quadriceps (but not in highly inflamed regions), while, in the diaphragm, macrophages did not differ significantly between the two models, in either region. Osteopontin mRNA was also significantly greater at 12 weeks in laser-dissected highly inflamed areas of the Sgcb-null quadriceps compared to the mdx quadriceps. TGF-β1 was present in areas of degeneration-regeneration, but levels were highly variable and in general did not differ significantly between the two models and controls. The roles of the various subtypes of macrophages in muscle repair and fibrosis in the two models require further study. The Sgcb-null mouse, which develops early fibrosis in limb muscles, appears more promising than the mdx mouse for probing pathogenetic mechanisms of muscle fibrosis and for developing anti-fibrotic treatments. Highlights • The Sgcb-null mouse develops severe muscular dystrophy, the mdx mouse does not. • Fibrosis developed earlier in Sgcb-null quadriceps and diaphragm than mdx. • Macrophages were commoner in mildly inflamed parts of Sgcb-null quadriceps than mdx. • The Sgcb-null model appears more useful than mdx for studying fibrotic mechanisms. • The Sgcb-null model also appears more useful for developing anti-fibrotic treatments.

  6. Critical role of calpain in inflammation (United States)

    Ji, Jingjing; Su, Lei; Liu, Zhifeng


    Calpains are a family of cysteine proteases, implicated in a wide range of cellular calcium-regulated functions. Evidence from previous studies using an inhibitor of calpain indicates that calpain activation is involved in the process of numerous inflammation-associated diseases. As a result of in-depth studies, calpains have been proposed to influence the process of inflammation via a variety of mechanisms. The aim of the present study is to provide an overview of recent reports regarding the role of calpain in the process of inflammation, including regulation of immune cell migration, modulation of the activation of inflammatory mediators, degradation of certain associated proteins and induction of cell apoptosis. Understanding these mechanisms may contribute to the investigation of novel therapeutic targets for inflammation-associated diseases. PMID:28101338

  7. Regulation of pulmonary inflammation by mesenchymal cells

    NARCIS (Netherlands)

    Alkhouri, Hatem; Poppinga, Wilfred Jelco; Tania, Navessa Padma; Ammit, Alaina; Schuliga, Michael


    Pulmonary inflammation and tissue remodelling are common elements of chronic respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and pulmonary hypertension (PH). In disease, pulmonary mesenchymal cells not only contribute to tissue

  8. Inflammation induced loss of skeletal muscle. (United States)

    Londhe, Priya; Guttridge, Denis C


    Inflammation is an important contributor to the pathology of diseases implicated in skeletal muscle dysfunction. A number of diseases and disorders including inflammatory myopathies and Chronic Obstructive Pulmonary Disorder (COPD) are characterized by chronic inflammation or elevation of the inflammatory mediators. While these disease states exhibit different pathologies, all have in common the loss of skeletal muscle mass and a deregulated skeletal muscle physiology. Pro-inflammatory cytokines are key contributors to chronic inflammation found in many of these diseases. This section of the review focuses on some of the known inflammatory disorders like COPD, Rheumatoid Arthritis (RA) and inflammatory myopathies that display skeletal muscle atrophy and also provides the reader an overview of the mediators of inflammation, their signaling pathways, and mechanisms of action. This article is part of a Special Issue entitled "Muscle Bone Interactions".

  9. Cholinergic regulation of airway inflammation and remodelling

    NARCIS (Netherlands)

    Kolahian, Saeed; Gosens, Reinoud


    Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway disease

  10. Hypoxic induction of caspase-11/caspase-1/interleukin-1beta in brain microglia. (United States)

    Kim, Nam-Gon; Lee, Heasuk; Son, Eunyung; Kwon, Oh-Young; Park, Jae-Yong; Park, Jae-Hoon; Cho, Gyeong Jae; Choi, Wan Sung; Suk, Kyoungho


    Caspase-11 is an inducible protease that plays an important role in both inflammation and apoptosis. Inflammatory stimuli induce and activate caspase-11, which is required for the activation of caspase-1 or interleukin-1beta (IL-1beta) converting enzyme (ICE). Caspase-1 in turn mediates the maturation of proinflammatory cytokines such as IL-1beta, which is one of the crucial mediators of neurodegeneration in the central nervous system. Here, we report that hypoxic exposure of cultured brain microglia (BV-2 mouse microglia cells and rat primary microglial cultures) induces expression and activation of caspase-11, which is accompanied by activation of caspase-1 and secretion of mature IL-1beta and IL-18. Hypoxic induction of caspase-11 was observed in both mRNA and protein levels, and was mediated through p38 mitogen-activated protein kinase pathway. Transient global ischemia in rats also induced caspase-11 expression and IL-1beta production in hippocampus supporting our in vitro findings. Caspase-11-expressing cells in hippocampus were morphologically identified as microglia. Taken together, our results indicate that hypoxia induces a sequential event-caspase-11 induction, caspase-1 activation, and IL-1beta release-in brain microglia, and point out the importance of initial caspase-11 induction in hypoxia-induced inflammatory activation of microglia.

  11. Glycemic control in diabetes is restored by therapeutic manipulation of cytokines that regulate beta cell stress. (United States)

    Hasnain, Sumaira Z; Borg, Danielle J; Harcourt, Brooke E; Tong, Hui; Sheng, Yonghua H; Ng, Choa Ping; Das, Indrajit; Wang, Ran; Chen, Alice C-H; Loudovaris, Thomas; Kay, Thomas W; Thomas, Helen E; Whitehead, Jonathan P; Forbes, Josephine M; Prins, Johannes B; McGuckin, Michael A


    In type 2 diabetes, hyperglycemia is present when an increased demand for insulin, typically due to insulin resistance, is not met as a result of progressive pancreatic beta cell dysfunction. This defect in beta cell activity is typically characterized by impaired insulin biosynthesis and secretion, usually accompanied by oxidative and endoplasmic reticulum (ER) stress. We demonstrate that multiple inflammatory cytokines elevated in diabetic pancreatic islets induce beta cell oxidative and ER stress, with interleukin-23 (IL-23), IL-24 and IL-33 being the most potent. Conversely, we show that islet-endogenous and exogenous IL-22, by regulating oxidative stress pathways, suppresses oxidative and ER stress caused by cytokines or glucolipotoxicity in mouse and human beta cells. In obese mice, antibody neutralization of IL-23 or IL-24 partially reduced beta cell ER stress and improved glucose tolerance, whereas IL-22 administration modulated oxidative stress regulatory genes in islets, suppressed ER stress and inflammation, promoted secretion of high-quality efficacious insulin and fully restored glucose homeostasis followed by restitution of insulin sensitivity. Thus, therapeutic manipulation of immune regulators of beta cell stress reverses the hyperglycemia central to diabetes pathology.

  12. The GERDA experiment on 0{nu}{beta}{beta} decay

    Energy Technology Data Exchange (ETDEWEB)

    Freund, Kai [Eberhard Karls Universitaet Tuebingen (Germany); Collaboration: GERDA-Collaboration


    The Gerda (Germanium Detector Array) collaboration searches for the neutrinoless double beta decay (0{nu}{beta}{beta}) of {sup 76}Ge. The existence of this decay would give rise to the assumption that the neutrino is a Majorana particle, i.e. its own antiparticle. A measured half-life could be used to determine the effective neutrino mass and hence resolve the neutrino mass hierarchy problem. Germanium diodes, isotopically enriched in {sup 76}Ge, are used as both source and detector. Due to the low rate of this decay (T{sub 1/2}>10{sup 25} y), the experimental background must be reduced to a level of 10{sup -2}counts/(kg y keV) or better in the region around Q{sub {beta}{beta}}. To minimize background from cosmogenically produced secondary particles, a low Z shielding is employed. Thus, the naked diodes are operated in a liquid argon cryostat, which is surrounded by a water tank acting as both passive shield and active muon Cherenkov veto. Gerda started the commissioning runs in 2010 and in November 2011, the first phase of data taking with enriched detectors has begun. In this talk, the first year of the experiment is summarized.

  13. Endothelial dysfunction and inflammation in asymptomatic proteinuria


    Paisley, K.E.; Beaman, M; Tooke, J. E.; Mohamed-Ali, V; Lowe, G. D. O.; Shore, A C


    Background. Proteinuria is associated with vascular risk and a systemic increase in vascular permeability. Endothelial dysfunction occurs early in atherosclerosis and modulates vascular permeability. Vascular risk and chronic inflammation are associated. This study investigates whether the increased vascular permeability in proteinuria reflects systemic endothelial dysfunction and chronic inflammation. Methods. Twenty-one patients with asymptomatic proteinuria (1.29 g/24 h; range 0.18 to 3.17...

  14. Malnutrition-Inflammation Score in Hemodialysis Patients


    Behrooz Ebrahimzadehkor; Atamohammad Dorri; Abdolhamed Yapan-Gharavi


    Background: Malnutrition is a prevalent complication in patients on maintenance hemodialysis. Malnutrition-inflammation score (MIS), comprehensive nutritional assessment tool, as the reference standard was used to examine protein-energy wasting (PEW) and inflammation in hemodialysis patients. Materials and Methods: In this descriptive- analytical study, 48 hemodialysis patients were selected with random sampling. All the patients were interviewed and the MIS of the patients was recorded. T...

  15. Stretching Impacts Inflammation Resolution in Connective Tissue. (United States)

    Berrueta, Lisbeth; Muskaj, Igla; Olenich, Sara; Butler, Taylor; Badger, Gary J; Colas, Romain A; Spite, Matthew; Serhan, Charles N; Langevin, Helene M


    Acute inflammation is accompanied from its outset by the release of specialized pro-resolving mediators (SPMs), including resolvins, that orchestrate the resolution of local inflammation. We showed earlier that, in rats with subcutaneous inflammation of the back induced by carrageenan, stretching for 10 min twice daily reduced inflammation and improved pain, 2 weeks after carrageenan injection. In this study, we hypothesized that stretching of connective tissue activates local pro-resolving mechanisms within the tissue in the acute phase of inflammation. In rats injected with carrageenan and randomized to stretch versus no stretch for 48 h, stretching reduced inflammatory lesion thickness and neutrophil count, and increased resolvin (RvD1) concentrations within lesions. Furthermore, subcutaneous resolvin injection mimicked the effect of stretching. In ex vivo experiments, stretching of connective tissue reduced the migration of neutrophils and increased tissue RvD1 concentration. These results demonstrate a direct mechanical impact of stretching on inflammation-regulation mechanisms within connective tissue.

  16. Resolution of Inflammation: What Controls Its Onset? (United States)

    Sugimoto, Michelle A; Sousa, Lirlândia P; Pinho, Vanessa; Perretti, Mauro; Teixeira, Mauro M


    An effective resolution program may be able to prevent the progression from non-resolving acute inflammation to persistent chronic inflammation. It has now become evident that coordinated resolution programs initiate shortly after inflammatory responses begin. In this context, several mechanisms provide the fine-tuning of inflammation and create a favorable environment for the resolution phase to take place and for homeostasis to return. In this review, we focus on the events required for an effective transition from the proinflammatory phase to the onset and establishment of resolution. We suggest that several mediators that promote the inflammatory phase of inflammation can simultaneously initiate a program for active resolution. Indeed, several events enact a decrease in the local chemokine concentration, a reduction which is essential to inhibit further infiltration of neutrophils into the tissue. Interestingly, although neutrophils are cells that characteristically participate in the active phase of inflammation, they also contribute to the onset of resolution. Further understanding of the molecular mechanisms that initiate resolution may be instrumental to develop pro-resolution strategies to treat complex chronic inflammatory diseases, in humans. The efforts to develop strategies based on resolution of inflammation have shaped a new area of pharmacology referred to as "resolution pharmacology."

  17. Resolution of Inflammation: What Controls Its Onset? (United States)

    Sugimoto, Michelle A.; Sousa, Lirlândia P.; Pinho, Vanessa; Perretti, Mauro; Teixeira, Mauro M.


    An effective resolution program may be able to prevent the progression from non-resolving acute inflammation to persistent chronic inflammation. It has now become evident that coordinated resolution programs initiate shortly after inflammatory responses begin. In this context, several mechanisms provide the fine-tuning of inflammation and create a favorable environment for the resolution phase to take place and for homeostasis to return. In this review, we focus on the events required for an effective transition from the proinflammatory phase to the onset and establishment of resolution. We suggest that several mediators that promote the inflammatory phase of inflammation can simultaneously initiate a program for active resolution. Indeed, several events enact a decrease in the local chemokine concentration, a reduction which is essential to inhibit further infiltration of neutrophils into the tissue. Interestingly, although neutrophils are cells that characteristically participate in the active phase of inflammation, they also contribute to the onset of resolution. Further understanding of the molecular mechanisms that initiate resolution may be instrumental to develop pro-resolution strategies to treat complex chronic inflammatory diseases, in humans. The efforts to develop strategies based on resolution of inflammation have shaped a new area of pharmacology referred to as “resolution pharmacology.” PMID:27199985

  18. Markers of inflammation are inversely associated with VO2 max in asymptomatic men. (United States)

    Kullo, Iftikhar J; Khaleghi, Mahyar; Hensrud, Donald D


    We investigated whether markers of inflammation, including a cytokine (IL-6), acute-phase reactants [C-reactive protein (CRP) and fibrinogen], and white blood cell (WBC) count are associated with maximal O(2) consumption (Vo(2 max)) in men without coronary heart disease (CHD). In asymptomatic men (n = 172, 51 +/- 9.3 yr old), Vo(2 max) was measured during a symptom-limited graded treadmill exercise test. Physical activity level was assessed by a standardized questionnaire. IL-6 and CRP were measured by immunoassays, fibrinogen by the Clauss method, and WBC count with a Coulter counter. IL-6 and CRP were logarithmically transformed to reduce skewness. Multivariable regression was used to assess whether markers of inflammation were associated with Vo(2 max) after adjustment for age, body mass index, CHD risk factors, and lifestyle variables (physical activity level, percent body fat, and alcohol intake). Vo(2 max) was 34.5 (SD 6.1). Log IL-6 (r = -0.38, P max). In separate multivariable linear regression models that adjusted for age, body mass index, CHD risk factors, and lifestyle variables, log IL-6 [beta-coeff = -1.66 +/- 0.63 (SE), P = 0.010], log CRP [beta-coeff = -0.99 +/- 0.33 (SE), P = 0.003], fibrinogen [beta-coeff = -1.51 +/- 0.44 (SE), P = 0.001], and WBC count [beta-coeff = -0.52 +/- 0.30 (SE), P = 0.088] were each inversely associated with Vo(2 max). In conclusion, higher circulating levels of IL-6, CRP, and fibrinogen are independently associated with lower Vo(2 max) in asymptomatic men.

  19. In-trap decay spectroscopy for {beta}{beta} decays

    Energy Technology Data Exchange (ETDEWEB)

    Brunner, Thomas


    The presented work describes the implementation of a new technique to measure electron-capture (EC) branching ratios (BRs) of intermediate nuclei in {beta}{beta} decays. This technique has been developed at TRIUMF in Vancouver, Canada. It facilitates one of TRIUMF's Ion Traps for Atomic and Nuclear science (TITAN), the Electron Beam Ion Trap (EBIT) that is used as a spectroscopy Penning trap. Radioactive ions, produced at the radioactive isotope facility ISAC, are injected and stored in the spectroscopy Penning trap while their decays are observed. A key feature of this technique is the use of a strong magnetic field, required for trapping. It radially confines electrons from {beta} decays along the trap axis while X-rays, following an EC, are emitted isotropically. This provides spatial separation of X-ray and {beta} detection with almost no {beta}-induced background at the X-ray detector, allowing weak EC branches to be measured. Furthermore, the combination of several traps allows one to isobarically clean the sample prior to the in-trap decay spectroscopy measurement. This technique has been developed to measure ECBRs of transition nuclei in {beta}{beta} decays. Detailed knowledge of these electron capture branches is crucial for a better understanding of the underlying nuclear physics in {beta}{beta} decays. These branches are typically of the order of 10{sup -5} and therefore difficult to measure. Conventional measurements suffer from isobaric contamination and a dominating {beta} background at theX-ray detector. Additionally, X-rays are attenuated by the material where the radioactive sample is implanted. To overcome these limitations, the technique of in-trap decay spectroscopy has been developed. In this work, the EBIT was connected to the TITAN beam line and has been commissioned. Using the developed beam diagnostics, ions were injected into the Penning trap and systematic studies on injection and storage optimization were performed. Furthermore, Ge

  20. Analysis of betaS and betaA genes in a Mexican population with African roots. (United States)

    Magaña, María Teresa; Ongay, Zoyla; Tagle, Juan; Bentura, Gilberto; Cobián, José G; Perea, F Javier; Casas-Castañeda, Maricela; Sánchez-López, Yoaly J; Ibarra, Bertha


    To investigate the origin of the beta(A) and beta(S) genes in a Mexican population with African roots and a high frequency of hemoglobin S, we analyzed 467 individuals (288 unrelated) from different towns in the states of Guerrero and Oaxaca in the Costa Chica region. The frequency of the sickle-cell trait was 12.8%, which may represent a public health problem. The frequencies of the beta-haplotypes were determined from 350 nonrelated chromosomes (313 beta(A) and 37 beta(S)). We observed 15 different beta(A) haplotypes, the most common of which were haplotypes 1 (48.9%), 2 (13.4%), and 3 (13.4%). The calculation of pairwise distributions and Nei's genetic distance analysis using 32 worldwide populations showed that the beta(A) genes are more closely related to those of Mexican Mestizos and North Africans. Bantu and Benin haplotypes and haplotype 9 were related to the beta(S) genes, with frequencies of 78.8, 18.2, and 3.0%, respectively. Comparison of these haplotypes with 17 other populations revealed a high similitude with the population of the Central African Republic. These data suggest distinct origins for the beta(A) and beta(S) genes in Mexican individuals from the Costa Chica region.

  1. The obese healthy paradox: is inflammation the answer? (United States)

    Barbarroja, Nuria; López-Pedrera, Rosario; Mayas, Maria Dolores; García-Fuentes, Eduardo; Garrido-Sánchez, Lourdes; Macías-González, M; El Bekay, Rajaa; Vidal-Puig, Antonio; Tinahones, Francisco J


    A paradoxical but common finding in the obesity clinic is the identification of individuals who can be considered 'inappropriately' healthy for their degree of obesity. We think that studying these obese but metabolically healthy individuals and comparing them with equally obese but insulin-resistant individuals could provide important insights into the mechanistic link between adipose tissue expansion and associated metabolic alterations. In the present study, we investigated whether there are differences in inflammatory and insulin signalling pathways in VAT (visceral adipose tissue) that could account for the metabolic differences exhibited by morbidly obese individuals who are either insulin-resistant (IR-MO) or paradoxically insulin-sensitive (NIR-MO). Our results indicate that there are pathways common to obesity and unrelated to insulin resistance and others that are discriminative for insulin resistance for a similar degree of obesity. For instance, all morbidly obese patients, irrespective of their insulin resistance, showed increased expression of TNFalpha (tumour necrosis factor alpha) and activation of JNK1/2 (c-Jun N-terminal kinase 1/2). However, the IR-MO group showed significantly elevated expression levels of IL (interleukin)-1beta and IL-6 and increased macrophage infiltrates compared with non-obese individuals and NIR-MO. IkappaBalpha [inhibitor of NF-kappaB (nuclear factor kappaB) alpha], the activation of ERK1/2 (extracellular-signal-regulated kinase 1/2) and NF-kappaB were discriminative of the state of insulin resistance and correlated with differential changes in IRS-1 (insulin receptor substrate 1) expression and Akt activation between IR-MO and NIR-MO individuals. Our results support the concept that NIR-MO individuals lack the inflammatory response that characterizes the IR-MO patient and that IL-6, IL-1beta, ERK and NF-kappaB are important effectors that mediate the inflammation effects promoting insulin resistance.

  2. Antioxidants, inflammation and cardiovascular disease. (United States)

    Mangge, Harald; Becker, Kathrin; Fuchs, Dietmar; Gostner, Johanna M


    Multiple factors are involved in the etiology of cardiovascular disease (CVD). Pathological changes occur in a variety of cell types long before symptoms become apparent and diagnosis is made. Dysregulation of physiological functions are associated with the activation of immune cells, leading to local and finally systemic inflammation that is characterized by production of high levels of reactive oxygen species (ROS). Patients suffering from inflammatory diseases often present with diminished levels of antioxidants either due to insufficient dietary intake or, and even more likely, due to increased demand in situations of overwhelming ROS production by activated immune effector cells like macrophages. Antioxidants are suggested to beneficially interfere with diseases-related oxidative stress, however the interplay of endogenous and exogenous antioxidants with the overall redox system is complex. Moreover, molecular mechanisms underlying oxidative stress in CVD are not fully elucidated. Metabolic dybalances are suggested to play a major role in disease onset and progression. Several central signaling pathways involved in the regulation of immunological, metabolic and endothelial function are regulated in a redox-sensitive manner. During cellular immune response, interferon γ-dependent pathways are activated such as tryptophan breakdown by the enzyme indoleamine 2,3-dioxygenase (IDO) in monocyte-derived macrophages, fibroblasts, endothelial and epithelial cells. Neopterin, a marker of oxidative stress and immune activation is produced by GTP-cyclohydrolase I in macrophages and dendritic cells. Nitric oxide synthase (NOS) is induced in several cell types to generate nitric oxide (NO). NO, despite its low reactivity, is a potent antioxidant involved in the regulation of the vasomotor tone and of immunomodulatory signaling pathways. NO inhibits the expression and function of IDO. Function of NOS requires the cofactor tetrahydrobiopterin (BH4), which is produced in

  3. beta (+)-Thalassaemia in the Po river delta region (northern Italy): genotype and beta globin synthesis. (United States)

    Del Senno, L; Pirastu, M; Barbieri, R; Bernardi, F; Buzzoni, D; Marchetti, G; Perrotta, C; Vullo, C; Kan, Y W; Conconi, F


    Six beta(+)-thalassaemic patients from the Po river delta region have been studied. Using synthetic oligonucleotides as specific hybridisation probes, the beta(+) IVS I mutation (G----A at position 108) was demonstrated. This lesion and the enzyme polymorphism pattern in the subjects examined are the same as have been described for other Mediterranean beta(+)-thalassaemias. Antenatal diagnosis through DNA analysis of beta(+)-thalassaemia is therefore possible. The production of beta globin in a beta(+), homozygote and in a beta (+), beta(0) 39 (nonsense mutation at codon 39) double heterozygote is approximately 20% and 10% respectively of total non-alpha globin synthesis. Despite some overlapping of the results, similar beta globin synthesis levels have been obtained in 43 beta(+)-thalassaemia patients. This suggests that in the Po river delta region the most common thalassaemic genes are beta(0) 39 and beta(+) IVS I. Images PMID:2580095

  4. CCAAT/enhancer binding protein {beta} deletion increases mitochondrial function and protects mice from LXR-induced hepatic steatosis

    Energy Technology Data Exchange (ETDEWEB)

    Rahman, Shaikh M., E-mail: [Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States); Choudhury, Mahua; Janssen, Rachel C.; Baquero, Karalee C. [Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States); Miyazaki, Makoto [Division of Renal Diseases and Hypertension, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States); Friedman, Jacob E. [Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States); Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, Aurora, CO 80045 (United States)


    Highlights: Black-Right-Pointing-Pointer LXR agonist activation increases liver TG accumulation by increasing lipogenesis. Black-Right-Pointing-Pointer C/EBP{beta}{sup -/-} mouse prevents LXR activation-mediated induction of hepatic lipogenesis. Black-Right-Pointing-Pointer C/EBP{beta} deletion increases mitochondrial transport chain function. Black-Right-Pointing-Pointer Beneficial effects of LXR activation on liver cholesterol metabolism did not change. Black-Right-Pointing-Pointer C/EBP{beta} inhibition might have important therapeutic potential. -- Abstract: Drugs designed specifically to activate liver X receptors (LXRs) have beneficial effects on lowering cholesterol metabolism and inflammation but unfortunately lead to severe hepatic steatosis. The transcription factor CCAAT/enhancer binding protein beta (C/EBP{beta}) is an important regulator of liver gene expression but little is known about its involvement in LXR-based steatosis and cholesterol metabolism. The present study investigated the role of C/EBP{beta} expression in LXR agonist (T0901317)-mediated alteration of hepatic triglyceride (TG) and lipogenesis in mice. C/EBP{beta} deletion in mice prevented LXR agonist-mediated induction of lipogenic gene expression in liver in conjunction with significant reduction of liver TG accumulation. Surprisingly, C/EBP{beta}{sup -/-} mice showed a major increase in liver mitochondrial electron chain function compared to WT mice. Furthermore, LXR activation in C/EBP{beta}{sup -/-} mice increased the expression of liver ATP-binding cassette transporter ABCG1, a gene implicated in cholesterol efflux and reducing blood levels of total and LDL-cholesterol. Together, these findings establish a central role for C/EBP{beta} in the LXR-mediated steatosis and mitochondrial function, without impairing the influence of LXR activation on lowering LDL and increasing HDL-cholesterol. Inactivation of C/EBP{beta} might therefore be an important therapeutic strategy to prevent LXR

  5. Cerebellar white matter inflammation and demyelination in chronic relapsing experimental allergic encephalomyelitis

    DEFF Research Database (Denmark)

    Wanscher, B.; Sørensen, P. S.; Juhler, M.;


    Experimental allergic encephalomyelitis, demyelination, inflammation, immunology, neuropathology......Experimental allergic encephalomyelitis, demyelination, inflammation, immunology, neuropathology...

  6. Smart Beta or Smart Alpha

    DEFF Research Database (Denmark)

    Winther, Kenneth Lillelund; Steenstrup, Søren Resen


    Smart beta has become the flavor of the decade in the investment world with its low fees, easy access to rewarded risk premiums, and appearance of providing good investment results relative to both traditional passive benchmarks and actively managed funds. Although we consider it well documented...... that smart beta investing probably will do better than passive market capitalization investing over time, we believe many are coming to a conclusion too quickly regarding active managers. Institutional investors are able to guide managers through benchmarks and risk frameworks toward the same well......-documented smart beta risk premiums and still motivate active managers to avoid value traps, too highly priced small caps, defensives, etc. By constructing the equity portfolios of active managers that resemble the most widely used risk premiums, we show that the returns and risk-adjusted returns measures...

  7. Regulation of inflammation in cancer by eicosanoids. (United States)

    Greene, Emily R; Huang, Sui; Serhan, Charles N; Panigrahy, Dipak


    Inflammation in the tumor microenvironment is now recognized as one of the hallmarks of cancer. Endogenously produced lipid autacoids, locally acting small molecule lipid mediators, play a central role in inflammation and tissue homeostasis, and have recently been implicated in cancer. A well-studied group of autacoid mediators that are the products of arachidonic acid metabolism include: the prostaglandins, leukotrienes, lipoxins and cytochrome P450 (CYP) derived bioactive products. These lipid mediators are collectively referred to as eicosanoids and are generated by distinct enzymatic systems initiated by cyclooxygenases (COX 1 and 2), lipoxygenases (5-LOX, 12-LOX, 15-LOXa, 15-LOXb), and cytochrome P450s, respectively. These pathways are the target of approved drugs for the treatment of inflammation, pain, asthma, allergies, and cardiovascular disorders. Beyond their potent anti-inflammatory and anti-cancer effects, non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 specific inhibitors have been evaluated in both preclinical tumor models and clinical trials. Eicosanoid biosynthesis and actions can also be directly influenced by nutrients in the diet, as evidenced by the emerging role of omega-3 fatty acids in cancer prevention and treatment. Most research dedicated to using eicosanoids to inhibit tumor-associated inflammation has focused on the COX and LOX pathways. Novel experimental approaches that demonstrate the anti-tumor effects of inhibiting cancer-associated inflammation currently include: eicosanoid receptor antagonism, overexpression of eicosanoid metabolizing enzymes, and the use of endogenous anti-inflammatory lipid mediators. Here we review the actions of eicosanoids on inflammation in the context of tumorigenesis. Eicosanoids may represent a missing link between inflammation and cancer and thus could serve as therapeutic target(s) for inhibiting tumor growth.

  8. The microbial oxidation of (-)-beta-pinene by Botrytis cinerea. (United States)

    Farooq, Afgan; Choudhary, M Iqbal; Tahara, Satoshi; Rahman, Atta-ur; Başer, K Hüsnü Can; Demirci, Fatih


    (-)-beta-pinene, a flavor and fragrance monoterpene is an important constituent of essential oils of many aromatic plants. It was oxidized by a plant-pathogenic fungus, Botrytis cinerea to afford four metabolites characterized as (-)-6a-hydroxy-beta-pinene, (-)-4beta,5beta-dihydroxy-beta-pinene, (-)-2beta,3beta-dihydroxypinane, and (-)-4beta-hydroxy-beta-pinene-6-one by detailed spectroscopic studies along with other known metabolites.

  9. Neutrinoless double beta decay experiments

    CERN Document Server

    Zuber, K


    The study of neutrinoless double beta decay is of outmost importance for neutrino physics. It is considered to be the gold plated channel to probe the fundamental character of neutrinos and to determine the neutrino mass. From the experimental point about nine different isotopes are explored for the search. After a general introduction follows a short discussion on nuclear matrix element calculations and supportive measurements. The current experimental status of double beta searches is presented followed by a short discussion of the ideas and proposals for large scale experiments.

  10. A {beta} - {gamma} coincidence; Metodo de coincidencias {beta} - {gamma}

    Energy Technology Data Exchange (ETDEWEB)

    Agullo, F.


    A {beta} - {gamma} coincidence method for absolute counting is given. The fundamental principles are revised and the experimental part is detailed. The results from {sup 1}98 Au irradiated in the JEN 1 Swimming pool reactor are given. The maximal accuracy is 1 per cent. (Author) 11 refs.

  11. Beta thalassaemia mutations in Turkish Cypriots. (United States)

    Sozuoz, A; Berkalp, A; Figus, A; Loi, A; Pirastu, M; Cao, A


    Using oligonucleotide hybridisation or restriction endonuclease analysis, we have characterised the molecular defect in 94 patients with thalassaemia major and four with thalassaemia intermedia of Turkish Cypriot descent. We found that four mutations, namely beta+ IVS-1 nt 110, beta zero IVS-1 nt, beta+ IVS-1 nt 6, and beta+ IVS-2 nt 745 were prevalent, accounting for 69.9%, 11.7%, 8.7%, and 5.6% respectively of the beta thalassaemia chromosomes. This information may help in the organisation of a large scale prevention programme based on fetal diagnosis of beta thalassaemia by DNA analysis in the Turkish population. PMID:3236356

  12. Downregulation of TGF-beta1 mRNA and protein in the muscles of patients with inflammatory myopathies after treatment with high-dose intravenous immunoglobulin. (United States)

    Amemiya, K; Semino-Mora, C; Granger, R P; Dalakas, M C


    We used reverse transcription-polymerase chain reaction to study the level of TGF-beta1 mRNA expression and immunocytochemistry to examine the immunoreactive TGF-beta1 in muscle biopsy specimens from five patients with dermatomyositis (DM) and five patients with inclusion body myositis (IBM) obtained before and after 3 months treatment with intravenous immunoglobulin (IVIg). At baseline, the mRNA expression of TGF-beta1 was increased up to fivefold in the muscles of DM patients compared to that of IBM patients. After IVIg, TGF-beta1 was downregulated and the TGF-beta1 mRNA decreased twofold in the muscles of patients with DM who had successfully responded to therapy, but remained unchanged in the muscles of patients with IBM who did not respond. The downregulation of TGF-beta1 in DM was associated with improvement of the muscle cytoarchitecture and reduction of the endomysial inflammation and connective tissue, suggesting that in DM the excess of TGF-beta1 may be involved in the pathogenesis of chronic inflammation, fibrosis, and accumulation of extracellular matrix proteins.

  13. Inflammation as a cause of venous thromboembolism. (United States)

    Saghazadeh, Amene; Rezaei, Nima


    Inflammatory markers are highly amenable to appraise and adjust and could already serve as a diagnostic indicator and also as a predictor of prognosis over the management of many health problems. Inflammation is implicated in venous thromboembolism (VTE). However there is still an intense curiosity about whether it is a cause or only a consequence of the thromboembolic process. The more likely scenario is that some inflammatory mediators contribute to the development of VTE, which per se induces an inflammatory reaction. Here we will review evidences supporting the role of inflammation as a cause of VTE. Genetic association studies have provided possible links between inflammation-related genetic variants, especially cytokines (e.g. IL-1, IL-4, IL-6, IL-10, and IL-13), and VTE, leading to establish the fundamental role of genetic background in predisposition to VTE and variable inflammatory processes in individuals. Additionally, several inflammation-related conditions including aging, autoimmune disease, cancer, cardiovascular diseases, hormone replacement therapy, infectious diseases, metabolic diseases, overweight or obesity, pregnancy or postpartum, respiratory diseases, and trauma have been associated with an increased risk of VTE. At this moment, despite their theoretical potential, to achieve the implementation of the inflammation-related laboratory tests in practice is a long task and future studies with larger sample sizes are required to address whether the properties of the inflammatory process, particularly intensity and duration, are useful in determining the risk of VTE and following outcomes.

  14. Influence of uterine inflammation on the estrous cycle in rats. (United States)

    Kaneko, Kazuyuki; Aoki, Hajime; Furuichi, Tomohiro; Hatori, Sachiko; Tanimoto, Hanako; Kawakami, Shizuo


    To investigate how uterine inflammation affects ovarian activity in rats, endometritis was induced and changes in the length of estrous cycle and serum concentrations of estradiol-17beta (E(2)) and progesterone (P(4)) were examined. A suspension of Staphylococcus aureus (bacterial solution) or iodine solution was infused into the uterine lumen at various estrous phases. When the bacterial solution was infused at estrus, metestrus, or the first day of diestrus, the following diestrus continued for 5 to 12 days. In the case of the iodine solution, regardless of the estrous phase of the infusion, the following diestrus continued for approximately 6 days. E(2) concentration after infusion of each solution did not fluctuate largely and remained at a low concentration (around 5 pg/ml). P(4) concentration was high (35-45 ng/ml) on the day following infusion, but decreased rapidly to base line values within a few days and remained thereafter at a low level (around 5 ng/ml). It is assumed that the endometritis caused by biological or chemical stimulation raises the concentration of P(4) to depress gonadotrophic hormone secretion, and hence this high P(4) concentration might inhibit the growth of ovarian follicles.

  15. IL-1beta-induced chemokine and Fas expression are inhibited by suppressor of cytokine signalling-3 in insulin-producing cells

    DEFF Research Database (Denmark)

    Jacobsen, M L B; Rønn, S G; Bruun, C;


    AIMS/HYPOTHESIS: Chemokines recruit activated immune cells to sites of inflammation and are important mediators of insulitis. Activation of the pro-apoptotic receptor Fas leads to apoptosis-mediated death of the Fas-expressing cell. The pro-inflammatory cytokines IL-1beta and IFN-gamma regulate...... the transcription of genes encoding the Fas receptor and several chemokines. We have previously shown that suppressor of cytokine signalling (SOCS)-3 inhibits IL-1beta- and IFN-gamma-induced nitric oxide production in a beta cell line. The aim of this study was to investigate whether SOCS-3 can influence cytokine......-induced Fas and chemokine expression in beta cells. METHODS: Using a beta cell line with inducible Socs3 expression or primary neonatal rat islet cells transduced with a Socs3-encoding adenovirus, we employed real-time RT-PCR analysis to investigate whether SOCS-3 affects cytokine-induced chemokine and Fas m...

  16. Beta Cell Workshop 2013 Kyoto

    DEFF Research Database (Denmark)

    Heller, R Scott; Madsen, Ole D; Nielsen, Jens Høiriis


    The very modern Kyoto International Conference Center provided the site for the 8th workshop on Beta cells on April 23-26, 2013. The preceding workshops were held in Boston, USA (1991); Kyoto, Japan (1994); Helsingør, Denmark (1997); Helsinki, Finland (2003); El Perello, Spain (2006); Peebles...

  17. Estimating $\\beta$-mixing coefficients

    CERN Document Server

    McDonald, Daniel J; Schervish, Mark


    The literature on statistical learning for time series assumes the asymptotic independence or ``mixing' of the data-generating process. These mixing assumptions are never tested, nor are there methods for estimating mixing rates from data. We give an estimator for the $\\beta$-mixing rate based on a single stationary sample path and show it is $L_1$-risk consistent.

  18. Beta-carotene as antioxidant

    NARCIS (Netherlands)

    Bast, A.; Plas, R.M. van der; Berg, H. van den; Haenen, G.R.M.M.


    Objective: Beta-carotene has been shown to exhibit a good radical-trapping antioxidant activity in vitro. We were interested to see if dietary β-carotene in combination with various intake levels for vitamin A would also inhibit lipid peroxidation. Design: Sixty male Wistar rats received vitamin A (

  19. Unexplained Aspects of Anemia of Inflammation

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Price


    Full Text Available Anemia of inflammation (AI, also known as anemia of chronic inflammation or anemia of chronic disease was described over 50 years ago as anemia in association with clinically overt inflammatory disease, and the findings of low plasma iron, decreased bone marrow sideroblasts and increased reticuloendothelial iron. Pathogenic features underlying AI include a mild shortening of red cell survival, impaired erythropoietin production, blunted responsiveness of the marrow to erythropoietin, and impaired iron metabolism mediated by inflammatory cytokines and the iron regulatory peptide, hepcidin. Despite marked recent advances in understanding AI, gaps remain, including understanding of the pathogenesis of AI associated with “noninflammatory” or mildly inflammatory diseases, the challenge of excluding iron deficiency anemia in the context of concomitant inflammation, and understanding more precisely the contributory role of hepcidin in the development of AI in human inflammatory diseases.

  20. Neurovascular aspects of skin neurogenic inflammation. (United States)

    Aubdool, Aisah A; Brain, Susan D


    Neurogenic inflammation is involved in skin inflammation. It is hypothesized that it is involved in the pathogenesis of the common chronic cutaneous vascular disorder rosacea, but the exact mechanism of action is currently unknown. Transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) are widely expressed on primary sensory neuron endings and non-neuronal cells such as keratinocytes. Here we describe the potential for TRPV1 and TRPA1 receptors to be involved in the pathophysiology of rosacea due to their polymodal activation, including cold and hot temperature, pungent products from vegetable and spices, reactive oxygen species, and mechanical stimuli. We discuss the role of both receptors and the sensory neuropeptides that they release in inflammation and pain sensation and evidence suggesting that both TRPV1 and TRPA1 receptors may be promising therapeutic targets for the treatment of the inflammatory symptoms of rosacea.

  1. An overview of inflammation: mechanism and consequences

    Institute of Scientific and Technical Information of China (English)

    Afsar U. AHMED


    Inflammation is an essential response provided by the immune systems that ensures the survival during infection and tissue injury.Inflammatory responses are essential for the maintenance of normal tissue homeostasis.The molecular mechanism of inflammation is quite a complicated process which is initiated by the recognition of specific molecular patterns associated with either infection or tissue injury.The entire process of the inflammatory response is mediated by several key regulators involved in the selective expression of proinflammatory molecules.Prolonged inflammations are often associated with severe detrimental side effects on health.Alterations in inflammatory responses due to persistent inducers or genetic variations are on the rise over the last couple of decades,causing a variety of inflammatory diseases and pathophysiological conditions.

  2. Glucocorticoids and central nervous system inflammation. (United States)

    Dinkel, Klaus; Ogle, William O; Sapolsky, Robert M


    Glucocorticoids (GCs) are well known for their anti-inflammatory and immunosuppressive properties in the periphery and are therefore widely and successfully used in the treatment of autoimmune diseases, chronic inflammation, or transplant rejection. This led to the assumption that GCs are uniformly anti-inflammatory in the periphery and the central nervous system (CNS). As a consequence, GCs are also used in the treatment of CNS inflammation. There is abundant evidence that an inflammatory reaction is mounted within the CNS following trauma, stroke, infection, and seizure, which can augment the brain damage. However an increasing number of studies indicate that the concept of GCs being universally immunosuppressive might be oversimplified. This article provides a review of the current literature, showing that under certain circumstances GCs might fail to have anti-inflammatory effects and sometimes even enhance inflammation.

  3. Early adversity, neural development, and inflammation. (United States)

    Chiang, Jessica J; Taylor, Shelley E; Bower, Julienne E


    Early adversity is a risk factor for poor mental and physical health. Although altered neural development is believed to be one pathway linking early adversity to psychopathology, it has rarely been considered a pathway linking early adversity to poor physical health. However, this is a viable pathway because the central nervous system is known to interact with the immune system via the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). In support of this pathway, early adversity has been linked to changes in neural development (particularly of the amygdala, hippocampus, and prefrontal cortex), HPA axis and ANS dysregulation, and higher levels of inflammation. Inflammation, in turn, can be detrimental to physical health when prolonged. In this review, we present these studies and consider how altered neural development may be a pathway by which early adversity increases inflammation and thus risk for adverse physical health outcomes.

  4. Inflammation: maladies, models, mechanisms and molecules. (United States)

    Stewart, A G; Beart, P M


    The continued focus of attention on the diversity of mechanisms underpinning inflammation has improved our understanding of the potential to target specific pathways in the inflammatory network to achieve meaningful therapeutic gains. In this themed issue of the British Journal of Pharmacology our scope was deliberately broad, ranging across both acute and chronic disease in various organs. Pro- and anti-inflammatory mechanisms receive attention as does the phenotype of macrophages. Whilst the manifestations of neuro-inflammation are less obvious than those in peripheral tissues, central innate and adaptive immunity in brain and the M1/M2 phenotypes of microglia are topics of special interest. The contributions to the inflammatory milieu of cytokines, chemokines and associated signalling cascades are considered. Overall, the coverage herein advances the basic science underpinning our understanding of inflammation and emphasizes its importance in different pathologies.

  5. Neurobiology of inflammation-associated anorexia

    Directory of Open Access Journals (Sweden)

    Laurent Gautron


    Full Text Available Compelling data demonstrate that inflammation-associated anorexia directly results from the action of pro-inflammatory factors, primarily cytokines and prostaglandins E2, on the nervous system. For instance, the aforementioned pro-inflammatory factors can stimulate the activity of peripheral sensory neurons, and induce their own de novo synthesis and release into the brain parenchyma and cerebrospinal fluid. Ultimately, it results in the mobilization of a specific neural circuit that shuts down appetite. The present article describes the different cell groups and neurotransmitters involved in inflammation-associated anorexia and examines how they interact with neural systems regulating feeding such as the melanocortin system. A better understanding of the neurobiological mechanisms underlying inflammation-associated anorexia will help to develop appetite stimulants for cancer and AIDS patients.

  6. Microbe- and danger-induced inflammation. (United States)

    Broggi, Achille; Granucci, Francesca


    The ability of the immune system to give rise to an effective response against pathogens while maintaining tolerance towards self-tissues has always been an object of keen interest for immunologist. Over the years, different theories have been proposed to explain if and how the immune system is able to discriminate between self and non-self, including the Infectious Non-self theory from Charles Janeway and Polly Matzinger's Danger theory. Nowadays we know Janeway's theory is largely true, however the immune system does respond to injured, stressed and necrotic cells releasing danger signals (DAMPs) with a potent inflammatory response. To avoid unwanted prolonged autoimmune reactions, though, danger-induced inflammation should be tightly regulated. In the present review we discuss how prototypic DAMPs are able to induce inflammation and the peculiarity of danger-induced inflammation, as opposed to a complete immune response to fight pathogen invasions.

  7. Topical Application of Fingolimod Perturbs Cutaneous Inflammation. (United States)

    Sun, Wai Y; Dimasi, David P; Pitman, Melissa R; Zhuang, YiZhong; Heddle, Robert; Pitson, Stuart M; Grimbaldeston, Michele A; Bonder, Claudine S


    The prevalence of allergies, including rhinitis, eczema, and anaphylaxis, is rising dramatically worldwide. This increase is especially problematic in children who bear the greatest burden of this rising trend. Increasing evidence identifies neutrophils as primary perpetrators of the more severe and difficult to manage forms of inflammation. A newly recognized mechanism by which neutrophils are recruited during the early phase of histamine-induced inflammation involves the sphingosine kinase (SK)/sphingosine-1-phosphate axis. This study examines whether topical application of fingolimod, an established SK/sphingosine-1-phosphate antagonist already in clinical use to treat multiple sclerosis, may be repurposed to treat cutaneous inflammation. Using two mouse models of ear skin inflammation (histamine- and IgE-mediated passive cutaneous anaphylaxis) we topically applied fingolimod prophylactically, as well as after establishment of the inflammatory response, and examined ear swelling, SK activity, vascular permeability, leukocyte recruitment, and production of proinflammatory mediators. The present study reveals that when applied topically, fingolimod attenuates both immediate and late-phase responses to histamine with reduced extravasation of fluid, SK-1 activity, proinflammatory cytokine and chemokine production, and neutrophil influx and prevents ear swelling. Intravital microscopy demonstrates that histamine-induced neutrophil rolling and adhesion to the postcapillary venules in the mouse ears is significantly attenuated even after 24 h. More importantly, these effects are achievable even once inflammation is established. Translation into humans was also accomplished with epicutaneous application of fingolimod resolving histamine-induced and allergen-induced inflammatory reactions in forearm skin. Overall, this study demonstrates, to our knowledge for the first time, that fingolimod may be repurposed to treat cutaneous inflammation.

  8. Understanding migraine: Potential role of neurogenic inflammation

    Directory of Open Access Journals (Sweden)

    Rakesh Malhotra


    Full Text Available Neurogenic inflammation, a well-defined pathophysiologial process is characterized by the release of potent vasoactive neuropeptides, predominantly calcitonin gene-related peptide (CGRP, substance P (SP, and neurokinin A from activated peripheral nociceptive sensory nerve terminals (usually C and A delta-fibers. These peptides lead to a cascade of inflammatory tissue responses including arteriolar vasodilation, plasma protein extravasation, and degranulation of mast cells in their peripheral target tissue. Neurogenic inflammatory processes have long been implicated as a possible mechanism involved in the pathophysiology of various human diseases of the nervous system, respiratory system, gastrointestinal tract, urogenital tract, and skin. The recent development of several innovative experimental migraine models has provided evidence suggestive of the involvement of neuropeptides (SP, neurokinin A, and CGRP in migraine headache. Antidromic stimulation of nociceptive fibers of the trigeminal nerve resulted in a neurogenic inflammatory response with marked increase in plasma protein extravasation from dural blood vessels by the release of various sensory neuropeptides. Several clinically effective abortive antimigraine medications, such as ergots and triptans, have been shown to attenuate the release of neuropeptide and neurogenic plasma protein extravasation. These findings provide support for the validity of using animal models to investigate mechanisms of neurogenic inflammation in migraine. These also further strengthen the notion of migraine being a neuroinflammatory disease. In the clinical context, there is a paucity of knowledge and awareness among physicians regarding the role of neurogenic inflammation in migraine. Improved understanding of the molecular biology, pharmacology, and pathophysiology of neurogenic inflammation may provide the practitioner the context-specific feedback to identify the novel and most effective therapeutic

  9. Neutron Beta Decay Studies with Nab

    CERN Document Server

    Baeßler, S; Alonzi, L P; Balascuta, S; Barrón-Palos, L; Bowman, J D; Bychkov, M A; Byrne, J; Calarco, J R; Chupp, T; Vianciolo, T V; Crawford, C; Frlež, E; Gericke, M T; Glück, F; Greene, G L; Grzywacz, R K; Gudkov, V; Harrison, D; Hersman, F W; Ito, T; Makela, M; Martin, J; McGaughey, P L; McGovern, S; Page, S; Penttilä, S I; Počanić, D; Rykaczewski, K P; Salas-Bacci, A; Tompkins, Z; Wagner, D; Wilburn, W S; Young, A R


    Precision measurements in neutron beta decay serve to determine the coupling constants of beta decay and allow for several stringent tests of the standard model. This paper discusses the design and the expected performance of the Nab spectrometer.

  10. Models of Inflammation: Carrageenan Air Pouch. (United States)

    Duarte, Djane B; Vasko, Michael R; Fehrenbacher, Jill C


    The subcutaneous air pouch is an in vivo model that can be used to study the components of acute and chronic inflammation, the resolution of the inflammatory response, the oxidative stress response, and potential therapeutic targets for treating inflammation. Injection of irritants into an air pouch in rats or mice induces an inflammatory response that can be quantified by the volume of exudate produced, the infiltration of cells, and the release of inflammatory mediators. The model presented in this unit has been extensively used to identify potential anti-inflammatory drugs.

  11. Reparative inflammation takes charge of tissue regeneration. (United States)

    Karin, Michael; Clevers, Hans


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

  12. The beta-decay of Al-22

    NARCIS (Netherlands)

    Achouri, NL; Santos, FDO; Lewitowicz, M; Blank, B; Aysto, J; Canchel, G; Czajkowski, S; Dendooven, P; Emsallem, A; Giovinazzo, J; Guillet, N; Jokinen, A; Larid, AM; Longour, C; Perajarvi, K; Smirnova, N; Stanoiu, M


    In an experiment performed at the LISE3 facility of GANIL, we studied the decay of Al-22 produced by the fragmentation of a Ar-36 primary beam. A beta-decay half-life of T-1/2 = 91.1 +/- 0.5ms was measured. The beta-delayed one- and two-proton emission as well as beta-alpha and beta-delayed gamma-de

  13. Naturally occurring lung CD4(+)CD25(+) T cell regulation of airway allergic responses depends on IL-10 induction of TGF-beta. (United States)

    Joetham, Anthony; Takeda, Katsuyuki; Takada, Katsuyuki; Taube, Christian; Miyahara, Nobuaki; Matsubara, Shigeki; Matsubara, Satoko; Koya, Toshiyuki; Rha, Yeong-Ho; Dakhama, Azzeddine; Gelfand, Erwin W


    Peripheral tolerance to allergens is mediated in large part by the naturally occurring lung CD4(+)CD25(+) T cells, but their effects on allergen-induced airway responsiveness have not been well defined. Intratracheal, but not i.v., administration of naive lung CD4(+)CD25(+) T cells before allergen challenge of sensitized mice, similar to the administration of the combination of rIL-10 and rTGF-beta, resulted in reduced airway hyperresponsiveness (AHR) and inflammation, lower levels of Th2 cytokines, higher levels of IL-10 and TGF-beta, and less severe lung histopathology. Significantly, CD4(+)CD25(+) T cells isolated from IL-10(-/-) mice had no effect on AHR and inflammation, but when incubated with rIL-10 before transfer, suppressed AHR, and inflammation, and was associated with elevated levels of bronchoalveolar lavage TGF-beta levels. By analogy, anti-TGF-beta treatment reduced regulatory T cell activity. These data identify naturally occurring lung CD4(+)CD25(+) T cells as capable of regulating lung allergic responses in an IL-10- and TGF-beta-dependent manner.

  14. Suppression of human monocyte interleukin-1beta production by ajulemic acid, a nonpsychoactive cannabinoid. (United States)

    Zurier, Robert B; Rossetti, Ronald G; Burstein, Sumner H; Bidinger, Bonnie


    Oral administration of ajulemic acid (AjA), a cannabinoid acid devoid of psychoactivity, reduces joint tissue damage in rats with adjuvant arthritis. Because interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNFalpha) are central to the progression of inflammation and joint tissue injury in patients with rheumatoid arthritis, we investigated human monocyte IL-1beta and TNFalpha responses after the addition of AjA to cells in vitro. Peripheral blood and synovial fluid monocytes (PBM and SFM) were isolated from healthy subjects and patients with inflammatory arthritis, respectively, treated with AjA (0-30 microM) in vitro, and then stimulated with lipopolysaccharide. Cells were harvested for mRNA, and supernatants were collected for cytokine assay. Addition of AjA to PBM and SFM in vitro reduced both steady-state levels of IL-1beta mRNA and secretion of IL-1beta in a concentration-dependent manner. Suppression was maximal (50.4%) at 10 microM AjA (Parthritis. Development of nonpsychoactive therapeutically useful synthetic analogs of Cannabis constituents, such as AjA, may help resolve the ongoing debate about the use of marijuana as medicine.


    NARCIS (Netherlands)



    We have identified a new protein fold-the alpha/beta-hydrolase fold-that is common to several hydrolytic enzymes of widely differing phylogenetic origin and catalytic function. The core of each enzyme is similar: an alpha/beta-sheet, not barrel, of eight beta-sheets connected by alpha-helices. These

  16. Beta-lactamases in Enterobacteriaceae in broilers

    NARCIS (Netherlands)

    Dierikx, C.M.


    Resistance to cephalosprins due to the production of extended spectrum beta-lactamases (ESBLs) or plasmid mediated AmpC beta-lactamases is increasingly found in infections in humans outside the hospital. The genes encoding for these beta-lactamases are located on mobile DNA (plasmids), which can be

  17. Higher-Order Beta Matching with Solutions in Long Beta-Eta Normal Form

    DEFF Research Database (Denmark)

    Støvring, Kristian


    up to beta-eta equivalence is a long-standing open problem.We show that higher-order matching up to beta-eta equivalence is decidable if and only if a restricted form of higher-order matching up to beta equivalence is decidable: the restriction is that solutions must be in long beta-eta normal form....

  18. Carbon nanotubes induce inflammation but decrease the production of reactive oxygen species in lung. (United States)

    Crouzier, D; Follot, S; Gentilhomme, E; Flahaut, E; Arnaud, R; Dabouis, V; Castellarin, C; Debouzy, J C


    With the rapid spread of carbon nanotubes (CNTs) applications, the respiratory toxicity of these compounds has attracted the attention of many scientists. Several studies have reported that after lung administration, CNTs could induce granuloma, fibrosis, or inflammation. By comparison with the mechanisms involved with other toxic particles such as asbestos, this effect could be attributed to an increase of oxidative stress. The aim of the present work was to test this hypothesis in vivo. Mice were intranasally instilled with 1.5mg/kg of double walled carbon nanotubes (DWCNTs). Six, 24, or 48h after administration, inflammation and localisation of DWCNTs in lungs were microscopically observed. Local oxidative perturbations were investigated using ESR spin trapping experiments, and systemic inflammation was assessed by measuring the plasma concentration of cytokines TNF-alpha, IL-1alpha, IL-1beta, IL-6, IGF-1, Leptin, G-CSF, and VEGF. Examination of lungs and the elevation of proinflammatory cytokines in the plasma (Leptin and IL-6 at 6h) confirmed the induction of an inflammatory reaction. This inflammatory reaction was accompanied by a decrease in the local oxidative stress. This effect could be attributed to the scavenger capability of pure CNTs.

  19. REM sleep deprivation in rats results in inflammation and interleukin-17 elevation. (United States)

    Yehuda, Shlomo; Sredni, Benjamin; Carasso, Rafi L; Kenigsbuch-Sredni, Dvora


    Sleep deprivation is a major health problem in modern society. Deprivation of rapid eye movement (REM) sleep is particularly damaging to cognition and to spatial memory; however, the mechanisms that mediate these deteriorations in function are not known. We explored the possibility that REM sleep deprivation may provoke major changes in the immune system by inducing inflammation. Rats were subjected to 72 h of REM sleep deprivation, and the plasma levels of proinflammatory cytokines (IL-1, IL-1beta, IL-6, IL-17A, and TNF-alpha), an anti-inflammatory cytokine (IL-10), the inflammatory markers homocysteine, corticosterone, and hyperthermia were measured immediately after the deprivation period, and 7 days later. The results indicate that REM sleep deprivation induced an inflammatory response. The levels of the proinflammatory cytokines and markers were significantly elevated in sleep-deprived rats as compared to control rats. After 7 days of recovery, the levels of some markers, including hyperthermia, remained higher in sleep-deprived rats versus the control animals. IL-17A appears to play a pivotal role in coordinating the inflammation. These data shed new light on the mechanism of sleep deprivation-induced inflammation.

  20. Beta blockers, norepinephrine, and cancer: an epidemiological viewpoint

    Directory of Open Access Journals (Sweden)

    Fitzgerald PJ


    Full Text Available Paul J FitzgeraldThe Zanvyl Krieger Mind/Brain Institute, Solomon H Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD, USAAbstract: There is growing evidence that the neurotransmitter norepinephrine (NE and its sister molecule epinephrine (EPI (adrenaline affect some types of cancer. Several recent epidemiological studies have shown that chronic use of beta blocking drugs (which antagonize NE/EPI receptors results in lower recurrence, progression, or mortality of breast cancer and malignant melanoma. Preclinical studies have shown that manipulation of the levels or receptors of NE and EPI with drugs affects experimentally induced cancers. Psychological stress may play an etiological role in some cases of cancer (which has been shown epidemiologically, and this could be partly mediated by NE and EPI released by the sympathetic nervous system as part of the body’s “fight or flight” response. A less well-appreciated phenomenon is that the genetic tone of NE/EPI may play a role in cancer. NE and EPI may affect cancer by interacting with molecular pathways already implicated in abnormal cellular replication, such as the P38/MAPK pathway, or via oxidative stress. NE/EPI-based drugs other than beta blockers also may prevent or treat various types of cancer, as may cholinesterase inhibitors that inhibit the sympathetic nervous system, which could be tested epidemiologically.Keywords: clonidine, guanfacine, aspirin, acetylcholine, epinephrine, adrenaline, sympathetic nervous system, parasympathetic nervous system, inflammation

  1. Pleiotropic genes for metabolic syndrome and inflammation

    DEFF Research Database (Denmark)

    Kraja, Aldi T; Chasman, Daniel I; North, Kari E


    , PDXDC1, FTO, MC4R and TOMM40. Based on large data evidence, we conclude that inflammation is a feature of MetS and several gene variants show pleiotropic genetic associations across phenotypes and might explain a part of MetS correlated genetic architecture. These findings warrant further functional...

  2. Genes, inflammation, and age-related diseases

    NARCIS (Netherlands)

    Trompet, Stella


    The general objective of this thesis was to investigate associations between genetic variants involved in inflammation and epigenetics and age-related diseases in an elderly cohort to get more insights in the patho-physiological mechanisms involved in age-related diseases, like cardiovascular diseas

  3. Research sheds light on treatment of inflammation

    Institute of Scientific and Technical Information of China (English)


    @@ The latest research breakthrough on the molecular mechanism and treatment of inflammation, contributed by scientists from the Shanghai Institutes for Biological Sciences (SIBS) under the Chinese Academy of Sciences and their American collaborators, was reported online by Nature Immunology on July 16, 2007.

  4. Scintigraphic visualization of inflammation in neurodegenerative disorders

    NARCIS (Netherlands)

    Versijpt, J; Van Laere, K; Dierckx, RA; Dumont, F; De Deyn, PP; Slegers, G; Korf, J


    In the past few decades, our understanding of the central nervous system has evolved from one of an immune-privileged site, to one where inflammation is pathognomonic for some of the most prevalent and tragic neurodegenerative diseases. Current research indicates that diseases as diverse as multiple

  5. Maternal inflammation during pregnancy and childhood adiposity

    NARCIS (Netherlands)

    R. Gaillard (Romy); S.L. Rifas-Shiman (Sheryl); Perng, W. (Wei); E. Oken (Emily); M.W. Gillman (Matthew W.)


    textabstractObjective: Maternal pre-pregnancy obesity is associated with offspring obesity. Underlying mechanisms may involve a maternal obesity-mediated proinflammatory state during pregnancy. Maternal C-reactive protein (CRP) level during pregnancy is a biomarker of low-grade systemic inflammation

  6. Molecular Basis Linking Platelet to Inflammation

    Institute of Scientific and Technical Information of China (English)



    @@ Introduction Blood platelets not only play an important role in hemostasis and thrombosis,but increasing evidence show that they participate in the induction of inflammation.Firstly,platelets contain and release cytokines and immune mediators.And platelets are able to modulate and regulate the function of surrounding cells by adhesion molecules or by the release of various factors.

  7. Cysteine redox potential determines pro-inflammatory IL-1beta levels.

    Directory of Open Access Journals (Sweden)

    Smita S Iyer

    Full Text Available BACKGROUND: Cysteine (Cys and its disulfide, cystine (CySS represent the major extracellular thiol/disulfide redox control system. The redox potential (E(h of Cys/CySS is centered at approximately -80 mV in the plasma of healthy adults, and oxidation of E(h Cys/CySS is implicated in inflammation associated with various diseases. METHODOLOGY/PRINCIPAL FINDINGS: The purpose of the present study was to determine whether oxidized E(h Cys/CySS is a determinant of interleukin (IL-1beta levels. Results showed a 1.7-fold increase in secreted pro-IL-1beta levels in U937 monocytes exposed to oxidized E(h Cys/CySS (-46 mV, compared to controls exposed to a physiological E(h of -80 mV (P<0.01. In LPS-challenged mice, preservation of plasma E(h Cys/CySS from oxidation by dietary sulfur amino acid (SAA supplementation, was associated with a 1.6-fold decrease in plasma IL-1beta compared to control mice fed an isonitrogenous SAA-adequate diet (P<0.01. Analysis of E(h Cys/CySS and IL-1beta in human plasma revealed a significant positive association between oxidized E(h Cys/CySS and IL-1beta after controlling for age, gender, and BMI (P<0.001. CONCLUSIONS/SIGNIFICANCE: These data show that oxidized extracellular E(h Cys/CySS is a determinant of IL-1beta levels, and suggest that strategies to preserve E(h Cys/CySS may represent a means to control IL-1beta in inflammatory disease states.

  8. Diabetes and beta cell function: from mechanisms to evaluation and clinical implications. (United States)

    Cernea, Simona; Dobreanu, Minodora


    Diabetes is a complex, heterogeneous condition that has beta cell dysfunction at its core. Many factors (e.g. hyperglycemia/glucotoxicity, lipotoxicity, autoimmunity, inflammation, adipokines, islet amyloid, incretins and insulin resistance) influence the function of pancreatic beta cells. Chronic hyperglycaemia may result in detrimental effects on insulin synthesis/secretion, cell survival and insulin sensitivity through multiple mechanisms: gradual loss of insulin gene expression and other beta-cell specific genes; chronic endoplasmic reticulum stress and oxidative stress; changes in mitochondrial number, morphology and function; disruption in calcium homeostasis. In the presence of hyperglycaemia, prolonged exposure to increased free fatty acids result in accumulation of toxic metabolites in the cells ("lipotoxicity"), finally causing decreased insulin gene expression and impairment of insulin secretion. The rest of the factors/mechanisms which impact on the course of the disease are also discusses in detail. The correct assessment of beta cell function requires a concomitant quantification of insulin secretion and insulin sensitivity, because the two variables are closely interrelated. In order to better understand the fundamental pathogenetic mechanisms that contribute to disease development in a certain individual with diabetes, additional markers could be used, apart from those that evaluate beta cell function. The aim of the paper was to overview the relevant mechanisms/factors that influence beta cell function and to discuss the available methods of its assessment. In addition, clinical considerations are made regarding the therapeutical options that have potential protective effects on beta cell function/mass by targeting various underlying factors and mechanisms with a role in disease progression.

  9. beta (+)-Thalassaemia in the Po river delta region (northern Italy): genotype and beta globin synthesis.


    del Senno, L; Pirastu, M; Barbieri, R.; De Bernardi, F.; Buzzoni, D; Marchetti, G.; Perrotta, C; Vullo, C; Kan, Y W; Conconi, F


    Six beta(+)-thalassaemic patients from the Po river delta region have been studied. Using synthetic oligonucleotides as specific hybridisation probes, the beta(+) IVS I mutation (G----A at position 108) was demonstrated. This lesion and the enzyme polymorphism pattern in the subjects examined are the same as have been described for other Mediterranean beta(+)-thalassaemias. Antenatal diagnosis through DNA analysis of beta(+)-thalassaemia is therefore possible. The production of beta globin in...

  10. Rat Cardiomyocytes Express a Classical Epithelial Beta-Defensin

    Directory of Open Access Journals (Sweden)

    Annika Linde


    Full Text Available Beta-defensins (BDs are classical epithelial antimicrobial peptides of immediate importance in innate host defense. Since recent studies have suggested that certain BDs are also expressed in non-traditional tissues, including whole heart homogenate and because effector molecules of innate immunity and inflammation can influence the development of certain cardiovascular disease processes, we hypothesized that BDs are produced by cardiomyocytes as a local measure of cardioprotection against danger signals. Here we report that at least one rat beta-defensin, rBD1, is expressed constitutively in cardiomyocytes specifically isolated using position-ablation-laser-microdissection (P.A.L.M. Microlaser Technologies. RT-PCR analysis showed expression of a single 318 bp transcript in adult rat heart (laser-excised cardiomyocytes and H9c2 cells (neonatal rat heart myoblasts. Moreover, the full length cDNA of rBD1 was established and translated into a putative peptide with 69 amino acid residues. The predicted amino acid sequence of the adult rat cardiac BD-1 peptide displayed 99% identity with the previously reported renal rBD1 and 88, 53, 53 and 50% identity with mouse, human, gorilla and rhesus monkey BD1 respectively. Furthermore, structural analysis of the cardiac rBD1 showed the classical six-cysteine conserved motif of the BD family with an alpha-helix and three beta-sheets. Additionally, rBD1 displayed a significantly greater number of amphoteric residues than any of the human analogs, indicating a strong pH functional dependence in the rat. We suggest that rBD1, which was initially believed to be a specific epithelium-derived peptide, may be also involved in local cardiac innate immune defense mechanisms.

  11. Lipoxins: nature's way to resolve inflammation

    Directory of Open Access Journals (Sweden)

    Chandrasekharan JA


    Full Text Available Jayashree A Chandrasekharan, Neelam Sharma-Walia HM Bligh Cancer Research Laboratories, Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USAAbstract: An effective host defense mechanism involves inflammation to eliminate pathogens from the site of infection, followed by the resolution of inflammation and the restoration of tissue homeostasis. Lipoxins are endogenous anti-inflammatory, pro-resolving molecules that play a vital role in reducing excessive tissue injury and chronic inflammation. In this review, the mechanisms of action of lipoxins at the site of inflammation and their interaction with other cellular signaling molecules and transcription factors are discussed. Emphasis has also been placed on immune modulatory role(s of lipoxins. Lipoxins regulate components of both the innate and adaptive immune systems including neutrophils, macrophages, T-, and B-cells. Lipoxins also modulate levels of various transcription factors such as nuclear factor κB, activator protein-1, nerve growth factor-regulated factor 1A binding protein 1, and peroxisome proliferator activated receptor γ and control the expression of many inflammatory genes. Since lipoxins and aspirin-triggered lipoxins have clinical relevance, we discuss their important role in clinical research to treat a wide range of diseases like inflammatory disorders, renal fibrosis, cerebral ischemia, and cancer. A brief overview of lipoxins in viral malignancies and viral pathogenesis especially the unexplored role of lipoxins in Kaposi's sarcoma-associated herpes virus biology is also presented. Keywords: lipoxins, epi-lipoxins, inflammation, pro-resolving, aspirin-triggered lipoxins, cyclooxygenases, lipoxygenases, therapeutic potential, transcription factors, Kaposi's sarcoma-associated herpes virus

  12. Melanin: A scavenger in gingival inflammation

    Directory of Open Access Journals (Sweden)

    S Nilima


    Full Text Available Background: One of the major direct or indirect targets of ultraviolet exposure of skin is the melanocyte or the melanin -forming cell. Epidermal melanocytes act as a trap for free radicals. Based on the protective role of melanocytes in medical literature, the role of melanin pigmentation in gingiva needs to be elucidated. Periodontal pathogens and their products demonstrate the ability to induce the generation of reactive oxygen species. Hence purpose of this study was to unravel the protective role of melanin (if any against the gingival inflammation. Materials and Methods: A total of 80 subjects; 20 in each group were selected. The selection of subjects regarding gingival pigmentation was based on Dummett′s scoring criteria 0, 3. A complete medical, dental history and an informed consent were obtained from the patients. After evaluation of clinical parameters the GCF was collected using microcapillary pipettes at the selected sites. IL-1β levels were quantitated using ELISA. Results: In non-pigmented healthy and gingivitis groups, there was a positive correlation between plaque index, gingival index and bleeding index versus IL-1β level: indicating an increase in the biochemical mediator of inflammation corresponding to an increase in the clinical parameters of inflammation. Also a positive correlation was found between the gingival index and bleeding index versus the IL-1β levels in the pigmented healthy group. The pigmented gingivitis groups showed a negative correlation between the plaque index, gingival index and bleeding index. Conclusions: The clinical markers of inflammation such as gingival index, bleeding index was of low numerical value in pigmented group than in the non-pigmented group, supposedly due to the protective action of melanin. The negative correlation of clinical markers of inflammation to the IL-1β levels in the pigmented gingivitis group could possibly be attributed to the protective role of melanins.

  13. Inflammation in Parkinson's disease: role of glucocorticoids. (United States)

    Herrero, María-Trinidad; Estrada, Cristina; Maatouk, Layal; Vyas, Sheela


    Chronic inflammation is a major characteristic feature of Parkinson's disease (PD). Studies in PD patients show evidence of augmented levels of potent pro-inflammatory molecules e.g., TNF-α, iNOS, IL-1β whereas in experimental Parkinsonism it has been consistently demonstrated that dopaminergic neurons are particularly vulnerable to activated glia releasing these toxic factors. Recent genetic studies point to the role of immune system in the etiology of PD, thus in combination with environmental factors, both peripheral and CNS-mediated immune responses could play important roles in onset and progression of PD. Whereas microglia, astrocytes and infiltrating T cells are known to mediate chronic inflammation, the roles of other immune-competent cells are less well understood. Inflammation is a tightly controlled process. One major effector system of regulation is HPA axis. Glucocorticoids (GCs) released from adrenal glands upon stimulation of HPA axis, in response to either cell injury or presence of pathogen, activate their receptor, GR. GR regulates inflammation both through direct transcriptional action on target genes and by indirectly inhibiting transcriptional activities of transcriptional factors such as NF-κB, AP-1 or interferon regulatory factors. In PD patients, the HPA axis is unbalanced and the cortisol levels are significantly increased, implying a deregulation of GR function in immune cells. In experimental Parkinsonism, the activation of microglial GR has a crucial effect in diminishing microglial cell activation and reducing dopaminergic degeneration. Moreover, GCs are also known to regulate human brain vasculature as well as blood brain barrier (BBB) permeability, any dysfunction in their actions may influence infiltration of cytotoxic molecules resulting in increased vulnerability of dopamine neurons in PD. Overall, deregulation of glucocorticoid receptor actions is likely important in dopamine neuron degeneration through establishment of chronic

  14. Role of Smooth Muscle in Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    Stephen M Collins


    Full Text Available The notion that smooth muscle function is altered in inflammation is prompted by clinical observations of altered motility in patients with inflammatory bowel disease (IBD. While altered motility may reflect inflammation-induced changes in intrinsic or extrinsic nerves to the gut, changes in gut hormone release and changes in muscle function, recent studies have provided in vitro evidence of altered muscle contractility in muscle resected from patients with ulcerative colitis or Crohn’s disease. In addition, the observation that smooth muscle cells are more numerous and prominent in the strictured bowel of IBD patients compared with controls suggests that inflammation may alter the growth of intestinal smooth muscle. Thus, inflammation is associated with changes in smooth muscle growth and contractility that, in turn, contribute to important symptoms of IBD including diarrhea (from altered motility and pain (via either altered motility or stricture formation. The involvement of smooth muscle in this context may be as an innocent bystander, where cells and products of the inflammatory process induce alterations in muscle contractility and growth. However, it is likely that intestinal muscle cells play a more active role in the inflammatory process via the elaboration of mediators and trophic factors, including cytokines, and via the production of collagen. The concept of muscle cells as active participants in the intestinal inflammatory process is a new concept that is under intense study. This report summarizes current knowledge as it relates to these two aspects of altered muscle function (growth and contractility in the inflamed intestine, and will focus on mechanisms underlying these changes, based on data obtained from animal models of intestinal inflammation.

  15. Specific Triazine Herbicides Induce Amyloid-beta(42) Production

    NARCIS (Netherlands)

    Portelius, Erik; Durieu, Emilie; Bodin, Marion; Cam, Morgane; Pannee, Josef; Leuxe, Charlotte; Mabondzo, Aloise; Oumata, Nassima; Galons, Herve; Lee, Jung Yeol; Chang, Young-Tae; Stuber, Kathrin; Koch, Philipp; Fontaine, Gaelle; Potier, Marie-Claude; Manousopoulou, Antigoni; Garbis, Spiros D.; Covaci, Adrian; Van Dam, Debby; De Deyn, Peter; Karg, Frank; Flajolet, Marc; Omori, Chiori; Hata, Saori; Suzuki, Toshiharu; Blennow, Kaj; Zetterberg, Henrik; Meijer, Laurent


    Proteolytic cleavage of the amyloid-beta protein precursor (A beta PP) ecretases leads to extracellular release of amyloid-beta (A beta) peptides. Increased production of A beta(42) over A beta(40) and aggregation into oligomers and plaques constitute an Alzheimer's disease (AD) hallmark. Identifyin

  16. Future double beta decay experiments

    Energy Technology Data Exchange (ETDEWEB)

    Piquemal, F. [Laboratoire Souterrain de Modane, Modane (France); Centre d' Etudes Nucleaire, Bordeaux-Gradignan (France)


    The search of neutrinoless double beta decay is very challenging because of the expected half-life of the process and the backgrounds from the natural radioactivity. Many projects exist to try to reach a sensitivity of ∼50 meV on the effective neutrino mass corresponding to a mass of isotopes of ∼100 kg. In this article some of the futur projects are presented.

  17. A molecular platform in neurons regulates inflammation after spinal cord injury. (United States)

    de Rivero Vaccari, Juan Pablo; Lotocki, George; Marcillo, Alex E; Dietrich, W Dalton; Keane, Robert W


    Vigorous immune responses are induced in the immune privileged CNS by injury and disease, but the molecular mechanisms regulating innate immunity in the CNS are poorly defined. The inflammatory response initiated by spinal cord injury (SCI) involves activation of interleukin-1beta (IL-1beta) that contributes to secondary cell death. In the peripheral immune response, the inflammasome activates caspase-1 to process proinflammatory cytokines, but the regulation of trauma-induced inflammation in the CNS is not clearly understood. Here we show that a molecular platform [NALP1 (NAcht leucine-rich-repeat protein 1) inflammasome] consisting of caspase-1, caspase-11, ASC (apoptosis-associated speck-like protein containing a caspase-activating recruitment domain), and NALP1 is expressed in neurons of the normal rat spinal cord and forms a protein assembly with the X-linked inhibitor of apoptosis protein (XIAP). Moderate cervical contusive SCI induced processing of IL-1beta, IL-18, activation of caspase-1, cleavage of XIAP, and promoted assembly of the multiprotein complex. Anti-ASC neutralizing antibodies administered to injured rats entered spinal cord neurons via a mechanism that was sensitive to carbenoxolone. Therapeutic neutralization of ASC reduced caspase-1 activation, XIAP cleavage, and interleukin processing, resulting in significant tissue sparing and functional improvement. Thus, rat spinal cord neurons contain a caspase-1, pro-ILbeta, and pro-IL-18 activating complex different from the human NALP1 inflammasome that constitutes an important arm of the innate CNS inflammatory response after SCI.

  18. Myokardinfarkt und Beta-Blocker

    Directory of Open Access Journals (Sweden)

    Stühlinger H-G


    Full Text Available Im Rahmen eines akuten koronaren Syndroms (akuter Herzinfarkt, Angina pectoris kommt es, aufgrund eines Ungleichgewichtes zwischen Angebot und Bedarf, zu einem akuten Mangel an Sauerstoff im Herzmuskel. Ursache ist eine reduzierte Sauerstoffzufuhr durch verengte bzw. verschlossene Gefäße. Bis zur Behebung der Ursache vergehen oft mehrere Stunden. In dieser Phase muß - durch Verminderung des Sauerstoffbedarfs im Herzmuskel - eine Verlangsamung der Nekroseentwicklung erreicht werden. Das Ausmaß der Nekrose wird reduziert, somit die für die Langzeitprognose wichtige Linksventrikelfunktion verbessert. Eine Verminderung des Sauerstoffbedarfs erreicht man durch kontrollierte Frequenzsenkung mittels intravenöser Beta-Blockade. In optimaler Weise wird diese Methode durch die Anwendung eines kardioselektiven Beta-Blockers mit kurzer Halbwertszeit durchgeführt. Beta-Blocker haben nicht nur auf die Nekroseentwicklung, sondern auch auf die Inzidenz von Rhythmusstörungen - besonders in der Akutphase - Auswirkungen. Vor allem die mit dieser therapeutischen Maßnahme verbundene Reduktion von Kammerflimmern ist von großer Bedeutung.

  19. Study Ties Inflammation, Gut Bacteria to Type 1 Diabetes (United States)

    ... news/fullstory_163143.html Study Ties Inflammation, Gut Bacteria to Type 1 Diabetes However, it's not yet ... Italian study finds. Those changes include different gut bacteria and inflammation in the small intestine. The differences ...

  20. $\\beta$-particle energy-summing correction for $\\beta$-delayed proton emission measurements

    CERN Document Server

    Meisel, Z; Crawford, H L; Cyburt, R H; Grinyer, G F; Langer, C; Montes, F; Schatz, H; Smith, K


    A common approach to studying $\\beta$-delayed proton emission is to measure the energy of the emitted proton and corresponding nuclear recoil in a double-sided silicon-strip detector (DSSD) after implanting the $\\beta$-delayed proton emitting ($\\beta$p) nucleus. However, in order to extract the proton-decay energy, the measured energy must be corrected for the additional energy implanted in the DSSD by the $\\beta$-particle emitted from the $\\beta$p nucleus, an effect referred to here as $\\beta$-summing. We present an approach to determine an accurate correction for $\\beta$-summing. Our method relies on the determination of the mean implantation depth of the $\\beta$p nucleus within the DSSD by analyzing the shape of the total (proton + recoil + $\\beta$) decay energy distribution shape. We validate this approach with other mean implantation depth measurement techniques that take advantage of energy deposition within DSSDs upstream and downstream of the implantation DSSD.

  1. Inflammation and the degenerative diseases of aging. (United States)

    McGeer, Patrick L; McGeer, Edith G


    Chronic inflammation is associated with a broad spectrum of neurodegenerative diseases of aging. Included are such disorders as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis, the Parkinson-dementia complex of Guam, all of the tauopathies, and age-related macular degeneration. Also included are such peripheral conditions as osteoarthritis, rheumatoid arthritis, atherosclerosis, and myocardial infarction. Inflammation is a two-edged sword. In acute situations, or at low levels, it deals with the abnormality and promotes healing. When chronically sustained at high levels, it can seriously damage viable host tissue. We describe this latter phenomenon as autotoxicity to distinguish it from autoimmunity. The latter involves a lymphocyte-directed attack against self proteins. Autotoxicity, on the other hand, is determined by the concentration and degree of activation of tissue-based monocytic phagocytes. Microglial cells are the brain representatives of the monocyte phagocytic system. Biochemically, the intensity of their activation is related to a spectrum of inflammatory mediators generated by a variety of local cells. The known spectrum includes, but is not limited to, prostaglandins, pentraxins, complement components, anaphylotoxins, cytokines, chemokines, proteases, protease inhibitors, adhesion molecules, and free radicals. This spectrum offers a huge variety of targets for new anti-inflammatory agents. It has been suggested, largely on the basis of transgenic mouse models, that stimulating inflammation rather than inhibiting it can be beneficial in such diseases as AD. If this were the case, administration of NSAIDs, or other anti-inflammatory drugs, would be expected to exacerbate conditions such as AD, PD, and atherosclerosis. However, epidemiological evidence overwhelmingly demonstrates that the reverse is true. This indicates that, at least in these diseases, the inflammation is harmful. So far, advantage has not been taken

  2. Genetic markers of inflammation may not contribute to metabolic traits in Mexican children

    Directory of Open Access Journals (Sweden)

    Neeti Vashi


    Full Text Available Background: Low-grade chronic inflammation is a common feature of obesity and its cardio-metabolic complications. However, little is known about a possible causal role of inflammation in metabolic disorders. Mexico is among the countries with the highest obesity rates in the world and the admixed Mexican population is a relevant sample due to high levels of genetic diversity. Methods: Here, we studied 1,462 Mexican children recruited from Mexico City. Six genetic variants in five inflammation-related genes were genotyped: rs1137101 (leptin receptor (LEPR, rs7305618 (hepatocyte nuclear factor 1 alpha (HNF1A, rs1800629 (tumor necrosis factor alpha (TNFA, rs1800896, rs1800871 (interleukin-10 (IL-10, rs1862513 (resistin (RETN. Ten continuous and eight binary traits were assessed. Linear and logistic regression models were used adjusting for age, sex, and recruitment centre. Results: We found that one SNP displayed a nominal evidence of association with a continuous trait: rs1800871 (IL-10 with LDL (beta = −0.068 ± 1.006, P = 0.01. Subsequently, we found one nominal association with a binary trait: rs7305618 (HNF1A with family history of hypertension (odds-ratio = 1.389 [1.054–1.829], P = 0.02. However, no P-value passed the Bonferroni correction for multiple testing. Discussion: Our data in a Mexican children population are consistent with previous reports in European adults in failing to demonstrate an association between inflammation-associated single nucleotide polymorphisms (SNPs and metabolic traits.

  3. VESGEN Mapping of Bioactive Protection against Intestinal Inflammation: Application to Human Spaceflight and ISS Experiments (United States)

    Parsons-Wingerter, P. A.; Chen, X.; Kelly, C. P.; Reinecker, H. C.


    Challenges to successful space exploration and colonization include adverse physiological reactions to micro gravity and space radiation factors. Constant remodeling of the microvasculature is critical for tissue preservation, wound healing, and recovery after ischemia. Regulation of the vascular system in the intestine is particularly important to enable nutrient absorption while maintaining barrier function and mucosal defense against micro biota. Although tremendous progress has been made in understanding the molecular circuits regulating neovascularization, our knowledge of the adaptations of the vascular system to environmental challenges in the intestine remains incomplete. This is in part because of the lack of methods to observe and quantify the complex processes associated with vascular responses in vivo. Developed by GRC as a mature beta version, pre-release research software, VESsel GENeration Analysis (VESGEN) maps and quantifies the fractal-based complexity of vascular branching for novel insights into the cytokine, transgenic and therapeutic regulation of angiogenesis, lymphangiogenesis and microvascular remodeling. Here we demonstrate that VESGEN can be used to characterize the dynamic vascular responses to acute intestinal inflammation and mucosal recovery from in vivo confocal microscopic 3D image series. We induced transient intestinal inflammation in mice by DSS treatment and investigated whether the ability of the pro biotic yeast Saccharomyces boulardii (Sb) to protect against intestinal inflammation was due to regulation of vascular remodeling. A primary characteristic of inflammation is excessive neovascularization (angiogenesis) resulting in fragile vessels prone to bleeding. Morphological parameters for triplicate specimens revealed that Sb treatment greatly reduced the inflammatory response of vascular networks by an average of 78%. This resulted from Sb inhibition of vascular endothelial growth factor receptor signaling, a major

  4. Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis.

    Directory of Open Access Journals (Sweden)

    John T Pesce


    Full Text Available Macrophage-specific expression of Arginase-1 is commonly believed to promote inflammation, fibrosis, and wound healing by enhancing L-proline, polyamine, and Th2 cytokine production. Here, however, we show that macrophage-specific Arg1 functions as an inhibitor of inflammation and fibrosis following infection with the Th2-inducing pathogen Schistosoma mansoni. Although susceptibility to infection was not affected by the conditional deletion of Arg1 in macrophages, Arg1(-/flox;LysMcre mice died at an accelerated rate. The mortality was not due to acute Th1/NOS2-mediated hepatotoxicity or endotoxemia. Instead, granulomatous inflammation, liver fibrosis, and portal hypertension increased in infected Arg1(-/flox;LysMcre mice. Similar findings were obtained with Arg1(flox/flox;Tie2cre mice, which delete Arg1 in all macrophage populations. Production of Th2 cytokines increased in the infected Arg1(-/flox;LysMcre mice, and unlike alternatively activated wild-type macrophages, Arg1(-/flox;LysMcre macrophages failed to inhibit T cell proliferation in vitro, providing an underlying mechanism for the exacerbated Th2 pathology. The suppressive activity of Arg1-expressing macrophages was independent of IL-10 and TGF-beta1. However, when exogenous L-arginine was provided, T cell proliferation was restored, suggesting that Arg1-expressing macrophages deplete arginine, which is required to sustain CD4(+ T cell responses. These data identify Arg1 as the essential suppressive mediator of alternatively activated macrophages (AAM and demonstrate that Arg1-expressing macrophages function as suppressors rather than inducers of Th2-dependent inflammation and fibrosis.

  5. Bosentan, a mixed endothelin receptor antagonist, inhibits superoxide anion-induced pain and inflammation in mice. (United States)

    Serafim, Karla G G; Navarro, Suelen A; Zarpelon, Ana C; Pinho-Ribeiro, Felipe A; Fattori, Victor; Cunha, Thiago M; Alves-Filho, Jose C; Cunha, Fernando Q; Casagrande, Rubia; Verri, Waldiceu A


    Bosentan is a mixed endothelin receptor antagonist widely used to treat patients with pulmonary arterial hypertension, and the emerging literature suggests bosentan as a potent anti-inflammatory drug. Superoxide anion is produced in large amounts during inflammation, stimulates cytokine production, and thus contributes to inflammation and pain. However, it remains to be determined whether endothelin contributes to the inflammatory response triggered by the superoxide anion. The present study investigated the effects of bosentan in a mouse model of inflammation and pain induced by potassium superoxide, a superoxide anion donor. Male Swiss mice were treated with bosentan (10-100 mg/kg) by oral gavage, 1 h before potassium superoxide injection, and the inflammatory response was evaluated locally and at spinal cord (L4-L6) levels. Bosentan (100 mg/kg) inhibited superoxide anion-induced mechanical and thermal hyperalgesia, overt pain-like behavior (abdominal writhings, paw flinching, and licking), paw edema, myeloperoxidase activity (neutrophil marker) in the paw skin, and leukocyte recruitment in the peritoneal cavity. Bosentan also inhibited superoxide anion-induced interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) production, while it enhanced IL-10 production in the paw skin and spinal cord. Bosentan inhibited the reduction of antioxidant capacity (reduced glutathione, ferric reducing antioxidant power, and ABTS radical scavenging ability) induced by the superoxide anion. Finally, we demonstrated that intraplantar injection of potassium superoxide induces the mRNA expression of prepro-endothelin-1 in the paw skin and spinal cord. In conclusion, our results demonstrated that superoxide anion-induced inflammation, pain, cytokine production, and oxidative stress depend on endothelin; therefore, these responses are amenable to bosentan treatment.

  6. Delayed inflammation associated with retained perfluorocarbon liquid

    Directory of Open Access Journals (Sweden)

    S Pradeep


    Full Text Available A 55-year-old woman, with history of cataract surgery 1 year back, presented with features of ocular inflammation for last 3 months. She had no history of any other intraocular surgery. On examination, anterior segment showed frothy material in the inferior angle with moderate anterior chamber reaction (cells+/flare+ and sulcus intraocular lens with large posterior capsule rent. Fundoscopy showed multiple, small to medium-sized transparent bubbles of perfluorocarbon liquid (PFCL with membranes in the vitreous cavity. Ultrasonography confirmed the presence of PFCL in the vitreous cavity. Pars plana vitrectomy with anterior chamber wash was done which led to good visual recovery. To conclude, retained PFCL can cause late onset fibrinous inflammation after a quiescent period but surgical intervention may lead to good visual outcome.

  7. Matrix Metalloproteinases as Regulators of Periodontal Inflammation (United States)

    Franco, Cavalla; Patricia, Hernández-Ríos; Timo, Sorsa; Claudia, Biguetti; Marcela, Hernández


    Periodontitis are infectious diseases characterized by immune-mediated destruction of periodontal supporting tissues and tooth loss. Matrix metalloproteinases (MMPs) are key proteases involved in destructive periodontal diseases. The study and interest in MMP has been fuelled by emerging evidence demonstrating the broad spectrum of molecules that can be cleaved by them and the myriad of biological processes that they can potentially regulate. The huge complexity of MMP functions within the ‘protease web’ is crucial for many physiologic and pathologic processes, including immunity, inflammation, bone resorption, and wound healing. Evidence points out that MMPs assemble in activation cascades and besides their classical extracellular matrix substrates, they cleave several signalling molecules—such as cytokines, chemokines, and growth factors, among others—regulating their biological functions and/or bioavailability during periodontal diseases. In this review, we provide an overview of emerging evidence of MMPs as regulators of periodontal inflammation. PMID:28218665

  8. Inflammation: therapeutic targets for diabetic neuropathy. (United States)

    Zhou, Jiyin; Zhou, Shiwen


    There are still no approved treatments for the prevention or of cure of diabetic neuropathy, and only symptomatic pain therapies of variable efficacy are available. Inflammation is a cardinal pathogenic mechanism of diabetic neuropathy. The relationships between inflammation and the development of diabetic neuropathy involve complex molecular networks and processes. Herein, we review the key inflammatory molecules (inflammatory cytokines, adhesion molecules, chemokines) and pathways (nuclear factor kappa B, JUN N-terminal kinase) implicated in the development and progression of diabetic neuropathy. Advances in the understanding of the roles of these key inflammatory molecules and pathways in diabetic neuropathy will facilitate the discovery of the potential of anti-inflammatory approaches for the inhibition of the development of neuropathy. Specifically, many anti-inflammatory drugs significantly inhibit the development of different aspects of diabetic neuropathy in animal models and clinical trials.

  9. Inflammation Induces TDP-43 Mislocalization and Aggregation.

    Directory of Open Access Journals (Sweden)

    Ana Sofia Correia

    Full Text Available TAR DNA-binding protein 43 (TDP-43 is a major component in aggregates of ubiquitinated proteins in amyotrophic lateral sclerosis (ALS and frontotemporal lobar degeneration (FTLD. Here we report that lipopolysaccharide (LPS-induced inflammation can promote TDP-43 mislocalization and aggregation. In culture, microglia and astrocytes exhibited TDP-43 mislocalization after exposure to LPS. Likewise, treatment of the motoneuron-like NSC-34 cells with TNF-alpha (TNF-α increased the cytoplasmic levels of TDP-43. In addition, the chronic intraperitoneal injection of LPS at a dose of 1mg/kg in TDP-43(A315T transgenic mice exacerbated the pathological TDP-43 accumulation in the cytoplasm of spinal motor neurons and it enhanced the levels of TDP-43 aggregation. These results suggest that inflammation may contribute to development or exacerbation of TDP-43 proteinopathies in neurodegenerative disorders.

  10. Role of inflammation in the aging bones. (United States)

    Abdelmagid, Samir M; Barbe, Mary F; Safadi, Fayez F


    Chronic inflammation in aging is characterized by increased inflammatory cytokines, bone loss, decreased adaptation, and defective tissue repair in response to injury. Aging leads to inherent changes in mesenchymal stem cell (MSC) differentiation, resulting in impaired osteoblastogenesis. Also, the pro-inflammatory cytokines increase with aging, leading to enhanced myelopoiesis and osteoclastogenesis. Bone marrow macrophages (BMMs) play pivotal roles in osteoblast differentiation, the maintenance of hematopoietic stem cells (HSCs), and subsequent bone repair. However, during aging, little is known about the role of macrophages in the differentiation and function of MSC and HSC. Aged mammals have higher circulating pro-inflammatory cytokines than young adults, supporting the hypothesis of increased inflammation with aging. This review will aid in the understanding of the potential role(s) of pro-inflammatory (M1) and anti-inflammatory (M2) macrophages in differentiation and function of osteoblasts and osteoclasts in relation to aging.

  11. Gaseous mediators in resolution of inflammation. (United States)

    Wallace, John L; Ianaro, Angela; Flannigan, Kyle L; Cirino, Giuseppe


    There are numerous gaseous substances that can act as signaling molecules, but the best characterized of these are nitric oxide, hydrogen sulfide and carbon monoxide. Each has been shown to play important roles in many physiological and pathophysiological processes. This article is focused on the effects of these gasotransmitters in the context of inflammation. There is considerable overlap in the actions of nitric oxide, hydrogen sulfide and carbon monoxide with respect to inflammation, and these mediators appear to act primarily as anti-inflammatory substances, promoting resolution of inflammatory processes. They also have protective and pro-healing effects in some tissues, such as the gastrointestinal tract and lung. Over the past two decades, significant progress has been made in the development of novel anti-inflammatory and cytoprotective drugs that release of one or more of these gaseous mediators.

  12. A link between inflammation and metastasis

    DEFF Research Database (Denmark)

    Hansen, M. T.; Forst, B.; Cremers, N.


    S100A4 is implicated in metastasis and chronic inflammation, but its function remains uncertain. Here we establish an S100A4-dependent link between inflammation and metastatic tumor progression. We found that the acute-phase response proteins serum amyloid A (SAA) 1 and SAA3 are transcriptional...... targets of S100A4 via Toll-like receptor 4 (TLR4)/nuclear factor-κB signaling. SAA proteins stimulated the transcription of RANTES (regulated upon activation normal T-cell expressed and presumably secreted), G-CSF (granulocyte-colony-stimulating factor) and MMP2 (matrix metalloproteinase 2), MMP3, MMP9...... and MMP13. We have also shown for the first time that SAA stimulate their own transcription as well as that of proinflammatory S100A8 and S100A9 proteins. Moreover, they strongly enhanced tumor cell adhesion to fibronectin, and stimulated migration and invasion of human and mouse tumor cells...

  13. Bioenergetic Approaches and Inflammation in MPTP Toxicity (United States)


    gliosis, heat shock protein 70, Hunt- 48% loss of dopaminergic neurons induced by MPTP in the ington, inflammation, Parkinson . substantia nigra al. 2001; tumor necrosis factor-o. © 2005 International Society for Neurochemistry , J. Neurochem. (2005) 94, 995-1004 995 996 C. Cleren et al. 1986...ndokTUA injection was perfonned 6 h after the first injection. Mice were © 2005 International Society for Neurochemistry , J. Neurochem. (2005) 94

  14. Genes, inflammation, and age-related diseases


    Trompet, Stella


    The general objective of this thesis was to investigate associations between genetic variants involved in inflammation and epigenetics and age-related diseases in an elderly cohort to get more insights in the patho-physiological mechanisms involved in age-related diseases, like cardiovascular disease, cognitive decline and cancer. For all analyses we used data of the participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). We have shown that subjects carrying gen...

  15. Sarcopenia correlates with systemic inflammation in COPD (United States)

    Byun, Min Kwang; Cho, Eun Na; Chang, Joon; Ahn, Chul Min; Kim, Hyung Jung


    Background Muscle wasting and chronic inflammation are predominant features of patients with COPD. Systemic inflammation is associated with an accelerated decline in lung function. In this study, the prevalence of sarcopenia and the relationships between sarcopenia and systemic inflammations in patients with stable COPD were investigated. Materials and methods In a cross-sectional design, muscle strength and muscle mass were measured by handgrip strength (HGS) and bioelectrical impedance analysis in 80 patients with stable COPD. Patients (≥40 years old) diagnosed with COPD were recruited from outpatient clinics, and then COPD stages were classified. Sarcopenia was defined as the presence of both low muscle strength (by HGS) and low muscle mass (skeletal muscle mass index [SMMI]). Levels of circulating inflammatory biomarkers (IL-6 and high-sensitivity TNFα [hsTNFα]) were measured. Results Sarcopenia was prevalent in 20 (25%) patients. Patients with sarcopenia were older, had lower body mass index, and a higher percentage of cardiovascular diseases. In addition, they had significantly higher modified Medical Research Council scores and lower 6-minute walk distance than those without sarcopenia. HGS was significantly correlated with age, modified Medical Research Council score, and COPD Assessment Test scores. Both HGS and SMMI had associations with IL-6 and hsTNFα (HGS, r=−0.35, P=0.002; SMMI, r=−0.246, P=0.044) level. In multivariate analysis, old age, lower body mass index, presence of cardiovascular comorbidities, and higher hsTNFα levels were significant determinants for sarcopenia in patients with stable COPD. Conclusion Sarcopenia is very common in patients with stable COPD, and is associated with more severe dyspnea-scale scores and lower exercise tolerance. Systemic inflammation could be an important contributor to sarcopenia in the stable COPD population. PMID:28255238

  16. Role of inflammation in developmental odontogenic pathosis

    Directory of Open Access Journals (Sweden)

    Sandeep S Gupta


    Full Text Available Periapical infection in the primary tooth may lead to periapical abscess, granuloma, radicular cyst and even osteomyelitis. The infection in primary teeth can also affect the developing successor teeth leading to hypomineralization, hypoplasia, arrest of tooth development, regional odontodysplasia, delayed eruption etc. The purpose of this article is to report a case of malformed permanent tooth in relation to overlying infected deciduous teeth. The probable role of inflammation in pathogenesis of the present condition is also being discussed.

  17. Inflammation in Parkinson's disease: role of glucocorticoids



    International audience; Chronic inflammation is a major characteristic feature of Parkinson’s disease (PD). Studies in PD patients show evidence of augmented levels of potent pro-inflammatory molecules e.g., TNF-α, iNOS, IL-1β whereas in experimental Parkinsonism it has been consistently demonstrated that dopaminergic neurons are particularly vulnerable to activated glia releasing these toxic factors. Recent genetic studies point to the role of immune system in the etiology of PD, thus in com...

  18. Tumor necrosis factor-alpha upregulates 11beta-hydroxysteroid dehydrogenase type 1 expression by CCAAT/enhancer binding protein-beta in HepG2 cells. (United States)

    Ignatova, Irena D; Kostadinova, Radina M; Goldring, Christopher E; Nawrocki, Andrea R; Frey, Felix J; Frey, Brigitte M


    The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyzes the conversion of inactive to active glucocorticoids. 11beta-HSD1 plays a crucial role in the pathogenesis of obesity and controls glucocorticoid actions in inflammation. Several studies have demonstrated that TNF-alpha increases 11beta-HSD1 mRNA and activity in various cell models. Here, we demonstrate that mRNA and activity of 11beta-HSD1 is increased in liver tissue from transgenic mice overexpressing TNF-alpha, indicating that this effect also occurs in vivo. To dissect the molecular mechanism of this increase, we investigated basal and TNF-alpha-induced transcription of the 11beta-HSD1 gene (HSD11B1) in HepG2 cells. We found that TNF-alpha acts via p38 MAPK pathway. Transient transfections with variable lengths of human HSD11B1 promoter revealed highest activity with or without TNF-alpha in the proximal promoter region (-180 to +74). Cotransfection with human CCAAT/enhancer binding protein-alpha (C/EBPalpha) and C/EBPbeta-LAP expression vectors activated the HSD11B1 promoter with the strongest effect within the same region. Gel shift and RNA interference assays revealed the involvement of mainly C/EBPalpha, but also C/EBPbeta, in basal and only of C/EBPbeta in the TNF-alpha-induced HSD11B1 expression. Chromatin immunoprecipitation assay confirmed in vivo the increased abundance of C/EBPbeta on the proximal HSD11B1 promoter upon TNF-alpha treatment. In conclusion, C/EBPalpha and C/EBPbeta control basal transcription, and TNF-alpha upregulates 11beta-HSD1, most likely by p38 MAPK-mediated increased binding of C/EBPbeta to the human HSD11B1 promoter. To our knowledge, this is the first study showing involvement of p38 MAPK in the TNF-alpha-mediated 11beta-HSD1 regulation, and that TNF-alpha stimulates enzyme activity in vivo.

  19. Beta therapy with 90strontium as single modality therapy for canine squamous cell carcinoma in third eyelid

    Directory of Open Access Journals (Sweden)

    Alexandre Lima de Andrade


    Full Text Available The purpose was to evaluate the effectiveness of beta-radiation with strontium-90 as single modality treatment of canine third eyelid squamous cell carcinoma (SCC. Nine dogs diagnosed with third eyelid SCC were treated with strontium-90. Radiation therapy was administered in four fractions of 100cGy per site every four days and at a depth of 0.2cm (Strontium-90 build' up in each fraction. Radiation with beta therapy was well tolerated in all animals with no occurrence of radiation induced cataracts. In all cases, there were increased signs of conjunctival inflammation around the mass, which subsided with topical anti-inflammatory. Two dogs required surgical treatment for local tumor recurrence at 150 days and 352 days. In the remaining seven cases, disease free interval ranged from 1239 days to 2555 days. Beta therapy using 90Sr may be a valid alternative for the treatment of third eyelid SCC in dogs

  20. Involvement of central microsomal prostaglandin E synthase-1 in IL-1beta-induced anorexia. (United States)

    Pecchi, E; Dallaporta, M; Thirion, S; Salvat, C; Berenbaum, F; Jean, A; Troadec, J-D


    In response to infection or inflammation, individuals develop a set of symptoms referred to as sickness behavior, which includes a decrease in food intake. The characterization of the molecular mechanisms underlying this hypophagia remains critical, because chronic anorexia may represent a significant health risk. Prostaglandins (PGs) constitute an important inflammatory mediator family whose levels increase in the brain during inflammatory states, and their involvement in inflammatory-induced anorexia has been proposed. The microsomal PGE synthase (mPGES)-1 enzyme is involved in the last step of PGE2 biosynthesis, and its expression is stimulated by proinflammatory agents. The present study attempted to determine whether an upregulation of mPGES-1 gene expression may account for the immune-induced anorexic behavior. We focused our study on mPGES-1 expression in the hypothalamus and dorsal vagal complex, two structures strongly activated during peripheral inflammation and involved in the regulation of food intake. We showed that mPGES-1 gene expression was robustly upregulated in these structures after intraperitoneal and intracerebroventricular injections of anorexigenic doses of IL-1beta. This increase was correlated with the onset of anorexia. The concomitant reduction in food intake and central mPGES-1 gene upregulation led us to test the feeding behavior of mice lacking mPGES-1 during inflammation. Interestingly, IL-1beta failed to decrease food intake in mPGES-1(-/-) mice, although these animals developed anorexia in response to a PGE2 injection. Taken together, our results demonstrate that mPGES-1, which is strongly upregulated during inflammation in central structures involved in feeding control, is essential for immune anorexic behavior and thus may constitute a potential therapeutic target.

  1. Molecular Imaging of Autoimmune Diseases and Inflammation

    Directory of Open Access Journals (Sweden)

    S. Anna Sargsyan


    Full Text Available Molecular imaging methods allow the noninvasive detection and localization of specific molecules. Agents that report on molecular disease biomarkers can be used to diagnose and monitor disease. Many inflammatory diseases have molecular signatures within altered tissues. Although tissue biopsy is still the gold standard for detecting these signatures, several molecular imaging markers have been developed. Pharmacologic agents that block specific immune molecules have recently entered the clinic, and these drugs have already transformed the way we care for patients with immune-mediated diseases. The use of immunomodulatory drugs is usually guided by clinical assessment of the patient's response. Unfortunately, clinical assessment may miss the signs of inflammation, and many of the serologic markers of immune-mediated diseases correlate poorly with the underlying inflammatory activity within target tissues. Molecular imaging methods have the potential to improve our ability to detect and characterize tissue inflammation. We discuss some of the molecular signatures of immune activation and review molecular imaging methods that have been developed to detect active tissue inflammation.

  2. Kaempferol and inflammation: From chemistry to medicine. (United States)

    Devi, Kasi Pandima; Malar, Dicson Sheeja; Nabavi, Seyed Fazel; Sureda, Antoni; Xiao, Jianbo; Nabavi, Seyed Mohammad; Daglia, Maria


    Inflammation is an important process of human healing response, wherein the tissues respond to injuries induced by many agents including pathogens. It is characterized by pain, redness and heat in the injured tissues. Chronic inflammation seems to be associated with different types of diseases such as arthritis, allergies, atherosclerosis, and even cancer. In recent years natural product based drugs are considered as the novel therapeutic strategy for prevention and treatment of inflammatory diseases. Among the different types of phyto-constituents present in natural products, flavonoids which occur in many vegetable foods and herbal medicines are considered as the most active constituent, which has the potency to ameliorate inflammation under both in vitro and in vivo conditions. Kaempferol is a natural flavonol present in different plant species, which has been described to possess potent anti-inflammatory properties. Despite the voluminous literature on the anti-inflammatory effects of kaempferol, only very limited review articles has been published on this topic. Hence the present review is aimed to provide a critical overview on the anti-inflammatory effects and the mechanisms of action of kaempferol, based on the current scientific literature. In addition, emphasis is also given on the chemistry, natural sources, bioavailability and toxicity of kaempferol.

  3. Lipid Mediators in the Resolution of Inflammation (United States)

    Serhan, Charles N.; Chiang, Nan; Dalli, Jesmond; Levy, Bruce D.


    Mounting of the acute inflammatory response is crucial for host defense and pivotal to the development of chronic inflammation, fibrosis, or abscess formation versus the protective response and the need of the host tissues to return to homeostasis. Within self-limited acute inflammatory exudates, novel families of lipid mediators are identified, named resolvins (Rv), protectins, and maresins, which actively stimulate cardinal signs of resolution, namely, cessation of leukocytic infiltration, counterregulation of proinflammatory mediators, and the uptake of apoptotic neutrophils and cellular debris. The biosynthesis of these resolution-phase mediators in sensu stricto is initiated during lipid-mediator class switching, in which the classic initiators of acute inflammation, prostaglandins and leukotrienes (LTs), switch to produce specialized proresolving mediators (SPMs). In this work, we review recent evidence on the structure and functional roles of these novel lipid mediators of resolution. Together, these show that leukocyte trafficking and temporal spatial signals govern the resolution of self-limited inflammation and stimulate homeostasis. PMID:25359497

  4. FRNK negatively regulates IL-4-mediated inflammation. (United States)

    Sharma, Ritu; Colarusso, Pina; Zhang, Hong; Stevens, Katarzyna M; Patel, Kamala D


    Focal adhesion kinase (FAK)-related nonkinase (PTK2 isoform 6 in humans, hereafter referred to as FRNK) is a cytoskeletal regulatory protein that has recently been shown to dampen lung fibrosis, yet its role in inflammation is unknown. Here, we show for the first time that expression of FRNK negatively regulates IL-4-mediated inflammation in a human model of eosinophil recruitment. Mechanistically, FRNK blocks eosinophil accumulation, firm adhesion and transmigration by preventing transcription and protein expression of VCAM-1 and CCL26. IL-4 activates STAT6 to induce VCAM-1 and CCL26 transcription. We now show that IL-4 also increases GATA6 to induce VCAM-1 expression. FRNK blocks IL-4-induced GATA6 transcription but has little effect on GATA6 protein expression and no effect on STAT6 activation. FRNK can block FAK or Pyk2 signaling and we, thus, downregulated these proteins using siRNA to determine whether signaling from either protein is involved in the regulation of VCAM-1 and CCL26. Knockdown of FAK, Pyk2 or both had no effect on VCAM-1 or CCL26 expression, which suggests that FRNK acts independently of FAK and Pyk2 signaling. Finally, we found that IL-4 induces the late expression of endogenous FRNK. In summary, FRNK represents a novel mechanism to negatively regulate IL-4-mediated inflammation.

  5. NOX2-dependent regulation of inflammation. (United States)

    Singel, Kelly L; Segal, Brahm H


    NADPH oxidase (NOX) isoforms together have multiple functions that are important for normal physiology and have been implicated in the pathogenesis of a broad range of diseases, including atherosclerosis, cancer and neurodegenerative diseases. The phagocyte NADPH oxidase (NOX2) is critical for antimicrobial host defence. Chronic granulomatous disease (CGD) is an inherited disorder of NOX2 characterized by severe life-threatening bacterial and fungal infections and by excessive inflammation, including Crohn's-like inflammatory bowel disease (IBD). NOX2 defends against microbes through the direct antimicrobial activity of reactive oxidants and through activation of granular proteases and generation of neutrophil extracellular traps (NETs). NETosis involves the breakdown of cell membranes and extracellular release of chromatin and neutrophil granular constituents that target extracellular pathogens. Although the immediate effects of oxidant generation and NETosis are predicted to be injurious, NOX2, in several contexts, limits inflammation and injury by modulation of key signalling pathways that affect neutrophil accumulation and clearance. NOX2 also plays a role in antigen presentation and regulation of adaptive immunity. Specific NOX2-activated pathways such as nuclear factor erythroid 2-related factor 2 (Nrf2), a transcriptional factor that induces antioxidative and cytoprotective responses, may be important therapeutic targets for CGD and, more broadly, diseases associated with excessive inflammation and injury.

  6. Congenital muscular dystrophy with inflammation: Diagnostic considerations

    Directory of Open Access Journals (Sweden)

    Kaumudi Konkay


    Full Text Available Background and Purpose: Muscle biopsy features of congenital muscular dystrophies (CMD vary from usual dystrophic picture to normal or nonspecific myopathic picture or prominent fibrosis or striking inflammatory infiltrate, which may lead to diagnostic errors. A series of patients of CMD with significant inflammatory infiltrates on muscle biopsy were correlated with laminin α 2 deficiency on immunohistochemistry (IHC. Material and Methods: Cryostat sections of muscle biopsies from the patients diagnosed as CMD on clinical and muscle biopsy features from 1996 to 2014 were reviewed with hematoxylin and eosin(H&E, enzyme and immunohistochemistry (IHC with laminin α 2. Muscle biopsies with inflammatory infiltrate were correlated with laminin α 2 deficiency. Results: There were 65 patients of CMD, with inflammation on muscle biopsy in 16. IHC with laminin α 2 was available in nine patients, of which six showed complete absence along sarcolemma (five presented with floppy infant syndrome and one with delayed motor milestones and three showed discontinuous, and less intense staining. Conclusions: CMD show variable degrees of inflammation on muscle biopsy. A diagnosis of laminin α 2 deficient CMD should be considered in patients of muscular dystrophy with inflammation, in children with hypotonia/delayed motor milestones.

  7. Gut inflammation and microbiome in spondyloarthritis. (United States)

    Kabeerdoss, Jayakanthan; Sandhya, Pulukool; Danda, Debashish


    Spondyloarthritis (SpA) is chronic inflammatory disease involving joints and the spine. Bowel inflammation is common in SpA, which may be classified as acute or chronic. Chronic gut inflammation is most common in SpA patients with axial involvement as compared to those presenting with peripheral involvement alone. The pathogenesis of gut inflammation in SpA could be explained by two factors-over-activation of immunological cells and altered gut microbiome. This is exemplified by SpA animal models, namely HLA-B27-expressing transgenic animals and SKG mice models. Immunological mechanisms include homing of activated T cells from gut into synovium, excess pro-inflammatory cytokines secretion by immune cells such as IL-23 and genetic variations in immunological genes. The evidence for role of gut microbiome in SpA is gradually emerging. Recently, metagenomic study of gut microbiome by sequencing of microbial nucleic acids has enabled identification of new microbial taxa and their functions in gut of patients with SpA. In SpA, the gut microbiome could emerge as diagnostic and prognostic marker of disease. Modulation of gut microbiome is slated to have therapeutic potential as well.

  8. Mechanisms of IgE Inflammation. (United States)

    Rosenwasser, Lanny J


    The prevalence of diseases such as allergic asthma and rhinitis continues to increase in the United States, affecting millions of people. It is well-established that allergy contributes to the pathogenesis of most asthma, especially in children and young adults. Despite current therapy (eg, inhaled corticosteroids, anti-leukotrienes, and bronchodilators), patients with moderate to severe asthma remain symptomatic and experience frequent exacerbations of disease requiring oral corticosteroids, emergency department treatments, and hospitalizations. Allergic diseases are traditionally referred to as immediate or type 1 hypersensitivity reactions, with IgE as a critical factor. IgE is involved in allergic inflammation, especially in early-phase response, but it may also be involved in the late-phase allergic response. A direct correlation between serum IgE levels and asthma exists. As logarithm IgE values increase, asthma prevalence increases linearly, even in patients who are categorized as having nonallergic asthma. In addition, there is a significant, although low association in allergic rhinitis with IgE levels and positive skin test reactivity to pollens. Recent advances in our understanding of the role of IgE in allergic inflammation have led to the development of a monoclonal antibody to IgE that reduces IgE levels, thereby reducing allergic inflammation. This review aims to provide an overview of the basic science of the IgE molecule and the clinical efficacy of anti-IgE therapy in allergic and asthmatic diseases.

  9. Silibinin attenuates allergic airway inflammation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yun Ho [Department of Anatomy, Medical School, Institute for Medical Sciences, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Jin, Guang Yu [Department of Radiology, Yanbian University Hospital, YanJi 133002 (China); Guo, Hui Shu [Centralab, The First Affiliated Hospital of Dalian Medical University, Dalian 116011 (China); Piao, Hong Mei [Department of Respiratory Medicine, Yanbian University Hospital, YanJi 133000 (China); Li, Liang chang; Li, Guang Zhao [Department of Anatomy and Histology and Embryology, Yanbian University School of Basic Medical Sciences, 977 Gongyuan Road, YanJi 133002, Jilin (China); Lin, Zhen Hua [Department of Pathology, Yanbian University School of Basic Medical Sciences, YanJi 133000 (China); Yan, Guang Hai, E-mail: [Department of Anatomy and Histology and Embryology, Yanbian University School of Basic Medical Sciences, 977 Gongyuan Road, YanJi 133002, Jilin (China)


    Highlights: Black-Right-Pointing-Pointer Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. Black-Right-Pointing-Pointer Silibinin reduces the levels of various cytokines into the lung of allergic mice. Black-Right-Pointing-Pointer Silibinin prevents the development of airway hyperresponsiveness in allergic mice. Black-Right-Pointing-Pointer Silibinin suppresses NF-{kappa}B transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-{kappa}B) pathway. Because NF-{kappa}B activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-{kappa}B activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-{kappa}B activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.

  10. The Enteric Nervous System in Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    Keith A Sharkey


    Full Text Available Since about the 1950s nerves in the wall of the intestine have been postulated to play a role in the pathogenesis of inflammatory bowel disease (IBD. Human and animal studies examining the role of nerves in intestinal inflammation are the focus of this review. Consideration is given to two possible ways that nerves are involved in IBD. First, nerves may play a role in the development or maintenance of inflammation through local release of transmitters. Second, once initiated (by whatever means, the processes of inflammation may disrupt the normal pattern of innervation and the interactions of nerves and their target tissues. Many of the functional disturbances observed in IBD are likely due to an alteration in the enteric nervous system either structurally through disruptions of nerve-target relationships or by modifications of neurotransmitters or their receptors. Finally, it appears that the enteric nervous system may be a potential therapeutic target in IBD and that neuroactive drugs acting locally can represent useful agents in the management of this disease.

  11. Inflammation in central nervous system injury. (United States)

    Allan, Stuart M; Rothwell, Nancy J


    Inflammation is a key component of host defence responses to peripheral inflammation and injury, but it is now also recognized as a major contributor to diverse, acute and chronic central nervous system (CNS) disorders. Expression of inflammatory mediators including complement, adhesion molecules, cyclooxygenase enzymes and their products and cytokines is increased in experimental and clinical neurodegenerative disease, and intervention studies in experimental animals suggest that several of these factors contribute directly to neuronal injury. Most notably, specific cytokines, such as interleukin-1 (IL-1), have been implicated heavily in acute neurodegeneration, such as stroke and head injury. In spite of their diverse presentation, common inflammatory mechanisms may contribute to many neurodegenerative disorders and in some (e.g. multiple sclerosis) inflammatory modulators are in clinical use. Inflammation may have beneficial as well as detrimental actions in the CNS, particularly in repair and recovery. Nevertheless, several anti-inflammatory targets have been identified as putative treatments for CNS disorders, initially in acute conditions, but which may also be appropriate to chronic neurodegenerative conditions.

  12. The effect of interferon-beta on black holes in patients with multiple sclerosis. (United States)

    Bagnato, Francesca; Evangelou, Iordanis E; Gallo, Antonio; Gaindh, Deeya; Yao, Karen


    Multiple sclerosis (MS) is an immunological disorder of the CNS. Linked to an initial transient inflammation as the result of blood-brain barrier leakage, the disease progresses into a neurodegenerative phase. MRI is the most powerful paraclinical tool for diagnosing and monitoring MS. Although contrast enhancing lesions are the visible events of blood-brain barrier breakdown, accumulation of hypointense lesions, namely black holes, are recognised as irreversible axonal loss. IFN-beta is administered as a first-line drug in MS patients. However, whether the effect of IFN-beta extends beyond just prevention of blood-brain barrier leakage and further prevents the formation of black holes or promotes their recovery once formed, is not yet understood.

  13. Resistance training & beta-hydroxy-beta-methylbutyrate supplementation on hormones

    Directory of Open Access Journals (Sweden)

    Hamid Arazi


    Full Text Available RESUMOIntroduction:In recent years, there was an increased interest on the effects of beta-hydroxy-beta-methylbutyrate (HMB supplementation on skeletal muscle due to its anti-catabolic effects.Objectives:To investigate the effect of HMB supplementation on body composition, muscular strength and anabolic-catabolic hormones after resistance training.Methods:Twenty amateur male athletes were randomly assigned to supplement and control groups in a double-blind crossover design and participated in four weeks resistance training. Before and after the test period fasting blood samples were obtained to determine anabolic (the growth hormone and testosterone and catabolic (cortisol hormones, and fat mass, lean body mass (LBM and muscular strength were measured. Dependent and independent t-tests were used to analyze data.Results:After the training period, there were no significant differen-ces between the groups with respect to fat mass, LBM and anabolic-catabolic hormones. HMB supplementation resulted in a significantly greater strength gain (p≤0.05.Conclusion:Greater increase in strength for HMB group was not accompanied by body composition and basal circulating anabolic-catabolic hormonal changes. It seems that HMB supplementation may have beneficial effects on neurological adaptations of strength gain.

  14. Abstraction Mechanisms in the BETA Programming Language

    DEFF Research Database (Denmark)

    Kristensen, Bent Bruun; Madsen, Ole Lehrmann; Møller-Pedersen, Birger


    ]) --- covering both data, procedural and control abstractions, substituting constructs like class, procedure, function and type. Correspondingly objects, procedure activation records and variables are all regarded as special cases of the basic building block of program executions: the entity. A pattern thus......The BETA programming language is developed as part of the BETA project. The purpose of this project is to develop concepts, constructs and tools in the field of programming and programming languages. BETA has been developed from 1975 on and the various stages of the language are documented in [BETA...... a]. The application area of BETA is programming of embedded as well as distributed computing systems. For this reason a major goal has been to develop constructs that may be efficiently implemented. Furthermore the BETA language is intended to have a few number of basic but general constructs...

  15. Circadian cycle-dependent EEG biomarkers of pathogenicity in adult mice following prenatal exposure to in utero inflammation. (United States)

    Adler, D A; Ammanuel, S; Lei, J; Dada, T; Borbiev, T; Johnston, M V; Kadam, S D; Burd, I


    Intrauterine infection or inflammation in preterm neonates is a known risk for adverse neurological outcomes, including cognitive, motor and behavioral disabilities. Our previous data suggest that there is acute fetal brain inflammation in a mouse model of intrauterine exposure to lipopolysaccharides (LPS). We hypothesized that the in utero inflammation induced by LPS produces long-term electroencephalogram (EEG) biomarkers of neurodegeneration in the exposed mice that could be determined by using continuous quantitative video/EEG/electromyogram (EMG) analyses. A single LPS injection at E17 was performed in pregnant CD1 dams. Control dams were injected with same volumes of saline (LPS n=10, Control n=8). At postnatal age of P90-100, 24-h synchronous video/EEG/EMG recordings were done using a tethered recording system and implanted subdural electrodes. Behavioral state scoring was performed blind to treatment group, on each 10s EEG epoch using synchronous video, EMG and EEG trace signatures to generate individual hypnograms. Automated EEG power spectrums were analyzed for delta and theta-beta power ratios during wake vs. sleep cycles. Both control and LPS hypnograms showed an ultradian wake/sleep cycling. Since rodents are nocturnal animals, control mice showed the expected diurnal variation with significantly longer time spent in wake states during the dark cycle phase. In contrast, the LPS-treated mice lost this circadian rhythm. Sleep microstructure also showed significant alteration in the LPS mice specifically during the dark cycle, caused by significantly longer average non-rapid eye movement (NREM) cycle durations. No significance was found between treatment groups for the delta power data; however, significant activity-dependent changes in theta-beta power ratios seen in controls were absent in the LPS-exposed mice. In conclusion, exposure to in utero inflammation in CD1 mice resulted in significantly altered sleep architecture as adults that were circadian

  16. Leptin is a coactivator of TGF-beta in unilateral ureteral obstructive kidney disease. (United States)

    Kümpers, Philipp; Gueler, Faikah; Rong, Song; Mengel, Michael; Tossidou, Irini; Peters, Imke; Haller, Hermann; Schiffer, Mario


    Progressive tubulointerstitial fibrosis is the common end point leading to end-stage renal disease in experimental and clinical settings. Since the peptide hormone leptin is involved not only in the regulation of obesity but also in the regulation of inflammation and fibrosis, we tested the hypothesis whether leptin deficiency has an impact on tubulointerstitial fibrosis in mice. Leptin-deficient (ob/ob) and leptin receptor-deficient mice (db/db) were exposed to 14 days of unilateral ureteral obstruction (UUO). The degree of fibrosis and inflammation was compared with that in sham-operated mice by performing immunohistochemistry, quantitative PCR, and Western blotting. We found that tubulointerstitial fibrosis was significantly reduced in the obstructed kidneys of ob/ob compared with db/db mice or control mice. Detailed analysis of infiltrating inflammatory cells by immunohistochemistry revealed a significant reduction of CD4(+) cells at 14 days after UUO in both ob/ob and db/db mice. In contrast, we could not detect significant differences in CD8(+) cells and macrophage content. Transforming growth factor (TGF)-beta mRNA levels, TGF-beta-induced Smad-2/3 activation, and the upregulation of downstream target genes were significantly reduced in ob/ob mice. In addition, we demonstrated that leptin could enhance TGF-beta signaling in normal rat kidney fibroblasts in vitro. We conclude that leptin can serve as a cofactor of TGF-beta activation and thus plays an important role in renal tubulointerstitial fibrosis. Therefore, selective blockade of the leptin axis might provide a therapeutic possibility to prevent or delay fibrotic kidney disease.

  17. RNF20 Links Histone H2B Ubiquitylation with Inflammation and Inflammation-Associated Cancer (United States)

    Tarcic, Ohad; Pateras, Ioannis S.; Cooks, Tomer; Shema, Efrat; Kanterman, Julia; Ashkenazi, Hadas; Boocholez, Hana; Hubert, Ayala; Rotkopf, Ron; Baniyash, Michal; Pikarsky, Eli; Gorgoulis, Vassilis G.; Oren, Moshe


    Summary Factors linking inflammation and cancer are of great interest. We now report that the chromatin-targeting E3 ubiquitin ligase RNF20/RNF40, driving histone H2B monoubiquitylation (H2Bub1), modulates inflammation and inflammation-associated cancer in mice and humans. Downregulation of RNF20 and H2Bub1 favors recruitment of p65-containing nuclear factor κB (NF-κB) dimers over repressive p50 homodimers and decreases the heterochromatin mark H3K9me3 on a subset of NF-κB target genes to augment their transcription. Concordantly, RNF20+/− mice are predisposed to acute and chronic colonic inflammation and inflammation-associated colorectal cancer, with excessive myeloid-derived suppressor cells (MDSCs) that may quench antitumoral T cell activity. Notably, colons of human ulcerative colitis patients, as well as colorectal tumors, reveal downregulation of RNF20/RNF40 and H2Bub1 in both epithelium and stroma, supporting the clinical relevance of our tissue culture and mouse model findings. PMID:26854224

  18. RNF20 Links Histone H2B Ubiquitylation with Inflammation and Inflammation-Associated Cancer

    Directory of Open Access Journals (Sweden)

    Ohad Tarcic


    Full Text Available Factors linking inflammation and cancer are of great interest. We now report that the chromatin-targeting E3 ubiquitin ligase RNF20/RNF40, driving histone H2B monoubiquitylation (H2Bub1, modulates inflammation and inflammation-associated cancer in mice and humans. Downregulation of RNF20 and H2Bub1 favors recruitment of p65-containing nuclear factor κB (NF-κB dimers over repressive p50 homodimers and decreases the heterochromatin mark H3K9me3 on a subset of NF-κB target genes to augment their transcription. Concordantly, RNF20+/− mice are predisposed to acute and chronic colonic inflammation and inflammation-associated colorectal cancer, with excessive myeloid-derived suppressor cells (MDSCs that may quench antitumoral T cell activity. Notably, colons of human ulcerative colitis patients, as well as colorectal tumors, reveal downregulation of RNF20/RNF40 and H2Bub1 in both epithelium and stroma, supporting the clinical relevance of our tissue culture and mouse model findings.

  19. Dynamic T-lymphocyte chemokine receptor expression induced by interferon-beta therapy in multiple sclerosis

    DEFF Research Database (Denmark)

    Krakauer, M; Sorensen, P S; Khademi, M;


    as these influence central nervous system (CNS) transmigration and inflammation. At 'steady state' (>/=1 day after the most recent IFN-beta injection), IFN-beta treatment increased CD4(+) T-cell surface expression of CC chemokine receptor (CCR)4, CCR5 and CCR7 after 3 months of treatment, whereas that of CXC...... chemokine receptor (CXCR)3 was unaltered. Conversely, at 9-12 h after the most recent IFN-beta injection, CCR4, CCR5 and CCR7 expressions were unaltered, while CXCR3 expression was reduced. CD4(+) T-cell surface expression of CCR4 was significantly lower in untreated MS patients compared with healthy...... volunteers. Of the plasma chemokines, only CXCL10 was increased by IFN-beta treatment; CCL3, CCL4, CCL5 and CXCL9 were unaltered. CCR5 mRNA expression in blood mononuclear cells correlated with the expression of T-helper type 1 (Th1)-associated genes whereas CCR4 and CCR7 mRNA expression correlated with Th2...

  20. Milk Intolerance, Beta-Casein and Lactose. (United States)

    Pal, Sebely; Woodford, Keith; Kukuljan, Sonja; Ho, Suleen


    True lactose intolerance (symptoms stemming from lactose malabsorption) is less common than is widely perceived, and should be viewed as just one potential cause of cows' milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows' milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows' milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed.

  1. Sawtooth crashes at high beta on JET

    Energy Technology Data Exchange (ETDEWEB)

    Alper, B.; Huysmans, G.T.A.; Sips, A.C.C. [Commission of the European Communities, Abingdon (United Kingdom). JET Joint Undertaking; Nave, M.F.F. [Universidade Tecnica, Lisbon (Portugal). Inst. Superior Tecnico


    The sawtooth crashes on JET display features which depend on beta. The main observation is a transient bulging of flux surfaces (duration inferior to 30 microsec.), which is predominantly on the low field side and extends to larger radii as beta increases. This phenomenon reaches the plasma boundary when beta{sub N} exceeds 0.5 and in these cases is followed by an ELM within 50 microsec. These sawtooth/ELM events limit plasma performance. Modelling of mode coupling shows qualitative agreement between observations of the structure of the sawtooth precursor and the calculated internal kink mode at high beta. (authors). 6 refs., 5 figs.

  2. Milk Intolerance, Beta-Casein and Lactose

    Directory of Open Access Journals (Sweden)

    Sebely Pal


    Full Text Available True lactose intolerance (symptoms stemming from lactose malabsorption is less common than is widely perceived, and should be viewed as just one potential cause of cows’ milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows’ milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows’ milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed.

  3. Challenges in Double Beta Decay

    Directory of Open Access Journals (Sweden)

    Oliviero Cremonesi


    Full Text Available In the past ten years, neutrino oscillation experiments have provided the incontrovertible evidence that neutrinos mix and have finite masses. These results represent the strongest demonstration that the electroweak Standard Model is incomplete and that new Physics beyond it must exist. In this scenario, a unique role is played by the Neutrinoless Double Beta Decay searches which can probe lepton number conservation and investigate the Dirac/Majorana nature of the neutrinos and their absolute mass scale (hierarchy problem with unprecedented sensitivity. Today Neutrinoless Double Beta Decay faces a new era where large-scale experiments with a sensitivity approaching the so-called degenerate-hierarchy region are nearly ready to start and where the challenge for the next future is the construction of detectors characterized by a tonne-scale size and an incredibly low background. A number of new proposed projects took up this challenge. These are based either on large expansions of the present experiments or on new ideas to improve the technical performance and/or reduce the background contributions. In this paper, a review of the most relevant ongoing experiments is given. The most relevant parameters contributing to the experimental sensitivity are discussed and a critical comparison of the future projects is proposed.

  4. The pharmacokinetics of beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin in the rat

    NARCIS (Netherlands)

    Frijlink, H W; Visser, J; Hefting, N R; Oosting, R; Meijer, D K; Lerk, C F


    Hydroxypropyl-beta-cyclodextrin was analyzed by HPLC using postcolumn complexation with phenolphthalein and negative colorimetric detection, with a detection limit of 20 micrograms/ml. The pharmacokinetics of beta-cyclodextrin and of hydroxypropyl-beta-cyclodextrin were studied after intravenous adm

  5. The impact of beta-elemene on beta-tubulin of human hepatoma hepg2 cells

    Institute of Scientific and Technical Information of China (English)

    Yuqiu Mao; Liying Ban; Jielin Zhang; Li Hou; Xiaonan Cui


    Objective:The aim of this study was to investigate the impact of beta-elemene injection on the growth and beta-tubulin of human hepatocarcinoma HepG2 cells. Methods:cellproliferation was assessed by MTT assay. cellcycle distribution was detected by flow cytometry (FCM). The mRNA expression of beta-tubulin was measured by RT-PCR. West-ern blot analysis was used to determine protein expression of beta-tubulin and the polymerization of beta-tubulin. Results:Beta-elemene injection inhibited HepG2 cells proliferation in a dose-and time-dependent manner;FCM analysis indicated beta-elemene injection induced cellcycle arrested at S phase. RT-PCR and western-blot analysis showed that beta-elemene injection down-regulated beta-tubulin expression at both mRNA and protein levels, presenting a dose-dependent manner. Moreover, beta-elemene injection reduced the polymerization of microtubules in a dose-dependent manner. Conclusion:Beta-elemene injection can inhibit the proliferation of hepatoma HepG2 cells, the mechanism might be partly related to the down-regulation of beta-tubulin and inhibition of microtubular polymerization.

  6. Expressions of GSK-3beta, Beta-Catenin and PPAR-Gamma in Medulloblastoma

    Institute of Scientific and Technical Information of China (English)

    Xiong Zhang; Lu Si; Yu Li; Can Mi


    Objective: To investigate the expressions of GSK-3beta, Beta-catenin and PPAR-gamma, and their relationship in medulloblastoma, and to explore their value in clinic application.Methods: Immunohistochemical staining with SP method was conducted to determine the expressions of GSK-3beta, Beta-catenin and PPAR-gamma in 48 cases of medulloblastoma and 10 normal cerebellar tissues.Results: The rate of abnormal expressions of beta-catenin and PPAR-gamma in MB was higher than that in normal. Conversely, GSK-3beta in MB was lower than that in the normal (P<0.05). Furthermore, in medulloblastoma, beta-catenin and GSK-3beta showed a negative correlation, PPAR-gamma and beta-catenin had a positive correlation.Conclusion: Abnormal expression of beta-catenin plays a crucial role in the development of medulloblastoma. Meanwhile, PPAR-gamma and GSK-3beta which are tightly related with beta-catenin are both involved in the genesis and development of medulloblastoma.

  7. Radiation-induced polymerization of {beta}(+)-pinene and synthesis of optically active {beta}(+)/{beta}(-)pinene polymers and copolymers

    Energy Technology Data Exchange (ETDEWEB)

    Cataldo, Franco, E-mail: franco.cataldo@fastwebnet.i [Lupi Chemical Research, Via Casilina 1626/A, 00133 Rome (Italy); Lilla, Edo; Ursini, Ornella [Institute of Chemical Methodologies, CNR, Via Salaria Km. 29300, Monterotondo Stazione 00016, Rome (Italy)


    Poly-{beta}(+)-pinene (pB(+)p) was synthesized with {gamma} irradiation of the monomer {beta}(+)-pinene in bulk under vacuum at 1181 kGy. Also scalemic mixtures of {beta}(+)-pinene and {beta}(-)-pinene were irradiated at 1181 kGy to obtain synthetic copolymers of pB(+)/B(-)p. For comparison also {beta}(-)-pinene was converted into poly-{beta}(-)-pinene (pB(-)p) under the identical conditions adopted for its enantiomer. Furthermore pB(+)p and pB(-)p were also synthesized by thermal processing under the action of a chemical free radical initiator. The optical rotatory dispersion (ORD) of all pBp resins synthesized were accurately studied in the spectral range comprised between 375 and 625 nm and a curious asymmetry in the ORD of pB(+)p versus the ORD of pB(-)p is reported. Furthermore, it is shown that (+)-p-menth-1-ene and (-)-p-menth-1-ene are useful as a model compounds for the pBp resins and for the explanation of the amplification of the optical activity of the {beta}(+)-pinene and {beta}(-)-pinene after their ring-opening polymerization to pB(+)p and pB(-)p. The pBp resins were studied also by FT-IR spectroscopy and by thermal analysis (TGA and DTG).

  8. Imperfect World of beta beta-decay Nuclear Data Sets

    Energy Technology Data Exchange (ETDEWEB)

    Pritychenko, B. [Brookhaven National Lab. (BNL), Upton, NY (United States). NNDC


    The precision of double-beta ββ-decay experimental half lives and their uncertainties is reanalyzed. The method of Benford's distributions has been applied to nuclear reaction, structure and decay data sets. First-digit distribution trend for ββ-decay T2v1/2 is consistent with large nuclear reaction and structure data sets and provides validation of experimental half-lives. A complementary analysis of the decay uncertainties indicates deficiencies due to small size of statistical samples, and incomplete collection of experimental information. Further experimental and theoretical efforts would lead toward more precise values of-decay half-lives and nuclear matrix elements.

  9. Beta-glucosidase I variants with improved properties

    Energy Technology Data Exchange (ETDEWEB)

    Bott, Richard R.; Kaper, Thijs; Kelemen, Bradley; Goedegebuur, Frits; Hommes, Ronaldus Wilhelmus; Kralj, Slavko; Kruithof, Paulien; Nikolaev, Igor; Van Der Kley, Wilhelmus Antonious Hendricus; Van Lieshout, Johannes Franciscus Thomas; Van Stigt Thans, Sander


    The present disclosure is generally directed to enzymes and in particular beta-glucosidase variants. Also described are nucleic acids encoding beta-glucosidase variants, compositions comprising beta-glucosidase variants, methods of using beta-glucosidase variants, and methods of identifying additional useful beta-glucosidase variants.

  10. Dosimetry of low-energy beta radiation

    Energy Technology Data Exchange (ETDEWEB)

    Borg, J.


    Useful techniques and procedures for determination of absorbed doses from exposure in a low-energy {beta} radiation field were studied and evaluated in this project. The four different techniques included were {beta} spectrometry, extrapolation chamber dosimetry, Monte Carlo (MC) calculations, and exoelectron dosimetry. As a typical low-energy {beta} radiation field a moderated spectrum from a {sup 14}C source (E{sub {beta}},{sub max} =156 keV) was chosen for the study. The measured response of a Si(Li) detector to photons (bremsstrahlung) showed fine agreement with the MC calculated photon response, whereas the difference between measured and MC calculated responses to electrons indicates an additional dead layer thickness of about 12 {mu}m in the Si(Li) detector. The depth-dose profiles measured with extrapolation chambers at two laboratories agreed very well, and it was confirmed that the fitting procedure previously reported for {sup 147}Pm depth-dose profiles is also suitable for {beta} radiation from {sup 14}C. An increasing difference between measured and MC calculated dose rates for increasing absorber thickness was found, which is explained by limitations of the EGS4 code for transport of very low-energy electrons (below 10-20 keV). Finally a study of the thermally stimulated exoelectron emission (TSEE) response of BeO thin film dosemeters to {beta} radiation for radiation fields with maximum {beta} energies ranging from 67 keV to 2.27 MeV is reported. For maximum {beta} energies below approximately 500 keV, a decrease in the response amounting to about 20% was observed. It is thus concluded that a {beta} dose higher than about 10 {mu}Gy can be measured with these dosemeters to within 0 to -20% independently of the {beta}energy for E{sub {beta}},{sub max} values down to 67 keV. (au) 12 tabs., 38 ills., 71 refs.

  11. Innate immune system and inflammation in Alzheimer's disease: from pathogenesis to treatment. (United States)

    Serpente, Maria; Bonsi, Rossana; Scarpini, Elio; Galimberti, Daniela


    Immune activation and inflammation, likely triggered by amyloid-beta (Aβ) deposition, play a remarkable role in the pathogenesis of Alzheimer's disease (AD), which is the most frequent cause of dementia in the elderly. The principal cellular elements of the brain innate immune system likely to be involved in such processes are microglia. In an attempt to search for new disease-modifying drugs, the immune system has been addressed, with the aim of removing deposition of Aβ or tau by developing vaccines and humanized monoclonal antibodies. The aim of this review is to summarize the current evidence regarding the role played by microglia and inflammatory molecules in the pathogenesis of AD. In addition, we will discuss the main active and passive immunotherapeutic approaches.

  12. Presenilin/γ-secretase and inflammation

    Directory of Open Access Journals (Sweden)

    Carlos A Saura


    Full Text Available Presenilins (PS are the catalytic components of γ-secretase, an aspartyl protease that regulates through proteolytic processing the function of multiple signaling proteins. Specially relevant is the γ-secretase-dependent cleavage of the β-amyloid precursor protein (APP since generates the β-amyloid (Aβ peptides that aggregate and accumulate in the brain of Alzheimer´s disease (AD patients. Abnormal processing and/or accumulation of Aβ disrupt synaptic and metabolic processes leading to neuron dysfunction and neurodegeneration. Studies in presenilin conditional knockout mice have revealed that presenilin-1 is essential for age-dependent Aβ accumulation and inflammation. By contrast, mutations in the presenilin genes reponsible for early onset familial AD cause rapid disease progression and accentuate clinical and pathological features including inflammation. In addition, a number of loss of function mutations in presenilin-1 have been recently associated to non-Alzheimer's dementias including frontotemporal dementia and dementia with Lewy bodies. In agreement, total loss of presenilin function in the brain results in striking neurodegeneration and inflammation, which includes activation of glial cells and induction of proinflammatory genes, besides altered inflammatory responses in the periphery. Interestingly, some non-steroidal anti-inflammatory drugs (NSAIDs that slow cognitive decline and reduce the risk of AD, decrease amyloidogenic Aβ42 levels by modulating allosterically PS/γ-secretase. In this review, I present current evidence supporting a role of presenilin/γ-secretase signaling on gliogenesis and gliosis in normal and pathological conditions. Understanding the cellular mechanisms regulated by presenilin/γ-secretase during chronic inflammatory processes may provide new approaches for the development of effective therapeutic strategies for AD.

  13. The role of adipokines in chronic inflammation

    Directory of Open Access Journals (Sweden)

    Mancuso P


    Full Text Available Peter Mancuso Department of Nutritional Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA Abstract: Adipose tissue has traditionally been defined as connective tissue that stores excess calories in the form of triacylglycerol. However, the physiologic functions attributed to adipose tissue are expanding, and it is now well established that adipose tissue is an endocrine gland. Among the endocrine factors elaborated by adipose tissue are the adipokines; hormones, similar in structure to cytokines, produced by adipose tissue in response to changes in adipocyte triacylglycerol storage and local and systemic inflammation. They inform the host regarding long-term energy storage and have a profound influence on reproductive function, blood pressure regulation, energy homeostasis, the immune response, and many other physiologic processes. The adipokines possess pro- and anti-inflammatory properties and play a critical role in integrating systemic metabolism with immune function. In calorie restriction and starvation, proinflammatory adipokines decline and anti-inflammatory adipokines increase, which informs the host of energy deficits and contributes to the suppression of immune function. In individuals with normal metabolic status, there is a balance of pro- and anti-inflammatory adipokines. This balance shifts to favor proinflammatory mediators as adipose tissue expands during the development of obesity. As a consequence, the proinflammatory status of adipose tissue contributes to a chronic low-grade state of inflammation and metabolic disorders associated with obesity. These disturbances are associated with an increased risk of metabolic disease, type 2 diabetes, cardiovascular disease, and many other pathological conditions. This review focuses on the impact of energy homeostasis on the adipokines in immune function. Keywords: calorie restriction, obesity, adipose tissue, type 2 diabetes, macrophage, infection, chronic

  14. Peroxisomes,oxidative stress,and inflammation

    Institute of Scientific and Technical Information of China (English)

    Stanley; R; Terlecky; Laura; J; Terlecky; Courtney; R; Giordano


    Peroxisomes are intracellular organelles mediating a wide variety of biosynthetic and biodegradative reactions.Included among these are the metabolism of hydrogen peroxide and other reactive species,molecules whose levels help define the oxidative state of cells.Loss of oxidative equilibrium in cells of tissues and organs potentiates inflammatory responses which can ultimately trigger human disease.The goal of this article is to review evidence for connections between peroxisome function,oxidative stress,and inflammation in the context of human health and degenerative disease.Dysregulated points in this nexus are identified and potential remedial approaches are presented.

  15. Unconventional Pathways of Secretion Contribute to Inflammation (United States)

    Daniels, Michael J. D.; Brough, David


    In the conventional pathway of protein secretion, leader sequence-containing proteins leave the cell following processing through the endoplasmic reticulum (ER) and Golgi body. However, leaderless proteins also enter the extracellular space through mechanisms collectively known as unconventional secretion. Unconventionally secreted proteins often have vital roles in cell and organism function such as inflammation. Amongst the best-studied inflammatory unconventionally secreted proteins are interleukin (IL)-1β, IL-1α, IL-33 and high-mobility group box 1 (HMGB1). In this review we discuss the current understanding of the unconventional secretion of these proteins and highlight future areas of research such as the role of nuclear localisation. PMID:28067797

  16. Mechanisms regulating skin immunity and inflammation. (United States)

    Pasparakis, Manolis; Haase, Ingo; Nestle, Frank O


    Immune responses in the skin are important for host defence against pathogenic microorganisms. However, dysregulated immune reactions can cause chronic inflammatory skin diseases. Extensive crosstalk between the different cellular and microbial components of the skin regulates local immune responses to ensure efficient host defence, to maintain and restore homeostasis, and to prevent chronic disease. In this Review, we discuss recent findings that highlight the complex regulatory networks that control skin immunity, and we provide new paradigms for the mechanisms that regulate skin immune responses in host defence and in chronic inflammation.

  17. Signaling from beta1- and beta2-adrenergic receptors is defined by differential interactions with PDE4

    DEFF Research Database (Denmark)

    Richter, Wito; Day, Peter; Agrawal, Rani


    Beta1- and beta2-adrenergic receptors (betaARs) are highly homologous, yet they play clearly distinct roles in cardiac physiology and pathology. Myocyte contraction, for instance, is readily stimulated by beta1AR but not beta2AR signaling, and chronic stimulation of the two receptors has opposing...

  18. Localization of thymosin beta-4 in tumors

    DEFF Research Database (Denmark)

    Larsson, L. -I.; Holck, Susanne


    Overexpression of thymosin beta-4 has been linked to malignant progression but the localization of this polypeptide within tumors is incompletely known. We therefore examined breast cancers for thymosin beta-4 using immunofluorescence. Reactive cells were identified with monoclonal cell marker...... in the tumor microenvironment may modulate tumor behavior....

  19. Nebivolol : third-generation beta-blockade

    NARCIS (Netherlands)

    de Boer, Rudolf A.; Voors, Adriaan A.; van Veldhuisen, Dirk J.


    Nebivolol is a third generation beta-blocker. It is highly selective for the beta 1-adrenoceptor, and has additional nitric oxide-mediated vasodilating and antioxidant properties, along with a favourable metabolic profile. Nebivolol is well tolerated by patients with hypertension and heart failure.

  20. The beta subunit of casein kinase II

    DEFF Research Database (Denmark)

    Boldyreff, B; Piontek, K; Schmidt-Spaniol, I;


    cDNAs encoding the beta subunit of pig and mouse CKII were isolated. The porcine cDNA was expressed as a fusion protein in Escherichia coli and used for the production of anti-CKII-beta subunit specific antibodies....

  1. Venus: Geology of Beta Regio rift system (United States)

    Nikishin, A. M.; Borozdin, V. K.; Bobina, N. N.


    Beta Regio is characterized by the existence of rift structures. We compiled new geologic maps of Beta Regio according to Magellan data. There are many large uplifted tesserae on beta upland. These tesserae are partly buried by younger volcanic cover. We can conclude, using these observations, that Beta upland formed mainly due to lithospheric tectonic uplifting and was only partly constructed by volcanism. Theia Mons is the center of the Beta rift system. Many rift belts are distributed radially to Theia Mons. Typical widths of rifts are 40-160 km. Rift valleys are structurally represented by crustal grabens or half-grabens. There are symmetrical and asymmetrical rifts. Many rifts have shoulder uplifts up to 0.5-1 km high and 40-60 km wide. Preliminary analysis for rift valley structural cross sections lead to the conclusion that rifts originated due to 5-10 percent crustal extension. Many rifts traverse Beta upland and spread to the surrounding lowlands. We can assume because of these data that Beta rift system has an active-passive origin. It formed due to regional tectonic lithospheric extension. Rifting was accelerated by upper-mantle hot spot origination under the center of passive extension (under the Beta Regio).

  2. Beta-agonists and animal welfare (United States)

    The use of beta-agonists in animal feed is a high profile topic within the U.S. as consumers and activist groups continue to question its safety. The only beta-agonist currently available for use in swine is ractopamine hydrochloride (RAC). This is available as Paylean™ (Elanco Animal Health – FDA a...

  3. Shielding for beta-gamma radiation. (United States)

    Fletcher, J J


    The build-up factor, B, for lead was expressed as a polynominal cubic function of the relaxation length, mu x, and incorporated in a "general beta-gamma shielding equation." A computer program was written to determine shielding thickness for polyenergetic beta-gamma sources without resorting to the conventional "add-one-HVL" method.

  4. Induction of neutrophil gelatinase-associated lipocalin expression by co-stimulation with interleukin-17 and tumor necrosis factor-alpha is controlled by IkappaB-zeta but neither by C/EBP-beta nor C/EBP-delta

    DEFF Research Database (Denmark)

    Karlsen, Joachim R; Borregaard, Niels; Cowland, Jack B


    Neutrophil gelatinase-associated lipocalin (NGAL) is a siderophore-binding antimicrobial protein that is up-regulated in epithelial tissues during inflammation. We demonstrated previously that the gene encoding NGAL (LCN2) is strongly up-regulated by interleukin (IL)-1beta in an NF-kappaB-depende...

  5. Precision measurements in 20F beta decay (United States)

    Hughes, Maximilian; Naviliat-Cuncic, Oscar; Voytas, Paul; George, Elizabeth; Paulauskas, Stan; Huyan, Xueying


    Precision measurements of the shape of the beta particle energy spectrum provide a sensitive window to search for new interactions beyond the standard model. The decay of 20F offers an attractive system due to the simple decay scheme for a coincidence measurement. A beam of 20F ions, produced at the National Superconducting Cyclotron Laboratory, was implanted into a beta-detector. A gamma-ray detection system surrounded the beta detector to detect the beta-delayed gammas in coincidence to reduce the background. Preliminary analysis of these data focus on the half-life of 20F due to the statistical inconsistency of previous work. Monte Carlo simulations are ongoing to analyze the shape of the beta energy spectrum. Results of the analysis of the half-life will be presented. Supported by National Science Foundation Grant PHY-1102511.

  6. Ranking Beta Sheet Topologies of Proteins

    DEFF Research Database (Denmark)

    Fonseca, Rasmus; Helles, Glennie; Winter, Pawel


    One of the challenges of protein structure prediction is to identify long-range interactions between amino acids.  To reliably predict such interactions, we enumerate, score and rank all beta-topologies (partitions of beta-strands into sheets, orderings of strands within sheets and orientations...... of paired strands) of a given protein.  We show that the beta-topology corresponding to the native structure is, with high probability, among the top-ranked. Since full enumeration is very time-consuming, we also suggest a method to deal with proteins with many beta-strands. The results reported...... in this paper are highly relevant for ab initio protein structure prediction methods based on decoy generation. The top-ranked beta-topologies can be used to find initial conformations from which conformational searches can be started. They can also be used to filter decoys by removing those with poorly...

  7. The search for neutrinoless double beta decay

    CERN Document Server

    Gomez-Cadenas, J J; Mezzetto, M; Monrabal, F; Sorel, M


    In the last few years the search for neutrinoless double beta decay has evolved from being almost a marginal activity in neutrino physics to one of the highest priorities for understanding neutrinos and the origin of mass. There are two main reasons for this paradigm shift: the discovery of neutrino oscillations, which clearly established the existence of massive neutrinos; and the existence of an unconfirmed, but not refuted, claim of evidence for neutrinoless double decay in 76Ge. As a consequence, a new generation of experiments, employing different detection techniques and {\\beta}{\\beta} isotopes, is being actively promoted by experimental groups across the world. In addition, nuclear theorists are making remarkable progress in the calculation of the neutrinoless double beta decay nuclear matrix elements, thus eliminating a substantial part of the theoretical uncertainties affecting the particle physics interpretation of this process. In this report, we review the main aspects of the double beta decay pro...

  8. Experimental beta-alaninuria induced by (aminooxyacetate.

    Directory of Open Access Journals (Sweden)

    Kurozumi Y


    Full Text Available Experimental beta-alaninuria was induced in rats by injection of (aminooxyacetate (AOA, a potent inhibitor of aminotransferases, in order to elucidate the pathogenesis of hyper-beta-alaninemia. A 27-fold increase of beta-alanine (BALA excretion was induced by subcutaneous injection of 1 5 mg of AOA per kg of body weight. A 13-fold and a 9-fold increase of beta-aminoisobutyric acid (BAIBA and gamma-aminobutyric acid (GABA, respectively, were also induced simultaneously by the AOA injection. Identification of BALA and BAIBA isolated from the rat urine was performed by chromatographic and mass spectrometric analyses. The effects of AOA injection on the tissue levels of these amino acids were also studied. Contents of BALA in the liver and kidney and GABA in the brain increased significantly in response to AOA injection. The present study indicates that BALA transaminase is involved in hyper-beta-alaninemia.

  9. Upregulation of B7 molecules (CD80 and CD86) and exacerbated eosinophilic pulmonary inflammatory response in mice lacking the IFN-beta gene

    DEFF Research Database (Denmark)

    Matheu, Victor; Treschow, Alexandra; Navikas, Vaidrius


    )-sensitized and OVA-challenged mice. RESULTS: OVA-sensitized and OVA-challenged mice with lack of the IFNB gene had more severe pulmonary inflammation with increased lung local response, including IL-4, IL-5, IL-13, IgE, eosinophilia, and goblet cells, than their litter mates (IFN-beta+/-), whereas no differences...... were observed in regard to local levels of IFN-gamma. Moreover, systemic response with IgE production is also enhanced. Lack of IFN-beta also results in significantly higher antigen-specific T cells, with higher levels of IL-4, IL-5, and IL-13, whereas no significant differences in IFN-gamma response...

  10. Complement activation by the amyloid proteins A beta peptide and beta 2-microglobulin

    DEFF Research Database (Denmark)

    Nybo, Mads; Nielsen, E H; Svehag, S E


    Complement activation (CA) has been reported to play a role in the pathogenesis of Alzheimer's disease (AD). To investigate whether CA may contribute to amyloidogenesis in general, the CA potential of different amyloid fibril proteins was tested. CA induced by A beta preparations containing soluble...... protein, protofilaments and some fibrils or only fibrils in a solid phase system (ELISA) was modest with a slow kinetics compared to the positive delta IgG control. Soluble A beta induced no detectable CA in a liquid phase system (complement consumption assay) while fibrillar A beta caused CA at 200 mg....../ml and higher concentrations. Soluble beta 2-microglobulin (beta 2M) purified from peritoneal dialysates was found to be as potent a complement activator as A beta in both solid and liquid phase systems while beta 2M purified from urine exhibited lower activity, a difference which may be explained...

  11. Clusters of conserved beta cell marker genes for assessment of beta cell phenotype

    DEFF Research Database (Denmark)

    Martens, Geert A; Jiang, Lei; Hellemans, Karine H;


    The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those...... of a large panel of other tissue and cell types, and transcripts with beta cell-abundant and -selective expression were identified. Iteration of this analysis in mouse, rat and human tissues generated a panel of conserved beta cell biomarkers. This panel was then used to compare isolated versus laser capture...... microdissected beta cells, monitor adaptations of the beta cell phenotype to fasting, and retrieve possible conserved transcriptional regulators....

  12. Painlev\\'e representation of Tracy-Widom$_\\beta$ distribution for $\\beta = 6$

    CERN Document Server

    Rumanov, Igor


    In \\cite{betaFP1}, we found explicit Lax pairs for the soft edge of beta ensembles with even integer values of $\\beta$. Using this general result, the case $\\beta=6$ is further considered here. This is the smallest even $\\beta$, when the corresponding Lax pair and its relation to Painlev\\'e II (PII) have not been known before, unlike cases $\\beta=2$ and $4$. It turns out that again everything can be expressed in terms of the Hastings-McLeod solution of PII. In particular, a second order nonlinear ODE for the logarithmic derivative of Tracy-Widom distribution for $\\beta=6$ involving the PII function in the coefficients, is found, which allows one to compute asymptotics for the distribution function. The ODE is a consequence of a linear system of three ODEs for which the local Painlev\\'e analysis yields series solutions with exponents in the set $4/3$, $1/3$ and $-2/3$.

  13. MicroRNA-155 Deficiency Attenuates Liver Steatosis and Fibrosis without Reducing Inflammation in a Mouse Model of Steatohepatitis.

    Directory of Open Access Journals (Sweden)

    Timea Csak

    Full Text Available MicroRNAs (miRs regulate hepatic steatosis, inflammation and fibrosis. Fibrosis is the consequence of chronic tissue damage and inflammation. We hypothesized that deficiency of miR-155, a master regulator of inflammation, attenuates steatohepatitis and fibrosis.Wild type (WT and miR-155-deficient (KO mice were fed methionine-choline-deficient (MCD or -supplemented (MCS control diet for 5 weeks. Liver injury, inflammation, steatosis and fibrosis were assessed.MCD diet resulted in steatohepatitis and increased miR-155 expression in total liver, hepatocytes and Kupffer cells. Steatosis and expression of genes involved in fatty acid metabolism were attenuated in miR-155 KO mice after MCD feeding. In contrast, miR-155 deficiency failed to attenuate inflammatory cell infiltration, nuclear factor κ beta (NF-κB activation and enhanced the expression of the pro-inflammatory cytokines tumor necrosis factor alpha (TNFα and monocyte chemoattractant protein-1 (MCP1 in MCD diet-fed mice. We found a significant attenuation of apoptosis (cleaved caspase-3 and reduction in collagen and α smooth muscle actin (αSMA levels in miR-155 KO mice compared to WTs on MCD diet. In addition, we found attenuation of platelet derived growth factor (PDGF, a pro-fibrotic cytokine; SMAD family member 3 (Smad3, a protein involved in transforming growth factor-β (TGFβ signal transduction and vimentin, a mesenchymal marker and indirect indicator of epithelial-to-mesenchymal transition (EMT in miR-155 KO mice. Nuclear binding of CCAAT enhancer binding protein β (C/EBPβ a miR-155 target involved in EMT was significantly increased in miR-155 KO compared to WT mice.Our novel data demonstrate that miR-155 deficiency can reduce steatosis and fibrosis without decreasing inflammation in steatohepatitis.

  14. Inflammation and coagulation in urticaria and angioedema. (United States)

    Cugno, Massimo; Asero, Riccardo; Tedeschi, Alberto; Lazzari, Riccardo; Marzano, Angelo V


    Urticaria is a skin disease characterised by short-lived surface swellings of the dermis (wheals) frequently accompanied by itching. It is classified as acute or chronic depending on whether the wheal recurrence occurs for less or more than six weeks. Acute urticaria is often due to a hypersensitivity reaction, whereas about 50% of the cases of chronic urticaria are regarded as autoimmune. Urticaria may occur alone or in association with a deeper swelling (angioedema) involving the subcutaneous and/or submucosal tissues, and last from hours to a few days. Angioedema can also develop alone, and may be idiopathic or be caused by allergies, inherited or acquired deficiencies of C1-inhibitor protein, or adverse drug reactions. An interplay between inflammation and coagulation has been proposed as a pathomechanism in urticaria and urticaria-associated angioedema (in which histamine and thrombin are involved), as well as in angioedema due to C1-inhibitor deficiency, which involves various biological systems. An increase in the plasma markers of thrombin generation, fibrinolysis and inflammation has been documented during exacerbations of urticaria and angioedema, with the marker levels decreasing to normal during remission. However, the hypercoagulable state in chronic urticaria and angioedema has not been reported to be associated with any increased risk of thrombosis, although there have been a number of reports of cardiovascular events occurring during episodes of acute urticaria. These observations have provided the rationale for the clinical evaluation of anticoagulant and antifibrinolytic drugs, the efficacy of which has sometimes been demonstrated.

  15. Acupuncture to Reduce HIV-Associated Inflammation

    Directory of Open Access Journals (Sweden)

    Barbara Swanson


    Full Text Available Background. HIV infection is associated with systemic inflammation that can increase risk for cardiovascular events. Acupuncture has been shown to have immunomodulatory effects and to improve symptoms in persons with inflammatory conditions. Objective. To test the anti-inflammatory effects of an acupuncture protocol that targets the cholinergic anti-inflammatory pathway (CAIP, a neural mechanism whose activation has been shown to reduce the release of proinflammatory cytokines, in persons with HIV-associated inflammation. Design, Setting, Participants, and Interventions. Double-blind, placebo-controlled clinical trial conducted in an outpatient clinic located in a medically underserved urban neighborhood. Twenty-five clinically-stable HIV-infected persons on antiretroviral therapy were randomized to receive once weekly CAIP-based acupuncture or sham acupuncture. Main Outcome Measures. Outcomes included plasma concentrations of high sensitivity C-reactive protein and D-dimer and fasting lipids. Results. Twenty-five participants completed the protocol (treatment group n=12, control group n=13. No adverse events related to the acupuncture protocol were observed. Compared to baseline values, the two groups did not significantly differ in any outcome measures at the end of the acupuncture protocol. Conclusions. CAIP-based acupuncture did not favorably modulate inflammatory or lipid parameters. Additional studies are warranted of CAIP-based protocols of different frequencies/durations.

  16. Inflammation and Hypertension: Are There Regional Differences?

    Directory of Open Access Journals (Sweden)

    Patricio López-Jaramillo


    Full Text Available Hypertension is a chronic disease with global prevalence and incidence rapidly increasing in low and medium income countries. The surveillance of cardiovascular risk factors, such as hypertension, is a global health priority in order to estimate the burden and trends, to appropriately direct resources, and to measure the effect of interventions. We propose here that the adoption of Western lifestyles in low and middle incomes countries has dramatically increased the prevalence of abdominal obesity, which is the main source of proinflammatory cytokines, and that the vascular systemic inflammation produced by adipose tissue contributes to the development of hypertension. The concentration of proinflammatory cytokines is higher in the Latin American population than that reported in developed countries, suggesting a higher susceptibility to develop systemic low-degree inflammation at a given level of abdominal obesity. These particularities are important to be considered when planning resources for health care programs. Moreover, studying these singularities may provide a better understanding of the causes of the burden of cardiovascular risk factors and the remarkable variability in the prevalence of these medical conditions within and between countries.

  17. The receptor RAGE: Bridging inflammation and cancer

    Directory of Open Access Journals (Sweden)

    Hess Jochen


    Full Text Available Abstract The receptor for advanced glycation end products (RAGE is a single transmembrane receptor of the immunoglobulin superfamily that is mainly expressed on immune cells, neurons, activated endothelial and vascular smooth muscle cells, bone forming cells, and a variety of cancer cells. RAGE is a multifunctional receptor that binds a broad repertoire of ligands and mediates responses to cell damage and stress conditions. It activates programs responsible for acute and chronic inflammation, and is implicated in a number of pathological diseases, including diabetic complications, stroke, atheriosclerosis, arthritis, and neurodegenerative disorders. The availability of Rage knockout mice has not only advanced our knowledge on signalling pathways within these pathophysiological conditions, but also on the functional importance of the receptor in processes of cancer. Here, we will summarize molecular mechanisms through which RAGE signalling contributes to the establishment of a pro-tumourigenic microenvironment. Moreover, we will review recent findings that provide genetic evidence for an important role of RAGE in bridging inflammation and cancer.

  18. Heme on innate immunity and inflammation

    Directory of Open Access Journals (Sweden)

    Fabianno Ferreira Dutra


    Full Text Available Heme is an essential molecule expressed ubiquitously all through our tissues. Heme plays major functions in cellular physiology and metabolism as the prostetic group of diverse proteins. Once released from cells and from hemeproteins free heme causes oxidative damage and inflammation, thus acting as a prototypic damage-associated molecular pattern. In this context, free heme is a critical component of the pathological process of sterile and infectious hemolytic conditions including malaria, hemolytic anemias, ischemia-reperfusion and hemorrhage. The plasma scavanger proteins hemopexin and albumin reduce heme toxicity and are responsible for transporting free heme to intracellular compartments where it is catabolized by heme-oxygenase enzymes. Upon hemolysis or severe cellular damage the serum capacity to scavange heme may saturate and increase free heme to sufficient amounts to cause tissue damage in various organs. The mechanism by which heme causes reactive oxygen generation, activation of cells of the innate immune system and cell death are not fully understood. Although heme can directly promote lipid peroxidation by its iron atom, heme can also induce ROS generation and production of inflammatory mediators through the activation of selective signaling pathways. Heme activates innate immune cells such as macrophages and neutrophils through activation of innate immune receptors. The importance of these events has been demonstrated in infectious and non-infectious diseases models. In this review we will discuss the mechanisms behind heme-induced citotoxicity and inflammation and the consequences of these events on different tissues and diseases.

  19. Purinergic Receptors in Thrombosis and Inflammation. (United States)

    Hechler, Béatrice; Gachet, Christian


    Under various pathological conditions, including thrombosis and inflammation, extracellular nucleotide levels may increase because of both active release and passive leakage from damaged or dying cells. Once in the extracellular compartment, nucleotides interact with plasma membrane receptors belonging to the P2 purinergic family, which are expressed by virtually all circulating blood cells and in most blood vessels. In this review, we focus on the specific role of the 3 platelet P2 receptors P2Y1, P2Y12, and P2X1 in hemostasis and arterial thrombosis. Beyond platelets, these 3 receptors, along with the P2Y2, P2Y6, and P2X7 receptors, constitute the main P2 receptors mediating the proinflammatory effects of nucleotides, which play important roles in various functions of circulating blood cells and cells of the vessel wall. Each of these P2 receptor subtypes specifically contributes to chronic or acute vascular inflammation and related diseases, such as atherosclerosis, restenosis, endotoxemia, and sepsis. The potential for therapeutic targeting of these P2 receptor subtypes is also discussed.

  20. Curbing Inflammation in the Ischemic Heart Disease

    Directory of Open Access Journals (Sweden)

    Paulo Roberto B. Evora


    Full Text Available A modern concept considers acute coronary syndrome as an autoinflammatory disorder. From the onset to the healing stage, an endless inflammation has been presented with complex, multiple cross-talk mechanisms at the molecular, cellular, and organ levels. Inflammatory response following acute myocardial infarction has been well documented since the 1940s and 1950s, including increased erythrocyte sedimentation rate, the C-reactive protein analysis, and the determination of serum complement. It is surprising to note, based on a wide literature overview including the following 30 years (decades of 1960, 1970, and 1980, that the inflammatory acute myocardium infarction lost its focus, virtually disappearing from the literature reports. The reversal of this historical process occurs in the 1990s with the explosion of studies involving cytokines. Considering the importance of inflammation in the pathophysiology of ischemic heart disease, the aim of this paper is to present a conceptual overview in order to explore the possibility of curbing this inflammatory process.

  1. The role of adipokines in chronic inflammation. (United States)

    Mancuso, Peter


    Adipose tissue has traditionally been defined as connective tissue that stores excess calories in the form of triacylglycerol. However, the physiologic functions attributed to adipose tissue are expanding, and it is now well established that adipose tissue is an endocrine gland. Among the endocrine factors elaborated by adipose tissue are the adipokines; hormones, similar in structure to cytokines, produced by adipose tissue in response to changes in adipocyte triacylglycerol storage and local and systemic inflammation. They inform the host regarding long-term energy storage and have a profound influence on reproductive function, blood pressure regulation, energy homeostasis, the immune response, and many other physiologic processes. The adipokines possess pro- and anti-inflammatory properties and play a critical role in integrating systemic metabolism with immune function. In calorie restriction and starvation, proinflammatory adipokines decline and anti-inflammatory adipokines increase, which informs the host of energy deficits and contributes to the suppression of immune function. In individuals with normal metabolic status, there is a balance of pro- and anti-inflammatory adipokines. This balance shifts to favor proinflammatory mediators as adipose tissue expands during the development of obesity. As a consequence, the proinflammatory status of adipose tissue contributes to a chronic low-grade state of inflammation and metabolic disorders associated with obesity. These disturbances are associated with an increased risk of metabolic disease, type 2 diabetes, cardiovascular disease, and many other pathological conditions. This review focuses on the impact of energy homeostasis on the adipokines in immune function.

  2. Nutritionally Mediated Oxidative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Alexandra Muñoz


    Full Text Available There are many sources of nutritionally mediated oxidative stress that trigger inflammatory cascades along short and long time frames. These events are primarily mediated via NFκB. On the short-term scale postprandial inflammation is characterized by an increase in circulating levels of IL-6 and TNF-α and is mirrored on the long-term by proinflammatory gene expression changes in the adipocytes and peripheral blood mononuclear cells (PBMCs of obese individuals. Specifically the upregulation of CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CXCL2/MIP-2α, and CXCL3/MIP-2β is noted because these changes have been observed in both adipocytes and PBMC of obese humans. In comparing numerous human intervention studies it is clear that pro-inflammatory and anti-inflammatory consumption choices mediate gene expression in humans adipocytes and peripheral blood mononuclear cells. Arachidonic acid and saturated fatty acids (SFAs both demonstrate an ability to increase pro-inflammatory IL-8 along with numerous other inflammatory factors including IL-6, TNFα, IL-1β, and CXCL1 for arachidonic acid and IGB2 and CTSS for SFA. Antioxidant rich foods including olive oil, fruits, and vegetables all demonstrate an ability to lower levels of IL-6 in PBMCs. Thus, dietary choices play a complex role in the mediation of unavoidable oxidative stress and can serve to exacerbate or dampen the level of inflammation.

  3. Modulation of Macrophage Efferocytosis in Inflammation

    Directory of Open Access Journals (Sweden)

    Darlynn R Korns


    Full Text Available A critical function of macrophages within the inflammatory milieu is the removal of dying cells by a specialized phagocytic process called efferocytosis (to carry to the grave. Through specific receptor engagement and induction of downstream signaling, efferocytosing macrophages promote resolution of inflammation by i efficiently engulfing dying cells, thus avoiding cellular disruption and release of inflammatory contents, and ii producing anti-inflammatory mediators such as IL-10 and TGF-β that dampen pro-inflammatory responses. Evidence suggests that plasticity in macrophage programming, in response to changing environmental cues, modulates efferocytic capability. Essential to programming for enhanced efferocytosis is activation of the nuclear receptors PPARγ, PPARδ, LXR and possibly RXRα. Additionally, a number of signals in the inflammatory milieu, including those from dying cells themselves, can influence efferocytic efficacy either by acting as immediate inhibitors/enhancers or by altering macrophage programming for longer-term effects. Importantly, sustained inflammatory programming of macrophages can lead to defective apoptotic cell clearance and is associated with development of autoimmunity and other chronic inflammatory disorders. This review summarizes the current knowledge of the multiple factors that modulate macrophage efferocytic ability and highlights emerging therapeutic targets with significant potential for limiting chronic inflammation.

  4. Chemically induced mouse models of intestinal inflammation. (United States)

    Wirtz, Stefan; Neufert, Clemens; Weigmann, Benno; Neurath, Markus F


    Animal models of intestinal inflammation are indispensable for our understanding of the pathogenesis of Crohn disease and ulcerative colitis, the two major forms of inflammatory bowel disease in humans. Here, we provide protocols for establishing murine 2,4,6-trinitro benzene sulfonic acid (TNBS)-, oxazolone- and both acute and chronic dextran sodium sulfate (DSS) colitis, the most widely used chemically induced models of intestinal inflammation. In the former two models, colitis is induced by intrarectal administration of the covalently reactive reagents TNBS/oxazolone, which are believed to induce a T-cell-mediated response against hapten-modified autologous proteins/luminal antigens. In the DSS model, mice are subjected several days to drinking water supplemented with DSS, which seems to be directly toxic to colonic epithelial cells of the basal crypts. The procedures for the hapten models of colitis and acute DSS colitis can be accomplished in about 2 weeks but the protocol for chronic DSS colitis takes about 2 months.

  5. Does Inflammation Mediate the Association Between Obesity and Insulin Resistance? (United States)

    Adabimohazab, Razieh; Garfinkel, Amanda; Milam, Emily C; Frosch, Olivia; Mangone, Alexander; Convit, Antonio


    In adult obesity, low-grade systemic inflammation is considered an important step in the pathogenesis of insulin resistance (IR). The association between obesity and inflammation is less well established in adolescents. Here, we ascertain the importance of inflammation in IR among obese adolescents by utilizing either random forest (RF) classification or mediation analysis approaches. The inflammation balance score, composed of eight pro- and anti-inflammatory makers, as well as most of the individual inflammatory markers differed significantly between lean and overweight/obese. In contrast, adiponectin was the only individual marker selected as a predictor of IR by RF, and the balance score only revealed a medium-to-low importance score. Neither adiponectin nor the inflammation balance score was found to mediate the relationship between obesity and IR. These findings do not support the premise that low-grade systemic inflammation is a key for the expression of IR in the human. Prospective longitudinal studies should confirm these findings.

  6. Stromal cells in chronic inflammation and tertiary lymphoid organ formation. (United States)

    Buckley, Christopher D; Barone, Francesca; Nayar, Saba; Bénézech, Cecile; Caamaño, Jorge


    Inflammation is an unstable state. It either resolves or persists. Why inflammation persists and the factors that define tissue tropism remain obscure. Increasing evidence suggests that tissue-resident stromal cells not only provide positional memory but also actively regulate the differential accumulation of inflammatory cells within inflamed tissues. Furthermore, at many sites of chronic inflammation, structures that mimic secondary lymphoid tissues are observed, suggesting that chronic inflammation and lymphoid tissue formation share common activation programs. Similarly, blood and lymphatic endothelial cells contribute to tissue homeostasis and disease persistence in chronic inflammation. This review highlights our increasing understanding of the role of stromal cells in inflammation and summarizes the novel immunological role that stromal cells exert in the persistence of inflammatory diseases.

  7. Expression of TGF-beta1, TGF-beta2, TGF-beta3 and the receptors TGF-betaRI and TGF-betaRII in placentomes of artificially inseminated and nuclear transfer derived bovine pregnancies. (United States)

    Ravelich, S R; Shelling, A N; Wells, D N; Peterson, A J; Lee, R S F; Ramachandran, A; Keelan, J A


    Bovine nuclear transfer pregnancies are characterized by a high incidence of placental abnormalities, notably, increased placentome size and deficiencies in trophoblast cell function and establishment of placental vasculature. Alterations in gene expression during placental growth and development may contribute to the appearance of large placentomes in pregnancies derived from nuclear transfer. The placenta synthesizes a number of cytokines and growth factors, including the transforming growth factor-betas (TGF-betas) that are involved in the establishment, maintenance and/or regulation of pregnancy. All forms of TGF-beta and their receptors are present at the fetal-maternal interface of the bovine placentome, where they are thought to play an important role in regulating growth, differentiation, and function of the placenta. Using real-time RT-PCR, we have examined the expression of TGF-beta1, TGF-beta2, TGF-beta3 and the receptors TGF-betaRI and TGF-betaRII in placentomes of artificially inseminated (AI) and nuclear transfer (NT)-derived bovine pregnancies at days 50, 100 and 150 of gestation. TGF-beta1, TGF-beta2 and TGF-beta3 mRNA expression increased by 2.0-2.8-fold, while TGF-betaRI and TGF-betaRII mRNA expression decreased by 1.7-2.0-fold in NT placentomes compared to AI controls at all gestational ages examined. These findings indicate that NT placentomes may be resistant to the growth suppressive effects of TGF-betas and could contribute to the placental proliferative abnormalities observed in NT-derived placentas. Alternatively, deficiencies in placentation may provide a mechanism whereby TGF-betas are dysregulated in NT pregnancies.

  8. Prevention of the β-amyloid peptide-induced inflammatory process by inhibition of double-stranded RNA-dependent protein kinase in primary murine mixed co-cultures

    Directory of Open Access Journals (Sweden)

    Terro F


    Full Text Available Abstract Background Inflammation may be involved in the pathogenesis of Alzheimer's disease (AD. There has been little success with anti-inflammatory drugs in AD, while the promise of anti-inflammatory treatment is more evident in experimental models. A new anti-inflammatory strategy requires a better understanding of molecular mechanisms. Among the plethora of signaling pathways activated by β-amyloid (Aβ peptides, the nuclear factor-kappa B (NF-κB pathway could be an interesting target. In virus-infected cells, double-stranded RNA-dependent protein kinase (PKR controls the NF-κB signaling pathway. It is well-known that PKR is activated in AD. This led us to study the effect of a specific inhibitor of PKR on the Aβ42-induced inflammatory response in primary mixed murine co-cultures, allowing interactions between neurons, astrocytes and microglia. Methods Primary mixed murine co-cultures were prepared in three steps: a primary culture of astrocytes and microglia for 14 days, then a primary culture of neurons and astrocytes which were cultured with microglia purified from the first culture. Before exposure to Aβ neurotoxicity (72 h, co-cultures were treated with compound C16, a specific inhibitor of PKR. Levels of tumor necrosis factor-α (TNFα, interleukin (IL-1β, and IL-6 were assessed by ELISA. Levels of PT451-PKR and activation of IκB, NF-κB and caspase-3 were assessed by western blotting. Apoptosis was also followed using annexin V-FITC immunostaining kit. Subcellular distribution of PT451-PKR was assessed by confocal immunofluorescence and morphological structure of cells by scanning electron microscopy. Data were analysed using one-way ANOVA followed by a Newman-Keuls' post hoc test Results In these co-cultures, PKR inhibition prevented Aβ42-induced activation of IκB and NF-κB, strongly decreased production and release of tumor necrosis factor (TNFα and interleukin (IL-1β, and limited apoptosis. Conclusion In spite of the

  9. Influence of calcitriol treatment on nutritional status, inflammation and oxidative stress of patients undergoing maintenance hemodialysis

    Institute of Scientific and Technical Information of China (English)

    Lin-Fang Zhang; Hong-Li Yan; Xin Chen


    Objective:To analyze influences of calcitriol treatment on nutritional status, inflammation and oxidative stress of patients undergoing maintenance hemodialysis.Methods:A total of 132 patients undergoing maintenance hemodialysis in our hospital were enrolled and randomly divided into observation group and control group. The observation group (n=66 cases) underwent calcitriol treatment, while control group (n=66 cases) underwent routine treatment. Nutrition status, micro inflammation and oxidative stress of the two groups were compared. Results: (1) After treatment, patients’ TSF, MAC, AMC, Hb levels of the observation group were higher than that of the control group (P<0.05); (2) After treatment, TGF-beta 1, CTGF levels of the observation group was significantly lower than that of the control group (P<0.05), but BMP-7 level was higher than control group (P<0.05). (3) Patients’ MPO, CAT, NO, TAC levels of the observation group were higher than control group (P<0.05).Conclusion:For patients with maintenance hemodialysis, Calcitriol can optimize patients' nutritional status, reduce systemic inflammatory response, enhance antioxidant capacity.

  10. Inhibition of chronic skin inflammation by topical anti-inflammatory flavonoid preparation, Ato Formula. (United States)

    Lim, Hyun; Son, Kun Ho; Chang, Hyeun Wook; Kang, Sam Sik; Kim, Hyun Pyo


    Flavonoids are known as natural anti-inflammatory agents. In this investigation, an anti-inflammatory potential of new topical preparation (SK Ato Formula) containing flavonoid mixtures from Scutellaria baicalensis Georgi roots and Ginkgo biloba L. leaves with an extract of Gentiana scabra Bunge roots was evaluated in an animal model of chronic skin inflammation. Multiple 12-O-tetradecanoylphorbol-13-acetate treatments for 7 consecutive days on ICR mouse ear provoked a chronic type of skin inflammation: dermal edema, epidermal hyperplasia and infiltration of inflammatory cells. When topically applied in this model, this new formulation (5-20 microL/ear/treatment) reduced these responses. Furthermore, it inhibited prostaglandin E2 generation (17.1-33.3%) and suppressed the expression of proinflammatory genes, cyclooxygenase-2 and interleulin-1beta in the skin lesion. Although the potency of inhibition was lower than that of prednisolone, all these results suggest that Ato Formula may be beneficial for treating chronic skin inflammatory disorders such as atopic dermatitis.

  11. Inhibition of airway inflammation and remodeling by sitagliptin in murine chronic asthma. (United States)

    Nader, Manar A


    In this study the role of sitagliptin, dipeptidyl peptidase inhibitor, DPP-4, and dexamethasone in ameliorating inflammation and remodeling of chronic asthma in a mouse model were investigated. Mice sensitized to ovalbumin were chronically challenged with aerosolized antigen for 3days a week continued for 8weeks. During this period animals were treated with sitagliptin or dexamethasone daily. Assessment of inflammatory cell, oxidative markers, total nitrate/nitrite (NOx), interleukin (IL)-13, transforming growth factor-beta1 (TGF-β1) in bronchoalveolar lavage (BAL) and/or lung tissue were done. Also histopathological and immuno-histochemical analysis for lung was carried out. Compared with vehicle alone, treatment with sitagliptin or dexamethasone significantly reduced accumulation of eosinophils and chronic inflammatory cells, subepithelial collagenization, and thickening of the airway epithelium. Also both drug reduced goblet cell hyperplasia, oxidative stress, TGF-β1, IL-13 and epithelial cytoplasmic immunoreactivity for nuclear factor κ-B (NFκ-B). These data indicate that sitagliptin like dexamethasone may play a beneficial role reducing airway inflammation and remodeling in chronic murine model of asthma.

  12. Decreased pulmonary inflammation after ethanol exposure and burn injury in intercellular adhesion molecule-1 knockout mice. (United States)

    Bird, Melanie D; Morgan, Michelle O; Ramirez, Luis; Yong, Sherri; Kovacs, Elizabeth J


    Clinical and laboratory evidence suggests that alcohol consumption dysregulates immune function. Burn patients who consume alcohol before their injuries demonstrate higher rates of morbidity and mortality, including acute respiratory distress syndrome, than patients without alcohol at the time of injury. Our laboratory observed higher levels of proinflammatory cytokines and leukocyte infiltration in the lungs of mice after ethanol exposure and burn injury than with either insult alone. To understand the mechanism of the increased pulmonary inflammatory response in mice treated with ethanol and burn injury, we investigated the role of intercellular adhesion molecule (ICAM)-1. Wild-type and ICAM-1 knockout (KO) mice were treated with vehicle or ethanol and subsequently given a sham or burn injury. Twenty-four hours postinjury, lungs were harvested and analyzed for indices of inflammation. Higher numbers of neutrophils were observed in the lungs of wild-type mice after burn and burn with ethanol treatment. This increase in pulmonary inflammatory cell accumulation was significantly lower in the KO mice. In addition, levels of KC, interleukin-1beta, and interleukin-6 in the lung were decreased in the ICAM-1 KO mice after ethanol exposure and burn injury. Interestingly, no differences were observed in serum or lung tissue content of soluble ICAM-1 24 hours postinjury. These data suggest that upregulation of adhesion molecules such as ICAM-1 on the vascular endothelium may play a critical role in the excessive inflammation seen after ethanol exposure and burn injury.

  13. Modulation of inflammation in the female reproductive tract


    Rajagopal, Shalini Priscilla


    Physiological inflammation occurs in the female reproductive tract, but pathological inflammation is implicated in reproductive pathologies such as preterm labour and endometrial cancer. Preterm labour (PTL, before 37 weeks of gestation) is the leading cause of preterm birth, neonatal mortality and perinatal morbidities. Endometrial cancer is the commonest gynaecological cancer, and its pathogenesis is characterised by chronic inflammation. The overall aims of this thesis were ...

  14. Unraveling the Complex Relationship Triad between Lipids, Obesity, and Inflammation


    Shahida A. Khan; Ashraf Ali; Khan, Sarah A.; Zahran, Solafa A.; Ghazi Damanhouri; Esam Azhar; Ishtiaq Qadri


    Obesity today stands at the intersection between inflammation and metabolic disorders causing an aberration of immune activity, and resulting in increased risk for diabetes, atherosclerosis, fatty liver, and pulmonary inflammation to name a few. Increases in mortality and morbidity in obesity related inflammation have initiated studies to explore different lipid mediated molecular pathways of attempting resolution that uncover newer therapeutic opportunities of anti-inflammatory components. M...

  15. Therapeutic Evaluation of Mesenchymal Stem Cells in Chronic Gut Inflammation (United States)


    1 AWARD NUMBER: W81XWH-11-1-0666 TITLE: Therapeutic Evaluation of Mesenchymal Stem Cells in Chronic Gut Inflammation PRINCIPAL INVESTIGATOR...4Aug2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-11-1-0666 Therapeutic Evaluation of Mesenchymal Stem Cells in Chronic Gut Inflammation a well-characterized mouse model of chronic colonic inflammation . Hypothesis: We propose that ex vivo-generated MSCs suppress chronic gut

  16. Roles of Inflammation, Oxidative Stress, and Vascular Dysfunction in Hypertension


    Quynh N. Dinh; DRUMMOND, Grant R.; Sobey, Christopher G.; Sophocles Chrissobolis


    Hypertension is a complex condition and is the most common cardiovascular risk factor, contributing to widespread morbidity and mortality. Approximately 90% of hypertension cases are classified as essential hypertension, where the precise cause is unknown. Hypertension is associated with inflammation; however, whether inflammation is a cause or effect of hypertension is not well understood. The purpose of this review is to describe evidence from human and animal studies that inflammation lead...

  17. Mu-opiate receptor and Beta-endorphin expression in nerve endings and keratinocytes in human skin. (United States)

    Bigliardi-Qi, M; Sumanovski, L T; Büchner, S; Rufli, T; Bigliardi, P L


    We have previously shown that human epidermal keratinocytes express a functionally active micro-opiate receptor, which adds a new dimension to the recently developed research in neuroimmunodermatology and neurogenic inflammation in skin diseases. Human keratinocytes specifically bind and also produce beta-endorphin, the endogenous micro-opiate receptor ligand. Using confocal imaging microscopy, we could now demonstrate that micro-opiate receptors are not only expressed in keratinocytes, but also on unmyelinated peripheral nerve fibers in the dermis and epidermis. Some of the peripheral nerve fibers also express the ligand beta-endorphin. The keratinocytes positive for beta-endorphin staining are clustered around the terminal ends of the unmyelinated nerve fibers. Therefore the opiate receptor system seems to be crucial in the direct communication between nerves and skin. The keratinocytes can influence the unmyelinated nerve fibers in the epidermis directly via secreting beta-endorphin. On the other hand, nerve fibers can also secrete beta-endorphin and influence the migration, differentiation and probably also the cytokine production pattern of keratinocytes.

  18. Systemic inflammation, endothelial dysfunction, and activation in clinically healthy children exposed to air pollutants. (United States)

    Calderón-Garcidueñas, L; Villarreal-Calderon, R; Valencia-Salazar, G; Henríquez-Roldán, C; Gutiérrez-Castrellón, P; Torres-Jardón, R; Osnaya-Brizuela, N; Romero, L; Torres-Jardón, R; Solt, A; Reed, W


    Mexico City children are chronically exposed to significant concentrations of air pollutants and exhibit chronic respiratory-tract inflammation. Epidemiological, controlled human exposures, laboratory-based animal models, and in vitro/in vivo studies have shown that inflammatory, endothelial dysfunction, and endothelial damage mediators are upregulated upon exposure to particulate matter (PM). Endothelial dysfunction is a critical event in cardiovascular disease. The focus of this work was to investigate whether exposure to ambient air pollution including PM(2.5) produces systemic inflammation and endothelial injury in healthy children. We measured markers of endothelial activation, and inflammatory mediators in 52 children age 8.6+/-0.1 yr, residents of Mexico City (n: 28) or of Polotitlán (n: 24), a city with low levels of pollutants. Mexico City children had significant increases in inflammatory mediators and vasoconstrictors, including tumor necrosis factor (TNF)alpha, prostaglandin (PG) E2, C-reactive protein, interleukin-1beta, and endothelin-1. There was a significant anti-inflammatory response, and a downregulation of vascular adhesion molecule-1, intercellular adhesion molecule-1 and -2, and selectins sE and sL. Results from linear regression found TNF a positively associated with 24- and 48-h cumulative levels of PM(2.5), while the 7-d PM(2.5) value was negatively associated with the numbers of white blood cells in peripheral blood in highly exposed children. Systemic subclinical inflammation, increased endothelin- 1, and significant downregulation of soluble adhesion molecules are seen in Mexico City children. Children chronically exposed to fine PM above the standard could be at risk of developing cardiovascular diseases, atherosclerosis, stroke, and other systemic effects later in life.

  19. Programmed cell death and its role in inflammation

    Institute of Scientific and Technical Information of China (English)

    Yong Yang; Ge-Ning Jiang; Peng Zhang; Jie Fan


    Cell death plays an important role in the regulation of inflammation and may be the result of inflammation. The maintenance of tissue homeostasis necessitates both the recognition and removal of invading microbial pathogens as well as the clearance of dying cells. In the past few decades, emerging knowledge on cell death and inflammation has enriched our molecular understanding of the signaling pathways that mediate various programs of cell death and multiple types of inflammatory responses. This review provides an overview of the major types of cell death related to inflammation. Modification of cell death pathways is likely to be a logical therapeutic target for inflammatory diseases.

  20. Muscle regeneration and inflammation in patients with facioscapulohumeral muscular dystrophy

    DEFF Research Database (Denmark)

    Hauerslev, S; Ørngreen, Mette Cathrine; Hertz, Jens Michael;


    The aim of this study was to investigate whether inflammation and regeneration are prominent in mildly affected muscles of patients with facioscapulohumeral muscular dystrophy type 1A (FSHD1A). Inflammation in muscle has been suggested by MRI studies in patients with FSHD1A.......The aim of this study was to investigate whether inflammation and regeneration are prominent in mildly affected muscles of patients with facioscapulohumeral muscular dystrophy type 1A (FSHD1A). Inflammation in muscle has been suggested by MRI studies in patients with FSHD1A....

  1. A defect in the inflammation-primed macrophage-activation cascade in osteopetrotic rats. (United States)

    Yamamoto, N; Lindsay, D D; Naraparaju, V R; Ireland, R A; Popoff, S N


    Macrophages were activated by administration of lysophosphatidylcholine (lyso-Pc) or dodecylglycerol (DDG) to wild-type rats but not in osteopetrotic (op) mutant rats. In vitro treatment of wild-type rat peritoneal cells with lyso-Pc or DDG efficiently activated macrophages whereas treatment of op mutant rat peritoneal cells with lyso-Pc or DDG did not activate macrophages. The inflammation-primed macrophage activation cascade in rats requires participation of B lymphocytes and vitamin D binding protein (DBP). Lyso-Pc-inducible beta-galactosidase of wild-type rat B lymphocytes can convert DBP to the macrophage-activating factor (MAF), whereas B lymphocytes of the op mutant rats were shown to be deficient in lyso-Pc-inducible beta-galactosidase. DBP is conserved among mammalian species. Treatment of human DBP (Gc1 protein) with commercial glycosidases yields an extremely high titrated MAF as assayed on mouse and rat macrophages. Because the enzymatically generated MAF (GcMAF) bypasses the role of lymphocytes in macrophage activation, the op mutant rat macrophages were efficiently activated by administration of a small quantity (100 pg/rat) of GcMAF. Likewise, in vitro treatment of op rat peritoneal cells with as little as 40 pg GcMAF/ml activated macrophages.

  2. Clusters of conserved beta cell marker genes for assessment of beta cell phenotype

    DEFF Research Database (Denmark)

    Martens, Geert A; Jiang, Lei; Hellemans, Karine H;


    The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those...... microdissected beta cells, monitor adaptations of the beta cell phenotype to fasting, and retrieve possible conserved transcriptional regulators.......The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those...... of a large panel of other tissue and cell types, and transcripts with beta cell-abundant and -selective expression were identified. Iteration of this analysis in mouse, rat and human tissues generated a panel of conserved beta cell biomarkers. This panel was then used to compare isolated versus laser capture...

  3. Ellagic acid promotes A{beta}42 fibrillization and inhibits A{beta}42-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Ying [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Yang, Shi-gao; Du, Xue-ting; Zhang, Xi; Sun, Xiao-xia; Zhao, Min [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Sun, Gui-yuan, E-mail: [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Liu, Rui-tian, E-mail: [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China)


    Smaller, soluble oligomers of {beta}-amyloid (A{beta}) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of A{beta} oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against A{beta} neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on A{beta}42 aggregation and neurotoxicity in vitro. EA promoted A{beta} fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited A{beta} aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in A{beta}42 samples co-incubated with EA in earlier phases of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic A{beta} aggregates to render them harmless, our MTT results showed that EA could significantly reduce A{beta}42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD.

  4. Evidence for Novel [beta]-Sheet Structures in Iowa Mutant [beta]-Amyloid Fibrils

    Energy Technology Data Exchange (ETDEWEB)

    Tycko, Robert; Sciarretta, Kimberly L.; Orgel, Joseph P.R.O.; Meredith, Stephen C.; (IIT); (NIH); (UC)


    Asp23-to-Asn mutation within the coding sequence of {beta}-amyloid, called the Iowa mutation, is associated with early onset, familial Alzheimer's disease and cerebral amyloid angiopathy, in which patients develop neuritic plaques and massive vascular deposition predominantly of the mutant peptide. We examined the mutant peptide, D23N-A{beta}40, by electron microscopy, X-ray diffraction, and solid-state NMR spectroscopy. D23N-A{beta}40 forms fibrils considerably faster than the wild-type peptide (k = 3.77 x 10{sup -3} min{sup -1} and 1.07 x 10{sup -4} min{sup -1} for D23N-A{beta}40 and the wild-type peptide WT-A{beta}40, respectively) and without a lag phase. Electron microscopy shows that D23N-A{beta}40 forms fibrils with multiple morphologies. X-ray fiber diffraction shows a cross-{beta} pattern, with a sharp reflection at 4.7 {angstrom} and a broad reflection at 9.4 {angstrom}, which is notably smaller than the value for WT-A{beta}40 fibrils (10.4 {angstrom}). Solid-state NMR measurements indicate molecular level polymorphism of the fibrils, with only a minority of D23N-A{beta}40 fibrils containing the in-register, parallel {beta}-sheet structure commonly found in WT-A{beta}40 fibrils and most other amyloid fibrils. Antiparallel {beta}-sheet structures in the majority of fibrils are indicated by measurements of intermolecular distances through 13C-13C and 15N-13C dipole-dipole couplings. An intriguing possibility exists that there is a relationship between the aberrant structure of D23N-A{beta}40 fibrils and the unusual vasculotropic clinical picture in these patients.

  5. Dosimetry of Low-Energy Beta Radiation

    DEFF Research Database (Denmark)

    Borg, Jette

    Useful techniques and procedures for derermination of absorbed doses from exposure in a low-energy beta radiation were studied and evaluated. The four techniques included were beta spectrometry, extrapolation chamber dosimetry, Monte Carlo (MC) calculations, and exoelectron dosimetry. As a typical...... low-energy beta radiation field a moderated spectrum from a carbon-14 source was used. The measured responce of a Si(Li) detector to photons (bremsstrahlung) showed fine agreemant with the MC calculated photon response, whereas the difference between measured and MC calculated response to electrons...

  6. Scintillating bolometers for Double Beta Decay search

    CERN Document Server

    Gironi, Luca


    In the field of Double Beta Decay (DBD) searches, the use of high resolution detectors in which background can be actively discriminated is very appealing. Scintillating bolometers containing a Double Beta Decay emitter can largely fulfill this very interesting possibility. In this paper we present the latest results obtained with CdWO4 and CaMoO4 crystals. Moreover we report, for the first time, a very interesting feature of CaMoO4 bolometers: the possibility to discriminate beta-gamma events from those induced by alpha particles thanks to different thermal pulse shape.

  7. Beta-2-mikroglobulin ved medicinske sygdomme

    DEFF Research Database (Denmark)

    Hansen, P B; Olsen, Niels Vidiendal


    -interstitial nephropathy, increased quantities of beta 2M are excreted in the urine. If the rate of glomerular filtration is reduced, serum-beta 2M is increased and this is also the case in persons with increased cell division despite normal renal function. Serum-beta 2M is, therefore, raised in numerous malignant...... must be presumed to be of value not only in the diagnosis of cerebral AIDS and other (latent) CNS infections but also to demonstrate complicating cerebral malignant lymphomata at an early stage....

  8. Silent ischemia and beta-blockade

    DEFF Research Database (Denmark)

    Egstrup, K


    and should also be directed at the other coronary artery risk factors of the patients. The effects of beta-blockers, which reduce the duration and frequency of silent ischemic episodes, is well described. The effect is most pronounced in the morning, when the frequency of ischemia is highest......, and the mechanism of action seems mainly mediated through a reduction in myocardial oxygen demand. beta-Blockers have shown effectiveness in both effort-induced angina and mixed angina, and increased anti-ischemic potency may be achieved by combination therapy with a calcium antagonist. Abrupt withdrawal of beta-blockers...

  9. Microglia, neuroinflammation, and beta-amyloid protein in Alzheimer's disease. (United States)

    Cai, Zhiyou; Hussain, M Delwar; Yan, Liang-Jun


    Compelling evidence from basic molecular biology has demonstrated the dual roles of microglia in the pathogenesis of Alzheimer's disease (AD). On one hand, microglia are involved in AD pathogenesis by releasing inflammatory mediators such as inflammatory cytokines, complement components, chemokines, and free radicals that are all known to contribute to beta-amyloid (Aβ) production and accumulation. On the other hand, microglia are also known to play a beneficial role in generating anti-Aβ antibodies and stimulating clearance of amyloid plaques. Aβ itself, an inducer of microglia activation and neuroinflammation, has been considered as an underlying and unifying factor in the development of AD. A vicious cycle of inflammation has been formed between Aβ accumulation, activated microglia, and microglial inflammatory mediators, which enhance Aβ deposition and neuroinflammation. Thus, inhibiting the vicious cycle seems to be a promising treatment to restrain further development of AD. With increasing research efforts on microglia in AD, intervention of microglia activation and neuroinflammation in AD may provide a potential target for AD therapy in spite of the provisional failure of nonsteroidal antiinflammatory drugs in clinical trials.

  10. Necrotizing granulomatous inflammation of the glans penis. (United States)

    Christodoulidou, Michelle; Bunker, Christopher B; Trevisan, Giorgia; Muneer, Asif


    We describe the case of a 73-year-old man who presented with a 10-month history of an ulcerating lesion on the glans penis. Initially this was thought to be an invasive squamous cell carcinoma but a biopsy showed histological features consistent with necrotizing granulomatous inflammation. Extensive serological, immunological and microbiological tests only showed a positive antinuclear and perinuclear antineutrophil cytoplasmic antibodies indicating a possible autoimmune aetiology but an underlying systemic cause was not identified. Treatment with oral corticosteroids limited the inflammatory process but due to the gross destruction of the glans penis, he still required a glansectomy and split-skin graft reconstruction from which he recovered well. Although this patient ultimately required surgery for this rare presentation, this case highlights the differential diagnosis of penile ulceration (that transcends neoplasia) and the importance of performing and interpreting penile biopsies before undertaking potentially mutilating definitive surgery.

  11. Maternal Obesity, Inflammation, and Developmental Programming

    Directory of Open Access Journals (Sweden)

    Stephanie A. Segovia


    Full Text Available The prevalence of obesity, especially in women of child-bearing age, is a global health concern. In addition to increasing the immediate risk of gestational complications, there is accumulating evidence that maternal obesity also has long-term consequences for the offspring. The concept of developmental programming describes the process in which an environmental stimulus, including altered nutrition, during critical periods of development can program alterations in organogenesis, tissue development, and metabolism, predisposing offspring to obesity and metabolic and cardiovascular disorders in later life. Although the mechanisms underpinning programming of metabolic disorders remain poorly defined, it has become increasingly clear that low-grade inflammation is associated with obesity and its comorbidities. This review will discuss maternal metainflammation as a mediator of programming in insulin sensitive tissues in offspring. Use of nutritional anti-inflammatories in pregnancy including omega 3 fatty acids, resveratrol, curcumin, and taurine may provide beneficial intervention strategies to ameliorate maternal obesity-induced programming.

  12. Dysregulation of laminins in intestinal inflammation. (United States)

    Spenlé, C; Hussenet, T; Lacroute, J; Lefebvre, O; Kedinger, M; Orend, G; Simon-Assmann, P


    Laminins are structural components of basement membranes that regulate and control many cellular functions. Changes in basement membrane composition play significant roles in etiology of diseases. Inflammatory bowel diseases are conditions that lead to defects in the mucosal barrier which includes the basement membrane underlying the epithelium. This review will summarize the main findings related to the involvement of laminins and of the laminin-binding receptors in inflammatory conditions such as Crohn's disease and ulcerative colitis. We will review the current literature devoted to studies in humans (immunolocalisation, genetic factors, microarray data), as well as experimental cell models that show that laminins contribute to the inflammation process probably linked to the deregulation of proinflammatory cytokines.

  13. Obesity, inflammation, and the gut microbiota. (United States)

    Cox, Amanda J; West, Nicholas P; Cripps, Allan W


    As the prevalence of obesity and associated disease continues to rise and concerns for the spiralling economic and social costs also escalate, innovative management strategies beyond primary prevention and traditional lifestyle interventions are urgently needed. The biological basis of disease is one avenue for further exploration in this context. Several key inflammatory markers have been consistently associated with both obesity and risk of adverse outcomes in obesity-associated diseases, which suggests that a persistent, low-grade, inflammatory response is a potentially modifiable risk factor. In this Review, we provide evidence supporting perturbation of the intestinal microbiota and changes in intestinal permeability as potential triggers of inflammation in obesity. Further characterisation of the mechanisms underpinning the triggers of such inflammatory responses in overweight and obese individuals could offer unique opportunities for intervention strategies to help ameliorate the risk of obesity-associated disease.

  14. Thyroid Hormones, Oxidative Stress, and Inflammation

    Directory of Open Access Journals (Sweden)

    Antonio Mancini


    Full Text Available Inflammation and oxidative stress (OS are closely related processes, as well exemplified in obesity and cardiovascular diseases. OS is also related to hormonal derangement in a reciprocal way. Among the various hormonal influences that operate on the antioxidant balance, thyroid hormones play particularly important roles, since both hyperthyroidism and hypothyroidism have been shown to be associated with OS in animals and humans. In this context, the nonthyroidal illness syndrome (NTIS that typically manifests as reduced conversion of thyroxine (T4 to triiodothyronine (T3 in different acute and chronic systemic conditions is still a debated topic. The pathophysiological mechanisms of this syndrome are reviewed, together with the roles of deiodinases, the enzymes responsible for the conversion of T4 to T3, in both physiological and pathological situations. The presence of OS indexes in NTIS supports the hypothesis that it represents a condition of hypothyroidism at the tissue level and not only an adaptive mechanism to diseases.

  15. Thyroid Hormones, Oxidative Stress, and Inflammation. (United States)

    Mancini, Antonio; Di Segni, Chantal; Raimondo, Sebastiano; Olivieri, Giulio; Silvestrini, Andrea; Meucci, Elisabetta; Currò, Diego


    Inflammation and oxidative stress (OS) are closely related processes, as well exemplified in obesity and cardiovascular diseases. OS is also related to hormonal derangement in a reciprocal way. Among the various hormonal influences that operate on the antioxidant balance, thyroid hormones play particularly important roles, since both hyperthyroidism and hypothyroidism have been shown to be associated with OS in animals and humans. In this context, the nonthyroidal illness syndrome (NTIS) that typically manifests as reduced conversion of thyroxine (T4) to triiodothyronine (T3) in different acute and chronic systemic conditions is still a debated topic. The pathophysiological mechanisms of this syndrome are reviewed, together with the roles of deiodinases, the enzymes responsible for the conversion of T4 to T3, in both physiological and pathological situations. The presence of OS indexes in NTIS supports the hypothesis that it represents a condition of hypothyroidism at the tissue level and not only an adaptive mechanism to diseases.

  16. Inflammation and its genesis in cystic fibrosis. (United States)

    Nichols, David P; Chmiel, James F


    The host inflammatory response in cystic fibrosis (CF) lung disease has long been recognized as a central pathological feature and an important therapeutic target. Indeed, many believe that bronchiectasis results largely from the oxidative and proteolytic damage comprised within an exuberant airway inflammatory response that is dominated by neutrophils. In this review, we address the longstanding argument of whether or not the inflammatory response is directly attributable to impairment of the cystic fibrosis transmembrane conductance regulator or only secondary to airway obstruction and chronic bacterial infection and challenge the importance of this distinction in the context of therapy. We also review the centrality of neutrophils in CF lung pathophysiology and highlight more recent data that suggest the importance of other cell types and signaling beyond NF-κB activation. We discuss how protease and redox imbalance are critical factors in CF airway inflammation and end by reviewing some of the more promising therapeutic approaches now under development.

  17. Systemic Treatments for Noninfectious Vitreous Inflammation

    Directory of Open Access Journals (Sweden)

    Angela Jiang


    Full Text Available Vitreous inflammation, or vitritis, may result from many causes, including both infectious and noninfectious, including rheumatologic and autoimmune processes. Vitritis is commonly vision threatening and has serious sequelae. Treatment is frequently challenging, but, today, there are multiple methods of systemic treatment for vitritis. These categories include corticosteroids, antimetabolites, alkylating agents, T-cell inhibitors/calcineurin inhibitors, and biologic agents. These treatment categories were reviewed last year, but, even over the course of just a year, many therapies have made progress, as we have learned more about their indications and efficacy. We discuss here discoveries made over the past year on both existing and new drugs, as well as reviewing mechanisms of action, clinical dosages, specific conditions that are treated, adverse effects, and usual course of treatment for each class of therapy.

  18. Toll-Like Receptors and Myocardial Inflammation

    Directory of Open Access Journals (Sweden)

    Yan Feng


    Full Text Available Toll-like receptors (TLRs are a member of the innate immune system. TLRs detect invading pathogens through the pathogen-associated molecular patterns (PAMPs recognition and play an essential role in the host defense. TLRs can also sense a large number of endogenous molecules with the damage-associated molecular patterns (DAMPs that are produced under various injurious conditions. Animal studies of the last decade have demonstrated that TLR signaling contributes to the pathogenesis of the critical cardiac conditions, where myocardial inflammation plays a prominent role, such as ischemic myocardial injury, myocarditis, and septic cardiomyopathy. This paper reviews the animal data on (1 TLRs, TLR ligands, and the signal transduction system and (2 the important role of TLR signaling in these critical cardiac conditions.

  19. Migraine pain, meningeal inflammation, and mast cells. (United States)

    Levy, Dan


    Migraine pain has been attributed to an episode of local sterile meningeal inflammation and the subsequent activation of trigeminal primary afferent nociceptive neurons that supply the intracranial meninges and their related large blood vessels. However, the origin of this inflammatory insult and the endogenous factors that contribute to the activation of meningeal nociceptors remain largely speculative. A particular class of inflammatory cells residing within the intracranial milieu, known as meningeal mast cells, was suggested to play a role in migraine pathophysiology more than five decades ago, but until recently the exact nature of their involvement remained largely unexplored. This review examines the evidence linking meningeal mast cells to migraine and highlights current experimental data implicating these immune cells as potent modulators of meningeal nociceptors' activity and the genesis of migraine pain.

  20. The Role of Inflammation in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Norbert eMüller


    Full Text Available AbstractHigh levels of pro-inflammatory substances such as cytokines have been described in the blood and cerebrospinal fluid of schizophrenia patients. Animal models of schizophrenia show that under certain conditions an immune disturbance during early life, such as an infection-triggered immune activation, might trigger lifelong increased immune reactivity. A large epidemiological study clearly demonstrated that severe infections and autoimmune disorders are risk factors for schizophrenia. Genetic studies have shown a strong signal for schizophrenia on chromosome 6p22.1, in a region related to the human leucocyte antigen (HLA system and other immune functions. Another line of evidence demonstrates that chronic (disstress is associated with immune activation. The vulnerability-stress-inflammation model of schizophrenia includes the contribution of stress on the basis of increased genetic vulnerability for the pathogenesis


    Directory of Open Access Journals (Sweden)

    E. Y. Gusev


    Full Text Available Abstract. Fourteen groups of patients have been investigated and divided into 2 classes. The first class included the following cohorts of patients: relatively healthy persons, age 18 to 55 yrs (n = 50; elderly persons 60 yrs old, as well as senior persons (n = 22; persons with chronic adnexitis, women in their 1st trimester of pregnancy (n = 16; climacteric syndrome (n = 16; autoimmune thyroiditis (n = 29. The second class of patients included following cohorts: elderly persons with chronic cardiac insufficiency (CCI II-III stage (n=49; valvular cardiac disease (rheumatism, n = 15; psoriatic arthritis (n = 12; reactive arthritis (n = 17; antiphospholipid syndrome, a sub-group in the 1st trimester of pregnancy (n = 5; systemic lupus erythematosus (n=49; decompensated atherosclerosis of femoral artery (n = 38; end-stage renal disease (n = 42. Plasma cytokines (TNFαα, IL-6, IL-8, IL-10, acute-phase C-reactive protein (CRP, cortisol, troponin I, myoglobin, D-dimers, interleukin-2 soluble receptor (IL-2sR, and eosinophil cationic protein (ECP were determined in all the patients, by means of immune chemiluminescent technique (Immulite; Siemens Medical Solutions Diagnostics, USA. The integral indices of systemic inflammatory reaction (SIR have been calculated, i.e., a Reactivity Coefficient (RC and a Reactivity Level (RL. In the patients belonging to Class 1 cohorts, an absence of chronic systemic inflammation features was revealed, despite of some signs of systemic inflammatory response. Meanwhile, a majority of Class 2 patients have shown the signs of chronic systemic inflammation stage I to III.

  2. Heme oxygenase-1, oxidation, inflammation and atherosclerosis

    Directory of Open Access Journals (Sweden)

    Jesus A Araujo


    Full Text Available Atherosclerosis is an inflammatory process of the vascular wall characterized by the infiltration of lipids and inflammatory cells. Oxidative modifications of infiltrating low density lipoproteins and induction of oxidative stress play a major role in lipid retention in the vascular wall, uptake by macrophages and generation of foam cells, a hallmark of this disorder. The vasculature has a plethora of protective resources against oxidation and inflammation, many of them regulated by the Nrf2 transcription factor. Heme oxygenase-1 (HO-1 is a Nrf2-regulated gene that plays a critical role in the prevention of vascular inflammation. It is the inducible isoform of heme oxygenase, responsible for the oxidative cleavage of heme groups leading to the generation of biliverdin, carbon monoxide and release of ferrous iron. HO-1 has important antioxidant, antiinflammatory, antiapoptotic, antiproliferative and immunomodulatory effects in vascular cells, most of which play a significant role in the protection against atherogenesis. HO-1 may also be an important feature in macrophage differentiation and polarization to certain subtypes. The biological effects of HO-1 are largely attributable to its enzymatic activity, which can be conceived as a system with three arms of action, corresponding to its three enzymatic byproducts. HO-1 mediated vascular protection may be due to a combination of systemic and vascular local effects. It is usually expressed at low levels but can be highly upregulated in the presence of several proatherogenic stimuli. The HO-1 system is amenable for use in the development of new therapies, some of them currently under experimental and clinical trials. Interestingly, in contrast to the HO-1 antiatherogenic actions, the expression of its transcriptional regulator Nrf2 leads to proatherogenic effects instead. This article reviews the evidence that supports the antiatherogenic role of HO-1, potential pathways and mechanisms mediating

  3. Obesity, inflammation and the immune system. (United States)

    de Heredia, Fátima Pérez; Gómez-Martínez, Sonia; Marcos, Ascensión


    Obesity shares with most chronic diseases the presence of an inflammatory component, which accounts for the development of metabolic disease and other associated health alterations. This inflammatory state is reflected in increased circulating levels of pro-inflammatory proteins, and it occurs not only in adults but also in adolescents and children. The chronic inflammatory response has its origin in the links existing between the adipose tissue and the immune system. Obesity, like other states of malnutrition, is known to impair the immune function, altering leucocyte counts as well as cell-mediated immune responses. In addition, evidence has arisen that an altered immune function contributes to the pathogenesis of obesity. This review attempts to briefly comment on the various plausible explanations that have been proposed for the phenomenon: (1) the obesity-associated increase in the production of leptin (pro-inflammatory) and the reduction in adiponectin (anti-inflammatory) seem to affect the activation of immune cells; (2) NEFA can induce inflammation through various mechanisms (such as modulation of adipokine production or activation of Toll-like receptors); (3) nutrient excess and adipocyte expansion trigger endoplasmic reticulum stress; and (4) hypoxia occurring in hypertrophied adipose tissue stimulates the expression of inflammatory genes and activates immune cells. Interestingly, data suggest a greater impact of visceral adipose tissue and central obesity, rather than total body fat, on the inflammatory process. In summary, there is a positive feedback loop between local inflammation in adipose tissue and altered immune response in obesity, both contributing to the development of related metabolic complications.

  4. Endocannabinoid degradation, endotoxic shock and inflammation. (United States)

    Maccarrone, M; Bari, M; Battista, N; Finazzi-Agrò, A


    Endocannabinoids are an emerging class of lipid mediators, which include amides and esters of long chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol (2-AG) are the main endogenous agonists of cannabinoid receptors. Endotoxic shock is a potentially lethal failure of multiple organs that can be initiated by the inflammatory agent lipopolysaccharide (LPS), present in the outer membrane of gram-negative bacteria. LPS has been recently shown to stimulate the production of AEA in rat macrophages, and of 2-AG in rat platelets. The mechanism responsible for this effect has not been elucidated. On the other hand, mast cells are multifunctional bone marrow-derived cells found in mucosal and connective tissues and in the nervous system, where they play an essential role in inflammation. As yet, little is known about endogenous modulators and mechanisms of mast cell activation. Here, we review recent literature on the role of endocannabinoids in endotoxic shock and inflammation, and report our recent research on the effects of LPS on the production of AEA and 2-AG in human lymphocytes, and on AEA degradation by a specific AEA membrane transporter (AMT) and an AEA-degrading enzyme (fatty acid amide hydrolase, FAAH). We also report the ability of the HMC-1 human mast cells to degrade AEA through a nitric oxide-sensitive AMT and a FAAH. The role of endocannabinoids in HMC-1 degranulation is discussed as well. Taken together, it can be suggested that human lymphocytes and mast cells take part in regulating the peripheral endocannabinoid system, which can affect some activities of these cells.

  5. Adipokines mediate inflammation and insulin resistance

    Directory of Open Access Journals (Sweden)

    Jeffrey E. Pessin


    Full Text Available For many years, adipose tissue was considered as an inert energy storage organ that accumulates and stores triacylglycerols during energy excess and releases fatty acids in times of systemic energy need. However, over the last two decades adipose tissue depots have been established as highly active endocrine and metabolically important organs that modulate energy expenditure and glucose homeostasis. In rodents, brown adipose tissue plays an essential role in non-shivering thermogenesis and in energy dissipation that can serve to protect against diet-induced obesity. White adipose tissue collectively referred too as either subcutaneous or visceral adipose tissue is responsible for the secretion of an array of signaling molecules, termed adipokines. These adipokines function as classic circulating hormones to communicate with other organs including brain, liver, muscle, the immune system and adipose tissue itself. The dysregulation of adipokines has been implicated in obesity, type 2 diabetes and cardiovascular disease. Recently, inflammatory responses in adipose tissue have been shown as a major mechanism to induce peripheral tissue insulin resistance. Although leptin and adiponectin regulate feeding behavior and energy expenditure, these adipokines are also involved in the regulation of inflammatory responses. Adipose tissue secrete various pro- and anti-inflammatory adipokines to modulate inflammation and insulin resistance. In obese humans and rodent models, the expression of pro-inflammatory adipokines is enhanced to induce insulin resistance. Collectively, these findings have suggested that obesity-induced insulin resistance may result, at least in part, from an imbalance in the expression of pro- and anti-inflammatory adipokines. Thus we will review the recent progress regarding the physiological and molecular functions of adipokines in the obesity-induced inflammation and insulin resistance with perspectives on future directions.

  6. Redox regulation in metabolic programming and inflammation. (United States)

    Griffiths, Helen R; Gao, Dan; Pararasa, Chathyan


    Energy metabolism and redox state are intrinsically linked. In order to mount an adequate immune response, cells must have an adequate and rapidly available energy resource to migrate to the inflammatory site, to generate reactive oxygen species using NADPH as a cofactor and to engulf bacteria or damaged tissue. The first responder cells of the innate immune response, neutrophils, are largely dependent on glycolysis. Neutrophils are relatively short-lived, dying via apoptosis in the process of bacterial killing through production of hypochlorous acid and release of extracellular NETs. Later on, the most prevalent recruited innate immune cells are monocytes. Their role is to complete a damage limitation exercise initiated by neutrophils and then, as re-programmed M2 macrophages, to resolve the inflammatory event. Almost twenty five years ago, it was noted that macrophages lose their glycolytic capacity and become anti-inflammatory after treatment with corticosteroids. In support of this we now understand that, in contrast to early responders, M2 macrophages are predominantly dependent on oxidative phosphorylation for energy. During early inflammation, polarisation towards M1 macrophages is dependent on NOX2 activation which, via protein tyrosine phosphatase oxidation and AKT activation, increases trafficking of glucose transporters to the membrane and consequently increases glucose uptake for glycolysis. In parallel, mitochondrial efficiency is likely to be compromised via nitrosylation of the electron transport chain. Resolution of inflammation is triggered by encounter with apoptotic membranes exposing oxidised phosphatidylserine that interact with the scavenger receptor, CD36. Downstream of CD36, activation of AMPK and PPARγ elicits mitochondrial biogenesis, arginase expression and a switch towards oxidative phosphorylation in the M2 macrophage. Proinflammatory cytokine production by M2 cells decreases, but anti-inflammatory and wound healing growth factor

  7. Dopamine beta-hydroxylase deficiency

    Directory of Open Access Journals (Sweden)

    Senard Jean-Michel


    Full Text Available Abstract Dopamine beta-hydroxylase (DβH deficiency is a very rare form of primary autonomic failure characterized by a complete absence of noradrenaline and adrenaline in plasma together with increased dopamine plasma levels. The prevalence of DβH deficiency is unknown. Only a limited number of cases with this disease have been reported. DβH deficiency is mainly characterized by cardiovascular disorders and severe orthostatic hypotension. First symptoms often start during a complicated perinatal period with hypotension, muscle hypotonia, hypothermia and hypoglycemia. Children with DβH deficiency exhibit reduced ability to exercise because of blood pressure inadaptation with exertion and syncope. Symptoms usually worsen progressively during late adolescence and early adulthood with severe orthostatic hypotension, eyelid ptosis, nasal stuffiness and sexual disorders. Limitation in standing tolerance, limited ability to exercise and traumatic morbidity related to falls and syncope may represent later evolution. The syndrome is caused by heterogeneous molecular alterations of the DBH gene and is inherited in an autosomal recessive manner. Restoration of plasma noradrenaline to the normal range can be achieved by therapy with the synthetic precursor of noradrenaline, L-threo-dihydroxyphenylserine (DOPS. Oral administration of 100 to 500 mg DOPS, twice or three times daily, increases blood pressure and reverses the orthostatic intolerance.

  8. Energetic, Structural, and Antimicrobial Analyses of [beta]-Lactam Side Chain Recognition by [beta]-Lactamases

    Energy Technology Data Exchange (ETDEWEB)

    Caselli, E.; Powers, R.A.; Blaszczak, L.C.; Wu, C.Y.E.; Prati, F.; Shoichet, B.K. (NWU)


    Penicillins and cephalosporins are among the most widely used and successful antibiotics. The emergence of resistance to these {beta}-lactams, most often through bacterial expression of {beta}-lactamases, threatens public health. To understand how {beta}-lactamases recognize their substrates, it would be helpful to know their binding energies. Unfortunately, these have been difficult to measure because {beta}-lactams form covalent adducts with {beta}-lactamases. This has complicated functional analyses and inhibitor design. To investigate the contribution to interaction energy of the key amide (R1) side chain of {beta}-lactam antibiotics, eight acylglycineboronic acids that bear the side chains of characteristic penicillins and cephalosporins, as well as four other analogs, were synthesized. These transition-state analogs form reversible adducts with serine {beta}-lactamases. Therefore, binding energies can be calculated directly from K{sub i} values. The K{sub i} values measured span four orders of magnitude against the Group I {beta}-lactamase AmpC and three orders of magnitude against the Group II {beta}-lactamase TEM-1. The acylglycineboronic acids have K{sub i} values as low as 20 nM against AmpC and as low as 390 nM against TEM-1. The inhibitors showed little activity against serine proteases, such as chymotrypsin. R1 side chains characteristic of {beta}-lactam inhibitors did not have better affinity for AmpC than did side chains characteristic of {beta}-lactam substrates. Two of the inhibitors reversed the resistance of pathogenic bacteria to {beta}-lactams in cell culture. Structures of two inhibitors in their complexes with AmpC were determined by X-ray crystallography to 1.90 {angstrom} and 1.75 {angstrom} resolution; these structures suggest interactions that are important to the affinity of the inhibitors. Acylglycineboronic acids allow us to begin to dissect interaction energies between {beta}-lactam side chains and {beta}-lactamases. Surprisingly

  9. Expression of Inflammation-Related Genes Is Altered in Gastric Tissue of Patients with Advanced Stages of NAFLD

    Directory of Open Access Journals (Sweden)

    Rohini Mehta


    Full Text Available Obesity is associated with chronic low-grade inflammation perpetuated by visceral adipose. Other organs, particularly stomach and intestine, may also overproduce proinflammatory molecules. We examined the gene expression patterns in gastric tissue of morbidly obese patients with nonalcoholic fatty liver disease (NAFLD and compared the changes in gene expression in different histological forms of NAFLD. Stomach tissue samples from 20 morbidly obese NAFLD patients who were undergoing sleeve gastrectomy were profiled using qPCR for 84 genes encoding inflammatory cytokines, chemokines, their receptors, and other components of inflammatory cascades. Interleukin 8 receptor-beta (IL8RB gene overexpression in gastric tissue was correlated with the presence of hepatic steatosis, hepatic fibrosis, and histologic diagnosis of nonalcoholic steatohepatitis (NASH. Expression levels of soluble interleukin 1 receptor antagonist (IL1RN were correlated with the presence of NASH and hepatic fibrosis. mRNA levels of interleukin 8 (IL8, chemokine (C-C motif ligand 4 (CCL4, and its receptor chemokine (C-C motif receptor type 5 (CCR5 showed a significant increase in patients with advanced hepatic inflammation and were correlated with the severity of the hepatic inflammation. The results of our study suggest that changes in expression patterns for inflammatory molecule encoding genes within gastric tissue may contribute to the pathogenesis of obesity-related NAFLD.

  10. Systematic Risk on Istanbul Stock Exchange: Traditional Beta Coefficient Versus Downside Beta Coefficient

    Directory of Open Access Journals (Sweden)

    Gülfen TUNA


    Full Text Available The aim of this study is to test the validity of Downside Capital Asset Pricing Model (D-CAPM on the ISE. At the same time, the explanatory power of CAPM's traditional beta and D-CAPM's downside beta on the changes in the average return values are examined comparatively. In this context, the monthly data for seventy three stocks that are continuously traded on the ISE for the period 1991-2009 is used. Regression analysis is applied in this study. The research results have shown that D-CAPM is valid on the ISE. In addition, it is obtained that the power of downside beta coefficient is higher than traditional beta coefficient on explaining the return changes. Therefore, it can be said that the downside beta is superior to traditional beta in the ISE for chosen period.

  11. Synthesis of mesoporous Beta and Sn-Beta zeolites and their catalytic performances. (United States)

    Jin, Junjiang; Ye, Xinxin; Li, Yongsheng; Wang, Yanqin; Li, Liang; Gu, Jinlou; Zhao, Wenru; Shi, Jianlin


    Mesoporous Beta zeolite has been successfully prepared through hydrothermal synthesis in the presence of cationic ammonium-modified chitosan as the meso-template. Through a subsequent solid-gas reaction between highly dealuminated mesoporous Beta zeolite and SnCl4 steam at an elevated temperature, mesoporous Sn-Beta has been facilely obtained. It was revealed that the addition of cationic chitosan induced the nanocrystal aggregation to particle sizes of ∼300 nm, giving rise to the intercrystalline/interparticle mesoporosity. In the Sn-implanting procedure, Sn species were demonstrated to be doped into the framework of the resulting mesoporous Beta zeolite in a tetrahedral environment without structural collapse. Due to the micro/mesoporous structures, both mesoporous Beta and Sn-Beta exhibited superior performances in α-pinene isomerization, Baeyer-Villiger oxidation of 2-adamantanone by hydrogen peroxide and the isomerization of glucose in water, respectively.

  12. Expression of transforming growth factor beta (TGF beta) receptors and expression of TGF beta 1, TGF beta 2 and TGF beta 3 in human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Damstrup, L; Rygaard, K; Spang-Thomsen, M;


    A panel of 21 small cell lung cancer cell (SCLC) lines were examined for the presence of Transforming growth factor beta receptors (TGF beta-r) and the expression of TGF beta mRNAs. By the radioreceptor assay we found high affinity receptors to be expressed in six cell lines. scatchard analysis...... of the binding data demonstrated that the cells bound between 4.5 and 27.5 fmol mg-1 protein with a KD ranging from 16 to 40 pM. TGF beta 1 binding to the receptors was confirmed by cross-linking TGF beta 1 to the TGF beta-r. Three classes of TGF beta-r were demonstrated, type I and type II receptors with M......(r) = 65,000 and 90,000 and the betaglycan (type III) with M(r) = 280,000. Northern blotting showed expression of TGF beta 1 mRNA in ten, TGF beta 2 mRNA in two and TGF beta 3 mRNA in seven cell lines. Our results provide, for the first time, evidence that a large proportion of a broad panel of SCLC cell...

  13. Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection

    Directory of Open Access Journals (Sweden)

    Hwang Jong-Hee


    Full Text Available Abstract Background Worldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences. Methods To better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5–12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. Histopathology in genetically resistant mice and cytokine and NRAMP knockout mice, effects of inoculation of isolated parasites, and treatment with sulfadiazine or αPD1 ligand were studied. Results Twelve months after infection, a time equivalent to middle to early elderly ages, mice had behavioral and neurological deficits, and brain MRIs showed mild to moderate ventricular dilatation. Lower brain weight correlated with greater magnitude of neurologic abnormalities and inflammation. Full genome microarrays of brains reflected inflammation causing neuronal damage (Gfap, effects on host cell protein processing (ubiquitin ligase, synapse remodeling (Complement 1q, and also increased expression of PD-1L (a ligand that allows persistent LCMV brain infection and CD 36 (a fatty acid translocase and oxidized LDL receptor that mediates innate immune response to beta amyloid which is associated with pro-inflammation in Alzheimer's disease. Immunostaining detected no inflammation around intra-neuronal cysts, practically no free tachyzoites, and only rare bradyzoites. Nonetheless, there were perivascular, leptomeningeal inflammatory cells, particularly contiguous to the aqueduct of

  14. Chronic inflammation induces telomere dysfunction and accelerates ageing in mice

    NARCIS (Netherlands)

    Jurk, Diana; Wilson, Caroline; Passos, Joao F.; Oakley, Fiona; Correia-Melo, Clara; Greaves, Laura; Saretzki, Gabriele; Fox, Chris; Lawless, Conor; Anderson, Rhys; Hewitt, Graeme; Pender, Sylvia L. F.; Fullard, Nicola; Nelson, Glyn; Mann, Jelena; van de Sluis, Bart; Mann, Derek A.; von Zglinicki, Thomas


    Chronic inflammation is associated with normal and pathological ageing. Here we show that chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-kappa B induces premature ageing in mice. We also show that these mice have reduced regenerati

  15. Comorbidity, systemic inflammation and outcomes in the ECLIPSE cohort

    DEFF Research Database (Denmark)

    Miller, Joy; Edwards, Lisa D; Agustí, Alvar


    Comorbidities, are common in COPD, have been associated with poor outcomes and are thought to relate to systemic inflammation. To investigate comorbidities in relation to systemic inflammation and outcomes we recorded comorbidities in a well characterized cohort (ECLIPSE study) for 2164 clinically...

  16. The relationship between inflammation and the coagulation system

    NARCIS (Netherlands)

    Choi, Goda; Schultz, Marcus J; Levi, Marcel; van der Poll, Tom


    Inflammation and coagulation play pivotal roles in host defence. As phylogenetically old responses, there is extensive cross-talk between inflammation and coagulation in enabling an adequate immune response against potentially injurious stimuli. Immune cells are important in the initiation of coagul

  17. Inflammation modulates human HDL composition and function in vivo (United States)

    Inflammation may directly impair HDL functions, in particular reverse cholesterol transport (RCT), but limited data support this concept in humans. Our study was designed to investigate this relationship. We employed low-dose human endotoxemia to assess the effects of inflammation on HDL and RCT-rel...

  18. Inflammation. Courseware Evaluation for Vocational and Technical Education. (United States)

    Yarbrough, Stephen

    This courseware evaluation rates the "Inflammation" program developed by Lane Community College in Eugene, Oregon. (This program--not contained in this document--introduces students to the possible causes, signs, and protective benefits of inflammation.) Part A describes the program in terms of subject area (allied health, nursing), and…

  19. Low grade inflammation as measured by levels of YKL-40

    DEFF Research Database (Denmark)

    Rathcke, Camilla Noelle; Raymond, Ilan; Kistorp, Caroline;


    BACKGROUND: Low grade inflammation is of pathogenic importance in the development of cardiovascular disease (CVD) and type 2 diabetes. The inflammation marker YKL-40 correlates with insulin resistance and is highly expressed in atherosclerotic plaques. We aimed to investigate whether YKL-40 could...

  20. 9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration. (United States)


    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Muscular inflammation, degeneration, or infiltration. 311.35 Section 311.35 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... PARTS § 311.35 Muscular inflammation, degeneration, or infiltration. (a) If muscular lesions are...

  1. Mechanistic Differences Leading to Infectious and Sterile Inflammation. (United States)

    Behnia, Faranak; Sheller, Samantha; Menon, Ramkumar


    Inflammation is a physiologic component of pregnancy and parturition. Overwhelming intrauterine inflammatory load promotes quiescent feto-maternal tissues into a contractile phenotype. Like inflammation, oxidative stress is an inevitable component of both pregnancy and parturition. Pathologic activation of host innate immune response to adverse pregnancy conditions can lead to premature activation of inflammatory and oxidative stress. Inflammation and oxidative stress markers seen with both sterile and infectious inflammation are often similar; therefore, it is difficult to understand causality of conditions like spontaneous preterm birth. This review demonstrates potential mechanistic pathways of activation of sterile and infectious inflammation. We demonstrate the activation of two unique pathways of inflammation by factors that are well-documented proxies for oxidative stress (cigarette smoke extract) and infection (lipopolysaccharide). Sterile inflammation seen after exposure to an oxidative stress inducer is due to cellular elemental damage resulting in p38 mitogen-activated protein kinase (MAPK) induced cellular senescence. Infectious inflammation is through activation of transcription factor NF-κB and independent of oxidative stress-associated damages and p38 MAPK-induced senescence. Understanding the differences in the inflammatory pathway activation by various risk factors is important to design better screening, diagnostic and intervention strategies to reduce the risks of adverse pregnancy outcomes.

  2. DMPD: Regulatory pathways in inflammation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17967718 Regulatory pathways in inflammation. Mantovani A, Garlanda C, Locati M, Ro....html) (.csml) Show Regulatory pathways in inflammation. PubmedID 17967718 Title Regulatory pathways in infl... B, Vecchi A. Publication Autoimmun Rev. 2007 Nov;7(1):8-11. Epub 2007 Mar 26. Pathway - PNG File (.png) SVG

  3. Microglia and Inflammation: Impact on Developmental Brain Injuries (United States)

    Chew, Li-Jin; Takanohashi, Asako; Bell, Michael


    Inflammation during the perinatal period has become a recognized risk factor for developmental brain injuries over the past decade or more. To fully understand the relationship between inflammation and brain development, a comprehensive knowledge about the immune system within the brain is essential. Microglia are resident immune cells within the…

  4. Characterization of inflammation in COPD : clinical and experimental approach

    NARCIS (Netherlands)

    Vernooy, J.H.J.


    Chronic inflammation is an important feature of COPD. This inflammatory response is not restricted to the local compartment - including airways, lung parenchyma, and pulmonary vasculature - but is also present in the circulation. However, the origin of the systemic inflammation present in COPD patie

  5. The Role of Brain Inflammation in Epileptogenesis in TSC (United States)


    future challenges. Epilepsia 2007;48:617- 630. 2. Ravizza T, Balosso S, Vezzani A. Inflammation and prevention of epileptogenesis. Neurosci Lett...development. Neurobiol Dis 2006;24:128-143. 7. Aronica E, Crino PB. Inflammation in epilepsy: clinical observations. Epilepsia 2011;52(Suppl.3);26

  6. Acidic Chitinase Limits Allergic Inflammation and Promotes Intestinal Nematode Expulsion (United States)

    Acidic mammalian chitinase (AMCase) is stereotypically induced during mammalian immune responses to helminths and allergens—yet, its precise role in immunity and inflammation is unclear. Here we show that in the lung, genetic ablation of AMCase failed to diminish type 2 inflammation against helmint...

  7. Research on airway inflammation: present status in Mainland China

    Institute of Scientific and Technical Information of China (English)

    WANG Zeng-li


    @@ Airway inflammation involving activated eosinophils, mast cells and T lymphocytes is an established feature of asthma and has been the key target to treatment. Airway structural changes that occur in patients with asthma in response to persistent inflammation are termed airway remodeling.

  8. Modulation of Brain Dead Induced Inflammation by Vagus Nerve Stimulation

    NARCIS (Netherlands)

    Hoeger, S.; Bergstraesser, C.; Selhorst, J.; Fontana, J.; Birck, R.; Waldherr, R.; Beck, G.; Sticht, C.; Seelen, M. A.; van Son, W. J.; Leuvenink, H.; Ploeg, R.; Schnuelle, P.; Yard, B. A.


    Because the vagus nerve is implicated in control of inflammation, we investigated if brain death (BD) causes impairment of the parasympathetic nervous system, thereby contributing to inflammation. BD was induced in rats. Anaesthetised ventilated rats (NBD) served as control. Heart rate variability (

  9. Gallium-labelled peptides for imaging of inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Roivainen, Anne [University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); University of Turku, Turku Center for Disease Modeling, Turku (Finland); Jalkanen, Sirpa [University of Turku, MediCity Research Laboratory, Turku (Finland); University of Turku, Department of Medical Microbiology and Immunology, Turku (Finland); Nanni, Cristina [Azienda Ospedaliero-Universitaria S.Orsola Malpighi, UO Medicina Nucleare, Bologna (Italy)


    Inflammation plays a major role in the development of many diseases. This review article summarizes recent research in the field of in vivo imaging of inflammation. Novel methodologies using PET with {sup 68}Ga peptides targeting, for example, vascular adhesion protein 1 are discussed. (orig.)

  10. Chemokines and chemokine receptors in inflammation of the nervous system

    DEFF Research Database (Denmark)

    Huang, D; Han, Yong-Chang; Rani, M R


    This article focuses on the production of chemokines by resident glial cells of the nervous system. We describe studies in two distinct categories of inflammation within the nervous system: immune-mediated inflammation as seen in experimental autoimmune encephalomyelitis (EAE) or multiple sclerosis...

  11. Beta-2 Microglobulin Kidney Disease Test (United States)

    ... Beta 2 Microglobulin, Serum or Urine Related tests: Albumin , Creatinine , BUN , Heavy Metals Were you looking for ... monitor persons with end-stage renal disease (ESRD) Excess B2M can accumulate in joint spaces ( synovitis ) in ...

  12. Probing neutrinoless double beta decay with SNO+

    CERN Document Server

    Arushanova, Evelina


    Probing neutrinoless double beta decay is one of the primary goals for SNO+, SNOLAB's multi-purpose neutrino detector. In order to achieve this goal the SNO detector has been adapted so that it can be filled with Te-loaded liquid scintillator. During the initial double beta phase the target loading is 0.3% natural Te, which equates to $\\sim790$ kg of double beta isotope. Estimating the sensitivity to neutrinoless double beta decay requires a well understood background model. For SNO+ this is provided by a comprehensive study considering all possible background contributions, whether they originate from within the liquid scintillator cocktail, the surrounding parts of the detector or other irreducible backgrounds. Given these considerations, for five years running in the initial phase, the expected sensitivity is $T_{1/2}^{0\

  13. Neutrino potential for neutrinoless double beta decay

    CERN Document Server

    Iwata, Yoritaka


    Neutrino potential for neutrinoless double beta decay is studied with focusing on its statistical property. The statistics provide a gross view of understanding amplitude of constitutional components of the nuclear matrix element.

  14. Beta cell proliferation and growth factors

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis; Svensson, C; Møldrup, Annette


    Formation of new beta cells can take place by two pathways: replication of already differentiated beta cells or neogenesis from putative islet stem cells. Under physiological conditions both processes are most pronounced during the fetal and neonatal development of the pancreas. In adulthood little...... increase in the beta cell number seems to occur. In pregnancy, however, a marked hyperplasia of the beta cells is observed both in rodents and man. Increased mitotic activity has been seen both in vivo and in vitro in islets exposed to placental lactogen (PL), prolactin (PRL) and growth hormone (GH......). Receptors for both GH and PRL are expressed in islet cells and are upregulated during pregnancy. By mutational analysis we have identified different functional domains of the cytoplasmic part of the GH receptor. Thus the mitotic signaling only requires the membrane proximal part of the receptor...

  15. Phenomenology of neutrinoless double beta decay

    CERN Document Server

    Gómez-Cadenas, J J


    This paper reviews the current status and future outlook of neutrinoless double beta decay searches, which try to provide an answer to the fundamental question of whether neutrinos are Dirac or Majorana particles.

  16. Literature in Focus Beta Beams: Neutrino Beams

    CERN Multimedia


    By Mats Lindroos (CERN) and Mauro Mezzetto (INFN Padova, Italy) Imperial Press, 2009 The beta-beam concept for the generation of electron neutrino beams was first proposed by Piero Zucchelli in 2002. The idea created quite a stir, challenging the idea that intense neutrino beams only could be produced from the decay of pions or muons in classical neutrino beams facilities or in future neutrino factories. The concept initially struggled to make an impact but the hard work by many machine physicists, phenomenologists and theoreticians over the last five years has won the beta-beam a well-earned position as one of the frontrunners for a possible future world laboratory for high intensity neutrino oscillation physics. This is the first complete monograph on the beta-beam concept. The book describes both technical aspects and experimental aspects of the beta-beam, providing students and scientists with an insight into the possibilities o...

  17. [Beta 3 adrenergic receptor polymorphism and obesity]. (United States)

    Yoshida, T; Umekawa, T


    The beta 3-adrenoceptor plays a significant role in the control of lipolysis and thermogenesis in the brown adipose tissue of rodents and humans. In human beta 3-adrenoceptor, a Trp to Arg replacement has recently been discovered. This change which occurs at position 64, in the first coding exon, has been correlated with increased weight gain, difficulty in losing weight, insulin resistance syndrome, and worsened diabetic situation. Higher percentages of this mutation are observed in Pima Indians (over 30%) and Japanese (20%). The possible functional mechanism of Trp54Arg is reported using human HEK293 cell line stably expressing the wild type and the [Arg64] beta 3-adrenoceptor type. Beta 3-adrenoceptor agonists available for humans are been also developing. In this paper we describe these points up-to-date.

  18. [Allergy to beta-lactam antibiotics]. (United States)

    Comte, D; Petitpierre, S; Spertini, F; Bart, P-A


    Beta-lactam antibiotics allergies are common. Up to 10% of the population describe a former allergy to penicillins. However only 10 to 15% of these individuals are actually allergic. In most cases, beta-lactam antibiotics will be avoided and replaced by other antibiotics such as quinolones. This fear of a serious allergic reaction has an economic impact and may lead to the emergence of antibiotic resistance. A thorough allergic work-up can accurately determine true allergic patients. Most of the patients with a proven allergy will be able to tolerate other antibiotics belonging to the beta-lactam family. This article focuses on the management of beta-lactam allergic patients.

  19. Metabolic response to various beta-adrenoceptor agonists in beta3-adrenoceptor knockout mice: evidence for a new beta-adrenergic receptor in brown adipose tissue. (United States)

    Preitner, F; Muzzin, P; Revelli, J P; Seydoux, J; Galitzky, J; Berlan, M; Lafontan, M; Giacobino, J P


    The beta3-adrenoceptor plays an important role in the adrenergic response of brown and white adipose tissues (BAT and WAT). In this study, in vitro metabolic responses to beta-adrenoceptor stimulation were compared in adipose tissues of beta3-adrenoceptor knockout and wild type mice. The measured parameters were BAT fragment oxygen uptake (MO2) and isolated white adipocyte lipolysis. In BAT of wild type mice (-)-norepinephrine maximally stimulated MO2 4.1+/-0.8 fold. Similar maximal stimulations were obtained with beta1-, beta2- or beta3-adrenoceptor selective agonists (dobutamine 5.1+/-0.3, terbutaline 5.3+/-0.3 and CL 316,243 4.8+/-0.9 fold, respectively); in BAT of beta3-adrenoceptor knockout mice, the beta1- and beta2-responses were fully conserved. In BAT of wild type mice, the beta1/beta2-antagonist and beta3-partial agonist CGP 12177 elicited a maximal MO2 response (4.7+/-0.4 fold). In beta3-adrenoceptor knockout BAT, this response was fully conserved despite an absence of response to CL 316,243. This unexpected result suggests that an atypical beta-adrenoceptor, distinct from the beta1-, beta2- and beta3-subtypes and referred to as a putative beta4-adrenoceptor is present in BAT and that it can mediate in vitro a maximal MO2 stimulation. In isolated white adipocytes of wild type mice, (-)-epinephrine maximally stimulated lipolysis 12.1+/-2.6 fold. Similar maximal stimulations were obtained with beta1-, beta2- or beta3-adrenoceptor selective agonists (TO509 12+/-2, procaterol 11+/-3, CL 316,243 11+/-3 fold, respectively) or with CGP 12177 (7.1+/-1.5 fold). In isolated white adipocytes of beta3-adrenoceptor knockout mice, the lipolytic responses to (-)epinephrine, to the beta1-, beta2-, beta3-adrenoceptor selective agonists and to CGP 12177 were almost or totally depressed, whereas those to ACTH, forskolin and dibutyryl cyclic AMP were conserved.

  20. Bioenergetic dysfunction and inflammation in alzheimer's disease: a possible connection

    Directory of Open Access Journals (Sweden)

    Heather M Wilkins


    Full Text Available Inflammation is observed in Alzheimer’s disease (AD subject brains. Inflammation-relevant genes are increasingly implicated in AD genetic studies, and inflammatory cytokines to some extent even function as peripheral biomarkers. What underlies AD inflammation is unclear, but no foreign agent has been implicated. This suggests that internally produced damage-associated molecular pattern molecules (DAMPs may drive inflammation in AD. A more complete characterization and understanding of AD-relevant DAMPs could advance our understanding of AD and suggest novel therapeutic strategies. In this review, we consider the possibility that mitochondria, intracellular organelles that resemble bacteria in many ways, trigger and maintain chronic inflammation in AD subjects. Data supporting the possible nexus between AD-associated bioenergetic dysfunction are discussed.

  1. Diabetes and the Brain: Oxidative Stress, Inflammation, and Autophagy

    Directory of Open Access Journals (Sweden)

    María Muriach


    Full Text Available Diabetes mellitus is a common metabolic disorder associated with chronic complications including a state of mild to moderate cognitive impairment, in particular psychomotor slowing and reduced mental flexibility, not attributable to other causes, and shares many symptoms that are best described as accelerated brain ageing. A common theory for aging and for the pathogenesis of this cerebral dysfunctioning in diabetes relates cell death to oxidative stress in strong association to inflammation, and in fact nuclear factor κB (NFκB, a master regulator of inflammation and also a sensor of oxidative stress, has a strategic position at the crossroad between oxidative stress and inflammation. Moreover, metabolic inflammation is, in turn, related to the induction of various intracellular stresses such as mitochondrial oxidative stress, endoplasmic reticulum (ER stress, and autophagy defect. In parallel, blockade of autophagy can relate to proinflammatory signaling via oxidative stress pathway and NFκB-mediated inflammation.

  2. Isotope Effects in the Bonds of beta-CrOOH and beta-CrOOD

    DEFF Research Database (Denmark)

    Nørlund Christensen, A.; Hansen, P.; Lehmann, M. S.


    Samples of orthorhombic chromium oxide hydroxide, beta -CrOOH, and the deuterated compound, beta -CrOOD, were prepared hydrothermally. The crystal structures were determined by powder profile refinement technique using neutron diffraction data. Unit cells are: beta -CrOOH: a equals 4. 862(2) A, b...... equals 4. 298(a) A, c equals 2. 995(1) A; beta -CrOOD: a equals 4. 873(5) A, b equals 4. 332(7) A, c equals 2. 963(2) A, with Z equals 2. The space group is P2//1nm or Pnnm....

  3. AE activity during transient beta drops in high poloidal beta discharges (United States)

    Huang, J.; Gong, X. Z.; Ren, Q. L.; Ding, S. Y.; Qian, J. P.; Pan, C. K.; Li, G. Q.; Heidbrink, W. W.; Garofalo, A. M.; McClenaghan, J.


    Enhanced AE activity has been observed during transient beta drops in high poloidal beta DIII-D discharges with internal transport barriers (ITBs). These drops in beta are believed to be caused by n=1 external kink modes. In some discharges, beta recovers within 200 ms but, in others, beta stays suppressed. A typical discharge has βP 3, qmin 3, and q95 12. The drop in beta affects both fast ions and thermal particles, and a drop is also observed in the density and rotation. The enhanced AE activity follows the instability that causes the beta drop, is largest at the lowest beta, and subsides as beta recovers. MHD stability analysis is planned. A database study of the plasma conditions associated with the collapse will be also presented. Supported in part by the US Department of Energy under DE-FC02-04ER54698, DE-AC05-06OR23100, and by the National Natural Science Foundation of China 11575249, and the National Magnetic Confinement Fusion Program of China No. 2015GB110005.

  4. Beta adrenergic receptors in human cavernous tissue

    Energy Technology Data Exchange (ETDEWEB)

    Dhabuwala, C.B.; Ramakrishna, C.V.; Anderson, G.F.


    Beta adrenergic receptor binding was performed with /sup 125/I iodocyanopindolol on human cavernous tissue membrane fractions from normal tissue and transsexual procedures obtained postoperatively, as well as from postmortem sources. Isotherm binding studies on normal fresh tissues indicated that the receptor density was 9.1 fmoles/mg. with a KD of 23 pM. Tissue stored at room temperature for 4 to 6 hours, then at 4C in saline solution for 19 to 20 hours before freezing showed no significant changes in receptor density or affinity, and provided evidence for the stability of postmortem tissue obtained within the same time period. Beta receptor density of 2 cavernous preparations from transsexual procedures was not significantly different from normal control tissues, and showed that high concentrations of estrogen received by these patients had no effect on beta adrenergic receptor density. Displacement of /sup 125/iodocyanopindolol by 5 beta adrenergic agents demonstrated that 1-propranolol had the greatest affinity followed by ICI 118,551, zinterol, metoprolol and practolol. When the results of these displacement studies were subjected to Scatfit, non- linear regression line analysis, a single binding site was described. Based on the relative potency of the selective beta adrenergic agents it appears that these receptors were of the beta 2 subtype.

  5. Estimating Security Betas Using Prior Information Based on Firm Fundamentals

    NARCIS (Netherlands)

    Cosemans, Mathijs; Frehen, Rik; Schotman, Peter; Bauer, Rob


    We propose a hybrid approach for estimating beta that shrinks rolling window estimates toward firm-specific priors motivated by economic theory. Our method yields superior forecasts of beta that have important practical implications. First, unlike standard rolling window betas, hybrid betas carry a

  6. beta(2)-Glycoprotein I : evolution, structure and function

    NARCIS (Netherlands)

    de Groot, P. G.; Meijers, J. C. M.


    beta(2)-Glycoprotein I (beta(2)-GPI) is a protein that circulates in blood at high concentrations. The function of beta(2)-GPI has long been an enigma. More than 20 years ago, it was discovered that beta(2)-GPI is the major antigen for the circulating antibodies in the antiphospholipid syndrome. How

  7. Elevated calprotectin levels reveal bowel inflammation in spondyloarthritis (United States)

    Cypers, H; Varkas, G; Beeckman, S; Debusschere, K; Vogl, T; Roth, J; Drennan, M B; Lavric, M; Foell, D; Cuvelier, C A; De Vos, M; Delanghe, J; Van den Bosch, F; Elewaut, D


    Introduction Microscopic bowel inflammation is present in up to 50% of patients with spondyloarthritis (SpA) and is associated with more severe disease. Currently no reliable biomarkers exist to identify patients at risk. Calprotectin is a sensitive marker of neutrophilic inflammation, measurable in serum and stool. Objectives To assess whether serum and faecal calprotectin in addition to C-reactive protein (CRP) can be used to identify patients with SpA at risk of microscopic bowel inflammation. Methods Serum calprotectin and CRP were measured in 125 patients with SpA. In 44 of these patients, faecal samples were available for calprotectin measurement. All 125 patients underwent an ileocolonoscopy to assess the presence of microscopic bowel inflammation. Results Microscopic bowel inflammation was present in 53 (42.4%) patients with SpA. Elevated serum calprotectin and CRP were independently associated with microscopic bowel inflammation. Faecal calprotectin was also significantly higher in patients with microscopic bowel inflammation. Patients with CRP and serum calprotectin elevated had a frequency of bowel inflammation of 64% vs 25% in patients with low levels of both. When either CRP or serum calprotectin was elevated, the risk was intermediate (40%) and measuring faecal calprotectin provided further differentiation. Hence we suggest a screening approach where initially serum calprotectin and CRP are assessed and, if necessary, faecal calprotectin. The model using this scenario provided an area under the ROC curve of 74.4% for detection of bowel inflammation. Conclusions Calprotectin measurements in stool and serum, in addition to CRP, may provide a promising strategy to identify patients with SpA at risk of bowel inflammation and could play a role in overall patient stratification. PMID:26698844

  8. News on $\\beta$-delayed particle emission from $^{14}$Be

    CERN Document Server

    Jeppesen, H; Borge, M J G; Cederkäll, J; Fynbo, H O U; Fedoseyev, V N; Hansper, V Y; Jonson, B; Markenroth, K; Mishin, V I; Nilsson, T; Nyman, G; Riisager, K; Tengblad, O; Wilhelmsen Rolander, K


    $\\beta$-delayed charged particles from $^{14}$Be have been measured and give an upper limit on $\\beta$-delayed $\\alpha$-particles of B($\\beta\\alpha$) < $\\,6.7\\times\\!10^{-5}$ and a tentative branching ratio on $\\beta$-delayed tritons of $7.5\\times\\!10^{-5}$ < B($\\beta$t) < $\\,3.9\\times\\!10^{-4}$. We combine the knowledge on $\\beta$-delayed particles from $^{14}$Be to deduce information on the $\\beta$-strength distribution.

  9. Continuous and Jump Betas: Implications for Portfolio Diversification

    Directory of Open Access Journals (Sweden)

    Vitali Alexeev


    Full Text Available Using high-frequency data, we decompose the time-varying beta for stocks into beta for continuous systematic risk and beta for discontinuous systematic risk. Estimated discontinuous betas for S&P500 constituents between 2003 and 2011 generally exceed the corresponding continuous betas. We demonstrate how continuous and discontinuous betas decrease with portfolio diversification. Using an equiweighted broad market index, we assess the speed of convergence of continuous and discontinuous betas in portfolios of stocks as the number of holdings increase. We show that discontinuous risk dissipates faster with fewer stocks in a portfolio compared to its continuous counterpart.

  10. DMPD: Immunoreceptor-like signaling by beta 2 and beta 3 integrins. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17913496 Immunoreceptor-like signaling by beta 2 and beta 3 integrins. Jakus Z, Fod...or S, Abram CL, Lowell CA, Mocsai A. Trends Cell Biol. 2007 Oct;17(10):493-501. (.png) (.svg) (.html) (.csml) Show Immunore...ceptor-like signaling by beta 2 and beta 3 integrins. PubmedID 17913496 Title Immunoreceptor-

  11. Des-Lys58-beta 2m and native beta 2m in rheumatoid arthritis serum and synovial fluid

    DEFF Research Database (Denmark)

    Williams, R C; Malone, C C; Nissen, Mogens Holst;


    OBJECTIVE. Levels of beta 2-microglobulin and modified beta 2-microglobulin (Des-Lys58-beta 2m) were measured in serum and synovial fluids from patients with rheumatoid arthritis (RA) and other inflammatory joint disorders using rabbit antisera prepared against the beta 2m peptide VEHSDLSFS...

  12. Characterization of beta-R1, a gene that is selectively induced by interferon beta (IFN-beta) compared with IFN-alpha. (United States)

    Rani, M R; Foster, G R; Leung, S; Leaman, D; Stark, G R; Ransohoff, R M


    We report preliminary characterization of a gene designated beta-R1, which is selectively expressed in response to interferon beta (IFN-beta) compared with IFN-alpha. In human astrocytoma cells, beta-R1 was induced to an equivalent extent by 10 IU/mL IFN-beta or 2500 IU/mL IFN-alpha2. To address the mechanism of this differential response, we analyzed induction of the beta-R1 gene in fibrosarcoma cells and derivative mutant cells lacking components required for signaling by type I IFNs. beta-R1 was readily induced by IFN-beta in the parental 2fTGH cell line, but not by recombinant IFN-alpha2, IFN-alpha Con1, or a mixture of IFN-alpha subtypes. IFN-alpha8 induced beta-R1 weakly. beta-R1 was not induced by IFN-beta in mutant cell lines U2A, U3A, U4A, and U6A, which lack, respectively, p48, STAT1, JAK1, and STAT2. U5A cells, which lack the Ifnar 2.2 component of the IFN-alpha and -beta receptor, also failed to express beta-R1. U1A cells are partially responsive to IFN-beta and IFN-alpha8 but lacked beta-R1 expression, indicating that TYK2 protein is essential for induction of this gene. Taken together, these results suggest that the expression of beta-R1 in response to type I IFN requires IFN-stimulated gene factor 3 plus an additional component, which is more efficiently formed on induction by IFN-beta compared with IFN-alpha.

  13. Amyloid Beta as a Modulator of Synaptic Plasticity


    Parihar, Mordhwaj S.; Gregory J. Brewer


    Alzheimer’s disease is associated with synapse loss, memory dysfunction and pathological accumulation of amyloid beta in plaques. However, an exclusively pathological role for amyloid beta is being challenged by new evidence for an essential function of amyloid beta at the synapse. Amyloid beta protein exists in different assembly states in the central nervous system and plays distinct roles ranging from synapse and memory formation to memory loss and neuronal cell death. Amyloid beta is pres...

  14. Induction of the expression of genes encoding TGF-beta isoforms and their receptors by inositol hexaphosphate in human colon cancer cells. (United States)

    Kapral, Małgorzata; Wawszczyk, Joanna; Hollek, Andrzej; Weglarz, Ludmiła


    Transforming growth factors-beta (TGF-beta) are multifunctional cytokines involved in the regulation of cell development, differentiation, survival and apoptosis. They are also potent anticancer agents that inhibit uncontrolled proliferation of cells. Incorrect TGF-beta regulation has been implicated in the pathogenesis of many diseases including inflammation and cancer. In humans, the TGF-beta family consists of three members (TGF-beta1, 2, 3) that show high similarity and homology. TGF-betas exert biological activities on various cell types including neoplastic cells via their specific receptors. Inositol hexaphosphate (phytic acid, IP6), a phytochemical has been reported to possess various health benefits. The aim of this study was to examine the effect of IP6 on the expression of genes encoding TGF-beta1, TGF-beta2, TGF-beta3 isoforms and their receptors TbetaRI, TbetaRII, TbetaRIII in human colorectal cancer cell line Caco-2. The cells were treated with 0.5, 1 and 2.5 mM IP6 for 3, 6 and 12 h. The untreated Caco-2 cells were used as the control. Quantification of genes expression was performed by real time QRT-PCR technique with a SYBR Green I chemistry. The experimental data revealed that the TGF-beta1 mRNA was the predominant isoform in Caco-2 cells and that IP6 enhanced transcriptional activity of genes of all three TGF-beta isoforms and their receptors TbetaRI, TbetaRII TbetaRIII in these cells. At concentrations up to 1 mM, IP6 over-expressed the genes in 6 h lasting cultures, and its higher dose (2.5 mM) caused successively increasing transcript level of TGF-beta isoforms and receptors with the duration of experiment up to 12 h. The findings of this study indicate that one of anti-cancer abilities of IP6 can be realized by enhancing the gene expression of TGF-beta isoforms and their receptors at the transcriptional level.

  15. Toll-like receptor 4 regulates lipopolysaccharide-induced inflammation and lactation insufficiency in a mouse model of mastitis. (United States)

    Glynn, Danielle J; Hutchinson, Mark R; Ingman, Wendy V


    Lactation mastitis is a debilitating inflammatory breast disease in postpartum women. Disease severity is associated with markers of inflammation rather than bacterial load, suggesting that immune-signaling pathways activated in the host are important in the disease pathology. The role of the innate pattern recognition receptor toll-like receptor 4 (TLR4) in progression and resolution of mastitislike disease was investigated in a mouse model. Lipopolysaccharide in Matrigel (10 μg/10 μl) was administered into the teat canal of lactating Tlr4 null mutant and wild-type mice to induce a localized area of inflammation. Mastitis induction resulted in a marked influx of RB6-positive neutrophils and F4/80-positive macrophages, which was higher in Tlr4(-/-) mice compared to wild-type mice. Tlr4 null mutation resulted in an altered immune-signaling fingerprint following induction of mastitis, with attenuated serum cytokines, including CXCL1, CCL2, interleukin 1 beta, and tumor necrosis factor alpha compared to wild-type mice. In both genotypes, the localized area of inflammation had resolved after 7 days, and milk protein was evident. However, the mammary glands of wild-type mice exhibited reduced capacity for milk production, with decreased percent area populated with glandular epithelium and decreased abundance of nuclear phosphorylated signal transducer and activator of transcription 5 compared to Tlr4 null mice. This study demonstrates that inflammatory pathways activated in the host are critically important in mastitis disease progression and suggests that lactation insufficiency associated with mastitis may be a consequence of TLR4-mediated inflammation, rather than the bacterial infection itself.

  16. Microglial NLRP3 inflammasome activation mediates IL-1β-related inflammation in prefrontal cortex of depressive rats. (United States)

    Pan, Ying; Chen, Xu-Yang; Zhang, Qing-Yu; Kong, Ling-Dong


    Depression is an inflammatory disorder. Pro-inflammatory cytokine interleukin-1 beta (IL-1β) may play a pivotal role in the central nervous system (CNS) inflammation of depression. Here, we investigated IL-1β alteration in serum, cerebrospinal fluid (CSF) and prefrontal cortex (PFC) of chronic unpredictable mild stress (CUMS)-exposed rats, a well-documented model of depression, and further explored the molecular mechanism by which CUMS procedure induced IL-1β-related CNS inflammation. We showed that 12-week CUMS procedure remarkably increased PFC IL-1β mRNA and protein levels in depressive-like behavior of rats, without significant alteration of serum and CSF IL-1β levels. We found that CUMS procedure significantly caused PFC nuclear factor kappa B (NF-κB) inflammatory pathway activation in rats. The intriguing finding in this study was the induced activation of nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome with the increased IL-1β maturation in PFC of CUMS rats, suggesting a new grade of regulatory mechanism for IL-1β-related CNS inflammation. Moreover, microglial activation and astrocytic function impairment were observed in PFC of CUMS rats. The increased co-location of NLRP3 and ionized calcium binding adaptor molecule 1 (Iba1) protein expression supported that microglia in glial cells was the primary contributor for CUMS-induced PFC NLRP3 inflammasome activation in rats. These alterations in CUMS rats were restored by chronic treatment of the antidepressant fluoxetine, indicating that fluoxetine-mediated rat PFC IL-1β reduction involves both transcriptional and post-transcriptional regulatory mechanisms. These findings provide in vivo evidence that microglial NLRP3 inflammasome activation is a mediator of IL-1β-related CNS inflammation during chronic stress, and suggest a new therapeutic target for the prevention and treatment of depression.

  17. Beta-adrenoceptors in obstetrics and gynecology. (United States)

    Modzelewska, Beata


    One hundred and twenty years after the description of extracts from the adrenal medulla, the use of beta-blockers and beta-agonists evolved from antianginal drugs and tocolytics to ligand-directed signaling. Beta-blockers in the fields of obstetrics and gynecology have so far been limited to the consideration of continuing treatment of disorders of the cardiovascular system and other dysfunctions that started before pregnancy. Studies in recent years have shown that beta-adrenoceptor signaling might be crucial in carcinogenesis and metastasis, apoptosis and anoikis. On the other hand, the use of beta-adrenoceptor agonists in tocolysis is, as yet, the primary method for inhibiting premature uterine contractions. Unfortunately, the efficacy of current pharmacological treatment for the management of preterm labor is regularly questioned. Moreover, studies related to non-pregnant myometrium performed to date indicate that the rhythmic contractions of the uterus are required for menstruation and have an important role in human reproduction. In turn, abnormal uterine contractility has been linked to dysmenorrhea, a condition associated with painful uterine cramping. The benefits of the use of beta2-adrenoceptor agonists in dysmenorrhea are still unclear and should be balanced against a wide range of adverse effects recognized with this class of medication. The ideal tocolytic agent is one which is effective for the pregnant or non-pregnant woman but has no side effects on either the woman or the baby. Looking to the future with both caution and hope, the potential metamorphosis of beta3-adrenoceptor agonists from experimental tools into therapeutic drugs for tocolysis warrants attention.

  18. Beta Gyres in Global Analysis Fields

    Institute of Scientific and Technical Information of China (English)



    A three-component decomposition is applied to global analysis data to show the existence of a beta gyre,which causes Tropical Cyclone (TC) to drift from a large-scale environmental steering current.Analyses from the Global Data Assimilation and Prediction System (GDAPS) of the Korea Meteorological Administration (KMA),the Global Forecast System (GFS) of NCEP,and the Navy Operational Global Atmospheric Prediction System (NOGAPS) are used in this study.The structure of the beta gyre obtained in our analyses is in good agreement with the theoretical structure,with a cyclonic circulation to the southwest of the TC center,an anticyclonic circulation to the northeast,and a ventilation flow directed northwestward near the center.The circulation of the beta gyre is strongest at the 850-hPa level where the cyclonically swirling primary circulation is strongest,and decreases with height,in a pyramid shape similar to the primary circulation.The individual structure of the beta gyre is case- and model-dependent.At a certain analysis time,one model may clearly reveal a well-defined beta gyre,but the other models may not.Within one model,the beta gyre may be well defined at some analysis times,but not at other times.The structure of the beta gyre in the analysis field is determined by the nature of the vortex initialization scheme and the model behavior during the 6-h forecast in the operational data assimilation cycle.

  19. [Transforming growth factor-beta controls pathogenesis of Crohn disease]. (United States)

    Friess, H; di Mola, F F; Egger, B; Scheuren, A; Kleeff, J; Zimmermann, A; Büchler, M W


    The pathogenetic mechanisms which contribute to the progression of Crohn's disease are still not known. Transforming growth factor-beta (TGF-beta) and its subtypes are multifunctional polypeptides which regulate immunological processes as well as the synthesis of the extracellular matrix and fibrogenesis. In the present study, Crohn's disease tissue samples of 18 patients undergoing intestinal resection were analyzed by Northern blot analysis, in situ hybridization and immunostaining for TGF-beta 1-3 and the TGF-beta receptors type I-III (T beta R-I, T beta R-II, T beta R-III). There was a marked overexpression of TGF-beta 1, TGF-beta 3 and T beta R-II in 94% of the Crohn's disease tissue samples. TGF-beta 2 and T beta R-I ALK5 and T beta R-III were enhanced in 72%, 72% and 82% of the Crohn tissue samples, respectively. In situ hybridization and immunostaining revealed that there was frequent coexpression of TGF-beta with its signaling receptors. Our data indicate that TGF-beta and their receptors seem to be involved in the pathogenesis of Crohn's disease. Their enhanced expression might contribute to the increase in extracellular matrix resulting in fibrosis and subsequently in intestinal obstruction.

  20. Inflammation Thread Runs across Medical Laboratory Specialities (United States)

    Lung, Thomas; Risch, Lorenz; Risch, Martin; Medina Escobar, Pedro; Bodmer, Thomas


    We work on the assumption that four major specialities or sectors of medical laboratory assays, comprising clinical chemistry, haematology, immunology, and microbiology, embraced by genome sequencing techniques, are routinely in use. Medical laboratory markers for inflammation serve as model: they are allotted to most fields of medical lab assays including genomics. Incessant coding of assays aligns each of them in the long lists of big data. As exemplified with the complement gene family, containing C2, C3, C8A, C8B, CFH, CFI, and ITGB2, heritability patterns/risk factors associated with diseases with genetic glitch of complement components are unfolding. The C4 component serum levels depend on sufficient vitamin D whilst low vitamin D is inversely related to IgG1, IgA, and C3 linking vitamin sufficiency to innate immunity. Whole genome sequencing of microbial organisms may distinguish virulent from nonvirulent and antibiotic resistant from nonresistant varieties of the same species and thus can be listed in personal big data banks including microbiological pathology; the big data warehouse continues to grow. PMID:27493451

  1. Sleep, immunity and inflammation in gastrointestinal disorders. (United States)

    Ali, Tauseef; Choe, James; Awab, Ahmed; Wagener, Theodore L; Orr, William C


    Sleep disorders have become a global issue, and discovering their causes and consequences are the focus of many research endeavors. An estimated 70 million Americans suffer from some form of sleep disorder. Certain sleep disorders have been shown to cause neurocognitive impairment such as decreased cognitive ability, slower response times and performance detriments. Recent research suggests that individuals with sleep abnormalities are also at greater risk of serious adverse health, economic consequences, and most importantly increased all-cause mortality. Several research studies support the associations among sleep, immune function and inflammation. Here, we review the current research linking sleep, immune function, and gastrointestinal diseases and discuss the interdependent relationship between sleep and these gastrointestinal disorders. Different physiologic processes including immune system and inflammatory cytokines help regulate the sleep. The inflammatory cytokines such as tumor necrosis factor, interleukin-1 (IL-1), and IL-6 have been shown to be a significant contributor of sleep disturbances. On the other hand, sleep disturbances such as sleep deprivation have been shown to up regulate these inflammatory cytokines. Alterations in these cytokine levels have been demonstrated in certain gastrointestinal diseases such as inflammatory bowel disease, gastro-esophageal reflux, liver disorders and colorectal cancer. In turn, abnormal sleep brought on by these diseases is shown to contribute to the severity of these same gastrointestinal diseases. Knowledge of these relationships will allow gastroenterologists a great opportunity to enhance the care of their patients.

  2. Inflammation Thread Runs across Medical Laboratory Specialities

    Directory of Open Access Journals (Sweden)

    Urs Nydegger


    Full Text Available We work on the assumption that four major specialities or sectors of medical laboratory assays, comprising clinical chemistry, haematology, immunology, and microbiology, embraced by genome sequencing techniques, are routinely in use. Medical laboratory markers for inflammation serve as model: they are allotted to most fields of medical lab assays including genomics. Incessant coding of assays aligns each of them in the long lists of big data. As exemplified with the complement gene family, containing C2, C3, C8A, C8B, CFH, CFI, and ITGB2, heritability patterns/risk factors associated with diseases with genetic glitch of complement components are unfolding. The C4 component serum levels depend on sufficient vitamin D whilst low vitamin D is inversely related to IgG1, IgA, and C3 linking vitamin sufficiency to innate immunity. Whole genome sequencing of microbial organisms may distinguish virulent from nonvirulent and antibiotic resistant from nonresistant varieties of the same species and thus can be listed in personal big data banks including microbiological pathology; the big data warehouse continues to grow.

  3. Understanding about the classification of pulp inflammation

    Directory of Open Access Journals (Sweden)

    Trijoedani Widodo


    Full Text Available Since most authors use the reversible pulpitis and irreversible pulpitis classification, however, many dentists still do not implement these new classifications. Research was made using a descriptive method by proposing questionnaire to dentists from various dental clinics. The numbers of the dentists participating in this research are 22 dentists. All respondents use the diagnosis sheet during their examinations on patients. Nonetheless, it can't be known what diagnosis card used and most of the dentists are still using the old classification. Concerning responses given towards the new classification: a the new classification had been heard, however, it was not clear (36.3%; b the new classification has never been heard at all (63.6%. Then, responses concerning whether a new development is important to be followed-up or not: a there are those who think that information concerning new development is very important (27.2%; b those who feel that it is important to have new information (68.3%; c those who think that new information is not important (8%. It concluded that information concerning the development of classification of pulp inflammation did not reach the dentists.

  4. OxInflammation in Rett syndrome. (United States)

    Pecorelli, Alessandra; Cervellati, Carlo; Hayek, Joussef; Valacchi, Giuseppe


    Rett syndrome (RTT) is an orphan progressive neurodevelopmental disease affecting almost exclusively females (frequency 1:10,000). RTT clinical expression is typically characterized by loss of purposeful hand movements, severe mental retardation and motor impairment, breathing disorders, ataxia and increased risk of sudden death. Although the main genetic cause, i.e. mutation in the methyl-CpG binding protein 2 gene (MECP2), has been already identified, the molecular and pathogenic mechanisms by which MECP2 deficiency drives pathology in RTT remains not fully understood. A wealth of evidence from our and other laboratories suggests a potential causal relationship between MECP2 dysfunction and systemic redox imbalance, a condition that has been widely found in association with RTT. In turn, a "short-circuit" of redox pathways may contribute to the systemic immune dysfunction expressed as cytokines/chemokines dysregulation, a feature clearly emerged from two recent studies on RTT patients. In this light, the purpose of this review is to describe and to stimulate a new discussion on the idea that systemic subclinical inflammation and oxidative stress are crucial players of a detrimental vicious circle, driving the pathogenesis and clinical course of RTT.

  5. Inflammation and Pharmacological Treatment in Diabetic Retinopathy (United States)

    Kaštelan, Snježana; Tomić, Martina; Gverović Antunica, Antonela; Salopek Rabatić, Jasminka; Ljubić, Spomenka


    Diabetic retinopathy (DR), the most common microvascular complication of diabetes mellitus, is estimated to be the leading cause of new blindness in the working population of developed countries. Primary interventions such as intensive glycemic control, strict blood pressure regulation, and lipid-modifying therapy as well as local ocular treatment (laser photocoagulation and pars plana vitrectomy) can significantly reduce the risk of retinopathy occurrence and progression. Considering the limitations of current DR treatments development of new therapeutic strategies, it becomes necessary to focus on pharmacological treatment. Currently, there is increasing evidence that inflammatory processes have a considerable role in the pathogenesis of DR with multiple studies showing an association of various systemic as well as local (vitreous and aqueous fluid) inflammatory factors and the progression of DR. Since inflammation is identified as a relevant mechanism, significant effort has been directed to the development of new concepts for the prevention and treatment of DR acting on the inflammatory processes and the use of pharmacological agents with anti-inflammatory effect. Inhibiting the inflammatory pathway could be an appealing treatment option for DR in future practices, and as further prospective randomized clinical trials accumulate data, the role and guidelines of anti-inflammatory pharmacologic treatments will become clearer. PMID:24288441

  6. Inflammation and Pharmacological Treatment in Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Snježana Kaštelan


    Full Text Available Diabetic retinopathy (DR, the most common microvascular complication of diabetes mellitus, is estimated to be the leading cause of new blindness in the working population of developed countries. Primary interventions such as intensive glycemic control, strict blood pressure regulation, and lipid-modifying therapy as well as local ocular treatment (laser photocoagulation and pars plana vitrectomy can significantly reduce the risk of retinopathy occurrence and progression. Considering the limitations of current DR treatments development of new therapeutic strategies, it becomes necessary to focus on pharmacological treatment. Currently, there is increasing evidence that inflammatory processes have a considerable role in the pathogenesis of DR with multiple studies showing an association of various systemic as well as local (vitreous and aqueous fluid inflammatory factors and the progression of DR. Since inflammation is identified as a relevant mechanism, significant effort has been directed to the development of new concepts for the prevention and treatment of DR acting on the inflammatory processes and the use of pharmacological agents with anti-inflammatory effect. Inhibiting the inflammatory pathway could be an appealing treatment option for DR in future practices, and as further prospective randomized clinical trials accumulate data, the role and guidelines of anti-inflammatory pharmacologic treatments will become clearer.

  7. The role of inflammation in cerebral aneurysms

    Directory of Open Access Journals (Sweden)

    Ali H Turkmani


    Full Text Available The natural history of unruptured intracranial aneurysms (IAs is poorly understood. At present, risk factors for aneurysm rupture are limited to demographics and rudimentary anatomic features of the aneurysm. The first sign of aneurysm destabilization and rupture may be subarachnoid hemorrhage, a potentially devastating brain injury with high morbidity and mortality. An emerging body of literature suggests a complex inflammatory cascade likely promotes aneurysm wall remodeling and progressive ballooning of the arterial wall, ultimately terminating in aneurysm rupture. These events likely begin with hemodynamic, flow-related endothelial injury; the injured endothelium stimulates inflammation, including the recruitment and transmigration of inflammatory cells, particularly macrophages. Various proteases are secreted by the inflammatory infiltrate, resulting in degradation of the extracellular matrix and the structural changes unique to IAs. Detailed understanding of these inflammatory processes may result in (1 early identification of patients at high risk for aneurysm rupture, perhaps via arterial wall imaging, and (2 targeted, noninvasive therapies to treat or even prevent cerebral aneurysms.

  8. Psychosocial stress and inflammation in cancer. (United States)

    Powell, N D; Tarr, A J; Sheridan, J F


    Stress-induced immune dysregulation results in significant health consequences for immune related disorders including viral infections, chronic autoimmune disease, and tumor growth and metastasis. In this mini-review we discuss the sympathetic, neuroendocrine and immunologic mechanisms by which psychosocial stress can impact cancer biology. Both human and animal studies have shown the sympathetic and neuroendocrine responses to psychosocial stress significantly impacts cancer, in part, through regulation of inflammatory mediators. Psychosocial stressors stimulate neuroendocrine, sympathetic, and immune responses that result in the activation of the hypothalamic-pituitary-adrenal (HPA)-axis, sympathetic nervous system (SNS), and the subsequent regulation of inflammatory responses by immune cells. Social disruption (SDR) stress, a murine model of psychosocial stress and repeated social defeat, provides a novel and powerful tool to probe the mechanisms leading to stress-induced alterations in inflammation, tumor growth, progression, and metastasis. In this review, we will focus on SDR as an important model of psychosocial stress in understanding neural-immune mechanisms in cancer.

  9. Modeling and Hemofiltration Treatment of Acute Inflammation

    Directory of Open Access Journals (Sweden)

    Robert S. Parker


    Full Text Available The body responds to endotoxins by triggering the acute inflammatory response system to eliminate the threat posed by gram-negative bacteria (endotoxin and restore health. However, an uncontrolled inflammatory response can lead to tissue damage, organ failure, and ultimately death; this is clinically known as sepsis. Mathematical models of acute inflammatory disease have the potential to guide treatment decisions in critically ill patients. In this work, an 8-state (8-D differential equation model of the acute inflammatory response system to endotoxin challenge was developed. Endotoxin challenges at 3 and 12 mg/kg were administered to rats, and dynamic cytokine data for interleukin (IL-6, tumor necrosis factor (TNF, and IL-10 were obtained and used to calibrate the model. Evaluation of competing model structures was performed by analyzing model predictions at 3, 6, and 12 mg/kg endotoxin challenges with respect to experimental data from rats. Subsequently, a model predictive control (MPC algorithm was synthesized to control a hemoadsorption (HA device, a blood purification treatment for acute inflammation. A particle filter (PF algorithm was implemented to estimate the full state vector of the endotoxemic rat based on time series cytokine measurements. Treatment simulations show that: (i the apparent primary mechanism of HA efficacy is white blood cell (WBC capture, with cytokine capture a secondary benefit; and (ii differential filtering of cytokines and WBC does not provide substantial improvement in treatment outcomes vs. existing HA devices.

  10. Vascular oxidant stress and inflammation in hyperhomocysteinemia. (United States)

    Papatheodorou, Louisa; Weiss, Norbert


    Elevated plasma levels of homocysteine are a metabolic risk factor for atherosclerotic vascular disease, as shown in numerous clinical studies that linked elevated homocysteine levels to de novo and recurrent cardiovascular events. High levels of homocysteine promote oxidant stress in vascular cells and tissue because of the formation of reactive oxygen species (ROS), which have been strongly implicated in the development of atherosclerosis. In particular, ROS have been shown to cause endothelial injury, dysfunction, and activation. Elevated homocysteine stimulates proinflammatory pathways in vascular cells, resulting in leukocyte recruitment to the vessel wall, mediated by the expression of adhesion molecules on endothelial cells and circulating monocytes and neutrophils, in the infiltration of leukocytes into the arterial wall mediated by increased secretion of chemokines, and in the differentiation of monocytes into cholesterol-scavenging macrophages. Furthermore, it stimulates the proliferation of vascular smooth muscle cells followed by the production of extracellular matrix. Many of these events involve redox-sensitive signaling events, which are promoted by elevated homocysteine, and result in the formation of atherosclerotic lesions. In this article, we review current knowledge about the role of homocysteine on oxidant stress-mediated vascular inflammation during the development of atherosclerosis.

  11. The novel amyloid-beta peptide aptamer inhibits intracellular amyloid-beta peptide toxicity

    Institute of Scientific and Technical Information of China (English)

    Xu Wang; Yi Yang; Mingyue Jia; Chi Ma; Mingyu Wang; Lihe Che; Yu Yang; Jiang Wu


    Amyloid β peptide binding alcohol dehydrogenase (ABAD) decoy peptide (DP) can competitively antagonize binding of amyloid β peptide to ABAD and inhibit the cytotoxic effects of amyloid β peptide. Based on peptide aptamers, the present study inserted ABAD-DP into the disulfide bond of human thioredoxin (TRX) using molecular cloning technique to construct a fusion gene that can express the TRX1-ABAD-DP-TRX2 aptamer. Moreover, adeno-associated virus was used to allow its stable expression. Immunofluorescent staining revealed the co-expression of the transduced fusion gene TRX1-ABAD-DP-TRX2 and amyloid β peptide in NIH-3T3 cells, indicating that the TRX1-ABAD-DP-TRX2 aptamer can bind amyloid β peptide within cells. In addition, cell morphology and MTT results suggested that TRX1-ABAD-DP-TRX2 attenuated amyloid β peptide-induced SH-SY5Y cell injury and improved cell viability. These findings confirmed the possibility of constructing TRX-based peptide aptamer using ABAD-DP. Moreover, TRX1-ABAD-DP-TRX2 inhibited the cytotoxic effect of amyloid β peptide.

  12. Detrimental effects of beta-blockers in COPD - A concern for nonselective beta-blockers

    NARCIS (Netherlands)

    van der Woude, HJ; Zaagsma, J; Postma, DS; Winter, TH; van Hulst, M; Aalbers, R


    Introduction: beta-Blockers are known to worsen FEV1 and airway hyperresponsiveness (AHR) in patients with asthma. Both characteristics determine the outcome of COPD, a disease with frequent cardiac comorbidity requiring beta-blocker treatment. Design: A double-blind, placebo-controlled, randomized,

  13. Exacerbation of CNS inflammation and neurodegeneration by systemic LPS treatment is independent of circulating IL-1 beta and IL-6

    LENUS (Irish Health Repository)

    Murray, Carol L


    Abstract Background Chronic neurodegeneration comprises an inflammatory response but its contribution to the progression of disease remains unclear. We have previously shown that microglial cells are primed by chronic neurodegeneration, induced by the ME7 strain of prion disease, to synthesize limited pro-inflammatory cytokines but to produce exaggerated responses to subsequent systemic inflammatory insults. The consequences of this primed response include exaggerated hypothermic and sickness behavioural responses, acute neuronal death and accelerated progression of disease. Here we investigated whether inhibition of systemic cytokine synthesis using the anti-inflammatory steroid dexamethasone-21-phosphate was sufficient to block any or all of these responses. Methods ME7 animals, at 18-19 weeks post-inoculation, were challenged with LPS (500 μg\\/kg) in the presence or absence of dexamethasone-21-phosphate (2 mg\\/kg) and effects on core-body temperature and systemic and CNS cytokine production and apoptosis were examined. Results LPS induced hypothermia and decreased exploratory activity. Dexamethasone-21-phosphate prevented this hypothermia, markedly suppressed systemic IL-1β and IL-6 secretion but did not prevent decreased exploration. Furthermore, robust transcription of cytokine mRNA occurred in the hippocampus of both ME7 and NBH (normal brain homogenate) control animals despite the effective blocking of systemic cytokine synthesis. Microglia primed by neurodegeneration were not blocked from the robust synthesis of IL-1β protein and endothelial COX-2 was also robustly synthesized. We injected biotinylated LPS at 100 μg\\/kg and even at this lower dose this could be detected in blood plasma. Apoptosis was acutely induced by LPS, despite the inhibition of the systemic cytokine response. Conclusions These data suggest that LPS can directly activate the brain endothelium even at relatively low doses, obviating the need for systemic cytokine stimulation to transduce systemic inflammatory signals into the brain or to exacerbate existing pathology.

  14. New insights into the relationship between airway inflammation and asthma. (United States)

    Wardlaw, A J; Brightling, C E; Green, R; Woltmann, G; Bradding, P; Pavord, I D


    Asthma is a condition characterized by variable airflow obstruction, airway hyper-responsiveness (AHR) and airway inflammation which is usually, but not invariably, eosinophilic. Current thoughts on the pathogenesis of asthma are focused on the idea that it is caused by an inappropriate response of the specific immune system to harmless antigens, particularly allergens such as cat dander and house dust mite, that result in Th2-mediated chronic inflammation. However, the relationship between inflammation and asthma is complex, with no good correlation between the severity of inflammation, at least as measured by the number of eosinophils, and the severity of asthma. In addition, there are a number of conditions, such as eosinophilic bronchitis and allergic rhinitis, in which there is a Th2-mediated inflammatory response, but no asthma, as measured by variable airflow obstruction or AHR. Bronchoconstriction can also occur without obvious airway inflammation, and neutrophilic inflammation can in some cases be associated with asthma. When we compared the immunopathology of eosinophilic bronchitis and asthma, the only difference we observed was that, in asthma, the airway smooth muscle (ASM) was infiltrated by mast cells, suggesting that airway obstruction and AHR are due to an ASM mast cell myositis. This observation emphasizes that the features that characterize asthma, as opposed to bronchitis, are due to abnormalities in smooth muscle responsiveness, which could be intrinsic or acquired, and that inflammation is only relevant in that it leads to these abnormalities. It also emphasizes the importance of micro-localization as an organizing principle in physiological responses to airway inflammation. Thus, if inflammation is localized to the epithelium and lamina propria, then the symptoms of bronchitis (cough and mucus hypersecretion) result, and it is only if the ASM is involved -- for reasons that remain to be established -- that asthma occurs.

  15. A Combined Marker of Inflammation in Individuals with Mania (United States)

    Dickerson, Faith; Stallings, Cassie; Origoni, Andrea; Vaughan, Crystal; Katsafanas, Emily; Khushalani, Sunil; Yolken, Robert


    Background Markers of immune activation have been associated with mania but have not been examined in combination. We studied the association between mania and an inflammation score based on four immune markers. Methods A total of 57 individuals with mania were assessed at up to three time points: the day of hospital admission, evaluation several days later, and six-month follow-up. Also assessed were 207 non-psychiatric controls and 330 individuals with recent onset psychosis, multi-episode schizophrenia, or bipolar disorder depression. A combined inflammation score was calculated by factor analysis of the levels of class-specific antibodies to the NR peptide of the NMDA receptor; gliadin; Mason-Pfizer monkey virus protein 24; and Toxoplasma gondii. Inflammation scores among groups were compared by multivariate analyses. The inflammation score of the mania group at evaluation was studied as a predictor of re-hospitalization in the follow-up period. Results The combined inflammation score of the mania group at hospital admission and at evaluation differed significantly from that of the non-psychiatric controls (t = 3.95, 4.10, p<.001). The inflammation score was significantly decreased at six month follow-up (F = 5.85, p = 0.004). There were not any significant differences in the inflammation scores of any of the other psychiatric groups and that of the controls. Within the mania group, an elevated inflammation score at evaluation predicted re-hospitalization (Hazard ratio = 7.12, p = .005). Conclusions Hospitalization for mania is associated with immune activation. The level of this activation is predictive of subsequent re-hospitalization. Interventions for the modulation of inflammation should be evaluated for the therapy of individuals with mania. PMID:24019926

  16. A combined marker of inflammation in individuals with mania.

    Directory of Open Access Journals (Sweden)

    Faith Dickerson

    Full Text Available BACKGROUND: Markers of immune activation have been associated with mania but have not been examined in combination. We studied the association between mania and an inflammation score based on four immune markers. METHODS: A total of 57 individuals with mania were assessed at up to three time points: the day of hospital admission, evaluation several days later, and six-month follow-up. Also assessed were 207 non-psychiatric controls and 330 individuals with recent onset psychosis, multi-episode schizophrenia, or bipolar disorder depression. A combined inflammation score was calculated by factor analysis of the levels of class-specific antibodies to the NR peptide of the NMDA receptor; gliadin; Mason-Pfizer monkey virus protein 24; and Toxoplasma gondii. Inflammation scores among groups were compared by multivariate analyses. The inflammation score of the mania group at evaluation was studied as a predictor of re-hospitalization in the follow-up period. RESULTS: The combined inflammation score of the mania group at hospital admission and at evaluation differed significantly from that of the non-psychiatric controls (t=3.95, 4.10, p<.001. The inflammation score was significantly decreased at six month follow-up (F=5.85, p=0.004. There were not any significant differences in the inflammation scores of any of the other psychiatric groups and that of the controls. Within the mania group, an elevated inflammation score at evaluation predicted re-hospitalization (Hazard ratio=7.12, p=.005. CONCLUSIONS: Hospitalization for mania is associated with immune activation. The level of this activation is predictive of subsequent re-hospitalization. Interventions for the modulation of inflammation should be evaluated for the therapy of individuals with mania.

  17. Markers of low-grade inflammation and endothelial dysfunction are related to reduced information processing speed and executive functioning in an older population - the Hoorn Study. (United States)

    Heringa, S M; van den Berg, E; Reijmer, Y D; Nijpels, G; Stehouwer, C D A; Schalkwijk, C G; Teerlink, T; Scheffer, P G; van den Hurk, K; Kappelle, L J; Dekker, J M; Biessels, G J


    Low-grade inflammation and endothelial dysfunction are related to cognitive decline and dementia, in a complex interplay with vascular factors and aging. We investigated, in an older population, low-grade inflammation and endothelial dysfunction in relation to detailed assessment of cognitive functioning. Furthermore, we explored this association within the context of vascular factors. 377 participants (73 ± 6 years) of the population-based Hoorn Study were included. In plasma samples of 2000-2001 (n=363) and/or 2005-2008 (n=323), biomarkers were determined of low-grade inflammation (CRP, TNF-alpha, IL-6, IL-8, SAA, MPO, and sICAM-1) and endothelial dysfunction (vWF, sICAM-1, sVCAM-1, sTM, sE-selectin). In 2005-2008, all participants underwent neuropsychological examination. Composite z-scores were computed for low-grade inflammation and endothelial dysfunction at both time points, and for six domains of cognitive functioning (abstract reasoning, memory, information processing speed, attention and executive functioning, visuoconstruction, and language). The association between low-grade inflammation and endothelial dysfunction, and cognitive functioning was evaluated with linear regression analysis. In secondary analyses, we explored the relation with vascular risk factors and cardiovascular disease. Low-grade inflammation and endothelial dysfunction were associated with worse performance on information processing speed and attention and executive functioning, in prospective and cross-sectional analyses (standardized betas ranging from -0.20 to -0.10). No significant relation with other cognitive domains was observed. Adjusting for vascular factors slightly attenuated the associations. Low-grade inflammation and endothelial dysfunction accounted for only 2.6% explained variance in cognitive functioning, on top of related vascular risk factors and cardiovascular disease. Bootstrapping analyses show that low-grade inflammation and endothelial dysfunction mediate the

  18. Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis. (United States)

    Cronstein, Bruce N; Sunkureddi, Prashanth


    It has been recently demonstrated that interleukin 1β (IL-1β) plays a central role in monosodium urate crystal-induced inflammation and that the NALP3 inflammasome plays a major role in IL-1β production. These discoveries have offered new insights into the pathogenesis of acute gouty arthritis. In this review, we discuss the molecular mechanisms by which monosodium urate crystals induce acute inflammation and examine the mechanisms of action (MOAs) of traditional anti-inflammatory drugs (e.g., nonsteroidal anti-inflammatory drugs, colchicine, and glucocorticoids) and biologic agents (e.g., the IL-1β antagonists anakinra, rilonacept, and canakinumab) to understand how their MOAs contribute to their safety profiles. Traditional anti-inflammatory agents may act on the IL-1β pathway at some level; however, their MOAs are broad-ranging, unspecific, and biologically complex. This lack of specificity may explain the range of systemic adverse effects associated with them. The therapeutic margins of nonsteroidal anti-inflammatory drugs, colchicine, and glucocorticoids are particularly low in elderly patients and in patients with cardiovascular, metabolic, or renal comorbidities that are frequently associated with gouty arthritis. In contrast, the IL-1β antagonists act on very specific targets of inflammation, which may decrease the potential for systemic adverse effects, although infrequent but serious adverse events (including infection and administration reactions) have been reported. Because these IL-1β antagonists target an early event immediately downstream from NALP3 inflammasome activation, they may provide effective alternatives to traditional agents with minimal systemic adverse effects. Results of ongoing trials of IL-1β antagonists will likely provide clarification of their potential role in the management of acute gouty arthritis.

  19. Neuro-inflammation, blood-brain barrier, seizures and autism

    Directory of Open Access Journals (Sweden)

    Theoharides Theoharis C


    Full Text Available Abstract Many children with Autism Spectrum Diseases (ASD present with seizure activity, but the pathogenesis is not understood. Recent evidence indicates that neuro-inflammation could contribute to seizures. We hypothesize that brain mast cell activation due to allergic, environmental and/or stress triggers could lead to focal disruption of the blood-brain barrier and neuro-inflammation, thus contributing to the development of seizures. Treating neuro-inflammation may be useful when anti-seizure medications are ineffective.

  20. Persistent low-grade inflammation and regular exercise

    DEFF Research Database (Denmark)

    Astrom, Maj-Briit; Feigh, Michael; Pedersen, Bente Klarlund;


    Persistent low-grade systemic inflammation is a feature of chronic diseases such as cardiovascular disease (CVD), type 2 diabetes and dementia and evidence exists that inflammation is a causal factor in the development of insulin resistance and atherosclerosis. Regular exercise offers protection...... against all of these diseases and recent evidence suggests that the protective effect of exercise may to some extent be ascribed to an anti-inflammatory effect of regular exercise. Visceral adiposity contributes to systemic inflammation and is independently associated with the occurrence of CVD, type 2...