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Sample records for cytokines content irradiated

  1. Cytokine production of the neutrophils and macrophages in time of phagocytosis under influence of infrared low-level laser irradiation

    NASA Astrophysics Data System (ADS)

    Rudik, Dmitry V.; Tikhomirova, Elena I.; Tuchina, Elena S.

    2006-08-01

    Influence of infrared low-level laser irradiation (LLLI) on induction of synthesis of some cytokines such as interleykin-1 (Il-1), tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), interleykin-8 (Il-8) and interleykin-4 (Il-4) by the neutrophils and macrophages in time of bacterial cells phagocytosis that was searched. As the object of analysis we used peritoneal macrophages from white mice and neutrophils from peripheral blood of healthy donors. We used the laser diod with spectrum maximum of 850 nm with doses 300, 900 and 1500 mJ (exposition -60, 180 and 300 s respectively; capacity - 5 mW). We carried out the Enzyme-Linked Immunospot Assay (ELISA) to determine cytokine content during phagocytosis after 3 h and 6 h. We found dynamics in production of the cytokines, which was different for the neutrophils and macrophages. We showed that the infrared LLLI has significant stimulating activity on the proinflammatory cytokines production by neutrophils and macrophages. Moreover we revealed dynamics changing in the Il-8 and Il-4 production.

  2. Short-term injection of antiapoptotic cytokine combinations soon after lethal gamma -irradiation promotes survival.

    PubMed

    Hérodin, Francis; Bourin, Philippe; Mayol, Jean-François; Lataillade, Jean-Jacques; Drouet, Michel

    2003-04-01

    Recovery from radiation-induced (RI) myelosuppression depends on hematopoietic stem and progenitor cell survival and the active proliferation/differentiation process, which requires early cytokine support. Single cytokine or late-acting growth factor therapy has proved to be inefficient in ensuring reconstitution after severe RI damage. This work was aimed at evaluating the in vivo survival effect of combinations of early-acting cytokines whose antiapoptotic activity has been demonstrated in vitro: stem cell factor (SCF [S]), FMS-like tyrosine kinase 3 ligand (FLT-3 ligand [F]), thrombopoietin (TPO [T]), interleukin-3 (IL-3 [3]), and stromal derived factor-1 (SDF-1). B6D2F1 mice underwent total body irradiation at 8 Gy cesium Cs 137 gamma radiation (ie, lethal dose 90% at 30 days) and were treated soon after irradiation, at 2 hours and at 24 hours, with recombinant murine cytokines, each given intraperitoneally at 50 microg/kg per injection. All treatments induced 30-day survival rates significantly higher than control (survival rate, 8.3%). 4F (SFT3) and 5F (4F + SDF-1) were the most efficient combinations (81.2% and 87.5%, respectively), which was better than 3F (SFT, 50%), TPO alone (58.3%), and SDF-1 alone (29.2%) and also better than 4F given at 10 microg/kg per injection (4F10, 45.8%) or as a 50 microg/kg single injection at 2 hours (4Fs, 62.5%). Despite delayed death occurring mainly from day 150 on and possible long-term hematopoiesis impairment, half the 30-day protective effects of 4F and 5F were preserved at 300 days. Our results show that short- and long-term survival after irradiation depends on appropriate multiple cytokine combinations and at optimal concentrations. The proposal is made that an emergency cytokine regimen could be applied to nuclear accident victims as part of longer cytokine treatment, cell therapy, or both.

  3. Evaluation of low level laser therapy irradiation parameters on rat muscle inflammation through systemic blood cytokines

    NASA Astrophysics Data System (ADS)

    Mantineo, Matias; Pinheiro, João. P.; Morgado, António M.

    2014-02-01

    Low level laser therapy (LLLT) has been used for inflammation treatment. Here, we evaluate the effect of different doses, using continuous (830 and 980 nm) and pulsed illumination (830 nm), in the treatment of inflammation induced in the gastrocnemius muscle of Wistar rats, through cytokines concentration in systemic blood and histological analysis of muscle tissue. Animals were randomly divided into five groups per wavelength (5 animals per group: 10, 20, 30, 40 and 50 mW) plus a control group. LLLT was applied during five days, with constant exposure time and irradiated area (3 minutes; 0.5026 cm2). Blood was collected on days 0, 3 and 6. TNF-α, IL-1β, IL-2 and IL-6 cytokines were quantified by ELISA. Rats were killed on day 6. Muscle inflammatory cells were counted using optical microscopy. Treatment effects occurred for all applied doses (largest effect at 40 mW: 7.2 J, 14 J/cm2 per irradiation), with reduction of proinflammatory TNF-α, IL-1β and IL-6 cytokines and lower number of inflammatory cells. Results were better for 830 nm. Identical methodology was used with pulsed illumination. Average power (40 mW) and duty cycle were kept constant (80%) at five frequencies (5, 25, 50, 100 and 200 Hz). Treatment effects were observed at higher frequencies, with no significant differences between them. However, the treatment effect was lower than for continuous illumination. LLLT effect on inflammation treatment can be monitored by measuring systemic blood cytokines. A larger treatment effect was observed with continuous illumination, where results seem to be compatible with a biphasic dose response.

  4. The influence of Gamma Irradiation on flavonoïds content during storage of irradiated clementina

    NASA Astrophysics Data System (ADS)

    Oufedjikh, H.; Mahrouz, M.; Lacroix, M.; Amiot, M. J.; Taccini, M.

    1998-06-01

    The influence of Gamma irradiation on content of some important flavonoïds (flavonones glycosides and polymethoxylated flavones) was evaluated during storage of Moroccan clementina treated at a mean dose of 0.3 kGy and stored three months at 3'C. Results shows that at day one, gamma irradiation induced degradation of small quantities of these flavonoïds, however after 14 days of storage, the content of these compounds was significantly higher (p≤0.05) in irradiated samples. Irradiation stimulated biosynthesis of flavonoïds after 14 days of storage. Hesperidin was the major flavanones compounds in clementines. Nobiletin and Heptamethoxyflavone were the major polymethoxylated flavones in clementines. Our study demonstrated that the content of these compounds was significantly higher (p≤0.05) in irradiated samples.

  5. [THE INFLUENCE OF EXTRACT FROM EMBRYONIC CHICKEN TISSUE ON THE DYNAMIC CHANGES OF MICE BLOOD SERUM C-REACTIVE PROTEIN AND CYTOKINES AFTER γ-IRRADIATION].

    PubMed

    Pogorelaya, M S

    2015-01-01

    The effect of preparations from embryonic chicken tissue on the dynamic changes in the levels of interleukins: 1β (IL-1 β), 6 (IL-6), 4 (IL-4) and C-reactive protein (CRP) were investigated in vivo, in the blood serum of white female laboratory mice exposed to single total γ-irradiation in a dose of 5 Gy. The experiments found that during the first days after the action of γ-radiation the indices of resistance of the organism undergoe significant destabilizing changes. These changes are manifested by an increase in IL-1β proinflammatory cytokine in response to external influences. However, the rapid decline in its level during the first days after irradiation reflects alterations in its production. The content of the serum IL-4 in all time points was higher than in the intact group. Moreover, the dynamics of its level during the first days after the irradiation was observed. An increased level of CRP was detected 6 hours after the exposure, indicating the dynamic changes of the severity of the inflammatory process. Administration of preparations from embryonic chicken tissue causes a considerable increase in the content of IL-1β and IL-6 in 3 and 6 hours after the r-irradiation, with stabilization after 12 hours. When using the preparations before an irradiation, a significantly lower level of CRP was detected in comparison to animals that did not get the preparations. When using the embryonic preparations, the stimulation of synthesis of IL-4 was observed, whose level increased in every time of taking blood samples. Possibility for induction of row of cytokines, in particular, IL-1β and IL-6, plays an important role in stimulation of hematopoiesis and provides a basis to consider this substance as an immunomodulator in pathologic immunosuppressive states. The decrease of serum CRP level can indicate the ability to reduce the severity of radiation injury. In the experimental conditions, an embryonic preparation exhibits inertness relative to the healthy

  6. Corrugated Waveguide Mode Content Analysis Using Irradiance Moments

    PubMed Central

    Jawla, Sudheer K.; Shapiro, Michael A.; Idei, Hiroshi; Temkin, Richard J.

    2015-01-01

    We present a novel, relatively simple method for determining the mode content of the linearly polarized modes of a corrugated waveguide using the moments of the intensity pattern of the field radiated from the end of the waveguide. This irradiance moment method is based on calculating the low-order irradiance moments, using measured intensity profiles only, of the radiated field from the waveguide aperture. Unlike the phase retrieval method, this method does not use or determine the phase distribution at the waveguide aperture. The new method was benchmarked numerically by comparison with sample mode mixtures. The results predict less than ±0.7% error bar in the retrieval of the mode content. The method was also tested using high-resolution experimental data from beams radiated from 63.5 mm and 19 mm corrugated waveguides at 170 and 250 GHz, respectively. The results showed a very good agreement of the mode content retrieved using the irradiance moment method versus the phase retrieval technique. The irradiance moment method is most suitable for cases where the modal power is primarily in the fundamental HE11 mode, with <8% of the power in high-order modes. PMID:25821260

  7. Effect of dietary vanadium on the ileac T cells and contents of cytokines in broilers.

    PubMed

    Wang, Kangping; Cui, Hengmin; Deng, Yuanxin; Peng, Xi; Fang, Jing; Zuo, Zhicai; Cui, Wei

    2012-06-01

    The purpose of this 42-day study was to examine the effect of dietary vanadium on the ileac T cells and contents of cytokines including interleukin-2 (IL-2), interleukin-6 (IL-6), and interferon-gamma (IFN-γ) in broilers by flow cytometry and enzyme-linked immunosorbent assay. A total of 420 one-day-old avian broilers were divided into six groups (seven replicates in each group and ten broilers in each replicate) and fed on control diet or the same diet supplemented with 5, 15, 30, 45, and 60 mg/kg vanadium in the form of ammonium metavanadate. The results showed that the percentages of CD3(+), CD3(+)CD4(+), and CD3(+)CD8(+) T cells in both ileac lamina propria lymphocytes (LPLs) and intraepithelial lymphocytes (IELs) were significantly lower (P < 0.05 or P < 0.01) in the 45- and 60-mg/kg groups than in the control group from 14 to 42 days of age. The CD4(+)/CD8(+) ratio was increased in ileac LPLs in the 60-mg/kg group at 28 days of age, and in ileac IELs in the 60-mg/kg group at 28 days of age and in the 45-mg/kg group at 42 days of age. Meanwhile, the ileac IL-2, IL-6 contents were decreased (P < 0.05 or P < 0.01) in the 60-mg/kg group from 14 to 42 days of age and in the 45-mg/kg group from 28 to 42 days of age in comparison with those of the control group. It was concluded that dietary vanadium in excess of 30 mg/kg reduced the ileac T cell population and percentages of T cell subsets, and IL-2, IL-6, and IFN-γ contents, implying that the immune function of local intestinal mucosa in broilers could be affected by the dietary vanadium.

  8. Effect of HeNe laser irradiation on extracellular matrix deposition and expression of cytokines and chemokines in paracoccidioidomycotic lesions.

    PubMed

    Nagib, Patrícia R A; Gameiro, Jacy; da Costa, Thiago Alves; Di Gangi, Rosária; Ribeiro, Júlia da Silva; Paulino, Luciana Campos; Verinaud, Liana

    2010-01-01

    Paracoccidioidomycosis is the most prevalent human mycosis in Latin America. Cutaneous lesions are extremely painful and sensitive, and current treatment with antifungal drugs is lengthy and may cause side effects to patients. In this perspective, the helium-neon (HeNe) laser emerges as a novel therapy form due to its ability to heal wounds without changing cell function. In this work, we evaluate the effects of HeNe laser irradiation on extracellular matrix deposition and expression of cytokines and chemokines in cutaneous lesions caused by experimental infection of Balb/c mice. Our results showed decreased levels of pro-inflammatory interleukin (IL)-17 and tumor necrosis factor-alpha, and of anti-inflammatory IL-10 cytokines in lesions exposed to HeNe laser irradiation. Chemokines CCL3 and CXCL10 showed decreased levels in laser-treated lesions, but no significant difference was observed in relation to CCL5 expression. We also detected decreased density of fibronectin and laminin in HeNe laser-treated lesions. Data presented herein support the validity of our previous results suggesting positive effects of HeNe laser in accelerating wound healing in this experimental model. We believe that HeNe laser is a new nonharmful strategy that may be used as adjuvant and/or alternative therapy for improving treatment of paracoccidioidomycotic lesions. PMID:20408980

  9. Chronic aspiration of gastric and duodenal contents and their effects on inflammatory cytokine production in respiratory system of rats.

    PubMed

    Samareh Fekri, Mitra; Poursalehi, Hamid Reza; Najafipour, Hamid; Shahouzahi, Beydolah; Bazargan Harandi, Nasrin

    2014-02-01

    Gastroesophageal reflux disease (GERD) is defined with clinical symptoms of heart burning and regurgitation. It may be associated with external esophageal symptoms such as chronic cough, asthma, laryngitis, chronic lung disease, sinusitis and pulmonary fibrosis. In the present study, rats with chronic aspiration of gastroduodenal contents were studied for cellular phenotypes and cytokine concentrations in bronchoalveolar lavage and lung tissue. Thirty-six male Albino N-MRI rats were randomly divided into six groups. After anesthesia and tracheal intubation, the animals received either 0.5ml/kg of normal saline (control), gastric juice, pepsin, hydrochloric acid or bile salts by injection into their lungs twice a week for 8 weeks. In sham group nothing was injected. Thereafter, cellular phenotypes and cytokine concentrations of Interleukine (IL)-1α, IL-1β, Transforming Growth Factor (TGF)-β, Tumor Necrosis Factor (TNF)-α, and IL-6 were assessed in bronchoalveolar lavage and lung tissue homogenates. The numbers of epithelial cells, macrophages, neutrophils and lymphocytes in BAL and levels of cytokines IL-1α, IL-6, TNF-α and TGF-β in BAL and lung tissue of test groups were significantly higher than the control group. Aspiration of bile salts caused more cytokine levels and inflammatory cells compared to other reflux components. It can be concluded that GERD with increased cytokines and inflammatory cells in lung could cause or exacerbate asthma and pulmonary fibrosis. PMID:24338227

  10. Régulation de la production, par des cellules endothéliales, de cytokines pro-inflammatoires après irradiation

    NASA Astrophysics Data System (ADS)

    van der Meeren, A.; Lafont, H.; Mathé, D.

    1998-04-01

    Gamma irradiation leads to an increased production of interleukin- (IL)-6 and IL-8 by human endothelial cells. In order to regulate the radio-induced production of these pro-inflammatory cytokines, we used the immunoregulatory cytokines IL-4 and IL-10. These agents were added either before or after a 10 Gy-irradiation. Our results show that it is possible to decrease the radio-induced production of IL-6 and IL-8 with the use of IL-4 and IL-10. Differences in the intensity of the response have been observed according to the time of treatment. The anti-inflammatory potential of both IL-4 and IL-10 was more pronounced when added after irradiation. Après irradiation gamma, des cellules endothéliales humaines ont une production accrue des interleukines (IL-) -6 et -8. Dans le but de réguler la production de ces cytokines pro-inflammatoires, nous avons utilisé des cytokines dites anti-inflammatoires, l'IL-4 et l'IL-10. Ces agents ont été ajoutés soit avant soit après une irradiation de 10Gy. Nos résultats montrent qu'il est possible de diminuer les productions radio-induites d'IL-6 et d'IL-8 par l'IL-4 et l'IL-10. Des différences dans l'intensité de la réponse ont toutefois été observées selon que l'IL-4 ou l'IL-10 ont été ajoutées avant ou après irradiation; leur efficacité anti-inflammatoire étant plus marquée lorsque les cytokines sont ajoutées après l'irradiation.

  11. Gene expression of hematoregulatory cytokines is elevated endogenously after sublethal gamma irradiation and is differentially enhanced by therapeutic administration of biologic response modifiers

    SciTech Connect

    Peterson, V.M.; Adamovicz, J.J.; Madonna, G.S.; Gause, W.C.; Elliott, T.B.; Moore, M.M.; Ledney, G.D.; Jackson, W.E. III

    1994-09-01

    Prompt, cytokine-mediated restoration of hematopoiesis is a prerequisite for survival after irradiation. Therapy with biologic response modifiers (BRMs), such as LPS, 3D monophosphoryl lipid A (MPL), and synthetic trehalose dicrynomycolate (S-TDCM) presumably accelerates hematopoietic recovery after irradiation are poorly defined. One hour after sublethal (7.0 Gy) {sup 60}Co gamma irradiation, B6D2F1/J female mice received a single i.p. injection of LPS, MPL, S-TDCM, an extract from Serratia marcescens (Sm-BRM), or Tween 80 in saline (TS). Five hours later, a quantitative reverse transcription-PCR assay demonstrated marked splenic gene expression for IL-1{beta}, IL-3, IL-6, and granulocyte-CSF (G-CSF). Enhanced gene expression for TNF-{alpha}, macrophage-CSF (M-CSF), and stem cell factor (SCF) was not detected. Injection of any BRM further enhanced cytokine gene expression and plasma levels of CSF activity within 24 h after irradiation and hastened bone marrow recovery. Mice injected with S-TDCM or Sm-BRM sustained expression of the IL-6 gene for at least 24 h after irradiation. Sm-BRM-treated mice exhibited greater gene expression for IL-1{beta}, IL-3, TNF-{alpha}, and G-CSF at day 1 than any other BRM. When challenged with 2 LD{sub 50/30} of Klebsiella pneumoniae 4 days after irradiation, 100% of Sm-BRM-treated mice and 70% of S-TDCM-treated mice survived, whereas {le}30% of mice treated with LPS, MPL, or TS survived. Thus, sublethal irradiation induces transient, splenic cytokine gene expression that can be differentially amplified and prolonged by BRMs. BRMs that sustained and/or enhanced irradiation-induced expression of specific cytokine genes improved survival after experimental infection. 67 refs., 7 figs., 1 tab.

  12. [Thiamine in irradiated foodstuffs. II. Combined effects of irradiation, storage and cooking on the thiamine content (author's transl)].

    PubMed

    Diehl, J F

    1975-06-30

    The effects of 10 MeV electron radiation, of storage for several months and of heating on the thiamine content of wheat flour, crushed oats, ground pork, and dried whole egg were studied. A synergistic effect of these treatments on thiamine losses was observed. In irradiated samples thiamine content was more affected by storage and heating than in unirradiated ones.

  13. ESR detection procedure of irradiated papaya containing high water content

    NASA Astrophysics Data System (ADS)

    Kikuchi, Masahiro; Shimoyama, Yuhei; Ukai, Mitsuko; Kobayashi, Yasuhiko

    2011-05-01

    ESR signals were recorded from irradiated papaya at liquid nitrogen temperature (77 K), and freeze-dried irradiated papaya at room temperature (295 K). Two side peaks from the flesh at the liquid nitrogen temperature indicated a linear dose response for 3-14 days after the γ-irradiation. The line shapes recorded from the freeze-dried specimens were sharper than those at liquid nitrogen temperature.

  14. Dose and dose rate effects of whole-body gamma-irradiation: II. Hematological variables and cytokines

    NASA Technical Reports Server (NTRS)

    Gridley, D. S.; Pecaut, M. J.; Miller, G. M.; Moyers, M. F.; Nelson, G. A.

    2001-01-01

    The goal of part II of this study was to evaluate the effects of gamma-radiation on circulating blood cells, functional characteristics of splenocytes, and cytokine expression after whole-body irradiation at varying total doses and at low- and high-dose-rates (LDR, HDR). Young adult C57BL/6 mice (n = 75) were irradiated with either 1 cGy/min or 80 cGy/min photons from a 60Co source to cumulative doses of 0.5, 1.5, and 3.0 Gy. The animals were euthanized at 4 days post-exposure for in vitro assays. Significant dose- (but not dose-rate-) dependent decreases were observed in erythrocyte and blood leukocyte counts, hemoglobin, hematocrit, lipopolysaccharide (LPS)-induced 3H-thymidine incorporation, and interleukin-2 (IL-2) secretion by activated spleen cells when compared to sham-irradiated controls (p < 0.05). Basal proliferation of leukocytes in the blood and spleen increased significantly with increasing dose (p < 0.05). Significant dose rate effects were observed only in thrombocyte counts. Plasma levels of transforming growth factor-beta 1 (TGF-beta 1) and splenocyte secretion of tumor necrosis factor-alpha (TNF-alpha) were not affected by either the dose or dose rate of radiation. The data demonstrate that the responses of blood and spleen were largely dependent upon the total dose of radiation employed and that an 80-fold difference in the dose rate was not a significant factor in the great majority of measurements.

  15. Role of Cytokines in Intervertebral Disc Degeneration: Pain and Disc-content

    PubMed Central

    Risbud, Makarand V.; Shapiro, Irving. M

    2014-01-01

    Degeneration of the intervertebral disc is the major contributor to back/neck and radicular pain. It is characterized by an elevation in levels of the inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1 α/β, IL-6 and IL-17 secreted by the disc cells themselves; these cytokines promote matrix degradation, chemokine production and changes in cell phenotype. The resulting imbalance between catabolic and anabolic responses leads to degeneration, as well as herniation and radicular pain. Release of chemokines from degenerating discs promote infiltration and activation of T and B cells, macrophages, neutrophils, and mast cells further amplifying the inflammatory cascade. Immunocyte migration into the disc is accompanied by the appearance of microvasculature and nerve fibers arising from the dorsal root ganglion (DRG). In this inflammatory milieu, neurogenic factors in particular nerve growth factor (NGF) and brain-derive neurotrophic factor (BDNF) generated by disc and immune cells induce expression of pain associated cation channels in DRGs. Depolarization of these channels is likely to promote discogenic and radicular pain and reinforce the cytokine-mediated degenerative cascade. Taken together, the enhanced understanding of the contribution of cytokines and immune cells to catabolic and nociceptive processes provide new targets for treating symptomatic disc disease. PMID:24166242

  16. Glioma-specific cytotoxic T cells can be effectively induced by subcutaneous vaccination of irradiated wild-type tumor cells without artificial cytokine production.

    PubMed

    Iwadate, Yasuo; Yamaura, Akira; Sakiyama, Shigeru; Sato, Yasuo; Tagawa, Masatoshi

    2003-08-01

    Effective induction of systemic antitumor immunity is a crucial step for success of immune gene therapy for intracerebral gliomas. We examined in this study the ability to induce glioma-specific cytotoxic T lymphocytes (CTL) by subcutaneous (s.c.) immunization of irradiated whole-tumor cell vaccine with or without artificial cytokine production, and also examined in vivo efficacy of the induced CTL against a rat brain tumor model with 9L gliosarcoma cells. Murine neuroblastoma C1300 cells transduced with the interleukin-2 (IL-2), IL-4 or granulocyte-macrophage colony-stimulating factor (GM-CSF) gene (C1300/IL-2, C1300/IL-4 or C1300/GM-CSF) were used as cytokine-producers. Glioma-specific CTL activity was equivalently induced in the rats vaccinated s.c. with irradiated 9L, irradiated IL-2-producing 9L cells or the mixed population of irradiated 9L and C1300/IL-2 cells, while the activity was relatively lower in the rats vaccinated with irradiated 9L cells mixed with either C1300/IL-4 or C1300/GM-CSF cells. In the rats immunized s.c. with irradiated 9L cells, intracerebral (i.c.) 9L tumors implanted together with either C1300/IL-2 or C1300/IL-4 were completely rejected. Pre-established brain tumor also could be eliminated by the s.c. immunization of irradiated 9L cells and i.c. transplantation of IL-2-producers. These results suggest that glioma-specific CTLs could be effectively induced by s.c. immunization of irradiated wild-type tumor cells without artificial cytokine production.

  17. Analysis of cytokine production and V beta T-cell receptor subsets in irradiated recipients receiving portal or peripheral venous reconstitution with allogeneic bone marrow cells, with or without additional anti-cytokine monoclonal antibodies.

    PubMed Central

    Gorczynski, R M; Chen, Z; Zeng, H; Gorczynski, L; Terzioglu, E

    1998-01-01

    Irradiated (800 rads) AKR mice received intravenous (i.v.) reconstitution with a mixture of B10.BR T-depleted bone marrow cells and spleen cells. Only in groups of mice treated additionally with i.v. cyclophosphamide (Cy; 150 mg/kg), 24 hr before transplantation, was long-term (> 60% at 50 days) survival seen. In mice receiving only irradiation all animals died by 30 days post-transplantation. Histological changes consistent with graft-versus-host disease (GVHD) were seen in the liver of reconstituted mice at 30 days, along with an organ-specific increase in V beta 3 T-cell receptor-positive (TCR+) cells. No such increase in V beta 3 TCR+ cells was seen in the spleen from the same mice. These data are consistent with a tissue antigen-driven expansion of V beta 3 TCR+ cells associated with GVHD in the liver in this model. When we analysed cytokine production in vitro from CD3+ cells restimulated with 'host' (AKR) antigen-presenting cells (APC), we found a transition in cytokine production from preferential synthesis of type-1 cytokines [interleukin-2 (IL-2) and interferon-gamma (IFN-gamma)] at early times (day 15) post-reconstitution to increased production of type-2 cytokines [IL-4, transforming growth factor-beta (TGF-beta) and IL-10] at later times (day 30) post-reconstitution in Cy-treated recipients. Animals not receiving Cy did not show this 'switch' in cytokine production at later time points. We have observed a similar polarization in cytokine production, along with increased graft survival, in recipients of vascularized and non-vascularized allografts after portal venous (p.v.), but not i.v., pretransplant donor-specific immunization. We next studied AKR mice receiving 800 rads and subsequently reconstituted with B10.BR stem cells via the p.v. route. Again these mice showed prolonged survival (> 50% at 50 days), with polarization to IL-4, IL-10 and TGF-beta on restimulation of CD3+ cells in vitro at 30 days post-transplant and increased V beta 3 TCR+ cells

  18. The Effect of Solar Irradiated Vibrio cholerae on the Secretion of Pro-Inflammatory Cytokines and Chemokines by the JAWS II Dendritic Cell Line In Vitro.

    PubMed

    Ssemakalu, Cornelius Cano; Ubomba-Jaswa, Eunice; Motaung, Keolebogile Shirley; Pillay, Michael

    2015-01-01

    The use of solar irradiation to sterilize water prior to its consumption has resulted in the reduction of water related illnesses in waterborne disease endemic communities worldwide. Currently, research on solar water disinfection (SODIS) has been directed towards understanding the underlying mechanisms through which solar irradiation inactivates the culturability of microorganisms in water, enhancement of the disinfection process, and the health impact of SODIS water consumption. However, the immunological consequences of SODIS water consumption have not been explored. In this study, we investigated the effect that solar irradiated V. cholerae may have had on the secretion of cytokines and chemokines by the JAWS II dendritic cell line in vitro. The JAWS II dendritic cell line was stimulated with the different strains of V. cholerae that had been: (i) prepared in PBS, (ii) inactivated through a combination of heat and chemical, (iii) solar irradiated, and (iv) non-solar irradiated, in bottled water. As controls, LPS (1 μg/ml) and CTB (1 μg/ml) were used as stimulants. After 48 hours of stimulation the tissue culture media from each treatment was qualitatively and quantitatively analysed for the presence of IL-1α, IL-1β, IL-6, IL-7, IL-10, IL-12p40, IL-12p70, IL-15, MIP-1α, MIP-1β, MIP-2, RANTES, TNF-α, IL-23 and IL-27. Results showed that solar irradiated cultures of V. cholerae induced dendritic cells to secrete significant (p<0.05) levels of pro-inflammatory cytokines in comparison to the unstimulated dendritic cells. Furthermore, the amount of pro-inflammatory cytokines secreted by the dendritic cells in response to solar irradiated cultures of V. cholerae was not as high as observed in treatments involving non-solar irradiated cultures of V. cholerae or LPS. Our results suggest that solar irradiated microorganisms are capable of inducing the secretion of pro-inflammatory cytokines and chemokines. This novel finding is key towards understanding the

  19. The Effect of Solar Irradiated Vibrio cholerae on the Secretion of Pro-Inflammatory Cytokines and Chemokines by the JAWS II Dendritic Cell Line In Vitro.

    PubMed

    Ssemakalu, Cornelius Cano; Ubomba-Jaswa, Eunice; Motaung, Keolebogile Shirley; Pillay, Michael

    2015-01-01

    The use of solar irradiation to sterilize water prior to its consumption has resulted in the reduction of water related illnesses in waterborne disease endemic communities worldwide. Currently, research on solar water disinfection (SODIS) has been directed towards understanding the underlying mechanisms through which solar irradiation inactivates the culturability of microorganisms in water, enhancement of the disinfection process, and the health impact of SODIS water consumption. However, the immunological consequences of SODIS water consumption have not been explored. In this study, we investigated the effect that solar irradiated V. cholerae may have had on the secretion of cytokines and chemokines by the JAWS II dendritic cell line in vitro. The JAWS II dendritic cell line was stimulated with the different strains of V. cholerae that had been: (i) prepared in PBS, (ii) inactivated through a combination of heat and chemical, (iii) solar irradiated, and (iv) non-solar irradiated, in bottled water. As controls, LPS (1 μg/ml) and CTB (1 μg/ml) were used as stimulants. After 48 hours of stimulation the tissue culture media from each treatment was qualitatively and quantitatively analysed for the presence of IL-1α, IL-1β, IL-6, IL-7, IL-10, IL-12p40, IL-12p70, IL-15, MIP-1α, MIP-1β, MIP-2, RANTES, TNF-α, IL-23 and IL-27. Results showed that solar irradiated cultures of V. cholerae induced dendritic cells to secrete significant (p<0.05) levels of pro-inflammatory cytokines in comparison to the unstimulated dendritic cells. Furthermore, the amount of pro-inflammatory cytokines secreted by the dendritic cells in response to solar irradiated cultures of V. cholerae was not as high as observed in treatments involving non-solar irradiated cultures of V. cholerae or LPS. Our results suggest that solar irradiated microorganisms are capable of inducing the secretion of pro-inflammatory cytokines and chemokines. This novel finding is key towards understanding the

  20. The Effect of Solar Irradiated Vibrio cholerae on the Secretion of Pro-Inflammatory Cytokines and Chemokines by the JAWS II Dendritic Cell Line In Vitro

    PubMed Central

    Ssemakalu, Cornelius Cano; Ubomba-Jaswa, Eunice; Motaung, Keolebogile Shirley; Pillay, Michael

    2015-01-01

    The use of solar irradiation to sterilize water prior to its consumption has resulted in the reduction of water related illnesses in waterborne disease endemic communities worldwide. Currently, research on solar water disinfection (SODIS) has been directed towards understanding the underlying mechanisms through which solar irradiation inactivates the culturability of microorganisms in water, enhancement of the disinfection process, and the health impact of SODIS water consumption. However, the immunological consequences of SODIS water consumption have not been explored. In this study, we investigated the effect that solar irradiated V. cholerae may have had on the secretion of cytokines and chemokines by the JAWS II dendritic cell line in vitro. The JAWS II dendritic cell line was stimulated with the different strains of V. cholerae that had been: (i) prepared in PBS, (ii) inactivated through a combination of heat and chemical, (iii) solar irradiated, and (iv) non-solar irradiated, in bottled water. As controls, LPS (1 μg/ml) and CTB (1 μg/ml) were used as stimulants. After 48 hours of stimulation the tissue culture media from each treatment was qualitatively and quantitatively analysed for the presence of IL-1α, IL-1β, IL-6, IL-7, IL-10, IL-12p40, IL-12p70, IL-15, MIP-1α, MIP-1β, MIP-2, RANTES, TNF-α, IL-23 and IL-27. Results showed that solar irradiated cultures of V. cholerae induced dendritic cells to secrete significant (p<0.05) levels of pro-inflammatory cytokines in comparison to the unstimulated dendritic cells. Furthermore, the amount of pro-inflammatory cytokines secreted by the dendritic cells in response to solar irradiated cultures of V. cholerae was not as high as observed in treatments involving non-solar irradiated cultures of V. cholerae or LPS. Our results suggest that solar irradiated microorganisms are capable of inducing the secretion of pro-inflammatory cytokines and chemokines. This novel finding is key towards understanding the

  1. Effects of helium content of microstructural development in Type 316 stainless steel under neutron irradiation

    SciTech Connect

    Maziasz, P.J.

    1985-11-01

    This work investigated the sensitivity of microstructural evolution, particularly precipitate development, to increased helium content during thermal aging and during neutron irradiation. Helium (110 at. ppM) was cold preinjected into solution annealed (SA) DO-heat type 316 stainess steel (316) via cyclotron irradiation. These specimens were then exposed side by side with uninjected samples. Continuous helium generation was increased considerably relative to EBR-II irradiation by irradiation in HFIR. Data were obtained from quantitative analytical electron microscopy (AEM) in thin foils and on extraction replicas. 480 refs., 86 figs., 19 tabs.

  2. Influence of nickel and beryllium content on swelling behavior of copper irradiated with fast neutrons

    SciTech Connect

    Singh, B.N.; Garner, F.A.; Edwards, D.J.; Evans, J.H.

    1996-10-01

    In the 1970`s, the effects of nickel content on the evolution of dislocation microstructures and the formation and growth of voids in Cu-Ni alloys were studied using 1 MeV electrons in a high voltage electron microscope. The swelling rate was found to decrease rapidly with increasing nickel content. The decrease in the swelling rate was associated with a decreasing void growth rate with increasing nickel content at irradiation temperatures up to 450{degrees}C. At 500{degrees}C, both void size and swelling rate were found to peak at 1 and 2% Ni, respectively, and then to decrease rapidly with increasing nickel content. However, recent work has demonstrated that the swelling behavior of Cu-5%Ni irradiated with fission neutrons is very similar for that of pure copper. The present experiments were designed to investigate this apparent discrepancy.

  3. The effects of gamma irradiation on the vitamin E content and sensory qualities of pecan nuts ( Carya illinoensis)

    NASA Astrophysics Data System (ADS)

    Taipina, Magda S.; Lamardo, Leda C. A.; Rodas, Maria A. B.; del Mastro, Nelida L.

    2009-07-01

    Pecan nuts ( Carya illinoensis) were treated with gamma irradiation and evaluated for changes in vitamin E content and sensory properties. Irradiation at 1 and 3 kGy resulted in no changes in vitamin E content measured as α-tocopherol equivalents by a colorimetric method. A trained sensory panel found that irradiation at 1 kGy produced no significant changes in appearance, aroma, texture and flavor attributes. The vitamin E content of irradiated pecan nuts remained stable, but from the point of view of sensory quality a dose of merely 1 kGy can be considered as recommendable.

  4. Subcutaneous vaccination with irradiated, cytokine-producing tumor cells stimulates CD8+ cell-mediated immunity against tumors located in the "immunologically privileged" central nervous system.

    PubMed Central

    Sampson, J H; Archer, G E; Ashley, D M; Fuchs, H E; Hale, L P; Dranoff, G; Bigner, D D

    1996-01-01

    Vaccination with cytokine-producing tumor cells generates potent immune responses against tumors outside the central nervous system (CNS). The CNS, however, is a barrier to allograft and xenograft rejection, and established tumors within the CNS have failed to respond to other forms of systemic immunotherapy. To determine what barriers the "immunologically privileged" CNS would pose to cytokine-assisted tumor vaccines and what cytokines would be most efficacious against tumors within the CNS, we irradiated B16 murine melanoma cells producing murine interleukin 2 (IL-2), IL-3, IL-4, IL-6, gamma-interferon, or granulocyte-macrophage colony stimulating factor (GM-CSF) and used these cells as subcutaneous vaccines against tumors within the brain. Under conditions where untransfected B16 cells had no effect, cells producing IL-3, IL-6, or GM-CSF increased the survival of mice challenged with viable B16 cells in the brain. Vaccination with B16 cells producing IL-4 or gamma-interferon had no effect, and vaccination with B16 cells producing IL-2 decreased survival time. GM-CSF-producing vaccines were also able to increase survival in mice with pre-established tumors. The response elicited by GM-CSF-producing vaccines was found to be specific to tumor type and to be abrogated by depletion of CD8+ cells. Unlike the immunity generated against subcutaneous tumors by GM-CSF, however, the effector responses generated against tumors in the CNS were not dependent on CD4+ cells. These data suggest that cytokine-producing tumor cells are very potent stimulators of immunity against tumors within the CNS, but effector responses in the CNS may be different from those obtained against subcutaneous tumors. Images Fig. 3 PMID:8816812

  5. Technical Letter Report on the Cracking of Irradiated Cast Stainless Steels with Low Ferrite Content

    SciTech Connect

    Chen, Y.; Alexandreanu, B.; Natesan, K.

    2014-11-01

    Crack growth rate and fracture toughness J-R curve tests were performed on CF-3 and CF-8 cast austenite stainless steels (CASS) with 13-14% of ferrite. The tests were conducted at ~320°C in either high-purity water with low dissolved oxygen or in simulated PWR water. The cyclic crack growth rates of CF-8 were higher than that of CF-3, and the differences between the aged and unaged specimens were small. No elevated SCC susceptibility was observed among these samples, and the SCC CGRs of these materials were comparable to those of CASS alloys with >23% ferrite. The fracture toughness values of unirradiated CF-3 were similar between unaged and aged specimens, and neutron irradiation decreased the fracture toughness significantly. The fracture toughness of CF-8 was reduced after thermal aging, and declined further after irradiation. It appears that while lowering ferrite content may help reduce the tendency of thermal aging embrittlement, it is not very effective to mitigate irradiation-induced embrittlement. Under a combined condition of thermal aging and irradiation, neutron irradiation plays a dominant role in causing embrittlement in CASS alloys.

  6. Literature review of United States utilities computer codes for calculating actinide isotope content in irradiated fuel

    SciTech Connect

    Horak, W.C.; Lu, Ming-Shih

    1991-12-01

    This paper reviews the accuracy and precision of methods used by United States electric utilities to determine the actinide isotopic and element content of irradiated fuel. After an extensive literature search, three key code suites were selected for review. Two suites of computer codes, CASMO and ARMP, are used for reactor physics calculations; the ORIGEN code is used for spent fuel calculations. They are also the most widely used codes in the nuclear industry throughout the world. Although none of these codes calculate actinide isotopics as their primary variables intended for safeguards applications, accurate calculation of actinide isotopic content is necessary to fulfill their function.

  7. Enhancing the growth, photosynthetic capacity and artemisinin content in Artemisia annua L. by irradiated sodium alginate

    NASA Astrophysics Data System (ADS)

    Aftab, Tariq; Khan, M. Masroor A.; Idrees, M.; Naeem, M.; Moinuddin; Hashmi, Nadeem; Varshney, Lalit

    2011-07-01

    Degrading the natural bioactive agents by ionizing radiation and then using them as growth promoting substances is a novel emerging technology to exploit the genetic potential of crops in terms of growth, yield and quality. Polysaccharides, such as sodium alginate, have proven to be wonderful growth promoting substances in their depolymerized form for various plants. The effect of depolymerized form of sodium alginate, produced by irradiating the latter by 60Co gamma rays, was studied on Artemisia annua L. with regard to growth attributes, physiological and biochemical parameters and artemisinin content. The study revealed that the irradiated sodium alginate (ISA), applied as leaf-sprays at a concentration of 20-120 mg L -1, improved the growth attributes, photosynthetic capability, enzyme activities and artemisinin content of the plant significantly. Application of ISA at 80 mg L -1 increased the values of the attributes studied to the maximum extent. The enhancement of leaf-artemisinin content was ascribed to the ISA-enhanced H 2O 2 content in the leaves.

  8. How do tissues respond to damage at the cellular level? The role of cytokines in irradiated tissues

    NASA Technical Reports Server (NTRS)

    Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

    1998-01-01

    The capacity of ionizing radiation to affect tissue function, control tumor growth and elicit pathological sequelae has been attributed in great part to its effects on cellular DNA, which, as the transmitter of genetic information, can both register damage and perpetuate it. Nonetheless, multicellular organisms function as the result of the cooperation of many cell types. What then occurs when individual cells are damaged by ionizing radiation? Is tissue response a sum of cellular effects such as cell death and DNA damage? Or does the tissue respond as a coherent unit to the damage of its parts? In this paper, data in support of the latter model that indicate a role for cytokines, in particular transforming growth factor beta1, as critical components of extracellular signaling pathways that mediate tissue response to radiation will be reviewed. The key to manipulating the consequences of radiation exposure lies in understanding the complex interplay of events initiated at the cellular level, but acting on the tissue.

  9. Water color affects the stratification, surface temperature, heat content, and mean epilimnetic irradiance of small lakes

    USGS Publications Warehouse

    Houser, J.N.

    2006-01-01

    The effects of water color on lake stratification, mean epilimnetic irradiance, and lake temperature dynamics were examined in small, north-temperate lakes that differed widely in water color (1.5-19.8 m -1). Among these lakes, colored lakes differed from clear lakes in the following ways: (i) the epilimnia were shallower and colder, and mean epilimnetic irradiance was reduced; (ii) the diel temperature cycles were more pronounced; (iii) whole-lake heat accumulation during stratification was reduced. The depth of the epilimnion ranged from 2.5 m in the clearest lake to 0.75 m in the most colored lake, and 91% of the variation in epilimnetic depth was explained by water color. Summer mean morning epilimnetic temperature was ???2??C cooler in the most colored lake compared with the clearest lake. In clear lakes, the diel temperature range (1.4 ?? 0.7??C) was significantly (p = 0.01) less than that in the most colored lake (2.1 ?? 1.0??C). Change in whole-lake heat content was negatively correlated with water color. Increasing water color decreased light penetration more than thermocline depth, leading to reduced mean epilimnetic irradiance in the colored lakes. Thus, in these small lakes, water color significantly affected temperature, thermocline depth, and light climate. ?? 2006 NRC.

  10. A Hyperlipidic Diet Combined with Short-Term Ovariectomy Increases Adiposity and Hyperleptinemia and Decreases Cytokine Content in Mesenteric Adipose Tissue

    PubMed Central

    Neto, Nelson Inacio Pinto; Rodrigues, Maria Elizabeth Sousa; Hachul, Ana Claudia Losinskas; Moreno, Mayara Franzoi; Boldarine, Valter Tadeu; Ribeiro, Eliane Beraldi; Oyama, Lila Missae; Oller do Nascimento, Claudia Maria

    2015-01-01

    Four-week-old female Wistar rats were divided into two groups and fed a control diet (C) or a hyperlipidic diet (H) for 4 weeks. Rats from each group underwent ovariectomy (OVX) or sham surgery (SHAM). They received C or H for the next four weeks. The body weight gain (BW), food efficiency (FE), and carcass lipid content were higher in the OVX H than in the SHAM H. The OVX H exhibited a higher serum leptin level than other groups. IL-6, TNF-α, and IL-10 content of mesenteric (MES) adipose tissue was lower in the OVX H than in the OVX C. IL-6, TNF-α, and IL-10 content of retroperitoneal (RET) adipose tissue was lower in the SHAM H than in the SHAM C. The SHAM H showed decreased TG relative to the SHAM C. Similar results were obtained in relation to IL-6Rα, TNFR1, TLR-4, and MyD88 contents in the MES and RET white adipose tissue among the groups. A hyperlipidic diet for 8 weeks combined with short-term ovariectomy decreases the cytokine content of MES adipose tissues but increases BW, enhancing FE and elevating serum leptin levels. These suggest that the absence of estrogens promotes metabolic changes that may contribute to installation of a proinflammatory process induced by a hyperlipidic diet. PMID:26170534

  11. Effects of irradiation and semistarvation on rat thyrotropin beta subunit messenger ribonucleic acid, pituitary thyrotropin content, and thyroid hormone levels

    SciTech Connect

    Litten, R.Z. ); Carr, F.E. ); Fein, H.G.; Smallridge, R.C. )

    1990-01-01

    The effect of radiation-induced anorexia on serum thyrotropin (TSH), pituitary TSH-{beta} mRNA, pituitary TSH content, serum thyroxine (T{sub 4}), and serum 3,5,3{prime}-triiodothyronine (T{sub 3}) was investigated using feed-matched controls. Rats received 10 Gy gamma whole-body irradiation and were examined 1-3 days postirradiation. Feed-matched and untreated controls were also studied. The average food intake of the irradiated and feed-matched groups was approximately 18% of the untreated controls. Over the three day period both the irradiated and feed-matched groups lost a significant amount of body weight. The serum T{sub 4} levels of both the irradiated and feed-matched groups were not significantly different from each other, but were significantly depressed when compared to the untreated control group. The serum TSH and T{sub 3} were, however, significantly greater in the irradiated than the feed-matched groups at day 3 posttreatment. To determine if the difference in the serum TSH level between the two groups was due to a pretranslational alteration in TSH production, we measured the TSH-{beta} mRNA using an RNA blot hybridization assay. We found that the TSH-{beta} mRNA level was the same in the irradiated and feed-matched groups, suggesting that the mechanism responsible for the radiation-induced increase in the serum TSH level is posttranscriptional. Pituitary TSH content in the irradiated rats was significantly less than in pair-fed controls, suggesting that irradiation may permit enhanced secretion of stored hormone.

  12. Effects of a Diet Enriched with Polyunsaturated, Saturated, or Trans Fatty Acids on Cytokine Content in the Liver, White Adipose Tissue, and Skeletal Muscle of Adult Mice

    PubMed Central

    dos Santos, Bruno; Estadella, Debora; Hachul, Ana Cláudia Losinskas; Okuda, Marcos Hiromu; Moreno, Mayara Franzoi; Oyama, Lila Missae; Ribeiro, Eliane Beraldi; Oller do Nascimento, Claudia Maria da Penha

    2013-01-01

    This study analyzed the effect of diet enriched with 30% lipids on cytokines content in different tissues. Swiss male mice were distributed into four groups treated for 8 weeks with control (C, normolipidic diet); soybean oil (S); lard (L); and hydrogenated vegetable fat (H). We observed an increase in carcass fat in groups S and L, and the total amount of fatty deposits was only higher in group L compared with C group. The serum levels of free fatty acids were lower in the L group, and insulin, adiponectin, lipid profile, and glucose levels were similar among the groups. IL-10 was lower in group L in mesenteric and retroperitoneal adipose tissues. H reduced IL-10 only in retroperitoneal adipose tissue. There was an increase in IL-6 in the gastrocnemius muscle of the L group, and a positive correlation between TNF-α and IL-10 was observed in the livers of groups C, L, and H and in the muscles of all groups studied. The results suggested relationships between the quantity and quality of lipids ingested with adiposity, the concentration of free fatty acids, and cytokine production in white adipose tissue, gastrocnemius muscle, and liver. PMID:24027356

  13. Phenolic Content and Antioxidant Activity of Extracts from Whole Buckwheat (Fagopyrum esculentum Moench) With or Without Microwave Irradiation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to evaluate the effectiveness of extracting phenolic compounds and antioxidant activity from buckwheat with water, 50% aqueous ethanol, or 100% ethanol using microwave irradiation or a water bath for 15 min at various temperatures (23 – 150 °C). The phenolic content of...

  14. Effects of gamma-irradiation on the free radical and antioxidant contents in nine aromatic herbs and spices.

    PubMed

    Calucci, Lucia; Pinzino, Calogero; Zandomeneghi, Maurizio; Capocchi, Antonella; Ghiringhelli, Silvia; Saviozzi, Franco; Tozzi, Sabrina; Galleschi, Luciano

    2003-02-12

    Nine spice and aromatic herb samples (i.e., basil, bird pepper, black pepper, cinnamon, nutmeg, oregano, parsley, rosemary, and sage) were gamma-irradiated at a dose of 10 kGy according to commercial practices. The effects of the disinfection treatment on the content of organic radicals and some nutrients (namely, vitamin C and carotenoids) in the samples were investigated by chromatographic and spectroscopic techniques. Irradiation resulted in a general increase of quinone radical content in all of the investigated samples, as revealed by electron paramagnetic resonance spectroscopy. The fate of these radicals after storage for 3 months was also investigated. The cellulose radical was clearly observed in a few samples. Significant losses of total ascorbate were found for black pepper, cinnamon, nutmeg, oregano, and sage, whereas a significant decrease of carotenoids content was observed for cinnamon, oregano, parsley, rosemary, bird pepper, and sage.

  15. Effect of various laser irradiations on the mineral content of dentin

    PubMed Central

    Dilber, Erhan; Malkoc, Meral Arslan; Ozturk, A. Nilgun; Ozturk, Firat

    2013-01-01

    Objective: The aim of this study was to evaluate the mineral content of dentin irradiation with Erbium: yttrium-aliminum-garnet (Er:YAG), Neodmiyum:yttrium-aliminum garnet (Nd:YAG) and potassium titanium phosphate (KTP) laser used for in the treatment of dentin hypersensitivity. Methods: Six extracted wisdom, unerupted molar teeth were used in this study. The enamel of the teeth was removed with a conventional bur under water cooling to expose the dentin surface. The teeth were mounted in a slow-speed, diamond-saw, sectioning machine. Two dentin slabs were obtained from each tooth and each slab was sectioned so that 4 slabs were made from each teeth. Then dentin slabs were randomly divided into four groups. Group A: Control Group, Group B: Er:YAG laser, Group C: Nd:YAG laser, Group D: KTP laser. The levels of Ca, K, Mg, Na,P and Ca/P mineral ratio in each dentin slab were measured by inductively coupled plasma-atomic emission spectrometry (ICP-AES). Data were analysed by one way analysis of variance (ANOVA) and Tukey HSD tests. One sample from each group was prepared for scanning electron microscopy (SEM). Results: There were no significant differences between the groups for Ca, K, Mg, Na,P and Ca/P mineral ratio (P>.05). SEM photographs indicated that there were melted areas around the exposed dentin tubules in groups treated with Er:YAG and KTP lasers. Conclusion: This study demonstrated that laser etching with the Er:YAG, Nd:YAG, KTP laser systems did not affect the compositional structure of the dentin surfaces. PMID:23407579

  16. Effect of supplemental UV-A irradiation in solid-state lighting on the growth and phytochemical content of microgreens

    NASA Astrophysics Data System (ADS)

    Brazaitytė, A.; Viršilė, A.; Jankauskienė, J.; Sakalauskienė, S.; Samuolienė, G.; Sirtautas, R.; Novičkovas, A.; Dabašinskas, L.; Miliauskienė, J.; Vaštakaitė, V.; Bagdonavičienė, A.; Duchovskis, P.

    2015-01-01

    In this study, we sought to find and employ positive effects of UV-A irradiation on cultivation and quality of microgreens. Therefore, the goal of our study was to investigate the influence of 366, 390, and 402 nm UV-A LED wavelengths, supplemental for the basal solid-state lighting system at two UV-A irradiation levels on the growth and phytochemical contents of different microgreen plants. Depending on the species, supplemental UV-A irradiation can improve antioxidant properties of microgreens. In many cases, a significant increase in the investigated phytochemicals was found under 366 and 390 nm UV-A wavelengths at the photon flux density (12.4 μmol m-2 s-1). The most pronounced effect of supplemental UV-A irradiation was detected in pak choi microgreens. Almost all supplemental UV-A irradiation treatments resulted in increased leaf area and fresh weight, in higher 2,2-diphenyl-1-picrylhydrazyl free-radical scavenging activity, total phenols, anthocyanins, ascorbic acid, and α-tocopherol.

  17. Effect of initial oxygen content on the void swelling behavior of fast neutron irradiated copper

    SciTech Connect

    Zinkle, S.J.; Garner, F.A.

    1998-03-01

    Density measurements were performed on high purity copper specimens containing {le}10 wt.ppm and {approximately}120 wt.ppm oxygen following irradiation in FFTF MOTA 2B. Significant amounts of swelling were observed in both the oxygen-free and oxygen-doped specimens following irradiation to {approximately}17 dpa at 375 C and {approximately}47 dpa at 430 C. Oxygen doping up to 360 appm (90 wt.ppm) did not significantly affect the void swelling of copper for these irradiation conditions.

  18. [Blood Content of Markers of Inflammation and Cytokines in Patients With Alcoholic Cardiomyopathy and Ischemic Heart Disease at Various Stages of Heart Failure].

    PubMed

    Panchenko, L F; Moiseev, V S; Pirozhkov, S V; Terebilina, N N; Naumova, T A; Baronets, V Iu; Goncharov, A S

    2015-01-01

    We conducted a comparative study of content proinflammatory cytokines, biomarkers of inflammatory process, biochemical indicators of congestive heart failure (CHF) and hemodynamic parameters in patients with alcoholic cardiomyopathy (ACMP) and ischemic heart disease (IHD) with various NYHA classes. We examined 62 men with ACMP (n = 45) and IHD (n = 17) and NYHA class III-IV CHF. Patients of both groups had lowered ejection fraction (EF), dilated cardiac chambers, and increased left ventricular (LV) myocardial mass index (MMI). Relative LV wall thickness was within normal limits but in the ACMP group it was significantly lower than in IHD group what corresponded to the eccentric type of myocardial hypertrophy. Higher NYHA class was associated with lower EF and larger end diastolic and end systolic LV dimensions. In ACMP it was also associated with larger dimension of the right ventricle while in IHD--with substantially larger (by 30%) dimension of atria. Substantial amount of endotoxin found in blood plasma of patients with IHD corresponded to the conception of increased intestinal permeability of in CHF. Alcohol abuse was an aggravating factor of endotoxin transmission and its concentration in patients with ACMP was 3 times higher than in patients with IHD. Patients with ACMP had substantially elevated blood concentrations of interleukins (IL) 6, 8, 12, tumor necrosis factor α (TNF-α), and its soluble receptor s-TNF-R; they also had twofold elevation of C-reactive protein concentration. ACMP was associated with manifold rise of blood content of brain natriuretic peptide (BNP). Patients with IHD also had elevated blood concentrations of IL 6, 8 and 12 but their values were 1.5-2 times lower than ACMP group. Blood content of TNF-α and s-TNF-R in IHD group was within normal limits. Higher NYHA class in ACMP patients was associated with higher concentrations of IL 6 and 8, TNF-a, and BNP. In both groups of patients contents of IL-12, s-TNF-R, TGF-1β and factors of

  19. Evaluation of protein content, lysine and sulfur-containing amino acids content and electrophoretic patterns of soluble proteins for gamma-irradiated semolina before and after milling of durum wheat

    NASA Astrophysics Data System (ADS)

    Azzeh, F. S.; Amr, A. S.

    2009-11-01

    Influenced of gamma irradiation (0, 0.25, 1, 2.5, 5 and 10 kGy) on total nitrogen, lysine and sulfur-containing amino acids content and electrophoretic patterns of soluble proteins of semolina was studied. The effect of irradiation before and after milling on previous parameters was also investigated. Protein content of semolina was not affected with gamma irradiation before and after milling. Up to 10 kGy dose, cystine and methionine were not significantly changed, although they increased slightly with increasing irradiation dose. Lysine content decreased significantly ( P≤0.05) at irradiation dose higher than 5 kGy. At 10 kGy dose, lysine decreased 5% and 14% for irradiated semolina and that obtained from irradiated wheat grains, respectively. The bands number and intensity of soluble proteins decreased with increasing irradiation dose higher than 5 kGy, as shown on SDS-PAGE electrophoresis. Irradiated semolina and semolina obtained from irradiated wheat grains at 10 kGy showed 13 and 15 bands, respectively. Unirradiated sample showed 19 bands.

  20. Radiological risks from irradiation of cargo contents with EURITRACK neutron inspection systems

    NASA Astrophysics Data System (ADS)

    Giroletti, E.; Bonomi, G.; Donzella, A.; Viesti, G.; Zenoni, A.

    2012-07-01

    The radiological risk for the population related to the neutron irradiation of cargo containers with a tagged neutron inspection system has been studied. Two possible effects on the public health have been assessed: the modification of the nutritional and organoleptic properties of the irradiated materials, in particular foodstuff, and the neutron activation of consumer products (i.e. food and pharmaceuticals). The result of this study is that irradiation of food and foodstuff, pharmaceutical and medical devices in container cargoes would neither modify the properties of the irradiated material nor produce effective doses of concern for public health. Furthermore, the dose received by possible stowaways present inside the container during the inspection is less than the annual effective dose limit defined by European Legislation for the public.

  1. The co-induced effects of molybdenum and cadmium on the mRNA expression of inflammatory cytokines and trace element contents in duck kidneys.

    PubMed

    Cao, Huabin; Gao, Feiyan; Xia, Bing; Xiao, Qingyang; Guo, Xiaoquan; Hu, Guoliang; Zhang, Caiying

    2016-11-01

    The aims of this study were determining the co-induced effects of dietary Cadmium (Cd) and high intake of Molybdenum (Mo) on renal toxicity in ducks. 240 healthy 11-day-old ducks were randomly divided into 6 groups, which were treated with Mo or/and Cd at different doses added to the basal diet for 120 days. Ducks of control group were fed with basal diet, LMo and HMo groups were fed with 15mg/kg Mo and 100mg/kg Mo respectively; ducks of Cd group were provided with 4mg/kg Cd which was added into basal diet. Two combination groups were treated with 15mg/kg Mo+4mg/kg Cd and 100mg/kg Mo+4mg/kg Cd respectively. On days 30, 60, 90 and 120, the mRNA expression levels of inflammatory cytokines and contents of trace elements were detected. In addition, transmission electron microscopic examination was used for ultrastructural studies. The results indicated that the mRNA expression levels of tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-κB), and cyclooxygenase-2 (COX-2) showed an upward tendency in treatment groups in comparison with control group, and in the later period of the experiment it showed a significant rise in joint groups compared with the Mo and Cd group (P<0.01); the contents of copper (Cu) and iron (Fe) decreased in joint groups in the later period (P<0.05) while the contents of Mo and Cd significantly increased (P<0.01); zinc (Zn) and selenium (Se) concentration had a slight downtrend in treated groups, but showed no significant difference (P>0.05). The ultrastructural analysis showed that kidney tissues were severely injured in joint groups on day 120. These results suggested that the combination of Mo and Cd could aggravate damages to the kidney. In addition, dietary of Mo or/and Cd caused the decrease of Cu, Fe, Zn, and Se contents, inflammatory response and pathological lesions whose mechanism is somehow linked with Mo and Cd deposition in kidney.

  2. The co-induced effects of molybdenum and cadmium on the mRNA expression of inflammatory cytokines and trace element contents in duck kidneys.

    PubMed

    Cao, Huabin; Gao, Feiyan; Xia, Bing; Xiao, Qingyang; Guo, Xiaoquan; Hu, Guoliang; Zhang, Caiying

    2016-11-01

    The aims of this study were determining the co-induced effects of dietary Cadmium (Cd) and high intake of Molybdenum (Mo) on renal toxicity in ducks. 240 healthy 11-day-old ducks were randomly divided into 6 groups, which were treated with Mo or/and Cd at different doses added to the basal diet for 120 days. Ducks of control group were fed with basal diet, LMo and HMo groups were fed with 15mg/kg Mo and 100mg/kg Mo respectively; ducks of Cd group were provided with 4mg/kg Cd which was added into basal diet. Two combination groups were treated with 15mg/kg Mo+4mg/kg Cd and 100mg/kg Mo+4mg/kg Cd respectively. On days 30, 60, 90 and 120, the mRNA expression levels of inflammatory cytokines and contents of trace elements were detected. In addition, transmission electron microscopic examination was used for ultrastructural studies. The results indicated that the mRNA expression levels of tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-κB), and cyclooxygenase-2 (COX-2) showed an upward tendency in treatment groups in comparison with control group, and in the later period of the experiment it showed a significant rise in joint groups compared with the Mo and Cd group (P<0.01); the contents of copper (Cu) and iron (Fe) decreased in joint groups in the later period (P<0.05) while the contents of Mo and Cd significantly increased (P<0.01); zinc (Zn) and selenium (Se) concentration had a slight downtrend in treated groups, but showed no significant difference (P>0.05). The ultrastructural analysis showed that kidney tissues were severely injured in joint groups on day 120. These results suggested that the combination of Mo and Cd could aggravate damages to the kidney. In addition, dietary of Mo or/and Cd caused the decrease of Cu, Fe, Zn, and Se contents, inflammatory response and pathological lesions whose mechanism is somehow linked with Mo and Cd deposition in kidney. PMID:27448956

  3. Ship-borne measurements of erythemal UV irradiance and ozone content in various climate zones.

    PubMed

    Wuttke, Sigrid; El Naggar, Saad; Bluszcz, Thaddäus; Schrems, Otto

    2007-10-01

    Ship-borne measurements of spectral as well as biologically effective UV irradiance have been performed on the German research vessel Polarstern during the Atlantic transect from Bremerhaven, Germany (53.5 degrees N, 8.5 degrees E), to Cape Town, South Africa (33.6 degrees S, 18.3 degrees E), from 13 October to 17 November 2005. Such measurements are required to study UV effects on marine organisms. They are also necessary to validate satellite-derived surface UV irradiance. Cloud free radiative transfer calculations support the investigation of this latitudinal dependence. Input parameters, such as total ozone column and aerosol optical depth have been measured on board as well. Using these measured parameters, the modelled cloudless noontime UVA irradiance (320-400 nm) shows the expected dependence on varying minimum solar zenith angles (SZA) at different latitudes. The modelled cloudless noontime UVB irradiance (290-320 nm) does not show this clear dependence on SZA due to the strong influence of ozone absorption in this spectral range. The maximum daily dose of erythemal irradiance of 5420 J m(-1) was observed on 14 November 2005, when the ship was in the tropical Atlantic south of the equator. The expected UV maximum should have been observed with the sun in the zenith during local noon (11 November). Stratiform clouds reduced the dose to 3835 J m(-1). In comparison, the daily erythemal doses in the mid-latitudinal Bay of Biscay only reached values between 410 and 980 J m(-1) depending on cloud conditions. The deviation in daily erythemal dose derived from different instruments is around 5%. The feasibility to perform ship-borne measurements of spectral UV irradiance is demonstrated.

  4. Evaluation of photon irradiation treatment upon calcium content of ribs of Wistar rats using micro-XRF

    NASA Astrophysics Data System (ADS)

    Nogueira, Liebert Parreiras; Barroso, Regina Cély; de Almeida, André Pereira; Braz, Delson; de Almeida, Carlos Eduardo; Salata, Camila; Andrade, Cherley Borba; da Silva, Claudia Marcello

    2012-05-01

    Therapeutic doses of radiation have been shown to have deleterious consequences on bone health. Among the treatment strategies used for breast cancer treatment, the most used are radiotherapy and chemotherapy. Radiotherapy may be given to destroy the cancer cells using high-dose x-rays. Protocols vary considerably, but generally whole body irradiation totals from 10 to 15 Gy, whereas local therapy totals from 40 to 70 Gy. In clinical practice, the quantitative evaluation of bone tissue relies on measurements of bone mineral density values, which are closely associated with the risk of osteoporotic fracture. Improved survivorship rates of cancer patients receiving radiotherapy increase the importance of understanding the mechanisms and long-term effects of radiation-induced bone loss. In this work, we investigated the variation on calcium distribution in ribs of female Wistar rats (Rattus norvegicus) submitted to photon irradiation with a single dose of 20 Gy. The determination of the calcium distribution was performed using synchrotron radiation microfluorescence (SR-μXRF) at the X-ray Fluorescence beamline at Brazilian Synchrotron Light Laboratory (LNLS). Animals were irradiated using the linear accelerator Varian® (CLINAC 2100) at the University Centre for Cancer Control of the State University of Rio de Janeiro (CUCC/UERJ). The total dose delivered was 20 Gy. The animals were about three months old and weighting about 200g. They were distributed into two groups (seven per group): control (did not receive any treatment) and irradiated (submitted to irradiation procedure) groups. Results showed that calcium content decreased within the dorsal ribs of rats submitted to radiotherapy in comparison to the control group.

  5. Evaluation of photon irradiation treatment upon calcium content of ribs of Wistar rats using micro-XRF

    SciTech Connect

    Parreiras Nogueira, Liebert; Barroso, Regina Cely; Pereira de Almeida, Andre; Braz, Delson; Almeida, Carlos Eduardo de; Salata, Camila; Andrade, Cherley Borba; Silva, Claudia Marcello da

    2012-05-17

    Therapeutic doses of radiation have been shown to have deleterious consequences on bone health. Among the treatment strategies used for breast cancer treatment, the most used are radiotherapy and chemotherapy. Radiotherapy may be given to destroy the cancer cells using high-dose x-rays. Protocols vary considerably, but generally whole body irradiation totals from 10 to 15 Gy, whereas local therapy totals from 40 to 70 Gy. In clinical practice, the quantitative evaluation of bone tissue relies on measurements of bone mineral density values, which are closely associated with the risk of osteoporotic fracture. Improved survivorship rates of cancer patients receiving radiotherapy increase the importance of understanding the mechanisms and long-term effects of radiation-induced bone loss. In this work, we investigated the variation on calcium distribution in ribs of female Wistar rats (Rattus norvegicus) submitted to photon irradiation with a single dose of 20 Gy. The determination of the calcium distribution was performed using synchrotron radiation microfluorescence (SR-{mu}XRF) at the X-ray Fluorescence beamline at Brazilian Synchrotron Light Laboratory (LNLS). Animals were irradiated using the linear accelerator Varian registered (CLINAC 2100) at the University Centre for Cancer Control of the State University of Rio de Janeiro (CUCC/UERJ). The total dose delivered was 20 Gy. The animals were about three months old and weighting about 200g. They were distributed into two groups (seven per group): control (did not receive any treatment) and irradiated (submitted to irradiation procedure) groups. Results showed that calcium content decreased within the dorsal ribs of rats submitted to radiotherapy in comparison to the control group.

  6. Effect of Cr content on the nanostructural evolution of irradiated ferritic/martensitic alloys: An object kinetic Monte Carlo model

    NASA Astrophysics Data System (ADS)

    Chiapetto, M.; Malerba, L.; Becquart, C. S.

    2015-10-01

    Self-interstitial cluster diffusivity in Fe-Cr alloys, model materials for high-Cr ferritic/martensitic steels, is known to be reduced in a non-monotonic way as a function of Cr concentration: it first decreases, then increases. This non-monotonic behaviour is caused by a relatively long-ranged attractive interaction between Cr atoms and crowdions and correlates well with the experimentally observed swelling in these alloys under neutron irradiation, also seen to first decrease and then increase with increasing Cr content, under comparable irradiation conditions. Moreover, recent studies reveal that C atoms dispersed in the Fe matrix form under irradiation complexes with vacancies which, in turn, act as trap for one-dimensionally migrating self-interstitial clusters. The mobility of one-dimensional migrating clusters is considered key to determine swelling susceptibility. However, no model has ever been built that quantitatively describes the dependence of swelling on Cr content, allowing for the presence of C in the matrix. In this work we developed physically-based sets of parameters for object kinetic Monte Carlo (OKMC) simulations intended to study the nanostructure evolution under irradiation in Fe-Cr-C alloys. The nanostructural evolution in Fe-C and in four Fe-Cr-C alloys (containing 2.5, 5, 9 and 12 wt.% Cr) neutron irradiated up to ∼0.6 dpa at 563 K was simulated according to the model and reference experiments were reproduced. Our model shows that the SIA cluster reduced mobility has a major influence on the nanostructural evolution: it increases the number of vacancy-SIA recombinations and thus leads to the suppression of voids formation. This provides a clear framework to interpret the non-monotonic dependence of swelling in Fe-Cr alloys versus Cr content. Our model also suggests that the amount of C in the matrix has an equally important role: high amounts of it may counteract the beneficial effect that Cr has in reducing swelling.

  7. Irradiation with a low-level diode laser induces the developmental endothelial locus-1 gene and reduces proinflammatory cytokines in epithelial cells.

    PubMed

    Fujimura, Takeki; Mitani, Akio; Fukuda, Mitsuo; Mogi, Makio; Osawa, Kazuhiro; Takahashi, Shinko; Aino, Makoto; Iwamura, Yuki; Miyajima, Shinichi; Yamamoto, Hiromitsu; Noguchi, Toshihide

    2014-05-01

    We demonstrated previously that low-level diode laser irradiation with an indocyanine green-loaded nanosphere coated with chitosan (ICG-Nano/c) had an antimicrobial effect, and thus could be used for periodontal antimicrobial photodynamic therapy (aPDT). Since little is known about the effects of aPDT on periodontal tissue, we here investigated the effect of low-level laser irradiation, with and without ICG-Nano/c, on cultured epithelial cells. Human oral epithelial cells were irradiated in a repeated pulse mode (duty cycle, 10 %; pulse width, 100 ms; peak power output, 5 W). The expression of the developmental endothelial locus 1 (Del-1), interleukin-6 (IL-6), IL-8, and the intercellular adhesion molecule-1 (ICAM-1) were evaluated in Ca9-22 cells stimulated by laser irradiation and Escherichia coli-derived lipopolysaccharide (LPS). A wound healing assay was carried out on SCC-25 cells irradiated by diode laser with or without ICG-Nano/c. The mRNA expression of Del-1, which is known to have anti-inflammatory activity, was significantly upregulated by laser irradiation (p < 0.01). Concurrently, LPS-induced IL-6 and IL-8 expression was significantly suppressed in the LPS + laser group (p < 0.01). ICAM-1 expression was significantly higher in the LPS + laser group than in the LPS only or control groups. Finally, compared with the control, the migration of epithelial cells was significantly increased by diode laser irradiation with or without ICG-Nano/c. These results suggest that, in addition to its antimicrobial effect, low-level diode laser irradiation, with or without ICG-Nano/c, can suppress excessive inflammatory responses via a mechanism involving Del-1, and assists in wound healing.

  8. Oxygen-Content-Controllable Graphene Oxide from Electron-Beam-Irradiated Graphite: Synthesis, Characterization, and Removal of Aqueous Lead [Pb(II)].

    PubMed

    Bai, Jing; Sun, Huimin; Yin, Xiaojie; Yin, Xianqiang; Wang, Shengsen; Creamer, Anne Elise; Xu, Lijun; Qin, Zhi; He, Feng; Gao, Bin

    2016-09-28

    A high-energy electron beam was applied to irradiate graphite for the preparation of graphene oxide (GO) with a controllable oxygen content. The obtained GO sheets were analyzed with various characterization tools. The results revealed that the oxygen-containing groups of GO increased with increasing irradiation dosages. Hence, oxygen-content-controllable synthesis of GO can be realized by changing the irradiation dosages. The GO sheets with different irradiation dosages were then used to adsorb aqueous Pb(II). The effects of contact time, pH, initial lead ion concentration, and ionic strength on Pb(II) sorption onto different GO sheets were examined. The sorption process was found to be very fast (completed within 20 min) at pH 5.0. Except ionic strength, which showed no/little effect on lead sorption, the other factors affected the sorption of aqueous Pb(II) onto GO. The maximum Pb(II) sorption capacities of GO increased with irradiation dosages, confirming that electron-beam irradiation was an effective way to increase the oxygen content of GO. These results suggested that irradiated GO with a controllable oxygen content is a promising nanomaterial for environmental cleanup, particularly for the treatment of cationic metal ions, such as Pb(II).

  9. Charging process of polyurethane based composites under electronic irradiation: Effects of cellulose fiber content

    NASA Astrophysics Data System (ADS)

    Hadjadj, Aomar; Jbara, Omar; Tara, Ahmed; Gilliot, Mickael; Dellis, Jean-Luc

    2013-09-01

    The study deals with the charging effect of polyurethanes-based composites reinforced with cellulose fibers, under electronic beam irradiation in a scanning electron microscope. The results indicate that the leakage current and the trapped charge as well as the kinetics of charging process significantly change beyond a critical concentration of 10% cellulose fibers. These features are correlated with the cellulose concentration-dependence of the electrical properties, specifically resistivity and capacitance, of the composite.

  10. Charging process of polyurethane based composites under electronic irradiation: Effects of cellulose fiber content

    SciTech Connect

    Hadjadj, Aomar; Jbara, Omar; Tara, Ahmed; Gilliot, Mickael; Dellis, Jean-Luc

    2013-09-23

    The study deals with the charging effect of polyurethanes-based composites reinforced with cellulose fibers, under electronic beam irradiation in a scanning electron microscope. The results indicate that the leakage current and the trapped charge as well as the kinetics of charging process significantly change beyond a critical concentration of 10% cellulose fibers. These features are correlated with the cellulose concentration-dependence of the electrical properties, specifically resistivity and capacitance, of the composite.

  11. Comparative effects of irradiation, fumigation, and storage on the free amino acids and sugar contents of green, black and oolong teas

    NASA Astrophysics Data System (ADS)

    Kausar, Tusneem; Akram, Kashif; Kwon, Joong-Ho

    2013-05-01

    Food irradiation or chemical fumigation can be used to ensure the hygienic quality of teas. The comparative effects of gamma irradiation (5 and 10 kGy) and fumigation (MeBr and PH3) were investigated on the amino acids and sugar contents of Camellia sinensis (green, black and oolong teas) during storage (15±12 °C). The major amino acids found in teas were theanine and glutamic acid. Irradiation increased amino acids such as, leucine, alanine, and glutamic acid, and decreased the histidine. PH3 fumigation resulted in a decrease of tyrosine content; however, the effect of MeBr fumigation was negligible. Storage showed no significant effect on the amino acid content of the irradiated and fumigated teas. Sucrose, glucose, and fructose contents significantly increased upon gamma irradiation (p≤0.05). However, fumigation and subsequent storage did not affect the sugar contents. Irradiation could be a preferred alternative choice to address food safety problems as fumigation is restricted in many countries.

  12. Peripheral blood corticotropin-releasing factor, adrenocorticotropic hormone and cytokine (Interleukin Beta, Interleukin 6, tumor necrosis factor alpha) levels after high- and low-dose total-body irradiation in humans

    SciTech Connect

    Girinsky, T.A.; Pallardy, M.; Comoy, E.; Benassi, T.; Roger, R.; Ganem, G.; Socie, G.; Cossett, J.M.; Magdelenat, H.

    1994-09-01

    Total-body irradiation (TBI) induces an increase in levels of granulocytes and cortisol in blood. To explore the underlying mechanisms, we studied 26 patients who had TBI prior to bone marrow transplantation. Our findings suggest that only a high dose of TBI (10 Gy) was capable of activating the hypothalamopituitary area since corticotropin-releasing factor and blood adrenocorticotropic hormone levels increased at the end of the TBI. There was a concomitant increase in the levels of interleukin 6 and tumor necrosis factor in blood, suggesting that these cytokines might activate the hypothalamo-pituitary adrenal axis. Interleukin 1 was not detected. Since vascular injury is a common after radiation treatment, it is possible that interleukin 6 was secreted by endothelial cells. The exact mechanisms of the production of cyctokines induced by ionizing radiation remain to be determined. 25 refs., 1 fig.

  13. Antioxidant Capacities and Total Phenolic Contents Enhancement with Acute Gamma Irradiation in Curcuma alismatifolia (Zingiberaceae) Leaves

    PubMed Central

    Taheri, Sima; Abdullah, Thohirah Lee; Karimi, Ehsan; Oskoueian, Ehsan; Ebrahimi, Mahdi

    2014-01-01

    The present study was conducted in order to assess the effect of various doses of acute gamma irradiation (0, 10, 15, and 20 Gy) on the improvement of bioactive compounds and their antioxidant properties of Curcuma alismatifolia var. Sweet pink. The high performance liquid chromatography (HPLC) and gas chromatography (GC) analysis uncovered that various types of phenolic, flavonoid compounds, and fatty acids gradually altered in response to radiation doses. On the other hand, antioxidant activities determined by 1,1-Diphenyl-2-picryl-hydrazyl (DPPH), ferric reduction, antioxidant power (FRAP), and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assay showed a higher irradiation level significantly increased the antioxidant properties. This study revealed an efficient effect of varying levels of gamma radiation, based on the pharmaceutical demand to enhance the accumulation and distribution of bioactive compounds such as phenolic and flavonoid compounds, fatty acids, as well as their antioxidant activities in the leaves of C. alismatifolia var. Sweet pink. PMID:25056545

  14. Modeling of secondary treated wastewater disinfection by UV irradiation: effects of suspended solids content.

    PubMed

    Brahmi, Mounaouer; Belhadi, Noureddine Hamed; Hamdi, Helmi; Hassen, Abdennaceur

    2010-01-01

    This work aimed to study UV-resistant strains of Pseudomonas aeruginosa, to propose a formulation of the kinetics of secondary treated wastewater disinfection and to underline the influence of suspended solids on the inactivation kinetics of these strains. Some investigations were carried out for the validation of some simulation models, from the simplest, the kinetics model of Chick-Watson reduced to first order, to rather complex models such as multi-kinetic and Collins-Selleck models. Results revealed that the involved processes of UV irradiation were too complex to be approached by a simplified formulation, even in the case of specific strains of microorganisms and the use of nearly constant UV radiation intensity. In fact, the application of Chick-Watson model in its original form is not representative of the kinetics of UV disinfection. Modification, taking into account the speed change during the disinfection process, has not significantly improved results. On the other hand, the application of Collins-Selleck model demonstrates that it was necessary to exceed a least dose of critical radiation to start the process of inactivation. To better explain the process of inactivation, we have assumed that the action of disinfectant on the survival of lonely microorganisms is faster than its action on suspended solids protected or agglomerated to each others. We can assume in this case the existence of two inactivation kinetics during the processes (parallel and independent) of the first-order. For this reason, the application of a new kinetic model by introducing a third factor reflecting the influence of suspended solids in water on disinfection kinetics appeared to be determinant for modeling UV inactivation of P. aeruginosa in secondary treated wastewater.

  15. Storage temperature and UV-irradiation influence on the ergosterol content in edible mushrooms.

    PubMed

    Villares, Ana; Mateo-Vivaracho, Laura; García-Lafuente, Ana; Guillamón, Eva

    2014-03-15

    Ergosterol (5,7,22-ergostatrien-3β-ol) and ergosteryl derivatives from different genera of edible mushrooms were separated and quantified by an isocratic reversed-phase high performance liquid chromatography (HPLC) method. The technique allowed a rapid separation of free ergosterol and two ergosteryl derivatives occurring in mushrooms. The ergosterol content varied considerably depending on the fungus. Thus, the species Agaricus bisporus and Hygrophorus marzuolus presented high quantities of ergosterol (6.4-6.8 mg/g, dry matter) followed by Pleurotus ostreatus, Calocybe gambosa, Lentinus edodes, and Boletus edulis (3.3-4.0mg/g). In contrast, other species, such as Cantharellus cibarius, Lactarius deliciosus and Craterellus cornucopioides, contained significantly lower ergosterol amounts (0.2-0.4 mg/g). Two ergosteryl derivatives were found in mushrooms and also the content depended on the fungus. The stability of ergosterol, in terms of the formation of ergosterol peroxide, was evaluated under different storage temperatures and UV radiation. The lower the temperature (-20°C) and the radiation time (10 min), the lower ergosterol oxidation was observed.

  16. Effect of gamma irradiation on the thiamine, riboflavin and vitamin B 6 content in two varieties of Brazilian beans

    NASA Astrophysics Data System (ADS)

    Villavicencio, A. L. C. H. A. L. C. H.; Mancini-Filho, J. J.; Delincée, H. H.; Bognár, A. A.

    2000-03-01

    The effect of 60Co gamma rays on the content of several B-vitamins in two varieties of Brazilian beans has been studied. Carioca ( Phaseolus vulgaris L. var. Carioca) and Macaçar beans ( Vigna unguiculata L. Walp, var. Macaçar) were irradiated at doses of 0, 0.5, 1.0, 2.5, 5.0 and 10 kGy, and subsequently stored at ambient temperature for 6 months. The content of vitamin B 1, B 2 and B 6 was analysed by HPLC. In addition, the optimum cooking time was established for each dose and bean variety. A taste panel evaluated sensory properties. Only slight changes were measured for thiamine and riboflavin, whereas a dose-dependent decrease was noted for pyridoxine, which, however, was significant only at the highest doses of 5 and 10 kGy. Cooking time was considerably reduced with increasing radiation dose, but accompanied by a loss of the sensory quality. However, at the disinfestation dose up to 1 kGy, acceptable ratings were obtained for the sensory evaluation. In conclusion, for insect disinfestation of Brazilian beans radiation processing is a promising technology.

  17. Effect of gamma irradiation on phenol content, antioxidant activity and biological activity of black maca and red maca extracts (Lepidium meyenii walp).

    PubMed

    Zevallos-Concha, A; Nuñez, D; Gasco, M; Vasquez, C; Quispe, M; Gonzales, G F

    2016-01-01

    This study was performed to determine the effects of gamma irradiation on UV spectrum on maca, total content of polyphenols, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activities and in vivo biological activities of red and black maca extracts (Lepidium meyenii). Adult mice of the strain Swiss aged 3 months and weighing 30-35 g in average were used to determine biological activities. Daily sperm production, effect on testosterone-induced prostate hyperplasia and forced swimming test were used to determine the effect of irradiation on biological activities of maca extracts. Irradiation did not show differences in UV spectrum but improves the amount of total polyphenols in red maca as well as in black maca extracts. In both cases, black maca extract has more content of polyphenols than red maca extract (p < 0.01). Gamma irradiation significantly increased the antioxidant capacity (p < 0.05). No difference was observed in daily sperm production when irradiated and nonirradiated maca extract were administered to mice (p > 0.05). Black maca extract but not red maca extract has more swimming endurance capacity in the forced swimming test. Irradiation of black maca extract increased the swimming time to exhaustion (p < 0.05). This is not observed with red maca extract (p > 0.05). Testosterone enanthate (TE) increased significantly the ventral prostate weight. Administration of red maca extract in animals treated with TE prevented the increase in prostate weight. Irradiation did not modify effect of red maca extract on prostate weight (p > 0.05). In conclusion, irradiation does not alter the biological activities of both black maca and red maca extracts. It prevents the presence of microorganisms in the extracts of black or red maca, but the biological activities were maintained. PMID:26633045

  18. Effect of gamma irradiation on phenol content, antioxidant activity and biological activity of black maca and red maca extracts (Lepidium meyenii walp).

    PubMed

    Zevallos-Concha, A; Nuñez, D; Gasco, M; Vasquez, C; Quispe, M; Gonzales, G F

    2016-01-01

    This study was performed to determine the effects of gamma irradiation on UV spectrum on maca, total content of polyphenols, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activities and in vivo biological activities of red and black maca extracts (Lepidium meyenii). Adult mice of the strain Swiss aged 3 months and weighing 30-35 g in average were used to determine biological activities. Daily sperm production, effect on testosterone-induced prostate hyperplasia and forced swimming test were used to determine the effect of irradiation on biological activities of maca extracts. Irradiation did not show differences in UV spectrum but improves the amount of total polyphenols in red maca as well as in black maca extracts. In both cases, black maca extract has more content of polyphenols than red maca extract (p < 0.01). Gamma irradiation significantly increased the antioxidant capacity (p < 0.05). No difference was observed in daily sperm production when irradiated and nonirradiated maca extract were administered to mice (p > 0.05). Black maca extract but not red maca extract has more swimming endurance capacity in the forced swimming test. Irradiation of black maca extract increased the swimming time to exhaustion (p < 0.05). This is not observed with red maca extract (p > 0.05). Testosterone enanthate (TE) increased significantly the ventral prostate weight. Administration of red maca extract in animals treated with TE prevented the increase in prostate weight. Irradiation did not modify effect of red maca extract on prostate weight (p > 0.05). In conclusion, irradiation does not alter the biological activities of both black maca and red maca extracts. It prevents the presence of microorganisms in the extracts of black or red maca, but the biological activities were maintained.

  19. Apparatus for in situ determination of burnup, cooling time and fissile content of an irradiated nuclear fuel assembly in a fuel storage pond

    DOEpatents

    Phillips, J.R.; Halbig, J.K.; Menlove, H.O.; Klosterbuer, S.F.

    1984-01-01

    A detector head for in situ inspection of irradiated nuclear fuel assemblies submerged in a water-filled nuclear fuel storage pond. The detector head includes two parallel arms which extend from a housing and which are spaced apart so as to be positionable on opposite sides of a submerged fuel assembly. Each arm includes an ionization chamber and two fission chambers. One fission chamber in each arm is enclosed in a cadmium shield and the other fission chamber is unshielded. The ratio of the outputs of the shielded and unshielded fission chambers is used to determine the boron content of the pond water. Correcting for the boron content, the neutron flux and gamma ray intensity are then used to verify the declared exposure, cooling time and fissile material content of the irradiated fuel assembly.

  20. Apparatus for in situ determination of burnup, cooling time and fissile content of an irradiated nuclear fuel assembly in a fuel storage pond

    DOEpatents

    Phillips, John R.; Halbig, James K.; Menlove, Howard O.; Klosterbuer, Shirley F.

    1985-01-01

    A detector head for in situ inspection of irradiated nuclear fuel assemblies submerged in a water-filled nuclear fuel storage pond. The detector head includes two parallel arms which extend from a housing and which are spaced apart so as to be positionable on opposite sides of a submerged fuel assembly. Each arm includes an ionization chamber and two fission chambers. One fission chamber in each arm is enclosed in a cadmium shield and the other fission chamber is unshielded. The ratio of the outputs of the shielded and unshielded fission chambers is used to determine the boron content of the pond water. Correcting for the boron content, the neutron flux and gamma ray intensity are then used to verify the declared exposure, cooling time and fissile material content of the irradiated fuel assembly.

  1. Cytokines in Radiobiological Responses: A Review

    PubMed Central

    Schaue, Dörthe; Kachikwu, Evelyn L.; McBride, William H.

    2013-01-01

    Cytokines function in many roles that are highly relevant to radiation research. This review focuses on how cytokines are structurally organized, how they are induced by radiation, and how they orchestrate mesenchymal, epithelial and immune cell interactions in irradiated tissues. Pro-inflammatory cytokines are the major components of immediate early gene programs and as such can be rapidly activated after tissue irradiation. They converge with the effects of ionizing radiation in that both generate free radicals including reactive oxygen and nitrogen species (ROS/RNS). “Self” molecules secreted or released from cells after irradiation feed the same paradigm by signaling for ROS and cytokine production. As a result, multilayered feedback control circuits can be generated that perpetuate the radiation tissue damage response. The pro-inflammatory phase persists until such times as perceived challenges to host integrity are eliminated. Antioxidant, anti-inflammatory cytokines then act to restore homeostasis. The balance between pro-inflammatory and anti-inflammatory forces may shift to and fro for a long time after radiation exposure, creating waves as the host tries to deal with persisting pathogenesis. Individual cytokines function within socially interconnected groups to direct these integrated cellular responses. They hunt in packs and form complex cytokine networks that are nested within each other so as to form mutually reinforcing or antagonistic forces. This yin-yang balance appears to have redox as a fulcrum. Because of their social organization, cytokines appear to have a considerable degree of redundancy and it follows that an elevated level of a specific cytokine in a disease situation or after irradiation does not necessarily implicate it causally in pathogenesis. In spite of this, “driver” cytokines are emerging in pathogenic situations that can clearly be targeted for therapeutic benefit, including in radiation settings. Cytokines can greatly

  2. [The effect of phospholipid hepatoprotectors on lipid peroxidation in liver and content of cytokines in the blood in experimental pathology caused by isoniazid].

    PubMed

    Udut, V V; Vengerovskiĭ, A I; Burkova, V N; Vaizova, O E; Korshunov, D A

    2012-01-01

    The purpose--to investigate the influence of hepatoprotective agents of phospholipids'structure essentiale, eplir and its combinations with amber acid on rats liver functional state, lipoperoxidation and bioenergetics, also tumor necrosis factor-a and interleukin-10 blood content in experimental isoniazid intoxication. These agents demonstrated antioxidant action, decreased the common and indirect bilirubine, tumor necrosis factor-alpha blood content, aminotransferase and alkaline phosphatase activity, increased the interleukin-10 blood content. Isonoazid uncoupled the substrate oxidation with ADP phosphorylation and inhibited the respiratory activity of liver mitochondrions. Essentiale and eplir increased the coupling of oxidation with ATP synthesis, in combination with amber acid improved kinetic characteristics of liver mitochondrions.

  3. Enhancement of antioxidant properties and increase of content of vitamin D2 and non-volatile components in fresh button mushroom, Agaricus bisporus (higher Basidiomycetes) by γ-irradiation.

    PubMed

    Tsai, Shu-Yao; Mau, Jeng-Leun; Huang, Shih-Jeng

    2014-01-01

    Agaricus bisporus is a popular culinary-medicinal mushroom in Taiwan, and γ-irradiation could extend its shelf life. Our objective was to study the content of vitamin D2 and the taste components and antioxidant properties of ethanolic extracts from A. bisporus with various doses of γ-irradiation. After irradiation, the vitamin D2 content of 5-10 kGy irradiated mushrooms was in the range of 5.22-7.90 µg/g, higher than that of the unirradiated control (2.24 µg/g). For all treatments, the total content of soluble sugars and polyols ranged from 113 to 142 mg/g, and the monosodium glutamate-like components ranged from 6.57 to 13.50 mg/g, among which the 2.5 kGy irradiated sample has the highest content of flavor 5'-nucleotide. About antioxidant properties, 10 kGy irradiated samples exhibited lower EC50 values than did other samples. EC50 values were less than 5 mg/mL for ethanolic extracts. Total phenols were the major antioxidant components and the total content was 13.24-22.78 mg gallic acid equivalents/g. Based on the results obtained, γ-irradiation could be used to improve the vitamin D2 content and intensity of umami taste in fresh mushrooms. In addition, γ-irradiation not only maintained the antioxidant properties of mushrooms but also enhanced the antioxidant properties to some extent.

  4. The dependence of helium generation rate on nickel content of Fe-Cr-Ni alloys irradiated at high dpa levels in fast reactors

    SciTech Connect

    Garner, F.A.; Oliver, B.M.; Greenwood, L.R.

    1997-04-01

    With a few exceptions in the literature, it is generally accepted that it is nickel in Fe-Cr-Ni alloys that produces most of the transmutant helium and that the helium generation rate should scale linearly with the nickel content. Surprisingly, this assumption is based only on irradiations of pure nickel and has never been tested in an alloy series. There have also been no extensive tests of the predictions for helium production in alloys in various fast reactors spectra.

  5. Hydrogen production via reforming of biogas over nanostructured Ni/Y catalyst: Effect of ultrasound irradiation and Ni-content on catalyst properties and performance

    SciTech Connect

    Sharifi, Mahdi; Haghighi, Mohammad; Abdollahifar, Mozaffar

    2014-12-15

    Highlights: • Synthesis of nanostructured Ni/Y catalyst by sonochemical and impregnation methods. • Enhancement of size distribution and active phase dispersion by employing sonochemical method. • Evaluation of biogas reforming over Ni/Y catalyst with different Ni-loadings. • Preparation of highly active and stable catalyst with low Ni content for biogas reforming. • Getting H{sub 2}/CO very close to equilibrium ratio by employing sonochemical method. - Abstract: The effect of ultrasound irradiation and various Ni-loadings on dispersion of active phase over zeolite Y were evaluated in biogas reforming for hydrogen production. X-ray diffraction, field emission scanning electron microscopy, energy dispersive X-ray, Brunauer–Emmett–Teller, Fourier transform infrared analysis and TEM analysis were employed to observe the characteristics of nanostructured catalysts. The characterizations implied that utilization of ultrasound irradiation enhanced catalyst physicochemical properties including high dispersion of Ni on support, smallest particles size and high catalyst surface area. The reforming reactions were carried out at GHSV = 24 l/g.h, P = 1 atm, CH{sub 4}/CO{sub 2} = 1 and temperature range of 550–850 °C. Activity test displayed that ultrasound irradiated Ni(5 wt.%)/Y had the best performance and the activity remained stable during 600 min. Furthermore, the proposed reaction mechanism showed that there are three major reaction channels in biogas reforming.

  6. Cytokines in psoriasis

    PubMed Central

    Baliwag, Jaymie; Barnes, Drew H.; Johnston, Andrew

    2015-01-01

    Psoriasis is a common inflammatory skin disease with an incompletely understood etiology. The disease is characterized by red, scaly and well-demarcated skin lesions formed by the hyperproliferation of epidermal keratinocytes. This hyperproliferation is driven by cytokines secreted by activated resident immune cells, an infiltrate of T cells, dendritic cells and cells of the innate immune system, as well as the keratinocytes themselves. Psoriasis has a strong hereditary character and has a complex genetic background. Genome-wide association studies have identified polymorphisms within or near a number of genes encoding cytokines, cytokine receptors or elements of their signal transduction pathways, further implicating these cytokines in the psoriasis pathomechanism. A considerable number of inflammatory cytokines have been shown to be elevated in lesional psoriasis skin, and the serum concentrations of a subset of these also correlate with psoriasis disease severity. The combined effects of the cytokines found in psoriasis lesions likely explain most of the clinical features of psoriasis, such as the hyperproliferation of keratinocytes, increased neovascularization and skin inflammation. Thus, understanding which cytokines play a pivotal role in the disease process can suggest potential therapeutic targets. A number of cytokines have been therapeutically targeted with success, revolutionizing treatment of this disease. Here we review a number of key cytokines implicated in the pathogenesis of psoriasis. PMID:25585875

  7. [Cytokines and allergic response].

    PubMed

    Guenounou, M

    1998-01-01

    Allergic reactions are under the control of several events that occur sequentially following allergen exposure, recognition by the immune system, IgE production and their interaction with effector cells bearing Fc epsilon receptors. The lymphocyte activation in response to allergens determines the intensity and the nature of the immune response. Cytokines produced by T (and non-T) cells are involved in the polarized development of the specific immune response. In particular, type 1 and type 2 cytokines are responsible for the control of the different steps during allergic reactions. Th2 cytokines and particularly IL4 are responsible for switching the immunoglobulin synthesis by B cells to IgE production. They also play a key role in the activation of effector cells that occurs following allergen interaction with fixed specific IgE and participate to the local inflammatory reaction. Cytokine profile determination appears to represent a helpful laboratory parameter in the understanding of the mechanisms underlying allergic diseases. The development of new technological tools may allow the use of cell activation parameters, and cytokine profiles determination in clinical biology. This review aims to analyze the involvement of the cytokine network in the mechanisms leading to IgE production and the involvement of cytokines in effector mechanisms of allergic reactions. It also analyses the potential use of cytokine profile determination for diagnosis purpose and survey of immune desensitization of allergic diseases.

  8. The effects of γ-irradiation on garlic oil content in garlic bulbs and on the radiolysis of allyl trisulfide

    NASA Astrophysics Data System (ADS)

    Genshuan, Wei; Guanghui, Wang; Ruipu, Yang; Jilan, Wu

    1996-02-01

    A study of the effects of γ-radiation on garlic oil content in garlic bulbs and on the radiolysis of allyl trisulfide and disulfide was carried out. The content of garlic oil in fresh garlic bulbs treated by gamma ray keeps nearly constant when stored for 10 months. The main components of garlic oil are allyl trisulfide (about 60%) and allyl disulfide (about 30%). The G values of radiolysis products of allyl disulfide and trisulfide in ethanol system were determined. The results show that allyl trisulfide is a very effective solvated electron scavenger and can oxidize CH 3CHOH radical into acetaldehyde, which means that the formation of 2,3-butanediol is extensively inhibited.

  9. Seasonal changes in photosynthesis, nitrogen content and nitrogen partitioning in Lindera umbellata leaves grown in high or low irradiance.

    PubMed

    Yasumura, Yuko; Hikosaka, Kouki; Hirose, Tadaki

    2006-10-01

    Seasonal changes in photosynthetic capacity, leaf nitrogen (N) content and N partitioning were studied from before leaf maturation (spring) until death (autumn) in high- and low-light-exposed leaves of a deciduous shrub, Lindera umbellata var. membranacea (Maxim.) Momiyama growing in a natural forest in northeast Japan. In spring, light-saturated photosynthetic rate (Pmax) was low despite high leaf N and Rubisco contents, indicating that the photosynthetic apparatus was not yet functionally developed. Rubisco seemed to be only partially active. In summer and autumn, Pmax per unit leaf N increased and changes in Pmax were correlated with changes in leaf N and two photosynthetic components, Rubisco and chlorophyll. Changes in these components paralleled the changes in leaf N. During leaf senescence, about 70% of leaf N was resorbed. Metabolic proteins that accounted for the majority of leaf N in summer were highly degradable and more than sufficient to explain the high N-resorption efficiency. Structural proteins represented only a small part of leaf N and were relatively resistant to degradation and thus contributed little to N resorption. Leaf N partitioning between metabolic and structural proteins determined the amount of retranslocatable N, but did not strictly determine the N content of a dead leaf or N-resorption efficiency.

  10. [Rheumatoid arthritis and cytokines].

    PubMed

    Kaneko, Shunta; Kondo, Yuya; Yokosawa, Masahiro; Sumida, Takayuki

    2016-06-01

    The cytokines are an important substance involved in the immune reaction and maintenance of homeostasis. An imbalance in the cytokine network may lead to inflammation and autoimmune diseases such as rheumatoid arthritis (RA). RA is an autoimmune and systemic inflammatory disorder characterized by synovial inflammation, destruction of cartilage and bone and systemic manifestations. The pro-inflammatory cytokines such as tumor necrosis factor α (TNFα), interleukin-1 (IL-1), IL-6 and IL-17 induce the inflammation of the joints and destruction of bone and cartilage via activation of macrophages, fibroblast like synoviocytes (FLS), helper T (Th) cells and osteoclasts. Recently, the available therapeutic agents that target these cytokines have excellent clinical effects in RA patients.

  11. [Immunostimulating drugs and cytokines].

    PubMed

    Lehners, Nicola; Goldschmidt, Hartmut; Raab, Marc S

    2011-11-01

    Cytokines are essential regulators of hematopoesis and the immune system. Genetic engineering of recombinant cytokines has facilitated their implementation in many clinical areas. In the field of oncology the granulopoetic human growth factors G-CSF and GM-CSF are of particular importance. They can be applied to prevent chemotherapy induced neutropenia. Furthermore, they allow for mobilization of hematopoetic stem cells in order to obtain peripheral blood stem cell transplants. Another class of cytokines, the interferons, possess immunomodulating, antiproliferative, and antiviral properties. While the significance of interferon alfa as an antitumor agent is dwindling, it still plays a very important role in the therapy of chronic hepatitis b and c. Interferon beta is successfully used to treat multiple sclerosis. Among the heterogenous group of interleukines in particular interleukin 2 has reached clinical practice as an immunostimulating agent in the therapy of metastatic renal cell carcinoma. Many other cytokines have yet to undergo clinical trials.

  12. Cytokines and acute pancreatitis.

    PubMed

    Brady, M; Christmas, S; Sutton, R; Neoptolemos, J; Slavin, J

    1999-07-01

    Cytokines have been shown to play a pivotal role in multiple organ dysfunction, a major cause of death in severe acute pancreatitis. Moreover, the two-hit hypothesis of the cytokine-induced systemic inflammatory response syndrome explains the variable individual response to severe acute pancreatitis and the impact of secondary events such as sepsis or therapeutic intervention. Many experimental anti-cytokine therapies have been administered following induction of experimental pancreatitis, and have proved to be therapeutic. Patients with severe pancreatitis present early because of pain. Clearly then a window for therapeutic intervention is available between onset of symptoms and peak pro-inflammatory cytokine expression. It is this fundamental observation that convinces many in the field that the treatment of AP will be one of the first clinical successes for novel drugs or therapy that seek to modulate the inflammatory response.

  13. Proteomic analysis of Spirogyra varians mutant with high starch content and growth rate induced by gamma irradiation.

    PubMed

    Yoon, Minchul; Choi, Jong-il; Kim, Gwang Hoon; Kim, Dong-Ho; Park, Don-Hee

    2013-06-01

    This study was conducted to develop a high-efficiency strain of Spirogyra varians for the production of biomass by radiation breeding. The characteristics of wild-type and mutant S. varians were analyzed through phenomenological and proteomic observations. The results of our phenomenological observations of the S. varians mutant demonstrated increases in growth rate and content of chlorophyll a, b, and a + b; in particular, a significant threefold increase was observed in starch accumulation. Proteomic analysis to investigate the differences in expression between wild-type and mutant proteins identified 18 proteins with significantly different expressions. From the literature review, it was confirmed that the up-regulated proteins were mainly involved in photosynthesis, carbohydrate biosynthesis, and energy metabolism. These results suggest the possibility of algae development by radiation breeding for the production of biofuel. PMID:23370702

  14. Proteomic analysis of Spirogyra varians mutant with high starch content and growth rate induced by gamma irradiation.

    PubMed

    Yoon, Minchul; Choi, Jong-il; Kim, Gwang Hoon; Kim, Dong-Ho; Park, Don-Hee

    2013-06-01

    This study was conducted to develop a high-efficiency strain of Spirogyra varians for the production of biomass by radiation breeding. The characteristics of wild-type and mutant S. varians were analyzed through phenomenological and proteomic observations. The results of our phenomenological observations of the S. varians mutant demonstrated increases in growth rate and content of chlorophyll a, b, and a + b; in particular, a significant threefold increase was observed in starch accumulation. Proteomic analysis to investigate the differences in expression between wild-type and mutant proteins identified 18 proteins with significantly different expressions. From the literature review, it was confirmed that the up-regulated proteins were mainly involved in photosynthesis, carbohydrate biosynthesis, and energy metabolism. These results suggest the possibility of algae development by radiation breeding for the production of biofuel.

  15. Interspecific prediction of photosynthetic light response curves using specific leaf mass and leaf nitrogen content: effects of differences in soil fertility and growth irradiance

    PubMed Central

    Lachapelle, Pierre-Philippe; Shipley, Bill

    2012-01-01

    Background and Aims Previous work has shown that the entire photosynthetic light response curve, based on both Mitscherlich and Michaelis–Menten functions, could be predicted in an interspecific context through allometric relations linking the parameters of these functions to two static leaf traits: leaf nitrogen (N) content and leaf mass per area (LMA). This paper describes to what extent these allometric relations are robust to changes in soil fertility and the growth irradiance of the plants. Methods Plants of 25 herbaceous species were grown under controlled conditions in factorial combinations of low/high soil fertility and low/high growth irradiance. Net photosynthetic rates per unit dry mass were measured at light intensities ranging from 0 to 700 µmol m−2 s−1 photosynthetically active radiation (PAR). Key Results The differing growth environments induced large changes in N, LMA and in each of the parameter estimates of the Mitscherlich and Michaelis–Menten functions. However, the differing growth environments induced only small (although significant) changes in the allometric relationships linking N and LMA to the parameters of the two functions. As a result, 88 % (Mitcherlich) and 89 % (Michaelis–Menten) of the observed net photosynthetic rates over the full range of light intensities (0–700 µmol m−2 s−1 PAR) and across all four growth environments could be predicted using only N and LMA using the same allometric relations. Conclusions These results suggest the possibility of predicting net photosynthetic rates in nature across species over the full range of light intensities using readily available data. PMID:22442344

  16. Jerusalem of cytokines.

    PubMed

    Levi, B Z; Sica, A; Müller-Newen, G; Takahashi, N; Vandenbeele, P; Fish, E

    1999-06-01

    The Second Joint Meeting of the International Cytokine Society and the International Society for Interferon and Cytokine Research was held on October 25-30, 1998 in Jerusalem, Israel. The nature of this Joint Meeting dictated that it was intensive and covered topics that included receptor-ligand interactions, signal transduction, transcriptional regulation, antiviral action and apoptotic pathways induced by cytokines such as interferons, interleukines and chemokines. Their roles in infectious diseases and cancers were considered. This overview is by no mean comprehensive and covers only part of the many topics and subjects that were presented in the many plenary talks, symposia and poster sessions. The meeting was held in an excellent scientific atmosphere, that was probably affected by the "divine presence" in Jerusalem, and special thanks for the excellent organization are owed to Drs. Kaempfer, Revel, Wallach and Witz.

  17. Autophagy and cytokines.

    PubMed

    Harris, James

    2011-11-01

    Autophagy is a highly conserved homoeostatic mechanism for the lysosomal degradation of cytosolic constituents, including long-lived macromolecules, organelles and intracellular pathogens. Autophagosomes are formed in response to a number of environmental stimuli, including amino acid deprivation, but also by both host- and pathogen-derived molecules, including toll-like receptor ligands and cytokines. In particular, IFN-γ, TNF-α, IL-1, IL-2, IL-6 and TGF-β have been shown to induce autophagy, while IL-4, IL-10 and IL-13 are inhibitory. Moreover, autophagy can itself regulate the production and secretion of cytokines, including IL-1, IL-18, TNF-α, and Type I IFN. This review discusses the potentially pivotal roles of autophagy in the regulation of inflammation and the coordination of innate and adaptive immune responses.

  18. Coordinate cytokine regulatory sequences

    DOEpatents

    Frazer, Kelly A.; Rubin, Edward M.; Loots, Gabriela G.

    2005-05-10

    The present invention provides CNS sequences that regulate the cytokine gene expression, expression cassettes and vectors comprising or lacking the CNS sequences, host cells and non-human transgenic animals comprising the CNS sequences or lacking the CNS sequences. The present invention also provides methods for identifying compounds that modulate the functions of CNS sequences as well as methods for diagnosing defects in the CNS sequences of patients.

  19. [Cytokines and the liver].

    PubMed

    Kershenobich, D; Borovoy, J; Guevara, L; Male, R; Alcocer, J

    1990-07-01

    The cytokines are proteins synthetized by lymphoid and monocyte/macrophage system cells in response to a wide variety of infectious stimulus, featuring bacterial endotoxins. These proteins have immunoregulatory effects and have been implicated in inflammation and fibrosis. In this review we refer to the interleukin-1, interleukin-6 and tumor necrosis factor because of their elevated basal levels in acute and chronic hepatopaties and in response to lipopolisacharide mainly in alcoholic liver disease. PMID:19256129

  20. Cytokine Therapies in Neurological Disease.

    PubMed

    Azodi, Shila; Jacobson, Steven

    2016-07-01

    Cytokines are a heterogeneous group of glycoproteins that coordinate physiological functions. Cytokine deregulation is observed in many neurological diseases. This article reviews current research focused on human clinical trials of cytokine and anticytokine therapies in the treatment of several neurological disease including stroke, neuromuscular diseases, neuroinfectious diseases, demyelinating diseases, and neurobehavioral diseases. This research suggests that cytokine therapy applications may play an important role in offering new strategies for disease modulation and treatment. Further, this research provides insights into the causal link between cytokine deregulation and neurological diseases. PMID:27388288

  1. Effect of electron beam irradiation and storage at 5 degrees C on thiobarbituric acid reactive substances and carbonyl contents in chicken breast meat infused with antioxidants and selected plant extracts.

    PubMed

    Rababah, Taha; Hettiarachchy, Navam; Horax, Ronny; Eswaranandam, Satchithanandam; Mauromoustakos, Andronikos; Dickson, James; Niebuhr, Steven

    2004-12-29

    This study evaluated the effectiveness of synthetic and natural antioxidants, green tea, commercial grape seed extracts/combinations, and TBHQ, with varying concentrations of lipid oxidation of nonirradiated and irradiated chicken breast meats stored at 5 degrees C for 12 days. Fresh boneless and skinless chicken breast meats were vacuum-infused with varying concentrations of antioxidants: green tea, grape seed extracts alone/in combination, and TBHQ. The irradiation dosage was 3.0 kGy. Carbonyl values of raw chicken meat and thiobarbituric acid reactive substances (TBARS) values of raw and cooked chicken meat were determined for 0-12 days at 5 degrees C storage. TBARS values for 0-12 days of storage at 5 degrees C ranged from 1.21 to 7.3 and 1.22 to 8.51 mg malondialdehyde/100 g chicken for nonirradiated and irradiated raw chicken, respectively. TBARS values of cooked chicken ranged from 2.19 to 35.83 and 2.45 to 45.72 mg malondialdehyde/100 g chicken for nonirradiated and irradiated chicken, respectively. Irradiation increased TBARS values of both controls and plant extracts. The carbonyl content in meat lipid ranged from 1.7 to 2.9 and 1.7 to 4.41 micromol acetophenone/10 g of nonirradiated and irradiated chicken meat, respectively, and meat protein ranged from 1.4 to 2.07 and 1.41 to 2.72 micromol/10 g meat. Infusion of chicken meat with selected plant extracts is an effective method to minimize lipid oxidation and volatiles developments caused by irradiation. PMID:15612823

  2. Experimental validation of a combined electromagnetic and thermal model for a microwave drying of capillary porous materials inside a rectangular wave guide (effects of irradiation time, particle sizes and initial moisture content).

    PubMed

    Ratanadecho, P; Aoki, K; Akahori, M

    2002-01-01

    In this paper, the experimental validation of a combined electromagnetic and thermal model for a microwave drying of capillary porous materials inside a rectangular wave guide is presented. The effects of the irradiation time, particle sizes and the variation of initial moisture content on the microwave drying kinetics are clarified in detail, considering the interference between incident and reflected waves in the capillary porous materials. The established model has allowed us to determine the space-time evolution of electric field, temperature and moisture content within capillary porous materials during microwave drying process.

  3. [Cytokines in bone diseases. Cytokine and postmenopausal osteoporosis].

    PubMed

    Inada, Masaki; Miyaura, Chisato

    2010-10-01

    Bone resorption is regulated by various cytokines. In postmenopausal osteoporosis, bone loss due to estrogen deficiency is closely related to the production of bone-resorbing cytokine. Especially, the increased production of IL-1, IL-6 and TNF-α could induce the expression of RANKL in bone tissues to enhance osteoclastogenesis. Relationship between estrogen deficiency and various cytokines is important to clarify the pathogenesis of postmenopausal osteoporosis.

  4. Modulation with cytokines of radiation injury: suggested mechanisms of action.

    PubMed Central

    Neta, R

    1997-01-01

    Cytokines, hormonelike proteins, produced by stimulated cells and tissues, were found to protect mice against lethal hematopoietic failure caused by ionizing radiation. Radioprotection was achieved by pretreatment with interleukin-1 (IL-1), tumor necrosis factor (TNF), IL-12, or stem cell factor (SCF) at 18 to 24 hr before irradiation. Pretreatment with antibodies to these cytokines rendered the mice more susceptible to radiation lethality, indicating that these cytokines play a role in innate resistance to radiation. In contrast, treatment with tumor growth factor beta (TGF-beta), a cytokine that inhibits cycling of primitive hematopoietic progenitors, sensitized mice to radiation lethality. The schedule of IL-1 administration was critical to its radioprotective effect. Evidence was obtained that this may be based on the induction of additional cytokines by IL-1. The radioprotective effects of cytokines can be based on induction of cycling of primitive progenitor cells (IL-1, SCF), prevention of apoptosis (SCF), and induction of scavenging proteins and enzymes (IL-1, TNF) that reduce oxidative damage. In contrast, radiosensitizing effects may be due to inhibition of progenitor cycling (TGF-beta) or enhanced progenitor cell apoptosis (TGF-beta). Thus, the insights gained from such studies at the whole-animal level promise a better understanding of the membrane and intracellular events associated with radiation damage and repair of such damage. PMID:9467064

  5. Cytokines and therapeutic oligonucleotides.

    PubMed

    Hartmann, G; Bidlingmaier, M; Eigler, A; Hacker, U; Endres, S

    1997-12-01

    Therapeutic oligonucleotides - short strands of synthetic nucleic acids - encompass antisense and aptamer oligonucleotides. Antisense oligonucleotides are designed to bind to target RNA by complementary base pairing and to inhibit translation of the target protein. Antisense oligonucleotides enable specific inhibition of cytokine synthesis. In contrast, aptamer oligonucleotides are able to bind directly to specific proteins. This binding depends on the sequence of the oligonucleotide. Aptamer oligonucleotides with CpG motifs can exert strong immunostimulatory effects. Both kinds of therapeutic oligonucleotides - antisense and aptamer oligonucleotides - provide promising tools to modulate immunological functions. Recently, therapeutic oligonucleotides have moved towards clinical application. An antisense oligonucleotide directed against the proinflammatory intercellular adhesion molecule 1 (ICAM-1) is currently being tested in clinical trials for therapy of inflammatory disease. Immunostimulatory aptamer oligonucleotides are in preclinical development for immunotherapy. In the present review we summarize the application of therapeutic oligonucleotides to modulate immunological functions. We include technological aspects as well as current therapeutic concepts and clinical studies.

  6. Depositional and irradiational history and noble gas contents of orange-black droplets in the 74002/1 core from Shorty Crater

    NASA Technical Reports Server (NTRS)

    Bogard, D. D.; Hirsch, W. C.

    1978-01-01

    Isotopic concentrations of noble gases were assessed in grain size separates of 14 soils from a 67-cm section of lunar regolith taken on the rim of Shorty Crater. The orange-black droplets in this section were probably formed from pyroclastic eruptions about 3.6 billion years ago; they give little indication of surface exposure. The isotopic concentrations suggest that cosmic ray irradiation of the core occurred in two stages and that the core stratigraphy was inverted between stages. The first irradiation stage may have taken place immediately after pyroclastic deposition of the droplets and could have lasted about 20 million years.

  7. The role of cytokines in skin aging.

    PubMed

    Borg, M; Brincat, S; Camilleri, G; Schembri-Wismayer, P; Brincat, M; Calleja-Agius, J

    2013-10-01

    Cutaneous aging is one of the major noticeable menopausal complications that most women want to fight in their quest for an eternally youthful skin appearance. It may contribute to some maladies that occur in aging which, despite not being life-threatening, affect the well-being, psychological state and quality of life of aged women. Skin aging is mainly affected by three factors: chronological aging, decreased levels of estrogen after menopause, and environmental factors. Aged skin is characterized by a decrease in collagen content and skin thickness which result in dry, wrinkled skin that is easily bruised and takes a longer time to heal. Cytokines play a crucial role in the manifestation of these features of old skin. The pro-inflammatory cytokine tumor necrosis factor-alpha inhibits collagen synthesis and enhances collagen degradation by increasing the production of MMP-9. It also lowers the skin immunity and thus increases the risk of cutaneous infections in old age. Deranged levels of several interleukins and interferons also affect the aging process. The high level of CCN1 protein in aged skin gives dermal fibroblasts an 'age-associated secretory phenotype' that causes abnormal homeostasis of skin collagen and leads to the loss of the function and integrity of skin. Further research is required especially to establish the role of cytokines in the treatment of cutaneous aging.

  8. Use of 5-Bromodeoxyuridine and irradiation for the estimation of the myoblast and myocyte content of primary rat heart cell cultures

    SciTech Connect

    Masse, M.J.O.; Harary, I.

    1980-11-01

    A method for killing dividing cells was adapted for the elimination of dividing heart muscle cells (myoblasts) in cultures. We have used this method to demonstrate their presence and to estimate their number as well as the number of nondividing heart muscle cells (myocytes) in the neo-natal rat heart. Cells were cultivated in BUdR (5-bromodeoxyuridine) 10/sup -4/ M for 3 days and then irradiated with long uv light. The selective elimination of dividing cells led to a loss of myosin Ca/sup 2 +/-activated ATPase in the cultures. The percent of ATPase left after irradiation was 32% of the control in cultures derived from 1-day postnatal rats and 48% in cultures from 4-day postnatal rats. This reflects an in vivo shift of myoblasts to myocytes in the muscle cell population as the rat ages.

  9. The Function of Fish Cytokines

    PubMed Central

    Zou, Jun; Secombes, Christopher J.

    2016-01-01

    What is known about the biological activity of fish cytokines is reviewed. Most of the functional studies performed to date have been in teleost fish, and have focused on the induced effects of cytokine recombinant proteins, or have used loss- and gain-of-function experiments in zebrafish. Such studies begin to tell us about the role of these molecules in the regulation of fish immune responses and whether they are similar or divergent to the well-characterised functions of mammalian cytokines. This knowledge will aid our ability to determine and modulate the pathways leading to protective immunity, to improve fish health in aquaculture. PMID:27231948

  10. Cytokines in systemic lupus erythematosus.

    PubMed

    Lourenço, Elaine V; La Cava, Antonio

    2009-04-01

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies that can form immune complexes and deposit in tissues, causing inflammation and organ damage. There is evidence that interferons and some interleukins can have an active role in the pathogenesis of SLE and can contribute significantly to the immune imbalance in the disease, whereas the role of some cytokines (such as TNF) is still debated. This review discusses the activity of several cytokines in SLE, their effects on the immune cells in relation to the disease pathogenesis, and the promise and limitations of cytokine-based therapies in clinical trials for lupus patients.

  11. Changes in contents and in vitro digestibility of laying-hens excreta used as feedstuffs due to drying and gamma irradiation.

    PubMed

    al-Masri, M R

    1998-07-01

    Experiments have been carried out to study the changes in the values of total nitrogen (N), in vitro digestible crude protein (IVDCP), in vitro apparent organic matter digestibility (IVOMD), in vitro digestible energy (IVDE), crude fibre (CF) and cell-wall constituents (NDF, ADF, ADL) for laying-hens excreta under the effects of: (1) two types of drying: (a) drying at 175 degrees C for 10 minutes (D1); (b) drying at 55 degrees C for 5 days (D2). (2) different doses of gamma irradiation [0, 10, 50, 100, 150 kilogray (kGy)]. The results indicated that there was a significant (P < 0.05) decrease in values of NDF and ADF (by 7%), CF and IVDCP (by 13%), and N (by 16%), and a significant increase in the values of IVOMD (by 12%) and IVDE (by 630 kJ/kg DM) as a result of drying (D1) in comparison with drying (D2). A significant (P < 0.05) decrease was observed in the values of NDF and ADF (by 6%), CF (by 12%) and a significant increase in the values of IVOMD (by 13%) and IVDE (by 980 kJ/kg DM) as a result of gamma irradiation treatment (100 kGy) in comparison to the control sample. There was no significant difference between doses (100 kGy and 150 kGy). Gamma irradiation had no effect on N, ADL and IVDCP values. Combined treatment (D1 + 100 kGy) resulted in a better effect in reducing the concentrations of CF, NDF and ADF and in increasing the values of IVOMD and IVDE.

  12. The influence of various irradiances of artificial light, twilight, and moonlight on the suppression of pineal melatonin content in the Syrian hamster.

    PubMed

    Brainard, G C; Richardson, B A; Hurlbut, E C; Steinlechner, S; Matthews, S A; Reiter, R J

    1984-01-01

    The purpose of the present studies using artificial light was to determine how the timing and duration of exposure influence the light-induced suppression of pineal melatonin levels in hamsters. An 8-min exposure to 0.186 microW/cm2 of cool white fluorescent light caused a continued depression of pineal melatonin even when animals were returned to darkness. In addition, the pineal gland does not appear to change its sensitivity to light throughout the night. A 20-min exposure to 0.019 microW/cm2 of cool white fluorescent light did not significantly suppress pineal melatonin during any time of the melatonin peak, whereas a 20-min exposure to 0.186 microW/cm2 was capable of always suppressing melatonin. Furthermore, increasing the duration of 0.019-microW/cm2 exposure to 30, 60, 120, or 180 min does not increase the capacity of this irradiance to depress melatonin. Similar to artifical light, natural light has a variable capacity for suppressing nocturnal levels of pineal melatonin. Twilight irradiances of 0.138 microW/cm2 or less did not suppress nocturnal melatonin whereas twilight irradiances of 3.0 microW/cm2 or greater did suppress pineal melatonin. A few animals did have lower melatonin after a 40-min exposure to full moonlight during July (0.045 microW/cm2) or January (0.240 microW/cm2). However, pineal melatonin levels remained high in the majority of animals exposed to full moonlight.

  13. Use of cytokines in infection.

    PubMed

    Aoki, Naoko; Xing, Zhou

    2004-11-01

    Infectious disease remains an ever-growing health concern worldwide due to increasing antibiotic-resistant microbial strains, immune-compromised populations, international traffic and globalisation, and bioterrorism. There exists an urgent need to develop novel prophylactic and therapeutic strategies. In addition to classic antibiotic therapeutics, immune-modulatory molecules such as cytokines or their inhibitors represent a promising form of antimicrobial therapeutics or immune adjuvant used for the purpose of vaccination. These molecules, in the form of either recombinant protein or transgene, exert their antimicrobial effect by enhancing infectious agent-specific immune activation or memory development, or by dampening undesired inflammatory and immune responses resulting from infection and host defence mechanisms. In the last two decades, a number of cytokine therapy-based experimental and clinical trials have been conducted, and some of these efforts have led to the routine clinical use of cytokines. For instance, although IFNs have been used to treat hepatitis C with great success, many other cytokines are yet to be fully evaluated for their antimicrobial potential. This review discusses the biology and therapeutic potential of selected immune modulatory cytokines and their inhibitors, including granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, IFN-gamma, IL-12 and TNF.

  14. Targeted cytokines for cancer immunotherapy.

    PubMed

    Lode, H N; Reisfeld, R A

    2000-01-01

    Targeting of cytokines into the tumor microenvironment using antibody-cytokine fusion proteins, called immunocytokines, represents a novel approach in cancer immunotherapy. This article summarizes therapeutic efficacy and immune mechanisms involved in targeting interleukin-2 (IL-2) to neuroectodermal tumors using ganglioside GD2-specific antibody-IL-2 fusion protein (ch14.18-IL-2). Treatment of established melanoma metastases with ch14.18-IL-2 resulted in eradication of disease followed by a vaccination effect protecting mice from lethal challenges with wild-type tumor calls. In a syngeneic neuroblastoma model, targeted IL-2 was effective in the amplification of a weak memory immune response previously induced by IL-12 gene therapy using an engineered linear version of this heterodimeric cytokine. These findings show that targeted IL-2 may provide an effective tool in cancer immunotherapy and establish the missing link between T cell-mediated vaccination and objective clinical responses.

  15. Photocatalytic performance of the SiO2 sphere/ n-type TiO2/ p-type CuBiS2 composite catalysts coated with different contents of Ag nanoparticles under ultraviolet and visible light irradiations

    NASA Astrophysics Data System (ADS)

    Abdullah, Hairus; Kuo, Dong-Hau

    2016-08-01

    Photocatalytic performance of the SiO2 sphere/ n-type TiO2/ p-type CuBiS2 composite catalysts with different contents of silver nanoparticles (abbreviated as SiO2/ n-TiO2/ p-CuBiS2/Ag) toward the photodegradation of Acid Black 1 ( AB 1) dye under ultraviolet (UV) and visible light was investigated. The composite catalyst spheres were analyzed their crystal structure, microstructure, optical absorbance capabilities, and photodegradation capabilities of AB 1 dye. The best photodegradation performances of the 20 mg composite powder with only ~5 mg photoactive catalysts showed the degradation of AB 1 dye in 5 min under UV and 60 min under visible light irradiations. The concept of composite catalyst with numerous nano p- n diodes and its photodegradation mechanism were proposed.

  16. IL-12 Family Cytokines: Immunological Playmakers

    PubMed Central

    Vignali, Dario A.A.; Kuchroo, Vijay K.

    2014-01-01

    The interleukin-12 (IL-12) family is unique in comprising the only heterodimeric cytokines, which includes IL-12, IL-23, IL-27 and IL-35. This endows these cytokines with a unique set of connections and functional interactions not shared within other cytokine families. Despite sharing many structural features and molecular partners, they mediate surprisingly diverse functional effects. Here we discuss the unique and unusual structural and functional characteristics of this cytokine family. We outline how cells might interpret seemingly similar cytokine signals to give rise to the diverse functional outcomes which characterize this cytokine family. We will also discuss the therapeutic implications of this complexity. PMID:22814351

  17. [Cytokines. Transmittor substances of the immune system].

    PubMed

    Pisa, P; Söder, O

    1995-07-12

    Cytokines are hormone-like proteins and peptides whose principal function is that of signalling substances within the immunoinflammatory and haematopoietic systems. Since the first cytokines were characterised 15 years ago, over 50 cytokines have been strictly defined and characterised. Cytokines are classified mainly on the basis of functional criteria into families--e.g, interleukins, interferons, colony stimulating factors, and chemokines. The article provides a broad review of cytokine physiology and pathophysiology with an emphasis on recent findings of their involvement in various diseases such as infections, autoimmune and haematological disorders, and cancer. Different treatment modalities that affect cytokine activity are discussed.

  18. Effect of microwave irradiation on TATB explosive.

    PubMed

    Yu, Weifei; Zhang, Tonglai; Huang, Yigang; Yang, Li; Li, Gang; Li, Haibo; Li, Jinshan; Huang, Hui

    2009-09-15

    Finished TATB (1,3,5-triamino-2,4,6-trinitrobenzene) explosive safety under 800W microwave irradiation was experimented. No burning, deflagration and detonation were observed during 30-min continuous irradiation and no remarkable change were observed after irradiation according to HPLC, particles size analysis, and differential thermal analysis. Wet TATB sampled from synthesis line was irradiated with microwave vacuum method and irradiated TATB was measured to accord with military standard specifications including appearance, moisture and volatile, chloride content, HPLC, mean particle size, DTA exothermic peak, ash, acetone soluble content, PH value, etc. Microwave vacuum desiccation was deemed laborsaving, energy-efficient, and practicable compared to conventional processing method. PMID:19324496

  19. Effect of microwave irradiation on TATB explosive.

    PubMed

    Yu, Weifei; Zhang, Tonglai; Huang, Yigang; Yang, Li; Li, Gang; Li, Haibo; Li, Jinshan; Huang, Hui

    2009-09-15

    Finished TATB (1,3,5-triamino-2,4,6-trinitrobenzene) explosive safety under 800W microwave irradiation was experimented. No burning, deflagration and detonation were observed during 30-min continuous irradiation and no remarkable change were observed after irradiation according to HPLC, particles size analysis, and differential thermal analysis. Wet TATB sampled from synthesis line was irradiated with microwave vacuum method and irradiated TATB was measured to accord with military standard specifications including appearance, moisture and volatile, chloride content, HPLC, mean particle size, DTA exothermic peak, ash, acetone soluble content, PH value, etc. Microwave vacuum desiccation was deemed laborsaving, energy-efficient, and practicable compared to conventional processing method.

  20. Photodegradation of ibuprofen by TiO2 co-doping with urea and functionalized CNT irradiated with visible light - Effect of doping content and pH.

    PubMed

    Yuan, Ching; Hung, Chung-Hsuang; Li, Huei-Wen; Chang, Wei-Hsian

    2016-07-01

    Ibuprofen (IBP) is one kind of non-steroidal anti-inflammatory drugs (NSAIDs), which are classified as Pharmaceuticals and Personal Care Products (PPCPs). IBP possesses bioactive property and the substantial use of IBP results in a harmful impact on bioreceptors even in small concentrations. Accordingly, the treatment of these wastewaters is important before discharging them into the ecosystem. The photodegradation of IBP with TiO2 co-doped with functionalized CNTs (CNT-COOH and CNT-COCl) and urea, named as N-doping CNT/TiO2, irradiated with visible light of 410 nm was investigated in this study. The titanium tetrachloride was used as the precursor of Ti. The N-doping CNT-COCl/TiO2 photocatalysts exhibited a better crystalline structure and smaller crystal size than the N-doping CNT-COOH/TiO2 photocatalyst. It might largely ascribe to strong binding between acyl chloride functional group and TiO2. About 85.0%-86.0% of IBP was degraded with N-doping CNT/TiO2 within 120 min at natural condition, which obeyed the pseudo first order reaction and the rate constant was 4.45 × 10(-3)-1.22 × 10(-2) min(-1) and 5.03 × 10(-3)-1.47 × 10(-2) min(-1) for N-doping CNT-COOH/TiO2 and N-doping CNT-COCl/TiO2, respectively. The best IBP degradation of 87.9%-89.0% was found at pH 5, which indicated superoxide radicals (O2(-)) played a key role. The optimal pH was majorly dominated by the nature of IBP and N-doping CNT/TiO2. A successful synergy effect of TiO2 and dopants was exhibited and this mainly attributed to the strong binding strength by functional group of acyl chloride (COCl) and carboxylic acid (COOH). In summary, IBP could be effectively photodegraded by the fabricated N-doping CNT/TiO2 photocatalysts.

  1. Cytokine Signature in Infective Endocarditis

    PubMed Central

    Araújo, Izabella Rodrigues; Ferrari, Teresa Cristina Abreu; Teixeira-Carvalho, Andréa; Campi-Azevedo, Ana Carolina; Rodrigues, Luan Vieira; Guimarães Júnior, Milton Henriques; Barros, Thais Lins Souza; Gelape, Cláudio Léo; Sousa, Giovane Rodrigo; Nunes, Maria Carmo Pereira

    2015-01-01

    Infective endocarditis (IE) is a severe disease with high mortality rate. Cytokines participate in its pathogenesis and may contribute to early diagnosis improving the outcome. This study aimed to evaluate the cytokine profile in IE. Serum concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12 and tumor necrosis factor (TNF)-α were measured by cytometric bead array (CBA) at diagnosis in 81 IE patients, and compared with 34 healthy subjects and 30 patients with non-IE infections, matched to the IE patients by age and gender. Mean age of the IE patients was 47±17 years (range, 15–80 years), and 40 (50%) were male. The IE patients had significantly higher serum concentrations of IL-1β, IL-6, IL-8, IL-10 and TNF-α as compared to the healthy individuals. The median levels of IL-1β, TNF-α and IL-12 were higher in the IE than in the non-IE infections group. TNF-α and IL-12 levels were higher in staphylococcal IE than in the non-staphylococcal IE subgroup. There was a higher proportion of both low IL-10 producers and high producers of IL-1β, TNF-α and IL-12 in the staphylococcal IE than in the non-staphylococcal IE subgroup. This study reinforces a relationship between the expression of proinflammatory cytokines, especially IL-1β, IL-12 and TNF-α, and the pathogenesis of IE. A lower production of IL-10 and impairment in cytokine network may reflect the severity of IE and may be useful for risk stratification. PMID:26225421

  2. Cytokine disturbances in systemic lupus erythematosus.

    PubMed

    Jacob, Noam; Stohl, William

    2011-07-06

    The pathogenesis of systemic lupus erythematosus (SLE) is complex, and the resulting disease manifestations are heterogeneous. Cytokine dysregulation is pervasive, and their protein and gene expression profiles may serve as markers of disease activity and severity. Importantly, biologic agents that target specific cytokines may represent novel therapies for SLE. Four cytokines (IL-6, TNFα, IFNα, and BLyS) are being evaluated as therapeutic targets in SLE. The present review will examine the roles of each of these cytokines in murine and human SLE, and will summarize results from clinical trials of agents that target these cytokines.

  3. Blue light irradiation suppresses dendritic cells activation in vitro.

    PubMed

    Fischer, Michael R; Abel, Manuela; Lopez Kostka, Susanna; Rudolph, Berenice; Becker, Detlef; von Stebut, Esther

    2013-08-01

    Blue light is a UV-free irradiation suitable for treating chronic skin inflammation, for example, atopic dermatitis, psoriasis, and hand- and foot eczema. However, a better understanding of the mode of action is still missing. For this reason, we investigated whether dendritic cells (DC) are directly affected by blue light irradiation in vitro. Here, we report that irradiation neither induced apoptosis nor maturation of monocyte-derived and myeloid DC. However, subsequent DC maturation upon LPS/IFNγ stimulation was impaired in a dose-dependent manner as assessed by maturation markers and cytokine release. Moreover, the potential of this DC to induce cytokine secretion from allogeneic CD4 T cells was reduced. In conclusion, unlike UV irradiation, blue light irradiation at high and low doses only resulted in impaired DC maturation upon activation and a reduced subsequent stimulatory capacity in allogeneic MLRs with strongest effects at higher doses. PMID:23879817

  4. DNA Repair and Cytokines: TGF-β, IL-6, and Thrombopoietin as Different Biomarkers of Radioresistance

    PubMed Central

    Centurione, Lucia; Aiello, Francesca B.

    2016-01-01

    Double strand breaks (DSBs) induced by radiotherapy are highly cytotoxic lesions, leading to chromosomal aberrations and cell death. Ataxia-telangiectasia-mutated (ATM)-dependent DNA-damage response, non-homologous end joining, and homologous recombination pathways coordinately contribute to repairing DSBs in higher eukaryotes. It is known that the expression of DSB repair genes is increased in tumors, which is one of the main reasons for radioresistance. The inhibition of DSB repair pathways may be useful to increase tumor cell radiosensitivity and may target stem cell-like cancer cells, known to be the most radioresistant tumor components. Commonly overexpressed in neoplastic cells, cytokines confer radioresistance by promoting proliferation, survival, invasion, and angiogenesis. Unfortunately, tumor irradiation increases the expression of various cytokines displaying these effects, including transforming growth factor-beta and interleukin-6. Recently, the capabilities of these cytokines to support DNA repair pathways and the ATM-dependent DNA response have been demonstrated. Thrombopoietin, essential for megakaryopoiesis and very important for hematopoietic stem cell (HSC) homeostasis, has also been found to promote DNA repair in a highly selective manner. These findings reveal a novel mechanism underlying cytokine-related radioresistance, which may be clinically relevant. Therapies targeting specific cytokines may be used to improve radiosensitivity. Specific inhibitors may be chosen in consideration of different tumor microenvironments. Thrombopoietin may be useful in fending off irradiation-induced loss of HSCs. PMID:27500125

  5. DNA Repair and Cytokines: TGF-β, IL-6, and Thrombopoietin as Different Biomarkers of Radioresistance.

    PubMed

    Centurione, Lucia; Aiello, Francesca B

    2016-01-01

    Double strand breaks (DSBs) induced by radiotherapy are highly cytotoxic lesions, leading to chromosomal aberrations and cell death. Ataxia-telangiectasia-mutated (ATM)-dependent DNA-damage response, non-homologous end joining, and homologous recombination pathways coordinately contribute to repairing DSBs in higher eukaryotes. It is known that the expression of DSB repair genes is increased in tumors, which is one of the main reasons for radioresistance. The inhibition of DSB repair pathways may be useful to increase tumor cell radiosensitivity and may target stem cell-like cancer cells, known to be the most radioresistant tumor components. Commonly overexpressed in neoplastic cells, cytokines confer radioresistance by promoting proliferation, survival, invasion, and angiogenesis. Unfortunately, tumor irradiation increases the expression of various cytokines displaying these effects, including transforming growth factor-beta and interleukin-6. Recently, the capabilities of these cytokines to support DNA repair pathways and the ATM-dependent DNA response have been demonstrated. Thrombopoietin, essential for megakaryopoiesis and very important for hematopoietic stem cell (HSC) homeostasis, has also been found to promote DNA repair in a highly selective manner. These findings reveal a novel mechanism underlying cytokine-related radioresistance, which may be clinically relevant. Therapies targeting specific cytokines may be used to improve radiosensitivity. Specific inhibitors may be chosen in consideration of different tumor microenvironments. Thrombopoietin may be useful in fending off irradiation-induced loss of HSCs. PMID:27500125

  6. Granzymes regulate proinflammatory cytokine responses.

    PubMed

    Wensink, Annette C; Hack, C Erik; Bovenschen, Niels

    2015-01-15

    Granzymes (Grs) are serine proteases mainly produced by cytotoxic lymphocytes and are traditionally considered to cause apoptosis in tumor cells and virally infected cells. However, the cytotoxicity of several Grs is currently being debated, and additional, predominantly extracellular, functions of Grs in inflammation are emerging. Extracellular soluble Grs are elevated in the circulation of patients with autoimmune diseases and infections. Additionally, Grs are expressed by several types of immune cells other than cytotoxic lymphocytes. Recent research has revealed novel immunomodulatory functions of Grs. In this review, we provide a comprehensive overview on the role of Grs in inflammation, highlighting their role in cytokine induction and processing.

  7. Cytokine profiles in axial spondyloarthritis

    PubMed Central

    Madej, Marta; Nowak, Beata; Sokolik, Renata; Chlebicki, Arkadiusz; Korman, Lucyna; Woytala, Patryk; Lubiński, Łukasz; Wiland, Piotr

    2015-01-01

    Objectives Current studies concentrate on the cytokine network and its role in the pathogenesis of spondyloarthritis (SpA). In this study, we analyzed whether the serum cytokine profile (interleukins: IL-10, IL-11, IL-12, IL-15, IL-17, IL-23 and IL-33) correlates with demographic data, clinical manifestations, disease activity and treatment outcome in a group of patients with axial spondyloarthritis. Material and methods Forty-nine patients with an established diagnosis of axial spondyloarthritis (aSpA) and 19 healthy volunteers as controls were enrolled in the study. Clinical evaluation included patient's medical history, 44 joint count, back pain intensity and global disease activity in the preceding week (VAS), the duration of morning stiffness and blood tests. Disease activity was assessed using BASDAI and ASDAS-CRP. Serum concentration of IL-10, IL-11, IL-12, IL-15, IL-17, IL-23 and IL-33 was determined. Results In patients with aSpA, elevated serum concentration of IL-10, IL-15, IL-17 and IL-23 was detected. In the aSpA group we detected higher values of serum concentration of IL-23 and IL-33 in the subgroup with anterior uveitis (83.1 ±184.0 pg/ml vs. 14.0 ±17.1 pg/ml, p < 0.0001 and 45.5 ±71.9 pg/ml vs. 18.4 ±14.3 pg/ml, p < 0.0001, respectively). Additionally, in the subgroup with peripheral arthritis, elevation of serum concentration of IL-12 (249.3 ±246.9 pg/ml vs. 99.9 ±105.9 pg/ml, p = 0.0001) was detected. Patients with preradiological SpA had higher serum concentration of IL-17 than patients with established diagnosis of AS (6.37 ±8.50 pg/ml vs. 2.04 ±2.98 pg/ml, p = 0.0295). No differences in serum concentration of analyzed cytokines were found between the subgroup with low to moderate disease activity and the subgroup with high to very high disease activity. Conclusions We report that in aSpA patients, compared to controls, elevated serum concentrations of IL-10, IL-15, IL-17 and IL-23 were observed. Some cytokines may predispose to a more

  8. Tissue irradiator

    DOEpatents

    Hungate, F.P.; Riemath, W.F.; Bunnell, L.R.

    1975-12-16

    A tissue irradiator is provided for the in-vivo irradiation of body tissue. The irradiator comprises a radiation source material contained and completely encapsulated within vitreous carbon. An embodiment for use as an in- vivo blood irradiator comprises a cylindrical body having an axial bore therethrough. A radioisotope is contained within a first portion of vitreous carbon cylindrically surrounding the axial bore, and a containment portion of vitreous carbon surrounds the radioisotope containing portion, the two portions of vitreous carbon being integrally formed as a single unit. Connecting means are provided at each end of the cylindrical body to permit connections to blood- carrying vessels and to provide for passage of blood through the bore. In a preferred embodiment, the radioisotope is thulium-170 which is present in the irradiator in the form of thulium oxide. A method of producing the preferred blood irradiator is also provided, whereby nonradioactive thulium-169 is dispersed within a polyfurfuryl alcohol resin which is carbonized and fired to form the integral vitreous carbon body and the device is activated by neutron bombardment of the thulium-169 to produce the beta-emitting thulium-170.

  9. Analysis of intracellular cytokines using flowcytometry.

    PubMed

    Arora, Sunil K

    2002-01-01

    Characterization of T-cell clones and identification of functional subsets of the helper T-cells with polarized cytokine production is based on testing of cytokine expression. Several methods have been developed that allow cytokine expression to be measured like ELISA, RT-PCR, ELISPOT, ISH and flowcytometry. Among all these methods, monitoring of cytokine production using flowcytometric analysis has its own advantages and disadvantages. Multi-parametric characterization of cytokine production on single cell basis, without long-term culture and cloning along with high throughput of samples is main feature attached to flowcytometric analysis. The interpretation may be difficult at times due to change in the phenotype of the cells. Cells with similar surface phenotype but synthesizing different cytokines and having different functional characteristics can be analyzed with this technique. PMID:12815288

  10. Bioanalytical Chemistry of Cytokines-A Review

    PubMed Central

    Stenken, Julie A.; Poschenrieder, Andreas J.

    2014-01-01

    Cytokines are bioactive proteins produced by many different cells of the immune system. Due to their role in different inflammatory disease states and maintaining homeostasis, there is enormous clinical interest in the quantitation of cytokines. The typical standard methods for quantitation of cytokines are immunoassay-based techniques including enzyme-linked immusorbent assays (ELISA) and bead-based immunoassays read by either standard or modified flow cytometers. A review of recent developments in analytical methods for measurements of cytokine proteins is provided. This review briefly covers cytokine biology and the analysis challenges associated with measurement of these biomarker proteins for understanding both health and disease. New techniques applied to immunoassay-based assays are presented along with the uses of aptamers, electrochemistry, mass spectrometry, optical resonator-based methods. Methods used for elucidating the release of cytokines from single cells as well as in vivo collection methods are described. PMID:25467452

  11. IRRADIATION EFFECTS ON THE PHYSICAL CHARACTERISTICS OF SEWAGE SLUDGE

    SciTech Connect

    Lee, M-J.; Lee, J-K.; Yoo, D-H.; Ho, K.

    2004-10-05

    The radiation effects on the physical characteristic of the sewage sludge were studied in order to obtain information which will be used for study on the enhancement of the sludge's dewaterability. Water contents, capillary suction time, zeta potential, irradiation dose, sludge acidity, total solid concentration, sludge particle size and microbiology before and after irradiation were investigated. Irradiation gave an effect on physical characteristics sludge. Water content in sludge cake could be reduced by irradiation at the dose of 10kGy.

  12. Cytokine-Modulating Strategies and Newer Cytokine Targets for Arthritis Therapy

    PubMed Central

    Venkatesha, Shivaprasad H.; Dudics, Steven; Acharya, Bodhraj; Moudgil, Kamal D.

    2014-01-01

    Cytokines are the key mediators of inflammation in the course of autoimmune arthritis and other immune-mediated diseases. Uncontrolled production of the pro-inflammatory cytokines such as interferon-γ (IFN-γ), tumor necrosis factor α (TNFα), interleukin-6 (IL-6), and IL-17 can promote autoimmune pathology, whereas anti-inflammatory cytokines including IL-4, IL-10, and IL-27 can help control inflammation and tissue damage. The pro-inflammatory cytokines are the prime targets of the strategies to control rheumatoid arthritis (RA). For example, the neutralization of TNFα, either by engineered anti-cytokine antibodies or by soluble cytokine receptors as decoys, has proven successful in the treatment of RA. The activity of pro-inflammatory cytokines can also be downregulated either by using specific siRNA to inhibit the expression of a particular cytokine or by using small molecule inhibitors of cytokine signaling. Furthermore, the use of anti-inflammatory cytokines or cytokine antagonists delivered via gene therapy has proven to be an effective approach to regulate autoimmunity. Unexpectedly, under certain conditions, TNFα, IFN-γ, and few other cytokines can display anti-inflammatory activities. Increasing awareness of this phenomenon might help develop appropriate regimens to harness or avoid this effect. Furthermore, the relatively newer cytokines such as IL-32, IL-34 and IL-35 are being investigated for their potential role in the pathogenesis and treatment of arthritis. PMID:25561237

  13. Current status and challenges of cytokine pharmacology

    PubMed Central

    Zídek, Z; Anzenbacher, P; Kmoníčková, E

    2009-01-01

    The major concern of pharmacology about cytokines has originated from plentiful data showing association between gross changes in their production and pathophysiological processes. Despite the enigmatic role of cytokines in diseases, a number of them have become a subject of cytokine and anti-cytokine immunotherapies. Production of cytokines can be influenced by many endogenous and exogenous stimuli including drugs. Cells of the immune system, such as macrophages and lymphocytes, are richly endowed with receptors for the mediators of physiological functions, such as biogenic amines, adenosine, prostanoids, steroids, etc. Drugs, agonists or antagonists of these receptors can directly or indirectly up- and down-regulate secretion of cytokines and expression of cytokine receptors. Vice versa, cytokines interfere with drug pharmacokinetics and pharmacodynamics through the interactions with cytochrome P450 and multiple drug resistance proteins. The aim of the review is to encourage more intensive studies in these fields of cytokine pharmacology. It also outlines major areas of searching promising candidates for immunotherapeutic interventions. PMID:19371342

  14. Cytokines and immune surveillance in humans

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald

    1993-01-01

    Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. Among the parameters shown, by us and others, to be affected is the production of interferons. Interferons are a family of cytokines that are antiviral and play a major role in regulating immune responses that control resistance to infection. Alterations in interferon and other cytokine production and activity could result in changes in immunity and a possible compromise of host defenses against both opportunistic and external infections. The purpose of the present study is to further explore the effects of space flight on cytokines and cytokine-directed immunological function.

  15. Irradiation subassembly

    DOEpatents

    Seim, O.S.; Filewicz, E.C.; Hutter, E.

    1973-10-23

    An irradiation subassembly for use in a nuclear reactor is described which includes a bundle of slender elongated irradiation -capsules or fuel elements enclosed by a coolant tube and having yieldable retaining liner between the irradiation capsules and the coolant tube. For a hexagonal bundle surrounded by a hexagonal tube the yieldable retaining liner may consist either of six segments corresponding to the six sides of the tube or three angular segments each corresponding in two adjacent sides of the tube. The sides of adjacent segments abut and are so cut that metal-tometal contact is retained when the volume enclosed by the retaining liner is varied and Springs are provided for urging the segments toward the center of the tube to hold the capsules in a closely packed configuration. (Official Gazette)

  16. Cytokine response to vitamin E supplementation is dependent on pre-supplementation cytokine levels.

    PubMed

    Belisle, Sarah E; Leka, Lynette S; Dallal, Gerard E; Jacques, Paul F; Delgado-Lista, Javier; Ordovas, Jose M; Meydani, Simin Nikbin

    2008-01-01

    Vitamin E supplementation has been suggested to improve immune response in the aged in part by altering cytokine production. However, there is not a consensus regarding the effect of supplemental vitamin E on cytokine production in humans. There is evidence that baseline immune health can affect immune response to supplemental vitamin E in the elderly. Thus, the effect of vitamin E on cytokines may depend on their pre-supplementation cytokine response. Using data from a vitamin E intervention in elderly nursing home residents, we examined if the effect of vitamin E on ex vivo cytokine production of IL-1 beta, IL-6, TNF-alpha, and IFN-gamma depended on baseline cytokine production. We observed that the effect of vitamin E supplementation on cytokine production depended on pre-supplementation production of the respective cytokines. The interactions between vitamin E and baseline cytokine production were not explained by covariates known to impact cytokine production. Our results offer evidence that baseline cytokine production should be considered in studies that examine the effect of supplemental vitamin E on immune and inflammatory responses. Our results could have implications in designing clinical trials to determine the impact of vitamin E on conditions in which cytokines are implicated such as infections and atherosclerotic disease.

  17. Cytokine response to vitamin E supplementation is dependent on pre-supplementation cytokine levels

    PubMed Central

    Belisle, Sarah E.; Leka, Lynette S.; Dallal, Gerard E.; Jacques, Paul F.; Delgado-Lista, Javier; Ordovas, Jose M.; Meydani, Simin Nikbin

    2009-01-01

    Vitamin E supplementation has been suggested to improve immune response in the aged in part by altering cytokine production. However, there is not a consensus regarding the effect of supplemental vitamin E on cytokine production in humans. There is evidence that baseline immune health can affect immune response to supplemental vitamin E in the elderly. Thus, the effect of vitamin E on cytokines may depend on their pre-supplementation cytokine response. Using data from a vitamin E intervention in elderly nursing home residents, we examined if the effect of vitamin E on ex vivo cytokine production of IL-1β, IL-6, TNF-α, and IFN-γ depended on baseline cytokine production. . We observed that the effect of vitamin E supplementation on cytokine production depended on pre-supplementation production of the respective cytokines. The interactions between vitamin E and baseline cytokine production were not explained covariates known to impact cytokine production. Our results offer evidence that baseline cytokine production should be considered in studies that examine the effect of supplemental vitamin E on immune and inflammatory responses. Our results could have implications in designing clinical trials to determine the impact of vitamin E on conditions in which cytokines are implicated such as infections and atherosclerotic disease. PMID:19478423

  18. Irradiated foods

    MedlinePlus

    ... it reduces the risk of food poisoning . Food irradiation is used in many countries. It was first approved in the U.S. to prevent sprouts on white potatoes, and to control insects on wheat and in certain spices and seasonings.

  19. Cytokine Regulation of Metastasis and Tumorigenicity.

    PubMed

    Yao, M; Brummer, G; Acevedo, D; Cheng, N

    2016-01-01

    The human body combats infection and promotes wound healing through the remarkable process of inflammation. Inflammation is characterized by the recruitment of stromal cell activity including recruitment of immune cells and induction of angiogenesis. These cellular processes are regulated by a class of soluble molecules called cytokines. Based on function, cell target, and structure, cytokines are subdivided into several classes including: interleukins, chemokines, and lymphokines. While cytokines regulate normal physiological processes, chronic deregulation of cytokine expression and activity contributes to cancer in many ways. Gene polymorphisms of all types of cytokines are associated with risk of disease development. Deregulation RNA and protein expression of interleukins, chemokines, and lymphokines have been detected in many solid tumors and hematopoetic malignancies, correlating with poor patient prognosis. The current body of literature suggests that in some tumor types, interleukins and chemokines work against the human body by signaling to cancer cells and remodeling the local microenvironment to support the growth, survival, and invasion of primary tumors and enhance metastatic colonization. Some lymphokines are downregulated to suppress tumor progression by enhancing cytotoxic T cell activity and inhibiting tumor cell survival. In this review, we will describe the structure/function of several cytokine families and review our current understanding on the roles and mechanisms of cytokines in tumor progression. In addition, we will also discuss strategies for exploiting the expression and activity of cytokines in therapeutic intervention. PMID:27613135

  20. Compartmentalized Cytokine Responses in Hidradenitis Suppurativa

    PubMed Central

    Savva, Athina; Kersten, Brigit; Pistiki, Aikaterini; van de Veerdonk, Frank L.; Netea, Mihai G.; van der Meer, Jos W.; Giamarellos-Bourboulis, Evangelos J.

    2015-01-01

    Background Favorable treatment outcomes with TNF blockade led us to explore cytokine responses in hidradenitis suppurativa (HS). Methods Blood monocytes of 120 patients and 24 healthy volunteers were subtyped by flow cytometry. Isolated blood mononuclear cells (PBMCs) were stimulated for cytokine production; this was repeated in 13 severe patients during treatment with etanercept. Cytokines in pus were measured. Results CD14brightCD16dim inflammatory monocytes and patrolling monocytes were increased in Hurley III patients. Cytokine production by stimulated PBMCs was low compared to controls but the cytokine gene copies did not differ, indicating post-translational inhibition. The low production of IL-17 was restored, when cells were incubated with adalimumab. In pus, high concentrations of pro-inflammatory cytokines were detected. Based on the patterns, six different cytokine profiles were discerned, which are potentially relevant for the choice of treatment. Clinical improvement with etanercept was predicted by increased production of IL-1β and IL-17 by PBMCs at week 8. Conclusions Findings indicate compartmentalized cytokine expression in HS; high in pus but suppressed in PBMCs. This is modulated through blockade of TNF. PMID:26091259

  1. Time course of cytokine levels in sepsis.

    PubMed

    Thijs, L G; Hack, C E

    1995-11-01

    In severe sepsis, a network of proinflammatory cytokines (TNF, IL-1 beta, IL-6, IL-8) is activated and blood levels of these cytokines are elevated, albeit inconsistently and with large individual variations. In addition, elevated blood levels of anti-inflammatory cytokines (IL-10), as well as of soluble cytokine receptors (sTNF-RI and II, IL-1ra), have been found. They seem to have a regulatory function in the host response. Levels of TNF and IL-6 are usually highest at the time of admission, whereas the time course of IL-1 beta levels (when detectable) can vary considerably. Limited data on IL-8 levels suggest that they may remain elevated for longer periods. Elevated levels of sTNFR and IL-1ra may also persist for a prolonged period of time. The pathogenetic significance of these observations is still unclear, but persistingly high levels of proinflammatory cytokines may be associated with organ failure and mortality.

  2. Cytokines in juvenile rheumatoid arthritis (JRA).

    PubMed

    Mangge, H; Schauenstein, K

    1998-06-01

    Juvenile rheumatoid arthritis (JRA), unlike rheumatoid arthritis of adulthood (RA), is a heterogenous disease comprising at least five subtypes that differ in clinical course and prognosis, and require different therapeutical approaches. As compared to RA, the production of local and systemic cytokines in JRA have not yet been as extensively investigated. In this article we review the available literature on cytokine expression in serum and synovial fluid in all five different subtypes of JRA. Even though the data are still fragmentary, the evidence so far suggests that the determination of serum cytokines yields relevant information as to clinical subtype and inflammatory activity of the disease. Furthermore, the cytokine data suggest that the pathogenesis of JRA may even by more heterogenous than defined by the clinical subtypes. Finally, future directions of research in this area are proposed, and-based on the latest results-arguments for (anti)cytokine therapies in JRA are critically discussed.

  3. Interactions between Autophagy and Inhibitory Cytokines.

    PubMed

    Wu, Tian-Tian; Li, Wei-Min; Yao, Yong-Ming

    2016-01-01

    Autophagy is a degradative pathway that plays an essential role in maintaining cellular homeostasis. Most early studies of autophagy focused on its involvement in age-associated degeneration and nutrient deprivation. However, the immunological functions of autophagy have become more widely studied in recent years. Autophagy has been shown to be an intrinsic cellular defense mechanism in the innate and adaptive immune responses. Cytokines belong to a broad and loose category of proteins and are crucial for innate and adaptive immunity. Inhibitory cytokines have evolved to permit tolerance to self while also contributing to the eradication of invading pathogens. Interactions between inhibitory cytokines and autophagy have recently been reported, revealing a novel mechanism by which autophagy controls the immune response. In this review, we discuss interactions between autophagy and the regulatory cytokines IL-10, transforming growth factor-β, and IL-27. We also mention possible interactions between two newly discovered cytokines, IL-35 and IL-37, and autophagy.

  4. Interactions between Autophagy and Inhibitory Cytokines

    PubMed Central

    Wu, Tian-tian; Li, Wei-Min; Yao, Yong-Ming

    2016-01-01

    Autophagy is a degradative pathway that plays an essential role in maintaining cellular homeostasis. Most early studies of autophagy focused on its involvement in age-associated degeneration and nutrient deprivation. However, the immunological functions of autophagy have become more widely studied in recent years. Autophagy has been shown to be an intrinsic cellular defense mechanism in the innate and adaptive immune responses. Cytokines belong to a broad and loose category of proteins and are crucial for innate and adaptive immunity. Inhibitory cytokines have evolved to permit tolerance to self while also contributing to the eradication of invading pathogens. Interactions between inhibitory cytokines and autophagy have recently been reported, revealing a novel mechanism by which autophagy controls the immune response. In this review, we discuss interactions between autophagy and the regulatory cytokines IL-10, transforming growth factor-β, and IL-27. We also mention possible interactions between two newly discovered cytokines, IL-35 and IL-37, and autophagy. PMID:27313501

  5. The volume effect in irradiated mouse colorectum

    NASA Astrophysics Data System (ADS)

    Skwarchuk, Mark William

    1997-11-01

    Damage of the colorectum is the dose-limiting normal tissue complication following radiotherapy of prostate and cervical cancers. One approach for decreasing complications is to physically reduce the treatment volume. Mathematical models have been previously developed to describe the change in associated toxicity with a change in irradiated volume, i.e. the 'volume effect', for serial-type normal tissues including the colorectum. The first goal of this thesis was to test the hypothesis that there would not be a threshold length in the development of obstruction after irradiation of mouse colorectum, as predicted by the Probability model of the volume effect. The second goal was to examine if there were differences in the threshold and in the incidence of colorectal obstruction after irradiation of two mouse strains, C57B1/6 (C57) and C3Hf/Kam (C3H), previously found to be fibrosis-prone and-resistant, respectively, after lung irradiation due, in part, to genetic differences. The hypothesis examined was that differences in incidence between strains were due to the differential expression of the fibrogenic cytokines TGF/beta and TNF/alpha. Various lengths of C57 and C3H mouse colorectum were irradiated and the incidence of colorectal obstruction was followed up to 15 months. A threshold length was observed for both mouse strains, in contradiction of model predictions. The mechanism of the threshold was epithelial regeneration after irradiation. C57 mice had significantly higher incidence of colorectal obstruction compared to C3H mice, especially at smaller irradiated lengths. Colorectal tissue was obtained at various times after irradiation and prepared for histology, immunohistochemistry and RNase protection assay for measurement of TGF/beta 1, 2, 3 and TNF/alpha mRNA. Distinct strain differences in the histological time of appearance and spatial locations of fibrosis were observed. However, there were no consistent strain difference in mRNA levels or

  6. Evaluation of reduced allergenicity of irradiated peanut extract using splenocytes from peanut-sensitized mice

    NASA Astrophysics Data System (ADS)

    Oh, Sejo; Jang, Da-In; Lee, Ju-Woon; Kim, Jae-Hun; Byun, Myung-Woo; Lee, Soo-Young

    2009-07-01

    Peanut (PN) allergy is one of the most serious forms of IgE-mediated food hypersensitivity. Gamma irradiation has been widely used for the preservation of food. The results of our previous studies showed that the IgE-binding capacity to several antigens were profoundly reduced after gamma irradiation. In this study, we evaluated the changes of allergenecity and cytokine production profiles after exposure of irradiated PN extract in a PN-allergy mouse model. Mice were sensitized to PN extract by intragastric administration on days 0, 1, 2, and 7, and then challenged on day 21. Four weeks later, we evaluated the cytokine production patterns and proliferation responses of splenocytes that were stimulated with intact PN extract, compared to 10 and 50 kGy irradiated PN extract. When the cells were stimulated with 10 kGy of irradiated PN extract, a higher level of production of IFN-γ and IL-10 cytokines was observed. However, stimulation with 50 kGy of irradiated PN extract resulted in a higher level of production of only IFN-γ cytokines. In addition, the Th1/Th2 ratio increased in response to treatment with gamma-irradiated PNs. The results of this study show that the allergenicity of PN extracts could be reduced by gamma irradiation which caused downregulation of Th2 lymphocyte activity in the PN-sensitized mice.

  7. Targeted cytokine delivery to neuroblastoma.

    PubMed

    Dehal, P K; Embleton, M J; Kemshead, J T; Hawkins, R E

    2002-08-01

    The aim of this study was to construct a fusion protein from the cytokine granulocyte/macrophage colony-stimulating factor (GM-CSF) and a single-chain Fv fragment (scFv D29) and to investigate its potential to activate cells of the immune system against neuroblastoma cells expressing neural cell adhesion molecule (NCAM). Mammalian cell expression of the scFv D29-GM-CSF fusion protein was compared using a number of vectors, including retroviral and adenoviral vectors. The resultant fusion protein, expressed by HeLa cells, was found by ELISA to bind immobilized recombinant NCAM. Moreover, FACS analysis confirmed binding to the human neuroblastoma cell line SKNBE and a murine neuroblastoma cell line engineered to express the glycosylphosphatidylinositol form of human NCAM (N2A-rKNIE). The fusion protein was also found to stimulate the proliferation of the FDC-P1 haemopoietic cell line, which is dependent on GM-CSF (or interleukin 3) for continued growth. In vitro clonogenic assays indicated that scFv-GM-CSF could selectively induce growth inhibition of SKNBE cells by murine lymphoid cells.

  8. Inflammatory cytokines in newborn infants.

    PubMed Central

    Sarandakou, A; Giannaki, G; Malamitsi-Puchner, A; Rizos, D; Hourdaki, E; Protonotariou, E; Phocas, I

    1998-01-01

    Serum levels of IL-1beta, IL-6 and TNF-alpha were measured in 48 healthy, termed neonates on the 1st (N1), 5th (N5) and 40th (N40) day after birth, compared with those in maternal serum (MS), umbilical cord (UC) and adult controls. Cytokine values in N1 and N5 were significantly elevated, than those in UC and in controls (P<0.0001). IL-1beta and IL-6 declined significantly from N1 to N40 (P<0.0001), while TNF-alpha increased significantly from N1 to N5 and declined thereafter. MS infinity IL-1beta and IL-6, but not MS infinity TNF-alpha, were significantly higher than those of controls (P<0.0001). IL-1beta values depended on the mode of delivery. In conclusion, the increased concentrations of IL-1beta, IL-6 and TNF-alpha during the perinatal period might suggest their involvement in an inflammation-like process during normal parturition, and reflect also a newborn immune response to the stress of delivery and environmental changes. PMID:9883964

  9. Inflammatory cytokines in newborn infants.

    PubMed

    Sarandakou, A; Giannaki, G; Malamitsi-Puchner, A; Rizos, D; Hourdaki, E; Protonotariou, E; Phocas, I

    1998-01-01

    Serum levels of IL-1beta, IL-6 and TNF-alpha were measured in 48 healthy, termed neonates on the 1st (N1), 5th (N5) and 40th (N40) day after birth, compared with those in maternal serum (MS), umbilical cord (UC) and adult controls. Cytokine values in N1 and N5 were significantly elevated, than those in UC and in controls (P<0.0001). IL-1beta and IL-6 declined significantly from N1 to N40 (P<0.0001), while TNF-alpha increased significantly from N1 to N5 and declined thereafter. MS infinity IL-1beta and IL-6, but not MS infinity TNF-alpha, were significantly higher than those of controls (P<0.0001). IL-1beta values depended on the mode of delivery. In conclusion, the increased concentrations of IL-1beta, IL-6 and TNF-alpha during the perinatal period might suggest their involvement in an inflammation-like process during normal parturition, and reflect also a newborn immune response to the stress of delivery and environmental changes.

  10. [Immunity and cytokine status after surgeries on the large intestine].

    PubMed

    Voloshin, A G; Nikoda, V V; Buniatian, K A; Inviiaeva, E V; Vinnitskiĭ, L I; Bondarenko, A V; Tsar'kov, P V

    2011-01-01

    The aim of our study was to examine the effect of individual schemes of multimodal analgesia on indicators of immunity and inflammation markers after operations on the colon. Patients of group 1 (n=15) received paracetamol, lornoxicam and epidural ropivacaine, 2nd group of patients (n=15)-paracetamol, epidural ropivacaine and tramadol. Comparison group (n=10) patients underwent patient controlled analgesia by promedol. Before surgery, 1st and 3rd days after surgery we examined the contents of cytokines in plasma: interleukin 12p70, interleukin 10, interleukin 6, and TNF. Before surgery and at 5-7 days after surgery indicators of cellular, fagocytal and humoral immunity were monitored. Before surgery patients with colorectal cancer revealed changes in the indices of different components of immunity, as well as an increase in pro-and anti-inflammatory cytokines compared with healthy donors. Multimodal analgesia in patients after operations on the colon is not accompanied by changes in plasma concentrations of cytokines and parameters of immune status in comparison with monoanalgesia by promedol.

  11. Modulation of cytokine production by carnitine

    PubMed Central

    De Simone, Claudio

    1993-01-01

    The ability of carnitine congeners to modulate cytokine production by human peripheral blood mononuclear cells (PBMC) was investigated. Modulation of cytokine production by PBMC of young (30 years of age or younger) and old (70 years of age or older) normal donors was first compared. The PBMC were collected over Ficoll–Hypaque and incubated in the presence of various concentrations of acetyl L-carnitine for 24 h. Subsequently the supernatants were collected and examined for cytokine production. The presence of cytokines in tissue culture supernatants was examined by ELISA. The cytokines measured included IL-1α, IL-1β, IL-2, IL-4, IL-6, TNFα, GM–CSF, and IFNγ. The results showed that at 50 μg/ml of acetyl L-carnitine the most significant response was obtained for TNFα. In this regard four of five young donors responded, but only one of five old donors responded. More recently these studies were expanded to examine the ability of L-carnitine to modulate cytokine production at higher doses, 200 and 400 μg/ml, in young donors. The results of these studies showed that in addition to TNFα, significant production of IL-1β and IL-6 was observed. These preliminary studies provide evidence that carnitine may modulate immune functions through the production of selected cytokines. PMID:18475565

  12. Cytokine medicines in clinical practice: current issues.

    PubMed

    Barnes, Theresa; Moots, Robert J; Goodacre, John

    2005-10-21

    Cytokine medicines have been licensed for the treatment of rheumatoid arthritis since 2000. The rheumatology community has accrued a large amount of experience in the use of these medications. This experience has led to the development of guidelines for their use that include ongoing vigilance for long term adverse events and efficacy using the Biologics Register. Delivery of these expensive therapies has prompted extensive system developments within rheumatology. The cytokine medicines have provided important tools to probe the pathogenesis of rheumatoid and other inflammatory diseases. Further cytokine medicines, in various stages of development, are on the horizon and continue to stimulate excitement within this fast expanding field.

  13. Temporal Onset of Hypoxia and Oxidative Stress After Pulmonary Irradiation

    SciTech Connect

    Fleckenstein, Katharina; Zgonjanin, Larisa; Chen Liguang; Rabbani, Zahid; Jackson, Isabel L.; Thrasher, Bradley; Kirkpatrick, John; Foster, W. Michael; Vujaskovic, Zeljko . E-mail: vujas@radonc.duke.edu

    2007-05-01

    Purpose: To investigate the temporal onset of hypoxia following irradiation, and to show how it relates to pulmonary vascular damage, macrophage accumulation, and the production of reactive oxygen species and cytokines. Our previous studies showed that tissue hypoxia in the lung after irradiation contributed to radiation-induced injury. Methods and Materials: Female Fisher 344 rats were irradiated to the right hemithorax with a single dose of 28 Gy. Serial studies were performed up to 20 weeks following irradiation. Radionuclide lung-perfusion studies were performed to detect changes in pulmonary vasculature. Immunohistochemical studies were conducted to study macrophages, tissue hypoxia (carbonic anhydrase-9 marker), oxidative stress (8-hydroxy-2'-deoxyguanosine), and the expression of profibrogenic (transforming growth factor-{beta} [TGF-{beta}]) and proangiogenic (vascular endothelial growth factor [VEGF]) cytokines. Results: Significant changes in lung perfusion along with tissue hypoxia were observed 3 days after irradiation. Significant oxidative stress was detected 1 week after radiation, whereas macrophages started to accumulate at 4 weeks. A significant increase in TGF-{beta} expression was seen within 1 day after radiation, and for VEGF at 2 weeks after radiation. Levels of hypoxia, oxidative stress, and both cytokines continued to rise with time after irradiation. The steepest increase correlated with vast macrophage accumulation. Conclusions: Early changes in lung perfusion, among other factors initiate, the development of hypoxia and chronic oxidative stress after irradiation. Tissue hypoxia is associated with a significant increase in the activation of macrophages and their continuous production of reactive oxygen species, stimulating the production of fibrogenic and angiogenic cytokines, and maintaining the development of chronic radiation-induced lung injury.

  14. [Targeted therapy in inflammatory disease: cytokines].

    PubMed

    von Frenckell, C; Malaise, M G

    2012-01-01

    Summarizing 15 years of therapeutic development of a discipline into a few lines is not an easy thing to do. There are many potential targets involved in the inflammatory of auto-immune diseases. Due to the development of biotherapies the choice has become larger, and it is now possible to target practically any molecule (cytokine, chemokine or surface receptor for example). Cytokines represent the first example of therapeutic target that played a major role in the revolution of our discipline. The first part of presentation will focus on the pro-inflammatory cytokines (TNFalpha, and interleukines 1 and 6). We shall then, detail the development of a new cytokinic target: BLyS (B lymphocyte stimulator) whose role in the autoimmune diseases appeared recently.

  15. Dynamical Systems, Cytokine Storms, and Blood Filtration

    NASA Astrophysics Data System (ADS)

    Foster, Glenn; Hubler, Alfred

    2008-03-01

    Various infections and non-infectious diseases can trigger immune cells and the proteins (cytokines) the cells use to communicate with each other to be caught in a positive feedback loop; this ``cytokine storm'' is frequently fatal. By examining the network of cytokine-immune cell interactions we will illustrate why anti-mediator drugs have been generally ineffective in stopping this feedback. A more effective approach may be to try and reduce interactions by dampening many signals at once by filtering the cytokines out of the blood directly (think dialysis). We will argue that feedback on an out of control nonlinear dynamical system is easier to understand than its normal healthy state and apply filtration to a toy model of immune response.

  16. Cytokines in neuroblastoma: from pathogenesis to treatment.

    PubMed

    Pistoia, Vito; Bianchi, Giovanna; Borgonovo, Giacomo; Raffaghello, Lizzia

    2011-07-01

    Cytokines released by cancer cells or by cells of the tumor microenvironment stimulate angiogenesis, act as autocrine or paracrine growth factors for malignant cells, promote tumor cell migration and metastasis or create an immunosuppressive microenvironment. These tumor-promoting effects of cytokines also apply to neuroblastoma (NB), a pediatric neuroectodermal malignancy with frequent metastatic presentation at diagnosis and poor prognosis. IL-6 and VEGF are the best characterized cytokines that stimulated tumor growth and metastasis, while others such as IFN-γ can exert anti-NB activity by inducing tumor cell apoptosis and inhibiting angiogenesis. On the other hand, cytokines are part of the anti-NB therapeutic armamentarium, as exemplified by IL-2 and granulocyte-macrophage colony stimulating factor that potentiate the activity of anti-NB antibodies. These recent results raise hope for more efficacious treatment of this ominous pediatric malignancy.

  17. Anti cytokine therapy in chronic inflammatory arthritis.

    PubMed

    Thompson, Charlotte; Davies, Ruth; Choy, Ernest

    2016-10-01

    This is a review looking at anti cytokine therapy in Rheumatoid Arthritis (RA), Psoriatic Arthritis (PSA) and Ankylosing Spondylitis (AS). The review explores the similarities and differences in the clinical features, as well as treatments and cytokines involved in the development and propagation of the disease. Particular attention is paid to TNFα inhibitors IL-1ra, IL-6 and JAK kinase Inhibitors, anti IL23 and IL-12 and the new developments with anti-IL-17. PMID:27497159

  18. The role of cytokines in cancer.

    PubMed

    Oppenheim, J; Fujiwara, H

    1996-10-01

    The role of cytokines was intensively discussed over the course of a two and a half day meeting sponsored by the US-JAPAN Cancer Cooperative Research Program of the Office of International Affairs, National Cancer Institute and held at The National Institutes of Health, Bethesda, Maryland on 15-17 January 1996. Most of the first day was devoted to a discussion of the role of cytokines in modulating angiogenesis and the consequent effect of this on tumor growth and metastases. This was followed by sessions on the effect of various cytokines in enhancing or suppressing immunological responses to tumors. Several presentations focused on the direct inhibitory or growth promoting effects of cytokines on tumor growth. The final session consisted of a comparison of the efficacy of different approaches to tumor vaccination including gene therapy, enhanced antigen presentation, use of polymeric carriers or of DNA vectors. For background information the reader is referred to appropriate chapters on the role of cytokines in neoplastic diseases (Oppenheim JJ, Rossio JL, Gearing AJH, eds. In Clinical Application of Cytokines: Role of Pathogenesis, Diagnosis and Therapy. Oxford University Press, New York, 1993 [1]).

  19. Cytokine expression in muscle following traumatic injury

    PubMed Central

    Jackson, Wesley M.; Aragon, Amber B.; Onodera, Jun; Koehler, Steven M.; Ji, Youngmi; Bulken-Hoover, Jamie D.; Vogler, Jared A.; Tuan, Rocky S.; Nesti, Leon J.

    2011-01-01

    Heterotopic ossification (HO) occurs at a high frequency in severe orthopaedic extremity injuries; however, the etiology of traumatic HO is virtually unknown. Osteogenic progenitor cells have previously been identified within traumatized muscle. Although the signaling mechanisms that lead to this dysregulated differentiation pathway have not been identified, it is assumed that inflammation and fibrosis, which contribute to an osteoinductive environment, are necessary for the development of HO. The hypothesis of this study was that cytokines related to chronic inflammation, fibrogenesis and osteogenesis become up-regulated following severe muscle trauma where HO forms. Classification of these cytokines by their differential expression relative to control muscle will provide guidance for further study of the mechanisms leading to HO. Real-time RT-PCR analysis revealed no significant up-regulation of cytokines typically associated with HO (e.g., BMP-4, as observed in the genetic form of heterotopic ossification, Fibrodysplasia Ossificans Progressiva). Instead, the cytokine gene expression profile associated with the traumatized muscle included up-regulation of cytokines associated with osteogenesis and fibrosis (i.e., BMP-1 and TGF-beta1). Using immunohistochemistry, these cytokines were localized to fibroproliferative lesions, which have previously been implicated in HO. This study identifies other cell and tissue-level interactions in traumatized muscle that should be investigated further to better define the etiology of HO. PMID:21452302

  20. Serum cytokine changes in systemic vasculitis.

    PubMed Central

    Grau, G E; Roux-Lombard, P; Gysler, C; Lambert, C; Lambert, P H; Dayer, J M; Guillevin, L

    1989-01-01

    Cytokines are known to alter a number of vascular tissue cell functions. The aim of this retrospective study was to determine serum cytokine levels in patients with vasculitis and to analyse the possible relation to the severity of the disease. Tumour necrosis factor alpha (TNF alpha), interleukin-1 (IL-1)beta, IL-2, interferon (IFN)- and IFN-gamma were assayed in 33 patients with polyarteritis nodosa (PAN) or Churg and Strauss angiitis (CSA), and three with Wegener granulomatosis (WG). Serum cytokine changes were observed in most patients with active disease, i.e. before treatment was started. In the majority of patients with PAN or CSA, there was a marked increase in serum IFN-alpha and IL-2 levels, while TNF-alpha and IL-beta levels were moderately elevated. Serum IFN-gamma remained undetectable in all but one of these patients. In patients with WG, serum IFN-alpha and IL-2 levels were also elevated, whereas IL-1 beta, IFN-gamma and TNF alpha levels remained within normal limits. In paired samples of patients with PAN, IFN-alpha and IL-2 levels were significantly higher before than after treatment. These preliminary data suggest that a particular pattern of cytokine changes is associated with vasculitis and that cytokines might be involved in the pathogenesis of PAN/CSA and WG. Prospective studies are warranted to determine whether cytokines could be considered for the monitoring of disease activity and therapy. PMID:2478451

  1. Rapid differentiation between gamma-irradiated and non irradiated potato tubers

    NASA Astrophysics Data System (ADS)

    Jona, Roberto; Fronda, Anna

    The use of gamma irradiation as commercial method for the preservation of fruits and vegetables calls for methods of differentiation between irradiated and non-irradiated foodstuffs. In a previous research, the polysaccharidic content of cell walls of irradiated tissue has been investigated, but it required rather long time to reach the result. A method devised to ascertain the vitality of cells has been applied to distinguish irradiated from non-irradiated potato tubers. 500 mg of tissue excised from tubers have been infiltrated with tetrazolium chloride 0.6% in phosphate buffer, pH 7.4. After 15 hrs of incubation at 30°C the treated tissues have been extracted with 95% ethanol whose O.D. has been measured at 530 mμ wavelength. The colour intensity of the alcohol allowed a very clearcut recognition of the irradiated tubers.

  2. Cytokine Production in the Serum and Spleen of Mice from Day 6 to 14 of Gestation: Cytokines/Placenta/ Spleen/Serum

    PubMed Central

    Iconomidou, Bessy

    1995-01-01

    Pregnancy, like most biologic phenomena, involves the action of cytokines. These proteins have a short half-life and are believed to exert their effect close to their site of production, where diagnostic tests cannot be easily performed. Here we show that the cytokine content in the maternal serum reflects cytokine production and secretion from maternal spleen cells, which also correlates with production from decidual cells. We show that GM-CSF, IL- 3, and IL-10 are present in the serum at specific time intervals during the first half of murine pregnancy, which correlates with their production from maternal spleen cells. Purified GM-CSF and IL-3 from spleen-cell-culture supernatants are biologically active molecules, able to stimulate placental-cell proliferation. Furthermore, TNF-0, which has been identified in many cases of fetal rejection as well as in labor, is shown to be naturally produced during the second half of pregnancy. Additionally, within the limits of the sensitivity of the technique we have used, the detection of IL-4 and the absence of detectable levels of IL- 2 in the maternal serum strongly comforts the hypothesis that pregnancy is a Th2-dependent phenomenon. The results presented in this paper show that the cytokine profile during pregnancy can be monitored by simple blood tests, which may be of relevance both in the followup of a physiological human pregnancy and to the diagnosis of recurrent abortions due to cytokine imbalance. PMID:8924760

  3. Bystander Effects Induced by Medium From Irradiated Cells: Similar Transcriptome Responses in Irradiated and Bystander K562 Cells

    SciTech Connect

    Herok, Robert; Konopacka, Maria; Polanska, Joanna; Swierniak, Andrzej; Rogolinski, Jacek; Jaksik, Roman; Hancock, Ronald; Rzeszowska-Wolny, Joanna

    2010-05-01

    Purpose: Cells exposed to ionizing radiation release factors that induce deoxyribonucleic acid damage, chromosomal instability, apoptosis, and changes in the proliferation rate of neighboring unexposed cells, phenomena known as bystander effects. This work analyzes and compares changes in global transcript levels induced by direct irradiation and by bystander effects in K562 (human erythroleukemia) cells. Methods and Materials: Cells were X-irradiated with 4 Gy or transferred into culture medium collected from cells 1 h after irradiation (irradiation-conditioned medium). Global transcript profiles were assessed after 36 h of growth by use of Affymetrix microarrays (Affymetrix, Santa Clara, CA) and the kinetics of change of selected transcripts by quantitative reverse transcriptase-polymerase chain reaction. Results: The level of the majority (72%) of transcripts changed similarly (increase, decrease, or no change) in cells grown in irradiation-conditioned medium or irradiated, whereas only 0.6% showed an opposite response. Transcript level changes in bystander and irradiated cells were significantly different from those in untreated cells grown for the same amount of time and were confirmed by quantitative reverse transcriptase-polymerase chain reaction for selected genes. Signaling pathways in which the highest number of transcripts changed in both conditions were found in the following groups: neuroactive ligand-receptor, cytokine-cytokine receptor interaction, Janus Kinase-Signal Transducers and Activators of Transcription (JAK-STAT) and Mitogen-Activated Protein Kinase (MAPK) In control cells more transcripts were downregulated than in irradiated and bystander cells with transcription factors YBX1 and STAT5B, heat shock protein HSPA1A, and ribonucleic acid helicase DDX3X as examples. Conclusions: The transcriptomes of cells grown in medium from X-irradiated cells or directly irradiated show very similar changes. Signals released by irradiated cells may cause

  4. A genetic contribution to circulating cytokines and obesity in children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cytokines are considered to be involved in obesity-related metabolic diseases. Study objectives are to determine the heritability of circulating cytokine levels, to investigate pleiotropy between cytokines and obesity traits, and to present genome scan results for cytokines in 1030 Hispanic children...

  5. Effect of gamma irradiation on quality of kiwifruit ( Actinidia deliciosa var. deliciosa cv. Hayward)

    NASA Astrophysics Data System (ADS)

    kim, Kyoung-Hee; Yook, Hong-Sun

    2009-06-01

    Ionizing radiation is able to inactivate the three pathogens of Botrytis cinerea, Diaporthe actinidiae, and Botryosphaeria dothidea in kiwifruit. Irradiated kiwifruits appeared softer compared to non-irradiated kiwifruits. The color and organic acid content of kiwifruits were minimally affected by the irradiation. Irradiated fruits showed a decrease in the total soluble solids content with increasing irradiation dose. Irradiation of kiwifruit up to 3 kGy had negative effects on vitamin C content and antioxidant activity, but it contributed to improving sensory quality.

  6. Avian cytokines - the natural approach to therapeutics.

    PubMed

    Lowenthal, J W; Lambrecht, B; van den Berg, T P; Andrew, M E; Strom, A D; Bean, A G

    2000-01-01

    While the effective use of antibiotics for the control of human disease has saved countless lives and has increased life expectancy over the past few decades, there are concerns arising from their usage in livestock. The use of antibiotic feed additives in food production animals has been linked to the emergence in the food chain of multiple drug-resistant bacteria that appear impervious to even the most powerful antimicrobial agents. Furthermore, the use of chemical antimicrobials has led to concerns involving environmental contamination and unwanted residues in food products. The imminent banning of antibiotic usage in livestock feed has intensified the search for environmentally-friendly alternative methods to control disease. Cytokines, as natural mediators and regulators of the immune response, offer exciting new alternatives to conventional chemical-based therapeutics. The utilisation of cytokines is becoming more feasible, particularly in poultry, with the recent cloning of a number of avian cytokine genes. Chickens offer an attractive small animal model system with which to study the effectiveness of cytokine therapy in the control of disease in intensive livestock. In this report we will review the status of avian cytokines and focus on our recent studies involving the therapeutic potential of chicken interferon gamma (ChIFN-gamma) as a vaccine adjuvant and a growth promoter. PMID:10717298

  7. Cytokines and hypothalamic-pituitary function.

    PubMed

    Jones, T H; Kennedy, R L

    1993-11-01

    Several cytokines are now known to affect the release of anterior pituitary hormones by an action on the hypothalamus and/or the pituitary gland. The major cytokines involved are IL-1, IL-2, IL-6, TNF-alpha and interferon-tau. Their predominant effects are to stimulate the hypothalamic-pituitary-adrenal axis and to suppress the hypothalamic-pituitary-thyroid and gonadal axes, and growth hormone release. The relative importance of systemically and locally produced cytokines in achieving these responses and their precise sites of action have not been fully established. There are indeed conflicting reports on the individual effects of each cytokine which need to be clarified. There is now cumulating evidence that there are important interactions between the immune and neuroendocrine systems which may explain in part, some of the effects on growth, thyroid, adrenal and reproductive functions which occur in acute and chronic disease. This article reviews the current knowledge of the effects of some cytokines on hypothalamic-pituitary function.

  8. Interleukin-1 Family Cytokines in Liver Diseases

    PubMed Central

    Tsutsui, Hiroko; Cai, Xianbin; Hayashi, Shuhei

    2015-01-01

    The gene encoding IL-1 was sequenced more than 30 years ago, and many related cytokines, such as IL-18, IL-33, IL-36, IL-37, IL-38, IL-1 receptor antagonist (IL-1Ra), and IL-36Ra, have since been identified. IL-1 is a potent proinflammatory cytokine and is involved in various inflammatory diseases. Other IL-1 family ligands are critical for the development of diverse diseases, including inflammatory and allergic diseases. Only IL-1Ra possesses the leader peptide required for secretion from cells, and many ligands require posttranslational processing for activation. Some require inflammasome-mediated processing for activation and release, whereas others serve as alarmins and are released following cell membrane rupture, for example, by pyroptosis or necroptosis. Thus, each ligand has the proper molecular process to exert its own biological functions. In this review, we will give a brief introduction to the IL-1 family cytokines and discuss their pivotal roles in the development of various liver diseases in association with immune responses. For example, an excess of IL-33 causes liver fibrosis in mice via activation and expansion of group 2 innate lymphoid cells to produce type 2 cytokines, resulting in cell conversion into pro-fibrotic M2 macrophages. Finally, we will discuss the importance of IL-1 family cytokine-mediated molecular and cellular networks in the development of acute and chronic liver diseases. PMID:26549942

  9. Induction of inflammatory cytokines by cartilage extracts.

    PubMed

    Merly, Liza; Simjee, Shabana; Smith, Sylvia L

    2007-03-01

    Shark cartilage extracts were examined for induction of cytokines and chemokines in human peripheral blood leukocytes. Primary leukocyte cultures were exposed to a variety of aqueous and organic extracts prepared from several commercial brands of shark cartilage. From all commercial sources of shark cartilage tested the acid extracts induced higher levels of TNFalpha than other extracts. Different commercial brands of shark cartilage varied significantly in cytokine-inducing activity. TNFalpha induction was seen as early as 4 h and IFNgamma at detectable levels for up to four days. Shark cartilage extracts did not induce physiologically significant levels of IL-4. Results suggest that shark cartilage, preferentially, induces Th1 type inflammatory cytokines. When compared to bovine cartilage extract, collagen, and chondroitin sulfate, shark cartilage induced significantly higher levels of TNFalpha. Treatment with digestive proteases (trypsin and chymotrypsin) reduced the cytokine induction response by 80%, suggesting that the active component(s) in cartilage extracts is proteinaceous. The induction of Th1 type cytokine response in leukocytes is a significant finding since shark cartilage, taken as a dietary supplement for a variety of chronic degenerative diseases, would be contraindicated in cases where the underlying pathology of the chronic condition is caused by inflammation. PMID:17276897

  10. Cytokines in Neuropathic Pain and Associated Depression.

    PubMed

    Lees, Justin G; Fivelman, Brett; Duffy, Samuel S; Makker, Preet G S; Perera, Chamini J; Moalem-Taylor, Gila

    2015-01-01

    Neuropathic pain occurs as a result of lesion or disease affecting the somatosensory nervous system and is present in a diverse set of peripheral and central pathologies such as nerve trauma, diabetic neuropathy, post-herpetic neuralgia, chemotherapy-induced peripheral neuropathy, spinal cord injury and multiple sclerosis. Debilitating symptoms including allodynia, hyperalgesia and spontaneous pain have a substantial negative impact on patients' quality of life. The currently available therapeutic treatments are generally ineffective and characterised by poor response rates. Accumulating evidence suggests that neuroinflammation and cytokine signalling play a critical role in neuropathic pain. Numerous experimental studies have demonstrated that certain pro-inflammatory cytokines are elevated in neuropathic pain conditions, and administration of these cytokines can elicit pain hypersensitivity in the absence of injury or disease. This phenomenon is also apparent in the 'sickness response', which encompasses a broad inflammatory response to disease and injury and involves a series of physiological and behavioural changes including pain hypersensitivity. Interestingly, the 'sickness response' is also similar in nature to some of the defining characteristics of the depressed state of affective disorder. In this review, we explore links that may relate the co-existence of depression in neuropathic pain patients with the activity of cytokines and discuss the role of several key pro-inflammatory and anti-inflammatory cytokines in neuropathic pain. PMID:26437375

  11. Local brain heavy ion irradiation induced Immunosuppression

    NASA Astrophysics Data System (ADS)

    Lei, Runhong; Deng, Yulin; Huiyang Zhu, Bitlife.; Zhao, Tuo; Wang, Hailong; Yu, Yingqi; Ma, Hong; Wang, Xiao; Zhuang, Fengyuan; Qing, Hong

    Purpose: To investigate the long term effect of acute local brain heavy ion irradiation on the peripheral immune system in rat model. Methodology: Only the brain of adult male Wistar rats were radiated by heavy ions at the dose of 15 Gy. One, two and three months after irradiation, thymus and spleen were analyzed by four ways. Tunel assay was performed to evaluate the percentage of apoptotic cells in thymus and spleen, level of Inflammatory cytokines (IL-2, IL-6, SSAO, and TNF-α) was detected by ELISA assay, the differentiation of thymus T lymphocyte subsets were measured by flow cytometry and the relative expression levels of genes related to thymus immune cell development were measured by using quantitative real-time PCR. Results: Thymus and spleen showed significant atrophy from one month to three months after irradiation. A high level of apoptosis in thymus and spleen were obtained and the latter was more vulnerable, also, high level of inflammatory cytokines were found. Genes (c-kit, Rag1, Rag2 and Sca1) related to thymus lymphocytes’ development were down-regulated. Conclusion: Local area radiation in the rat brain would cause the immunosuppression, especially, the losing of cell-mediated immune functions. In this model, radiation caused inflammation and then induced apoptosis of cells in the immune organs, which contributed to immunosuppression.

  12. Treatment of Cancer Pain by Targeting Cytokines

    PubMed Central

    Vendrell, I.; Macedo, D.; Alho, I.; Dionísio, M. R.; Costa, L.

    2015-01-01

    Inflammation is one of the most important causes of the majority of cancer symptoms, including pain, fatigue, cachexia, and anorexia. Cancer pain affects 17 million people worldwide and can be caused by different mediators which act in primary efferent neurons directly or indirectly. Cytokines can be aberrantly produced by cancer and immune system cells and are of particular relevance in pain. Currently, there are very few strategies to control the release of cytokines that seems to be related to cancer pain. Nevertheless, in some cases, targeted drugs are available and in use for other diseases. In this paper, we aim to review the importance of cytokines in cancer pain and targeted strategies that can have an impact on controlling this symptom. PMID:26538839

  13. [Plant-Producers Of Recombinant Cytokines (Review)].

    PubMed

    Burlakovskii, M S; Yemel'yanov, V V; Lutova, L A

    2016-01-01

    Cytokines are a family of signaling polypeptides involved in cell-cell interactions in the process of the immune response, as well as in the regulation of a number of normal physiological functions. Cytokines are used in medicine for the treatment of cancer, immune disorders, viral infections, and other socially significant diseases, but the extent of their use is limited by the high production cost of the active agent. The development of this area of pharmacology is associated with the success of genetic engineering, which allows the production of significant amounts of protein by transgenic organisms. The review discusses the latest advances in the production of various cytokines with the use of genetically modified plants. PMID:27266244

  14. The role of cytokines in pulp inflammation.

    PubMed

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

    2011-01-01

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

  15. Kitasato symposium 2010: new prospects for cytokines

    PubMed Central

    2010-01-01

    The Second Kitasato Symposium: New Prospects for Cytokines brought together researchers and rheumatologists to consider the essential role of cytokines in health and their contributions to autoimmunity. Topics addressed during the Symposium - which was held in Berlin, Germany from 27 to 29 May 2010 - included established and new cytokine targets in arthritis and autoimmunity and innovative aspects of osteoimmunology as well as current perspectives from translational and clinical studies. The keynote lecture, delivered by George Kollias, focused on insights gained from animal models into the mechanisms of TNF function in chronic inflammation and autoimmunity. The presentations at the Symposium resulted in productive discussions regarding potential new targets for the treatment of rheumatoid arthritis and other autoimmune disorders. PMID:21235827

  16. Cytokine production associated with smallpox vaccine responses.

    PubMed

    Simon, Whitney L; Salk, Hannah M; Ovsyannikova, Inna G; Kennedy, Richard B; Poland, Gregory A

    2014-01-01

    Smallpox was eradicated 34 years ago due to the success of the smallpox vaccine; yet, the vaccine continues to be studied because of its importance in responding to potential biological warfare and the adverse events associated with current smallpox vaccines. Interindividual variations in vaccine response are observed and are, in part, due to genetic variation. In some cases, these varying responses lead to adverse events, which occur at a relatively high rate for the smallpox vaccine compared with other vaccines. Here, we aim to summarize the cytokine responses associated with smallpox vaccine response to date. Along with a description of each of these cytokines, we describe the genetic and adverse event data associated with cytokine responses to smallpox vaccination.

  17. Spectrophotometric analysis of irradiated spices.

    PubMed

    Josimović, L; Cudina, I

    1987-01-01

    Seven different spices (thyme, cinnamon, coriander, caraway, pimento, paprika, black pepper) were treated by gamma radiation at an absorbed dose of 10 kGy, and the effect on chemical quality was determined. The effects of this dose were assessed by spectrophotometric analysis of some water-soluble constituents of spices (carbohydrates; carbonyl compounds) and on the content of water-insoluble steam-volatile oils. The colour of paprika and the content of piperine in pepper held in different packaging materials were measured in unirradiated and irradiated samples as a function of storage time. In all cases irradiation does not bring about any distinct qualitative or quantitative chemical changes based on spectrophotometric analysis of spice extracts.

  18. Cancer Therapeutic Effects of Titanium Dioxide Nanoparticles Are Associated with Oxidative Stress and Cytokine Induction.

    PubMed

    Fujiwara, Rina; Luo, Yi; Sasaki, Takamitsu; Fujii, Kiyomu; Ohmori, Hitoshi; Kuniyasu, Hiroki

    2015-01-01

    Nanoparticles (NPs) are considered to influence the inflammatory process; however, the precise mechanism and the significance in tumors are still not clear. In this study, when CT26 and LL2 mouse cancer cells were treated with 6-nm anatase titanium dioxide NPs (TDNPs) without ultraviolet irradiation, oxidative stress and induction of inflammatory cytokines were observed. Oxidative stress was further increased by disease-associated conditions such as high glucose concentrations and hypoxia. Inhaled or orally administered TDNPs generated granulomatous lesions in the lungs and colon of the rodent models tested, with increased oxidative stress and inflammatory cytokines. Oxidative stress and inflammatory cytokines were also found in cancer cells treated with gold or carbon black NPs. Treatment of CT26 cells with 10- to 70-nm rutile TDNPs showed that smaller NPs produced more oxidative stress and inflammatory cytokines than larger ones did. To avoid diffusion of TDNPs and to minimize toxicity, 10-nm TDNPs were suspended in a collagen gel inserted into a subcutaneous tumor in a CT26 mouse. A single TDNP treatment via this method inhibited tumor growth in a size- and dose-dependent manner, and resulted in lower levels of urinary 8-OHdG when compared to systemically administered TDNPs. These findings suggest that TDNPs might be useful for the local treatment of tumors. PMID:26485713

  19. RERTR-8 Irradiation Summary Report

    SciTech Connect

    D. M. Perez; M. A. Lillo; G. S. Chang; G. A. Roth; N. E. Woolstenhulme; D. M. Wachs

    2011-12-01

    The Reduced Enrichment for Research and Test Reactor (RERTR) experiment RERTR-8, was designed to test monolithic mini-fuel plates fabricated via hot isostatic pressing (HIP), the effect of molybdenum (Mo) content on the monolithic fuel behavior, and the efficiency of ternary additions to dispersion fuel particles on the interaction layer behavior at higher burnup. The following report summarizes the life of the RERTR-8 experiment through end of irradiation, including as-run neutronic analysis, thermal analysis and hydraulic testing results.

  20. Cytokine Reduction in the Treatment of Joint Conditions

    PubMed Central

    Martel-Pelletier, J.; Otterness, I. G.; Pelletier, J.-P.

    1994-01-01

    The destruction of joints caused by rheumatoid arthritis and osteoarthritis is characterized by an imbalance of enzyme catalysed cartilage breakdown and regeneration. A complex cytokine network perpetuates joint conditions by direct regulation of metalloproteases, by indirect recruitment of cells that secrete degradative enzymes, and by inhibition of reparative processes. The destructive action of cytokines such as interleukin-1, interleukin-6 and tumour necrosis factor-α can be modulated at multiple points associated either with cytokine production or with cytokine action. Potential agents for cytokine reduction include selective anti-cytokine antibodies, anticytokine receptor antibodies, cytokine receptor antagonist proteins, and soluble and chimeric cytokine receptor molecules. Pharmacologic regulation of IL-1 and TNFα remain primary targets for treatment of arthritis, and results of early clinical trials are promising. However, the results of long-term clinical trials will be required to support the value of anti-cytokine therapy in treatment of arthritis. PMID:18472950

  1. Microbiological decontamination of natural honey by irradiation

    NASA Astrophysics Data System (ADS)

    Migdał, W.; Owczarczyk, H. B.; K ȩdzia, B.; Hołderna-K ȩdzia, E.; Madajczyk, D.

    2000-03-01

    Degree of microbiological decontamination, organoleptic and physico-chemical properties of natural honeys were investigated after radiation treatment. Seven kinds of honeys were irradiated with the beams of 10 MeV electrons from a 10 kW linear accelerator "Elektronika 10-10" at the dose 10 kGy. It was shown, that after irradiation, the total count of aerobic and anaerobic bacteria and moulds decrease by 99%. The antibiotic value in investigated honeys increased in turn from 1.67 to 2.67 after irradiation. Such factors and parameters of investigated honeys as their consistency, content of water and saccharose, acidity, the diastase and 5-HMF values were not changed significantly after irradiation. Decontamination by irradiation is a process which allows us to obtain high microbiological purity of honeys. It is especially needed, when honeys are used in surgical treatment of injuries and in nutrition of babies with food deficiency.

  2. Use of Irradiated Foods

    NASA Technical Reports Server (NTRS)

    Brynjolfsson, A.

    1985-01-01

    The safety of irradiated foods is reviewed. Guidelines and regulations for processing irradiated foods are considered. The radiolytic products formed in food when it is irradiated and its wholesomeness is discussed. It is concluded that food irradiation processing is not a panacea for all problems in food processing but when properly used will serve the space station well.

  3. Pro-inflammatory cytokines downregulate Hsp27 and cause apoptosis of human retinal capillary endothelial cells

    PubMed Central

    Nahomi, Rooban B.; Palmer, Allison; Roth, Katelyn E.; Fort, Patrice E.; Nagaraj, Ram H.

    2013-01-01

    The formation of acellular capillaries in the retina, a hallmark feature of diabetic retinopathy, is caused by apoptosis of endothelial cells and pericytes. The biochemical mechanism of such apoptosis remains unclear. Small heat shock proteins play an important role in the regulation of apoptosis. In the diabetic retina, pro-inflammatory cytokines are upregulated. In this study, we investigated the effects of pro-inflammatory cytokines on small heat shock protein 27 (Hsp27) in human retinal endothelial cells (HREC). In HREC cultured in the presence of cytokine mixtures (CM), a significant downregulation of Hsp27 at the protein and mRNA level occurred, with no effect on HSF-1, the transcription factor for Hsp27. The presence of high glucose (25 mM) amplified the effects of cytokines on Hsp27. CM activated indoleamine 2,3-dioxygenase (IDO) and enhanced the production of kynurenine and ROS. An inhibitor of IDO, 1-methyl tryptophan (MT), inhibited the effects of CM on Hsp27. CM also upregulated NOS2 and, consequently, nitric oxide (NO). A NOS inhibitor, L-NAME, and a ROS scavenger blocked the CM-mediated Hsp27 downregulation. While a NO donor in the culture medium did not decrease the Hsp27 content, a peroxynitrite donor and exogenous peroxynitrite did. The cytokines and high glucose-induced apoptosis of HREC were inhibited by MT and L-NAME. Downregulation of Hsp27 by a siRNA treatment promoted apoptosis in HREC. Together, these data suggest that pro-inflammatory cytokines induce the formation of ROS and NO, which, through the formation of peroxynitrite, reduce the Hsp27 content and bring about apoptosis of retinal capillary endothelial cells. PMID:24252613

  4. [Clinical variations of chronic generalized periodontitis, genetic polymorphism and systemic production of inflammatory cytokines].

    PubMed

    Grigorovich, E Sh; Pomorgailo, E G; Khomutova, E Yu; Stepanov, S S

    2015-01-01

    Carriage of polymorphic alleles of genes of cytokines-interleukines IL-1β, IL-1RN, TNFα, IL-4 can be a specific feature of chronic periodontitis patients. Genetic tests can be used to predict the course of the disease at its early manifestations. Objective: To establish the relationship of clinical manifestations of periodontal disease, inflammatory cytokines gene polymorphism and systemic levels of cytokine production. Periodontal tissue assessment and cone-beam computed tomography (CBCT) were performed in 150 periodontitis patients. A molecular--genetic testing for the presence of polymorphic alleles of genes IL-1β -511 C>T and +3953 C>T, IL-1RN (VNTR intron 2), IL-4 (VNTR intron 3), TNFα-308 G>A; content determined IL-1β, TNFα, IL-4 in peripheral blood was carried out in 150 patients with periodontitis and 150 healthy donors. Based on the analysis of the speed and nature of the supporting bone resorption and clinical manifestations patients are divided in "aggressive", "moderately progressive" and "slowly progressive" periodontits course groups. Disease severity was associated with distribution of genotypes and alleles of polymorphic genes cytokine IL-1RN (VNTR intron 2), TNFα-308 G>A and IL-4 (VNTR intron 3); haplotype IL-1β-511 TIL-1β +3953 T/IL-1RN 2R. There was no statistically significant difference in systemic level of IL-1β, TNFα and IL-4 between periodontitis groups but the donor level of cytokines was 2-4 times less.

  5. Cytokines and immune surveillance in humans

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald

    1994-01-01

    Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. Among the parameters shown, by us and others, to be affected is the production of interferons. Interferons are a family of cytokines that are antiviral and play a major role in regulating immune responses that control resistance to infection. Alterations in interferon and other cytokine production and activity could result in changes in immunity and a possible compromise of host defenses against both opportunistic and external infections. The purpose of the present study is to explore further the effects of space flight on cyotokines and cytokine-directed immunological function. Among the tests carried out are interferon-alpha production, interferon-gamma production, interleukin-1 and -2 production, signal transduction in neutrophils, signal transduction in monocytes, and monocyte phagocytic activity. The experiments will be performed using peripheral blood obtained from human subjects. It is our intent to eventually carry out these experiments using astronauts as subjects to determine the effects of space flight on cytokine production and activity. However, these subjects are not currently available. Until they become available, we will carry out these experiments using subjects maintained in the bed-rest model for microgravity.

  6. Cytokine therapeutics: lessons from interferon alpha.

    PubMed Central

    Gutterman, J U

    1994-01-01

    Cytokines are soluble proteins that allow for communication between cells and the external environment. Interferon (IFN) alpha, the first cytokine to be produced by recombinant DNA technology, has emerged as an important regulator of growth and differentiation, affecting cellular communication and signal transduction pathways as well as immunological control. This review focuses on the biological and clinical activities of the cytokine. Originally discovered as an antiviral substance, the efficacy of IFN-alpha in malignant, viral, immunological, angiogenic, inflammatory, and fibrotic diseases suggests a spectrum of interrelated pathophysiologies. The principles learned from in vivo studies will be discussed, particularly hairy cell leukemia, chronic myelogenous leukemia, certain angiogenic diseases, and hepatitis. After the surprising discovery of activity in a rare B-cell neoplasm, IFN-alpha emerged as a prototypic tumor suppressor protein that represses the clinical tumorigenic phenotype in some malignancies capable of differentiation. Regulatory agencies throughout the world have approved IFN-alpha for treatment of 13 malignant and viral disorders. The principles established with this cytokine serve as a paradigm for future development of natural proteins for human disease. PMID:8108387

  7. Cytokine levels as biomarkers for leptospirosis patients.

    PubMed

    Chirathaworn, C; Supputtamongkol, Y; Lertmaharit, S; Poovorawan, Y

    2016-09-01

    Inflammatory mediators were suggested to be biomarkers for prediction of disease severity. In this study, we investigated the levels of IL-6, IL-8, IL-10 and TNF-α in leptospirosis patients with mild or severe illnesses. Sera samples were divided into two groups. The OI group and NOI groups included sera from patients with and without organ involvement, respectively. Each group consisted of 20 pairs of sera. Twenty-five sera from healthy individuals were included as controls. Cytokine levels were compared. Although IL-6, IL-8 and IL-10 levels in acute sera from the OI group were significantly higher than NOI group, only IL-8 level was significantly higher in the OI group when cytokine levels in convalescent sera were compared. TNF-α, an inflammatory cytokine widely studied in leptospirosis was not significantly different between two groups of patients. Our data suggested that IL-6, IL-8 and IL-10 were involved in disease severity. However, time of specimen collection could affect the significant levels of cytokines especially as biomarkers for monitoring disease severity. PMID:27295614

  8. Interleukin-12 family cytokines and sarcoidosis.

    PubMed

    Ringkowski, Sabine; Thomas, Paul S; Herbert, Cristan

    2014-01-01

    Sarcoidosis is a systemic granulomatous disease predominantly affecting the lungs. It is believed to be caused by exposure to pathogenic antigens in genetically susceptible individuals but the causative antigen has not been identified. The formation of non-caseating granulomas at sites of ongoing inflammation is the key feature of the disease. Other aspects of the pathogenesis are peripheral T-cell anergy and disease progression to fibrosis. Many T-cell-associated cytokines have been implicated in the immunopathogenesis of sarcoidosis, but it is becoming apparent that IL-12 cytokine family members including IL-12, IL-23, IL-27, and IL-35 are also involved. Although the members of this unique cytokine family are heterodimers of similar subunits, their biological functions are very diverse. Whilst IL-23 and IL-12 are pro-inflammatory regulators of Th1 and Th17 responses, IL-27 is bidirectional for inflammation and the most recent family member IL-35 is inhibitory. This review will discuss the current understanding of etiology and immunopathogenesis of sarcoidosis with a specific focus on the bidirectional impact of IL-12 family cytokines on the pathogenesis of sarcoidosis.

  9. Cytokines as biomarkers of nanoparticle immunotoxicity

    PubMed Central

    Elsabahy, Mahmoud; Wooley, Karen L.

    2013-01-01

    Nanoscale objects, whether of biologic origin or synthetically created, are being developed into devices for a variety of bionanotechnology diagnostic and pharmaceutical applications. However, the potential immunotoxicity of these nanomaterials and mechanisms by which they may induce adverse reactions have not received sufficient attention. Nanomaterials, depending on their characteristics and compositions, can interact with the immune system in several ways and either enhance or suppress immune system function. Cytokines perform pleiotropic functions to mediate and regulate the immune response and are generally recognized as biomarkers of immunotoxicity. While the specificity and validity of certain cytokines as markers of adverse immune response has been established for chemicals, small and macromolecular drugs, research on their applicability for predicting and monitoring the immunotoxicity of engineered nanomaterials is still ongoing. The goal of this review is to provide guidelines as to important cytokines that can be utilized for evaluating the immunotoxicity of nanomaterials and to highlight the role of those cytokines in mediating adverse reactions, which is of particular importance for the clinical development of nanopharmaceuticals and other nanotechnology-based products. Importantly, the rational design of nanomaterials of low immunotoxicity will be discussed, focusing on synthetic nanodevices, with emphasis on both the nanoparticle-forming materials and the embedded cargoes. PMID:23549679

  10. Topical Administration of Manuka Oil Prevents UV-B Irradiation-Induced Cutaneous Photoaging in Mice

    PubMed Central

    Kwon, Oh Sook; Yang, Beom Seok

    2013-01-01

    Manuka tree is indigenous to New Zealand, and its essential oil has been used as a traditional medicine to treat wounds, fever, and pain. Although there is a growing interest in the use of manuka oil for antiaging skin care products, little is known about its bioactivity. Solar ultraviolet (UV) radiation is the primary environmental factor causing skin damage and consequently premature aging. Therefore, we evaluated manuka oil for its effects against photoaging in UV-B-irradiated hairless mice. Topical application of manuka oil suppressed the UV-B-induced increase in skin thickness and wrinkle grading in a dose-dependent manner. Application of 10% manuka oil reduced the average length, depth, and % area of wrinkles significantly, and this was correlated with inhibition of loss of collagen fiber content and epidermal hyperplasia. Furthermore, we observed that manuka oil could suppress UV-B-induced skin inflammation by inhibiting the production of inflammatory cytokines. Taken together, this study provides evidence that manuka oil indeed possesses antiphotoaging activity, and this is associated with its inhibitory activity against skin inflammation induced by UV irradiation. PMID:23762170

  11. Detection of irradiated liquor

    NASA Astrophysics Data System (ADS)

    Shengchu, Qi; Jilan, Wu; Rongyao, Yuan

    D-2,3-butanediol is formed by irradiation processes in irradiated liquors. This radiolytic product is not formed in unirradiated liquors and its presence can therefore be used to identify whether a liquor has been irradiated or not. The relation meso/dl≈1 for 2,3-butanediol and the amount present in irradiated liquors may therefore be used as an indication of the dose used in the irradiation.

  12. Influence of gamma ray irradiation on metakaolin based sodium geopolymer

    NASA Astrophysics Data System (ADS)

    Lambertin, D.; Boher, C.; Dannoux-Papin, A.; Galliez, K.; Rooses, A.; Frizon, F.

    2013-11-01

    Effects of gamma irradiation on metakaolin based Na-geopolymer have been investigated by external irradiation. The experiments were carried out in a gamma irradiator with 60Co sources up to 1000 kGy. Various Na-geopolymer with three H2O/Na2O ratios have been studied in terms of hydrogen radiolytic yield. The results show that hydrogen production increases linearly with water content. Gamma irradiation effects on Na-geopolymer microstructure have been investigated with porosity measurements and X-ray pair distribution function analysis. A change of pore size distribution and a structural relaxation have been found after gamma ray irradiation.

  13. Effect of re-irradiation by neutrons on mechanical properties of un-irradiated/irradiated SS316LN weldments

    NASA Astrophysics Data System (ADS)

    Tsuchiya, K.; Shimizu, M.; Kawamura, H.; Kalinin, G.

    2008-02-01

    Stainless steel of type SS316LN-IG (ITER Grade) is used for the branch pipeline connecting of the module coolant system and for other structures of ITER. One of the most important requirements for the branch pipeline connection is to recover various defects by welding. In the present study, characteristics of irradiated weldments were evaluated. SS316LN-IG specimens irradiated to helium contents of 3 and 10 appm He were prepared by the first neutron irradiation. Thereafter, the SS316LN-IG specimens with three different combinations of un-irradiation and irradiation were welded by a tungsten inert-gas (TIG) welding method. These weldments were re-irradiated at 150 °C up to a fast neutron fluence of about 7.5 × 10 24 n/m 2 ( E > 1 MeV). Tensile tests of the weldments and the base material were carried out at 20 and 150 °C after the re-irradiation. The results of the comparison before and after the re-irradiation showed that tensile properties of all weldment specimens with the different combinations were almost the same as those of the base materials.

  14. Cytokine balance and cytokine-driven natural killer cell dysfunction in systemic juvenile idiopathic arthritis.

    PubMed

    Avau, Anneleen; Put, Karen; Wouters, Carine H; Matthys, Patrick

    2015-02-01

    Systemic juvenile idiopathic arthritis (sJIA) is a severe inflammatory childhood disorder, characterized by a specific pattern of systemic features and a typical cytokine profile. Patients are at risk to develop macrophage activation syndrome (MAS), an acute life-threatening condition defined by excessive proliferation and activation of macrophages and T cells. Defects of unknown cause in the natural killer (NK) cell cytotoxic capacity are presumed to underlie the pathogenesis of MAS and have been detected in sJIA patients. Here, we provide an overview of the cytokine profiles in sJIA and related mouse models. We discuss the influence of cytokines on NK cell function, and hypothesize that NK cell dysfunction in sJIA is caused by altered cytokine profiles.

  15. 60Co irradiation of Shiga toxin (Stx)-producing Escherichia coli induces Stx phage.

    PubMed

    Yamamoto, Tatsuo; Kojio, Seiichi; Taneike, Ikue; Nakagawa, Saori; Iwakura, Nobuhiro; Wakisaka-Saito, Noriko

    2003-05-16

    Shiga toxin (Stx)-producing Escherichia coli (STEC), an important cause of hemolytic uremic syndrome, was completely killed by (60)Co irradiation at 1 x l0(3) gray (1 kGy) or higher. However, a low dose of irradiation (0.1-0.3 kGy) markedly induced Stx phage from STEC. Stx production was observed in parallel to the phage induction. Inactivation of Stx phage required a higher irradiation dose than that for bacterial killing. Regarding Stx, cytotoxicity was susceptible to irradiation, but cytokine induction activity was more resistant than Stx phage. The findings suggest that (1). although (60)Co irradiation is an effective means to kill the bacteria, it does induce Stx phage at a lower irradiation dose, with a risk of Stx phage transfer and emergence of new Stx-producing strains, and (2). irradiation differentially inactivates some activities of Stx.

  16. [Changes in the content of the thiol form of the acetylation coenzyme in the liver during administration of vitamin B3-active compounds to intact and locally irradiated animals].

    PubMed

    Rozanov, V A

    1984-01-01

    A local exposure of mouse head to gamma-rays caused phase changes in CoASH content of the liver. The administration of D-pantothenate-Ca and D-pantethine increased the level of CoASH in the liver of exposed animals; calcium D-homopantothenate did not influence the co-enzyme content. It is suggested that pantothenate and pantethine act like vitamins while the influence of homopantothenate is associated with the effects of calcium ions. PMID:6739738

  17. Workers’ cytokines profiling upon exposure to MWCNT aerosol in occupational settings

    NASA Astrophysics Data System (ADS)

    Fatkhutdinova, L. M.; Khaliullin, T. O.; Zalyalov, R. R.; Vasilyeva, O. L.; Valeeva, I. Kh; Mustafin, I. G.

    2015-11-01

    Recent studies have found that upon pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) animals develop primarily fibrosis and granulomas in lungs. In vitro and in vivo studies also give reason to assume that local exposure could be related to remote effects, including immune system and the endothelium. To investigate the remote effect hypothesis, we have analyzed blood, nasal lavage and induced sputum samples taken from workers in the frame of the Russian epidemiological study on Carbon Nanotubes Exposure and Risk Assessment (CNT-ERA). In serum and nasal lavage no significant differences between exposure and control groups were observed with a high variability to the cytokines content. In the samples of induced sputum from exposed workers the content of IL-1b, IL-6, IL-8, TNF-a, IL-4, IL-5, IFN-g exceeded the control group values, but after the regression models construction and bootstrap analysis, significant differences were found only for IL-1b. This study could not provide evidences of blood cytokines changes following local cytokine production in airways in workers exposed to MWCNTs. Cytokines variability in serum and nasal lavage may indicate the absence of severe systemic inflammatory response upon the existing occupational exposure to MWCNTs. Other systemic responses (including allergy-like or autoimmune reactions) should be regarded as well.

  18. Cytokine Correlations in Youth with Tic Disorders

    PubMed Central

    Parker-Athill, E. Carla; Ehrhart, Jared; Tan, Jun

    2015-01-01

    Abstract Background: Studies have noted immunological disruptions in patients with tic disorders, including increased serum cytokine levels. This study aimed to determine whether or not cytokine levels could be correlated with tic symptom severity in patients with a diagnosed tic disorder. Methods: Twenty-one patients, ages 4–17 years (average 10.63±2.34 years, 13 males), with a clinical diagnosis of Tourette's syndrome (TS) or chronic tic disorder (CTD), were selected based on having clinic visits that coincided with a tic symptom exacerbation and a remission. Ratings of tic severity were assessed using the Yale Global Tic Severity Scale (YGTSS) and serum cytokine levels (interleukin [IL]-2, IL-4, IL-5, IL-10, IL-12p70, IL-13, interferon [IFN]-γ, tumor necrosis factor [TNF]-α, and granulocyte macrophage-colony stimulating factor [GM-CSF]) were measured using Luminex xMAP technology. Results: During tic symptom exacerbation, patients had higher median serum TNF-α levels (z=−1.962, p=0.05), particularly those on antipsychotics (U=9.00, p=0.033). Increased IL-13 was also associated with antipsychotic use during exacerbation (U=4.00, p=0.043) despite being negatively correlated to tic severity scores (ρ=−0.599, p=018), whereas increased IL-5 was associated with antibiotic use (U=6.5, p=0.035). During tic symptom remission, increased serum IL-4 levels were associated with antipsychotic (U=6.00, p=0.047) and antibiotic (U=1.00, p=0.016) use, whereas increased IL-12p70 (U=4.00, p=0.037) was associated with antibiotic use. Conclusions: These findings suggest a role for cytokine dysregulation in the pathogenesis of tic disorders. It also points toward the mechanistic involvement and potential diagnostic utility of cytokine monitoring, particularly TNF-α levels. Larger, systematic studies are necessary to further delineate the role of cytokines and medication influences on immunological profiling in tic disorders. PMID:25658821

  19. Reduction of allergenicity of irradiated ovalbumin in ovalbumin-allergic mice

    NASA Astrophysics Data System (ADS)

    Seo, Ji-Hyun; Lee, Ju-Woon; Kim, Jae-Hun; Byun, Eui-Baek; Lee, Soo-Young; Kang, Il-Jun; Byun, Myung-Woo

    2007-11-01

    Egg allergy is one of the most serious of the immediate hypersensitivity reactions to foods. Such an allergic disorder is mediated by IgE antibodies stimulated by T-helper type 2 (Th2) lymphocytes. This study was undertaken to evaluate changes of allergenicity and cytokine profiles by exposure of irradiated ovalbumin (OVA), a major allergen of egg white, in the OVA-allergic mice model. OVA solutions (2 mg/ml in 0.01 M phosphate buffered saline (PBS) were gamma-irradiated to 50 and 100 kGy. The allergenicity in the OVA-allergy-induced mice model was remarkably reduced when challenged with irradiated OVA. Cultures of spleen cells harvested from OVA-sensitized mice showed a significant decrease in Th2 cytokine levels of ILs-4 and -5 with a concomitant increase in Th1 cytokine levels of IL-12 when co-cultured with irradiated OVA. However, IFN- γ level decreased dependant on the radiation dose of co-cultured OVA. The levels of IgEs and Th2-cytokine were reduced dependant on the radiation dose. These data show that the irradiated OVA could downregulate the activity of Th2 lymphocytes in OVA-sensitized mice.

  20. Alcoholic Liver Disease: Role of Cytokines.

    PubMed

    Neuman, Manuela G; Maor, Yaakov; Nanau, Radu M; Melzer, Ehud; Mell, Haim; Opris, Mihai; Cohen, Lawrence; Malnick, Stephen

    2015-01-01

    The present review spans a broad spectrum of topics dealing with alcoholic liver disease (ALD), including clinical and translational research. It focuses on the role of the immune system and the signaling pathways of cytokines in the pathogenesis of ALD. An additional factor that contributes to the pathogenesis of ALD is lipopolysaccharide (LPS), which plays a central role in the induction of steatosis, inflammation, and fibrosis in the liver. LPS derived from the intestinal microbiota enters the portal circulation, and is recognized by macrophages (Kupffer cells) and hepatocytes. In individuals with ALD, excessive levels of LPS in the liver affect immune, parenchymal, and non-immune cells, which in turn release various inflammatory cytokines and recruit neutrophils and other inflammatory cells. In this review, we elucidate the mechanisms by which alcohol contributes to the activation of Kupffer cells and the inflammatory cascade. The role of the stellate cells in fibrogenesis is also discussed. PMID:26343741

  1. Cytokines and Other Mediators in Alopecia Areata

    PubMed Central

    Gregoriou, Stamatis; Papafragkaki, Dafni; Kontochristopoulos, George; Rallis, Eustathios; Kalogeromitros, Dimitrios; Rigopoulos, Dimitris

    2010-01-01

    Alopecia areata, a disease of the hair follicles with multifactorial etiology and a strong component of autoimmune origin, has been extensively studied as far as the role of several cytokines is concerned. So far, IFN-γ, interleukins, TNF-α, are cytokines that are well known to play a major role in the pathogenesis of the disease, while several studies have shown that many more pathways exist. Among them, MIG, IP-10, BAFF, HLA antigens, MIG, as well as stress hormones are implicated in disease onset and activity. Within the scope of this paper, the authors attempt to shed light upon the complexity of alopecia areata underlying mechanisms and indicate pathways that may suggest future treatments. PMID:20300578

  2. Crustacean hematopoiesis and the astakine cytokines.

    PubMed

    Lin, Xionghui; Söderhäll, Irene

    2011-06-16

    Major contributions to research in hematopoiesis in invertebrate animals have come from studies in the fruit fly, Drosophila melanogaster, and the freshwater crayfish, Pacifastacus leniusculus. These animals lack oxygen-carrying erythrocytes and blood cells of the lymphoid lineage, which participate in adaptive immune defense, thus making them suitable model animals to study the regulation of blood cells of the innate immune system. This review presents an overview of crustacean blood cell formation, the role of these cells in innate immunity, and how their synthesis is regulated by the astakine cytokines. Astakines are among the first invertebrate cytokines shown to be involved in hematopoiesis, and they can stimulate the proliferation, differentiation, and survival of hematopoietic tissue cells. The astakines and their vertebrate homologues, prokineticins, share similar functions in hematopoiesis; thus, studies of astakine-induced hematopoiesis in crustaceans may not only advance our understanding of the regulation of invertebrate hematopoiesis but may also provide new evolutionary perspectives about this process.

  3. Novel cytokine-directed therapies for asthma.

    PubMed

    Walsh, Garry M

    2011-04-01

    For the majority of asthmatic patients, inhaled corticosteroid anti-inflammatory therapy is effective at controlling disease symptoms. However, this requires life-time therapy while a subset of patients remains symptomatic despite optimal treatment creating a clear unmet medical need. Biopharmaceutical approaches have been used to target key elements in the complex pro-inflammatory processes controlling pro-inflammatory cell accumulation and the secretory function of these and structural cells within the asthmatic lung. Asthma-relevant cytokines or chemokines have been targeted in a number of ways. These include the use of humanized blocking mAb to their receptors, removal of cytokines or chemokines via their binding to soluble receptors or small molecule receptor antagonists. Other approaches include the development of biologics that block specific bioactive agents such as IgE. This review will discuss the current status, therapeutic potential and potential problems of these novel drug biologics in asthma therapy.

  4. Interferons lambda, new cytokines with antiviral activity.

    PubMed

    Lopušná, K; Režuchová, I; Betáková, T; Skovranová, L; Tomašková, J; Lukáčiková, L; Kabát, P

    2013-01-01

    Interferons (IFNs) are key cytokines in the establishment of a multifaceted antiviral response. Three distinct types of IFNs are now recognized (type I, type II, and type III) based on their receptor usage, structural features and biological activities. Although all IFNs are important mediators of antiviral protection, their roles in antiviral defence vary. Interferon lambda (IFN-λ) is a recently discovered group of small helical cytokines capable of inducing an antiviral response both in vitro as well as in vivo. They were discovered independently in 2003 by the groups of Sheppard and Kotenko. This family consists of three structurally related IFN-λ subtypes called IFN-λ1 (IL-29), IFN-λ2 (IL-28A), and IFN-λ3 (IL-28B). In this study we investigate the antiviral activities of IFN-λ1, λ2, and λ3 on some medically important viruses, influenza viruses, herpes viruses and lymphocytic choriomeningitis virus. PMID:23600875

  5. Cytokine signalling in mammary gland development.

    PubMed

    Watson, Christine J; Oliver, Carrie H; Khaled, Walid T

    2011-03-01

    Mammary gland development occurs in three distinct stages during the lifetime of the female mammal: in embryonic, pubertal and reproductive life. At each of these developmental stages, different signalling molecules induce changes in both the epithelium and the surrounding stroma. However, it is during pregnancy that the most dramatic changes occur, resulting in a massive increase in the number of epithelial cells and in their function. Pregnancy initiates the development of a new epithelial lineage, the alveolar cells, which form the milk-producing lobuloalveolar structures. These cells become redundant at the end of lactation and are removed in an exquisitely controlled process of tissue remodelling coupled with extensive cell death. All of these events require not only steroid hormones but also sequential signalling by cytokines. A recent surprising discovery was that the signalling pathways and cytokines that regulate lineage determination in T helper cells are also involved in mammary gland development during pregnancy.

  6. Inflammatory cytokines in atherosclerosis: current therapeutic approaches.

    PubMed

    Tousoulis, Dimitris; Oikonomou, Evangelos; Economou, Evangelos K; Crea, Filippo; Kaski, Juan Carlos

    2016-06-01

    The notion of atherosclerosis as a chronic inflammatory disease has intensified research on the role of cytokines and the way these molecules act and interact to initiate and sustain inflammation in the microenvironment of an atherosclerotic plaque. Cytokines are expressed by all types of cells involved in the pathogenesis of atherosclerosis, act on a variety of targets exerting multiple effects, and are largely responsible for the crosstalk among endothelial, smooth muscle cells, leucocytes, and other vascular residing cells. It is now understood that widely used drugs such as statins, aspirin, methotrexate, and colchicine act in an immunomodulatory way that may beneficially affect atherogenesis and/or cardiovascular disease progression. Moreover, advancement in pharmaceutical design has enabled the production of highly specific antibodies against key molecules involved in the perpetuation of the inflammatory cascade, raising hope for advances in the treatment of atherosclerosis. This review describes the actions and effects of these agents, their potential clinical significance, and future prospects. PMID:26843277

  7. A Comparitive Assessement of Cytokine Expression in Human-Derived Cell Lines Exposed to Alpha Particles and X-Rays

    PubMed Central

    Chauhan, Vinita; Howland, Matthew; Wilkins, Ruth

    2012-01-01

    Alpha- (α-) particle radiation exposure has been linked to the development of lung cancer and has been identified as a radiation type likely to be employed in radiological dispersal devices. Currently, there exists a knowledge gap concerning cytokine modulations associated with exposure to α-particles. Bio-plex technology was employed to investigate changes in proinflammatory cytokines in two human-derived cell lines. Cells were irradiated at a dose of 1.5 Gy to either α-particles or X-rays at equivalent dose rates. The two cell lines exhibited a unique pattern of cytokine expression and the response varied with radiation type. Of the 27 cytokines assessed, only vascular endothelin growth factor (VEGF) was observed to be modulated in both cell lines solely after α-particle exposure, and the expression of VEGF was shown to be dose responsive. These results suggest that certain proinflammatory cytokines may be involved in the biological effects related to α- particle exposure and the responses are cell type and radiation type specific. PMID:22619631

  8. Influence of irradiation upon few-layered graphene using electron-beams and gamma-rays

    SciTech Connect

    Wang, Yuqing; Feng, Yi Mo, Fei; Qian, Gang; Chen, Yangming; Yu, Dongbo; Wang, Yang; Zhang, Xuebin

    2014-07-14

    Few-layered graphene (FLG) is irradiated by electron beams and gamma rays. After 100 keV electron irradiation, the edges of FLG start bending, shrinking, and finally generate gaps and carbon onions due to sputtering and knock-on damage mechanism. When the electron beam energy is increased further to 200 keV, FLG suffers rapid and catastrophic destruction. Unlike electron irradiation, Compton effect is the dominant damage mechanism in gamma irradiation. The irradiation results indicate the crystallinity of FLG decreases first, then restores as increasing irradiation doses, additionally, the ratio (O/C) of FLG surface and the relative content of oxygen groups increases after irradiation.

  9. Cytokine disbalance in common human cancers.

    PubMed

    Culig, Zoran

    2011-02-01

    Interleukin (IL)-6, -4, and -8 levels have been elevated in most patients suffering from prostate, breast, or colon cancer. There is a large body of evidence suggesting that chronic inflammation is one of the etiologic factors in these tumors. IL-6 is a multifunctional cytokine which is known to influence proliferation, apoptosis, and angiogenesis in cancer. Its transcription factor STAT3 is known as an oncogene that is constitutively phosphorylated in these malignancies. However, IL-6-induced STAT3 phosphorylation may result in growth arrest. IL-6 activation of androgen receptor in prostate cancer may yield either tumor cell proliferation or differentiation. Prolonged treatment with IL-6 results in generation of sublines which express a more malignant phenotype. Therapy options against IL-6 have been established and the antibody siltuximab has been applied in preclinical and clinical studies. Recently, investigations of the role of suppressors of cytokine signaling have been carried out. IL-4 and -8 are implicated in regulation of apoptosis, migration, and angiogenesis in cancers associated with chronic inflammation. All cytokines mentioned above regulate cellular events in stem cells. These cells could not be targeted by most conventional cancer therapies. PMID:21167870

  10. Effects of exercise on lymphocytes and cytokines

    PubMed Central

    Pedersen, B. K.; Toft, A. D.

    2000-01-01

    Objectives—To review results on exercise induced changes in the immune system following strenuous and moderate exercise. Methods—A literature search over the past 15 years was conducted using Medline and selected papers. Results—After intense long term exercise, the immune system is characterised by concomitant impairment of the cellular immune system and increased inflammation. Thus low concentrations of lymphocytes, suppressed natural immunity, suppressed lymphocyte proliferation, and suppressed levels of secretory IgA in saliva are found simultaneously with high levels of circulating proinflammatory and anti-inflammatory cytokines. The underlying mechanisms are multifactorial and include neuroendocrinological and metabolic factors. The clinical consequences of the exercise induced immune changes have not formally been identified, but the exercise effect on lymphocyte dynamics and immune function may be linked to the exercise effects on resistance to infections and malignancy and the cytokine response may be linked to muscle damage or muscle cell growth. Conclusions—Moderate exercise across the life span seems to increase resistance to upper respiratory tract infections, whereas repeated strenuous exercise suppresses immune function. It is premature to offer advice on nutrition to athletes in order to alter the exercise induced immunosuppression found after exercise. Key Words: exercise; cytokine; lymphocytes; immunosuppression; nutrition PMID:10953894

  11. Cytokine-Induced Modulation of Colorectal Cancer

    PubMed Central

    Mager, Lukas F.; Wasmer, Marie-Hélène; Rau, Tilman T.; Krebs, Philippe

    2016-01-01

    The emergence of novel immunomodulatory cancer therapies over the last decade, above all immune checkpoint blockade, has significantly advanced tumor treatment. For colorectal cancer (CRC), a novel scoring system based on the immune cell infiltration in tumors has greatly improved disease prognostic evaluation and guidance to more specific therapy. These findings underline the relevance of tumor immunology in the future handling and therapeutic approach of malignant disease. Inflammation can either promote or suppress CRC pathogenesis and inflammatory mediators, mainly cytokines, critically determine the pro- or anti-tumorigenic signals within the tumor environment. Here, we review the current knowledge on the cytokines known to be critically involved in CRC development and illustrate their mechanisms of action. We also highlight similarities and differences between CRC patients and murine models of CRC and point out cytokines with an ambivalent role for intestinal cancer. We also identify some of the future challenges in the field that should be addressed for the development of more effective immunomodulatory therapies. PMID:27148488

  12. [Cytokines, endothelial dysfunction, and insulin resistance].

    PubMed

    de Carvalho, Maria Helena C; Colaço, André Luiz; Fortes, Zuleica Bruno

    2006-04-01

    Endothelial dysfunction is associated with several vascular conditions as atherosclerosis, hypertension, hyperlipidemia and diabetes mellitus. In all these conditions insulin resistance (IR) is present. Cytokines are low molecular weight proteins with several endocrine and metabolic functions that participate of inflammation and immune response. Several of these cytokines are independent risk factors for cerebrovascular and coronary artery disease. The major sources of cytokines (adipokines) are the visceral and subcutaneous adipose tissues. Thus, increased adipose tissue mass is associated with alteration in adipokine production as over expression of tumor necrosis factor alpha, interleukin 6, plasminogen activator inhibitor 1, and under expression of adiponectin in adipocite tissue. The pro-inflammatory status associated with these changes provides a potential link between IR and endothelial dysfunction, the early stage in the atherosclerotic process, in obese individuals, and type 2 diabetic patients. Reduction of adipose tissue mass through weight reduction in association with exercise reduces TNF-alpha, IL-6, and PAI-1, increases adiponectin, and is associated with improved insulin sensitivity and endothelial function. This review will focus on the evidence for regulation of endothelial function by insulin and the adypokines such as adyponectin, leptin, resistin, IL-6 and TNF-alpha. Interaction between insulin signaling and adypokines will be discussed, as well as the concept that aberrant adypokine secretion in IR and/or obesity impairs endothelial function and contributes further to reduce insulin sensitivity.

  13. Cytokine-Induced Modulation of Colorectal Cancer.

    PubMed

    Mager, Lukas F; Wasmer, Marie-Hélène; Rau, Tilman T; Krebs, Philippe

    2016-01-01

    The emergence of novel immunomodulatory cancer therapies over the last decade, above all immune checkpoint blockade, has significantly advanced tumor treatment. For colorectal cancer (CRC), a novel scoring system based on the immune cell infiltration in tumors has greatly improved disease prognostic evaluation and guidance to more specific therapy. These findings underline the relevance of tumor immunology in the future handling and therapeutic approach of malignant disease. Inflammation can either promote or suppress CRC pathogenesis and inflammatory mediators, mainly cytokines, critically determine the pro- or anti-tumorigenic signals within the tumor environment. Here, we review the current knowledge on the cytokines known to be critically involved in CRC development and illustrate their mechanisms of action. We also highlight similarities and differences between CRC patients and murine models of CRC and point out cytokines with an ambivalent role for intestinal cancer. We also identify some of the future challenges in the field that should be addressed for the development of more effective immunomodulatory therapies.

  14. Effects of Lipopolysaccharide on the response of C57BL/6J mice to whole thorax irradiation

    PubMed Central

    Zaidi, Asif; Jelveh, Salomeh; Mahmood, Javed; Hill, Richard P

    2013-01-01

    Background and Purpose Inflammatory and fibrogenic processes play a crucial role in the radiation-induced injury in the lung. The aim of the present study was to examine whether additive LPS exposure in the lung (to simulate respiratory infection) would affect pneumonitis or fibrosis associated with lung irradiation. Material and Methods Wildtype C57Bl/6J (WT-C57) and TNFα, TNFR1 and TNFR2 knockout (−/−) mice, in C57Bl/6J background, were given whole thorax irradiation (10Gy) with or without post-irradiation intratracheal administration of LPS (50μg/mice). Functional deficit was examined by measuring breathing rate at various times after treatment. Real-time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunohistochemistry were used to analyse the protein expression and m-RNA of Interleukin-1 alpha (IL-1α), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumour Necrosis Factor alpha (TNFα) and Transforming Growth Factor beta (TGFβ) in the lung at various times after treatment. Inflammatory cells were detected by Mac-3 (macrophages) and Toluidine Blue (mast cells) staining. Collagen content was estimated by hydroxyproline (total collagen) and Sircol assay (soluble collagen). Levels of oxidative damage were assessed by 8-hydroxy-2-deoxyguanosine (8-OHdG) staining. Results LPS exposure significantly attenuated the breathing rate increases following irradiation of WT-C57, TNFR1−/− and TNFR2−/− mice and to a lesser extent in TNFα−/− mice. Collagen content was significantly reduced after LPS treatment in WT-C57, TNFR1−/− and TNFα−/− mice and there was a trend in TNFR2−/− mice. Similarly there were lower levels of inflammatory cells and cytokines in the LPS treated mice. Conclusions This study reveals a mitigating effect of early exposure to LPS on injury caused by irradiation on lungs of C57Bl mice. The results suggest that immediate infection post irradiation may not impact lung response negatively in radiation

  15. Commercial food irradiation

    SciTech Connect

    Black, E.F.; Libby, L.M.

    1983-06-01

    Food irradiation is discussed. Irradiation exposes food to gamma rays from a cobalt-60 or a cesium-137 source, or to high-energy electrons emitted by an electron accelerator. A major advantage is that food can be packaged either before or after treatment. FDA regulations with regard to irradiation are discussed. Comments on an 'Advance Notice' on irradiation, published by the FDA in 1981 are summarized.

  16. Free-radical concentrations and other properties of pile-irradiated coals

    USGS Publications Warehouse

    Friedel, R.A.; Breger, I.A.

    1959-01-01

    Five coals reacted quite differently when they were exposed to pile-irradiation. Little or no change was found in free-radical content for the three coals of lowest carbon content, whereas the two coals of highest carbon content were found to have a considerable increase in free-radical content. The infrared spectra and the apparent hardness of the irradiated coals of higher carbon content indicate that polymerization occurred. Radiation of these coals in chemical reagents may promote reactivity.

  17. Differential Cytokine Responses in Human and Mouse Lymphatic Endothelial Cells to Cytokines in Vitro

    PubMed Central

    Chaitanya, G.V.; Franks, S.E.; Cromer, W.; Wells, S.R.; Bienkowska, M.; Jennings, M.H.; Ruddell, A.; Ando, T.; Wang, Y.; Gu, Y.; Sapp, M.; Mathis, J.M.; Jordan, P.A.; Minagar, A.

    2010-01-01

    Abstract Background Inflammatory cytokines dysregulate microvascular function, yet how cytokines affect lymphatic endothelial cells (LEC) are unclear. Methods and Results We examined effects of TNF-α, IL-1β, and IFN-γ on LEC proliferation, endothelial cell adhesion molecule (ECAM) expression, capillary formation, and barrier changes in murine (SV-LEC) and human LECs (HMEC-1a). Results All cytokines induced ICAM-1, VCAM-1, MAdCAM-1, and E-selectin in SV-LECs; TNF-α, IL-1β and IFN-γ induced ECAMs (but not MAdCAM-1) in HMEC-1a. IL-1β increased, while IFN-γ and TNF-α reduced SV-LEC proliferation. While TNF-α induced, IFN-γ decreased, and IL-1β did not show any effect on HMEC-1a proliferation. TNF-α, IL-1β, and IFN-γ each reduced capillary formation in SV-LEC and in HMEC-1a. TNF-α and IL-1β reduced barrier in SV-LEC and HMEC-1a; IFN-γ did not affect SV-LEC barrier, but enhanced HMEC-1a barrier. Inflammatory cytokines alter LEC growth, activation and barrier function in vitro and may disturb lymphatic clearance increasing tissue edema in vivo. Conclusion Therapies that maintain or restore lymphatic function (including cytokines blockade), may represent important strategies for limiting inflammation. PMID:20863268

  18. Metoprolol Reduces Proinflammatory Cytokines and Atherosclerosis in ApoE−/− Mice

    PubMed Central

    Ulleryd, Marcus A.; Bernberg, Evelina; Yang, Li Jin; Bergström, Göran M. L.; Johansson, Maria E.

    2014-01-01

    A few studies in animals and humans suggest that metoprolol (β1-selective adrenoceptor antagonist) may have a direct antiatherosclerotic effect. However, the mechanism behind this protective effect has not been established. The aim of the present study was to evaluate the effect of metoprolol on development of atherosclerosis in ApoE−/− mice and investigate its effect on the release of proinflammatory cytokines. Male ApoE−/− mice were treated with metoprolol (2.5 mg/kg/h) or saline for 11 weeks via osmotic minipumps. Atherosclerosis was assessed in thoracic aorta and aortic root. Total cholesterol levels and Th1/Th2 cytokines were analyzed in serum and macrophage content in lesions by immunohistochemistry. Metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta (P < 0.05 versus Control). Further, metoprolol reduced serum TNFα and the chemokine CXCL1 (P < 0.01 versus Control for both) as well as decreasing the macrophage content in the plaques (P < 0.01 versus Control). Total cholesterol levels were not affected. In this study we found that a moderate dose of metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta of ApoE−/− mice. Metoprolol also decreased serum levels of proinflammatory cytokines TNFα and CXCL1 and macrophage content in the plaques, showing that metoprolol has an anti-inflammatory effect. PMID:25105129

  19. Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

    SciTech Connect

    Lee, Eun-Jung; Kim, Jun Won; Yoo, Hyun; Kwak, Woori; Choi, Won Hoon; Cho, Seoae; Choi, Yu Jeong; Lee, Yoon-Jin; Cho, Jaeho

    2015-08-14

    We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm{sup 2} fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. - Highlights: • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33. • Vascular endothelial cells damaged by high-dose radiation secrete IL-33. • Blocking IL-33 suppressed migration of inflammatory cells and cytokine secretion. • IL

  20. Regulation of cytokines by small RNAs during skin inflammation

    PubMed Central

    2010-01-01

    Intercellular signaling by cytokines is a vital feature of the innate immune system. In skin, an inflammatory response is mediated by cytokines and an entwined network of cellular communication between T-cells and epidermal keratinocytes. Dysregulated cytokine production, orchestrated by activated T-cells homing to the skin, is believed to be the main cause of psoriasis, a common inflammatory skin disorder. Cytokines are heavily regulated at the transcriptional level, but emerging evidence suggests that regulatory mechanisms that operate after transcription play a key role in balancing the production of cytokines. Herein, we review the nature of cytokine signaling in psoriasis with particular emphasis on regulation by mRNA destabilizing elements and the potential targeting of cytokine-encoding mRNAs by miRNAs. The proposed linkage between mRNA decay mediated by AU-rich elements and miRNA association is described and discussed as a possible general feature of cytokine regulation in skin. Moreover, we describe the latest attempts to therapeutically target cytokines at the RNA level in psoriasis by exploiting the cellular RNA interference machinery. The applicability of cytokine-encoding mRNAs as future clinical drug targets is evaluated, and advances and obstacles related to topical administration of RNA-based drugs targeting the cytokine circuit in psoriasis are described. PMID:20594301

  1. How does Chinese medicine target cytokine imbalance in rheumatoid arthritis?

    PubMed

    Liu, Jian; Sun, Yue

    2013-11-01

    Rheumatoid arthritis (RA) manifests as an imbalance between pro- and anti-inflammatory cytokines. Cytokine imbalance is suggested to play critical roles in the development of RA. Currently, various treatments for RA, including biological agents such as antibodies against inflammation mediators, or Chinese herbal medicines, intervene the disease by restoring the balance of cytokines. Chinese medicine (CM) can not only suppress the expression of pro-inflammatory cytokines, but also induce the expression of cytokines with anti-inflammatory and immunomodulatory effects. Thus, Chinese medicine can effectively reduce inflammatory cell infiltration into synovial tissue, pannus formation, and degradation of the extracellular matrix surrounding cartilage cells, thereby reducing subchondral bone damage. This paper reviews the changes of cytokine profiling during development of RA and discuss the mechanisms by which Chinese medicine restores the cytokine balance.

  2. Multiple Circulating Cytokines Are Coelevated in Chronic Obstructive Pulmonary Disease.

    PubMed

    Selvarajah, Senthooran; Todd, Ian; Tighe, Patrick J; John, Michelle; Bolton, Charlotte E; Harrison, Timothy; Fairclough, Lucy C

    2016-01-01

    Inflammatory biomarkers, including cytokines, are associated with COPD, but the association of particular circulating cytokines with systemic pathology remains equivocal. To investigate this, we developed a protein microarray system to detect multiple cytokines in small volumes of serum. Fourteen cytokines were measured in serum from never-smokers, ex-smokers, current smokers, and COPD patients (GOLD stages 1-3). Certain individual circulating cytokines (particularly TNFα and IL-1β) were significantly elevated in concentration in the serum of particular COPD patients (and some current/ex-smokers without COPD) and may serve as markers of particularly significant systemic inflammation. However, numerous circulating cytokines were raised such that their combined, but not individual, elevation was significantly associated with severity of disease, and these may be further indicators of, and contributors to, the systemic inflammatory manifestations of COPD. The coelevation of numerous circulating cytokines in COPD is consistent with the insidious development, chronic nature, and systemic comorbidities of the disease. PMID:27524865

  3. Multiple Circulating Cytokines Are Coelevated in Chronic Obstructive Pulmonary Disease.

    PubMed

    Selvarajah, Senthooran; Todd, Ian; Tighe, Patrick J; John, Michelle; Bolton, Charlotte E; Harrison, Timothy; Fairclough, Lucy C

    2016-01-01

    Inflammatory biomarkers, including cytokines, are associated with COPD, but the association of particular circulating cytokines with systemic pathology remains equivocal. To investigate this, we developed a protein microarray system to detect multiple cytokines in small volumes of serum. Fourteen cytokines were measured in serum from never-smokers, ex-smokers, current smokers, and COPD patients (GOLD stages 1-3). Certain individual circulating cytokines (particularly TNFα and IL-1β) were significantly elevated in concentration in the serum of particular COPD patients (and some current/ex-smokers without COPD) and may serve as markers of particularly significant systemic inflammation. However, numerous circulating cytokines were raised such that their combined, but not individual, elevation was significantly associated with severity of disease, and these may be further indicators of, and contributors to, the systemic inflammatory manifestations of COPD. The coelevation of numerous circulating cytokines in COPD is consistent with the insidious development, chronic nature, and systemic comorbidities of the disease.

  4. Multiple Circulating Cytokines Are Coelevated in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Todd, Ian; John, Michelle; Bolton, Charlotte E.; Harrison, Timothy

    2016-01-01

    Inflammatory biomarkers, including cytokines, are associated with COPD, but the association of particular circulating cytokines with systemic pathology remains equivocal. To investigate this, we developed a protein microarray system to detect multiple cytokines in small volumes of serum. Fourteen cytokines were measured in serum from never-smokers, ex-smokers, current smokers, and COPD patients (GOLD stages 1–3). Certain individual circulating cytokines (particularly TNFα and IL-1β) were significantly elevated in concentration in the serum of particular COPD patients (and some current/ex-smokers without COPD) and may serve as markers of particularly significant systemic inflammation. However, numerous circulating cytokines were raised such that their combined, but not individual, elevation was significantly associated with severity of disease, and these may be further indicators of, and contributors to, the systemic inflammatory manifestations of COPD. The coelevation of numerous circulating cytokines in COPD is consistent with the insidious development, chronic nature, and systemic comorbidities of the disease. PMID:27524865

  5. Suppressed cytokine and immunoglobulin secretions by murine splenic lymphocytes infected in vitro with Toxoplasma gondii tachyzoites.

    PubMed

    Guk, S M; Kook, J; Jeon, Y H; Choi, J H; Han, E T; Shin, E H; Chai, J Y

    2005-04-01

    Mechanisms of host immunosuppression after infection with Toxoplasma gondii are unclear. This study was performed to observe cytokine and immunoglobulin secretions by murine splenic lymphocytes infected in vitro with live, nonreplicating (irradiated) RH tachyzoites on stimulation with concanavalin A (Con A) or lipopolysaccharide (LPS). For lymphocyte cultivation, 3 groups were prepared: coculture with live nonirradiated tachyzoites separated by a transwell (group T), live irradiated tachyzoites without a transwell (group R), and no tachyzoites (group C). Compared with group T, groups R and C, on stimulation with Con A, revealed significantly (P < 0.05) lower levels of interleukin-2 (IL-2) and IFN-gamma, but not IL-10. The levels of IgG1, IgG2a, IgG2b, IgG3, IgA, and IgM were also significantly (P < 0.05) lower in groups R and C than in group T after stimulation with LPS. The results suggest that intracellular infection of murine splenic lymphocytes with T. gondii tachyzoites could impair their capacity to produce cytokine and immunoglobulin secretions.

  6. Borrelia burgdorferi Induces the Production and Release of Proinflammatory Cytokines in Canine Synovial Explant Cultures

    PubMed Central

    Straubinger, Reinhard K.; Straubinger, Alix F.; Summers, Brian A.; Erb, Hollis N.; Härter, Luc; Appel, Max J. G.

    1998-01-01

    Canine synovial membrane explants were exposed to high- or low-passage Borrelia burgdorferi for 3, 6, 12, and 24 h. Spirochetes received no treatment, were UV light irradiated for 16 h, or were sonicated prior to addition to synovial explant cultures. In explant tissues, mRNA levels for the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1α (IL-1α), IL-1β, and IL-8 were surveyed semiquantitatively by reverse transcription-PCR. Culture supernatants were examined for numbers of total and motile (i.e., viable) spirochetes, TNF-like and IL-1-like activities, polymorphonuclear neutrophil (PMN) chemotaxis-inducing activities, and IL-8. During exposure to synovial explant tissues, the total number of spirochetes in the supernatants decreased gradually by ∼30%, and the viability also declined. mRNAs for TNF-α, IL-1α, IL-1β, and IL-8 were up-regulated in synovial explant tissues within 3 h after infection with untreated or UV light-irradiated B. burgdorferi, and mRNA levels corresponded to the results obtained with bioassays. During 24 h of coincubation, cultures challenged with untreated or UV light-irradiated spirochetes produced similar levels of TNF-like and IL-1-like activities. In contrast, explant tissues exposed to untreated B. burgdorferi generated significantly higher levels of chemotactic factors after 24 h of incubation than did explant tissues exposed to UV light-treated spirochetes. In identical samples, a specific signal for IL-8 was identified by Western blot analysis. High- and low-passage borreliae did not differ in their abilities to induce proinflammatory cytokines. No difference in cytokine induction between untreated and sonicated high-passage spirochetes was observed, suggesting that fractions of the organism can trigger the production and release of inflammatory mediators. The titration of spirochetes revealed a dose-independent cytokine response, where 103 to 107 B. burgdorferi organisms induced similar TNF

  7. Altered cytokine expression of peripheral blood lymphocytes in polymyositis and dermatomyositis

    PubMed Central

    Aleksza, M; Szegedi, A; Antal-Szalmas, P; Irinyi, B; Gergely, L; Ponyi, A; Hunyadi, J; Sipka, S; Zeher, M; Szegedi, G; Danko, K

    2005-01-01

    Objective: To investigate the intracellular and soluble cytokine levels and T cell subsets in peripheral blood of patients with active and inactive polymyositis and dermatomyositis. Methods: The frequencies of T and B lymphocytes, T helper (Th), and T cytotoxic (Tc) cells and of interferon γ (IFNγ), interleukin (IL)4, and IL10 expression of CD4+ or CD8+ cells were determined by flow cytometry. The concentrations of soluble cytokines were measured with commercial enzyme linked immunosorbent assays. Results: In active dermatomyositis there was a decreased percentage of T (CD3+) lymphocytes and Tc (CD8+) lymphocytes, decreased IFNγ expression of CD4+ and CD8+ cells, but an increase in B and IL4 producing CD4+ lymphocyte frequencies. These prominent changes disappeared in the inactive stage of the disease. In polymyositis no significant change in these lymphocyte subsets or in intracellular cytokine expression could be detected in either the active or the inactive form. The frequency of IL4+/IFNγ+ Th cells was calculated and a significantly increased Th2/Th1 frequency was found in active dermatomyositis, and a decreased frequency in inactive dermatomyositis, compared with the control population. Conclusions: There appears to be a difference between polymyositis and dermatomyositis in the level of peripheral blood lymphocytes and their intracellular cytokine content. These findings provide further evidence for a difference in the pathogenesis of polymyositis and dermatomyositis. PMID:15829578

  8. Revealing cytokine-induced changes in the extracellular matrix with secondary ion mass spectrometry

    PubMed Central

    Taylor, Adam J; Ratner, Buddy D; Buttery, Lee DK; Alexander, Morgan R

    2015-01-01

    Cell-secreted matrices (CSMs), where extracellular matrix (ECM) deposited by monolayer cell cultures are decellularized, have been increasingly used to produce surfaces that may be reseeded with cells. Such surfaces are useful to help us understand cell-ECM interactions in a microenvironment closer to the in vivo situation than synthetic substrates with adsorbed proteins. We describe the production of CSMs from mouse primary osteoblasts (mPObs) exposed to cytokine challenge during matrix secretion, mimicking in vivo inflammatory environments. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) data revealed that CSMs with cytokine challenge at day 7 or day 12 of culture can be chemically distinguished from one another and from untreated CSM using multivariate analysis. Comparison of the differences with reference spectra from adsorbed protein mixtures points towards cytokine challenge resulting in a decrease in collagen content. This is supported by immunocytochemical and histological staining, demonstrating a 44% loss of collagen mass and a 32% loss in collagen I coverage. CSM surfaces demonstrate greater cell adhesion than adsorbed ECM proteins. When mPObs were reseeded onto cytokine-challenged CSMs they exhibited reduced adhesion and elongated morphology compared to untreated CSMs. Such changes may direct subsequent cell fate and function and provide insights into pathological responses at sites of inflammation. PMID:25523877

  9. Solution assembly of cytokine receptor ectodomain complexes

    SciTech Connect

    Wu, Zining; Ciardelli, T.L.; Johnson, K.W.

    1995-09-01

    For the majority of single transmembrane-spanning cell surface receptors, signal transmission across the lipid bilayer barrier involves several discrete components of molecular recognition. The interaction between ligand and the extracellular segment of its cognate receptor (ectodomain) initiates either homomeric or heteromeric association of receptor subunits. Specific recognition among these subunits may then occur between ectodomain regions, within the membrane by interhelical contact or inside the cell between cytoplasmic domains. Any or all of these interactions may contribute to the stability of the signaling complex. It is the characteristics of ligand binding by the ectodomains of these receptors that controls the heteromeric or homomeric nature and the stoichiometry of the complex. Cytokines and their receptors belong to a growing family of macromolecular systems that exhibit these functional features and share many structural similarities as well. Interleukin-2 is a multifunctional cytokine that represents, perhaps, the most complex example to date of ligand recognition among the hematopoietin receptor family. It is the cooperative binding of IL-2 by all three proteins on the surface of activated T-lymphocytes, however, that ultimately results in crosslinking of the {beta}- and {gamma}-subunits and signaling via association of their cytoplasmic domains. Although the high-affinity IL-2R functions as a heterotrimer, heterodimers of the receptor subunits are also physiologically important. The {alpha}/{beta} heterodimer or {open_quotes}pseudo-high affinity{close_quotes} receptor captures IL-2 as a preformed cell surface complex while the {beta}/{gamma} intermediate affinity site exists, in the absence of the {alpha} subunit, on the majority of natural killer cells. We have begun to study stable complexes of cytokine receptor ectodomains of defined composition and that mimic the ligand binding characteristics of the equivalent cell surface receptor sites.

  10. Forecasting Cytokine Storms with New Predictive Biomarkers.

    PubMed

    Rouce, Rayne H; Heslop, Helen E

    2016-06-01

    T cells genetically modified with CD19 chimeric antigen receptors have produced impressive clinical responses in patients with refractory B-cell malignancies, but therapeutic responses are often accompanied by cytokine release syndrome (CRS), which can cause significant morbidity and mortality. Teachey and colleagues have identified predictive biomarkers for this complication that may allow testing of earlier intervention with agents such as the IL6 receptor blocker tocilizumab to evaluate whether CRS can be ameliorated without jeopardizing clinical responses. Cancer Discov; 6(6); 579-80. ©2016 AACR.See related article by Teachey et al., p. 664. PMID:27261481

  11. Cytokine production capacity in depression and anxiety

    PubMed Central

    Vogelzangs, N; de Jonge, P; Smit, J H; Bahn, S; Penninx, B W

    2016-01-01

    Recent studies have suggested that immune function may be dysregulated in persons with depressive and anxiety disorders. Few studies examined the expression of cytokines in response to ex vivo stimulation of blood by lipopolysaccharide (LPS) to study the innate production capacity of cytokines in depression and anxiety. To investigate this, baseline data from the Netherlands Study of Depression and Anxiety (NESDA) were used, including persons (18–65 years; 66% women) with current (that is, past month; N=591) or remitted (N=354) DSM-IV depressive or anxiety disorders and healthy controls (N=297). Depressive and anxiety symptoms were measured by means of the Inventory of Depressive Symptomatology (IDS) and the Beck Anxiety Inventory (BAI). Using Multi-Analyte Profiling technology, plasma levels of 13 cytokines were assayed after whole blood stimulation by addition of LPS. Basal plasma levels of C-reactive protein, interleukin-6 and tumor necrosis factor-α were also available. A basal and a LPS summary index were created. Results show that LPS-stimulated inflammation was associated with increased odds of current depressive/anxiety disorders (odds ratio (OR)=1.28, P=0.009), as was the case for basal inflammation (OR=1.28, P=0.001). These associations were no longer significant after adjustment for lifestyle and health (OR=1.13, P=0.21; OR=1.07, P=0.45, respectively). After adjustment for lifestyle and health, interleukin-8 was associated with both remitted (OR=1.25, P=0.02) and current (OR=1.28, P=0.005) disorders. In addition, LPS-stimulated inflammation was associated with more severe depressive (β=0.129, P<0.001) and anxiety (β=0.165, P<0.001) symptoms, as was basal inflammation. Unlike basal inflammation, LPS-stimulated inflammation was still associated with (anxiety) symptom severity after adjustment for lifestyle and health (IDS: IL-8, MCP-1, MMP2; BAI: LPS index, IL-6, IL-8, IL-10, IL-18, MCP-1, MMP2, TNF-β). To conclude, lifestyle and health factors may

  12. Infarction-induced cytokines cause local depletion of tyrosine hydroxylase in cardiac sympathetic nerves

    PubMed Central

    Parrish, Diana C.; Alston, Eric N.; Rohrer, Hermann; Nkadi, Paul; Woodward, William R.; Schütz, Günther; Habecker, Beth A.

    2010-01-01

    Myocardial infarction causes heterogeneity of noradrenergic transmission that contributes to the development of ventricular arrhythmias and sudden cardiac death. Ischemia-induced alterations in sympathetic transmission include regional variations in cardiac norepinephrine (NE) and in tyrosine hydroxylase, the rate-limiting enzyme in NE synthesis. Inflammatory cytokines that act through gp130 are elevated in the heart after myocardial infarction. These cytokines decrease expression of tyrosine hydroxylase in sympathetic neurons, and indirect evidence suggests they contribute to the local depletion of tyrosine hydroxylase in the damaged left ventricle. However, gp130 cytokines are also important for the survival of cardiac myocytes following damage to the heart. To examine the effect of cytokines on tyrosine hydroxylase and NE content in cardiac nerves we used gp130DBH-Cre/lox mice, which have a deletion of the gp130 receptor in neurons expressing dopamine beta hydroxylase. The absence of neuronal gp130 prevented the loss of tyrosine hydroxylase in cardiac sympathetic nerves innervating the left ventricle one week after ischemia-reperfusion. Surprisingly, restoring tyrosine hydroxylase in the damaged ventricle did not return neuronal NE content to normal levels. NE uptake into cardiac nerves was significantly lower in gp130 KO mice, contributing to the lack of neuronal NE stores. There were no significant differences in left ventricular peak systolic pressure, dP/dtMAX, or dP/dtMIN between the two genotypes after myocardial infarction, but ganglionic blockade revealed differences in autonomic tone between the genotypes. Stimulating the heart with dobutamine or releasing endogenous NE with tyramine generated similar responses in both genotypes. Thus, the removal of gp130 from sympathetic neurons prevents the post-infarct depletion of TH in the left ventricle, but does not alter NE content or cardiac function. PMID:19880537

  13. [Peculiarities of cytokine status in patients with vitiligo and stress in anamnesis].

    PubMed

    Tsiskarishvili, N V; Katsitadze, A; Tsiskarishvili, N I; Chitanava, L

    2014-10-01

    The aim of our study was to investigate the content of some proinflammatory cytokines (IL-2, IL-6) in the serum of patients with vitiligo and stress in anamnesis. Cytokine levels in serum were measured in 50 patients with vitiligo (20 men and 30 women aged from 18 to 65 years old.) All the patients were divided according to anamnesis (27 patients with stress in anamnesis and 23 patients, where the onset of the disease was not preceded by stress). Patients of both groups were similar in terms of shape (according to T. Fitzpatrick classification) and in terms of the dermatosis stages. Concomitant autoimmune or inflammatory diseases of the skin in our vitiligo patients were not observed. The cytokines in the blood serum of vitiligo patients were determined by ELISA using the corresponding monoclonal antibodies. Student's t-test was used for evaluation of statistical significance of received results (p < 0.05 was considered as a statistically significant). Content of IL-2 in the serum of patients with vitiligo, in which stress was not preceded dermatosis, was significantly higher than that in healthy individuals (25,5 ± 7,6 vs 10,5 ± 3,6 pg/ml, p < 0,05). But the same parameter in patients with stress in anamnesis was significantly lower than those in healthy individuals (3,5 ± 1,5 vs 10,5 ± 3,6 pg/l, p < 0.05). Changes in the content of IL-6 in the serum of vitiligo patients was a similar to changes in IL-2 content, and the most significant this indicator was in patients with generalized and progressive stage of the disease. Data on increased concentrations of IL-6 agree with the majority of studies conducted earlier. For a complete analysis of our results on the reduction of the cytokines (IL-2, IL-6) content in patients with a stress in anamnesis, that will allow to identify the most effective ways to treat patients with this pathology (including their cytokine status), further research is necessary.

  14. Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications

    PubMed Central

    Felger, Jennifer C.; Lotrich, Francis E.

    2013-01-01

    Mounting evidence indicates that inflammatory cytokines contribute to the development of depression in both medically ill and medically healthy individuals. Cytokines are important for development and normal brain function, and have the ability to influence neurocircuitry and neurotransmitter systems to produce behavioral alterations. Acutely, inflammatory cytokine administration or activation of the innate immune system produces adaptive behavioral responses that promote conservation of energy to combat infection or recovery from injury. However, chronic exposure to elevated inflammatory cytokines and persistent alterations in neurotransmitter systems can lead to neuropsychiatric disorders and depression. Mechanisms of cytokine behavioral effects involve activation of inflammatory signaling pathways in the brain that results in changes in monoamine, glutamate, and neuropeptide systems, and decreases in growth factors, e.g. brain derived neurotrophic factor. Furthermore, inflammatory cytokines may serve as mediators of both environmental (e.g. childhood trauma, obesity, stress, and poor sleep) and genetic (functional gene polymorphisms) factors that contribute to depression’s development. This review explores the idea that specific gene polymorphisms and neurotransmitter systems can confer protection from or vulnerability to specific symptom dimensions of cytokine-related depression. Additionally, potential therapeutic strategies that target inflammatory cytokine signaling or the consequences of cytokines on neurotransmitter systems in the brain to prevent or reverse cytokine effects on behavior are discussed. PMID:23644052

  15. Postharvest quality of dragon fruit (Hylocereus spp.) after x-ray irradiation quarantine treatment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The quality of three dragon fruit clones (Hylocereus sp.) was determined following x-ray irradiation for disinfestation of quarantine pests. Fruit were treated with irradiation doses of 0, 200, 400, 600, or 800 Gy and stored for 12 days at 10 °C. Irradiation did not affect soluble solids content, ti...

  16. Cytokine and anti-cytokine therapies in prevention or treatment of fibrosis in IBD.

    PubMed

    Jacob, Noam; Targan, Stephan R; Shih, David Q

    2016-08-01

    The frequency of fibrosing Crohn's disease (CD) is significant, with approximately 40% of CD patients with ileal disease developing clinically apparent strictures throughout their lifetime. Although strictures may be subdivided into fibrotic, inflammatory, or mixed forms, despite immunosuppressive therapy in CD patients in the form of steroids or immunomodulators, the frequency of fibrostenosing complications has still remained significant. A vast number of genetic and epigenetic variables are thought to contribute to fibrostenosing disease, including those that affect cytokine biology, and therefore highlight the complexity of disease, but also shed light on targetable pathways. Exclusively targeting fibrosis may be difficult, however, because of the relatively slow evolution of fibrosis in CD, and the potential adverse effects of inhibiting pathways involved in tissue repair and mucosal healing. Acknowledging these caveats, cytokine-targeted therapy has become the mainstay of treatment for many inflammatory conditions and is being evaluated for fibrotic disorders. The question of whether anti-cytokine therapy will prove useful for intestinal fibrosis is, therefore, acutely relevant. This review will highlight some of the current therapeutics targeting cytokines involved in fibrosis. PMID:27536363

  17. Anti-cytokine autoantibodies in autoimmune diseases

    PubMed Central

    Cappellano, Giuseppe; Orilieri, Elisabetta; Woldetsadik, Abiy D; Boggio, Elena; Soluri, Maria F; Comi, Cristoforo; Sblattero, Daniele; Chiocchetti, Annalisa; Dianzani, Umberto

    2012-01-01

    An overview of the current literature is showing that autoantibodies (AutoAbs) against cytokines are produced in several pathological conditions, including autoimmune diseases, but can also be detected in healthy individuals. In autoimmune diseases, these AutoAbs may also be prognostic markers, either negative (such as AutoAbs to IL-8 and IL-1α in rheumatoid arthritis) or positive (such as AutoAbs to IL-6 in systemic sclerosis and those to osteopontin in rheumatoid arthritis). They may have neutralizing activity and influence the course of the physiological and pathological immune responses. High levels of AutoAbs against cytokines may even lead to immunodeficiency, such as those to IL-17 in autoimmune polyendocrine syndrome type I or those to IFN-γ in mycobacterial infections. Their role in human therapy may be exploited not only through passive immunization but also through vaccination, which may improve the costs for long lasting treatments of autoimmune diseases. Detection and quantification of these AutoAbs can be profoundly influenced by the technique used and standardization of these methods is needed to increase the value of their analysis. PMID:23885320

  18. Education of hyporesponsive NK cells by cytokines.

    PubMed

    Juelke, Kerstin; Killig, Monica; Thiel, Andreas; Dong, Jun; Romagnani, Chiara

    2009-09-01

    NK-cell tolerance to self is mediated via engagement of inhibitory receptors by cognate MHC molecules. This event is critical for NK-cell education to achieve functional competence. Thus, NK cells expressing self-MHC-specific inhibitory receptors are responsive to activating stimuli while those lacking such receptors are hyporesponsive. Nevertheless, the mechanisms underlying NK-cell education are still poorly understood. Here, we show that after stimulation with cytokines, hyporesponsive NK cells acquire stable expression of killer Ig-like receptors (KIR) as reflected by DNA hypomethylation of their KIR locus. Remarkably, only hyporesponsive NK cells that acquire KIR in the presence of their cognate MHC molecule gain functional competence and this process can occur in the absence of any accessory cells. Acquisition of competence does not result in autoreactivity, since acquired KIR are functional and therefore able to inhibit NK-cell cytotoxicity. Our data demonstrate that competent NK cells can be generated by cytokine stimulation, suggesting that NK-cell education might not only be an early event which takes place during NK-cell development but might also occur in the periphery during an immune response.

  19. Cytokines as therapeutic targets in SLE.

    PubMed

    Rönnblom, Lars; Elkon, Keith B

    2010-06-01

    Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease involving most immune cells. Studies in both experimental animal models of lupus and patients with SLE have revealed a number of cytokine pathways that are important in the disease process. Among these are B-cell activating factor, which promotes B-cell survival and autoantibody production, interferon-alpha, which acts as an immune adjuvant, and tumor necrosis factor, which contributes to organ inflammation. This knowledge, in combination with the successful use of anti-TNF treatment in rheumatoid arthritis, has spurred the development of several biologic agents targeting different cytokines or their receptors in SLE. Consequently, many trials of anticytokine therapies for SLE are underway. Although most of these trials are small or in early phases, the results of some large studies have also been reported. In this Review, we discuss the rationale for anticytokine therapies in SLE and review agents currently in use, and those being developed and tested experimentally. We present the results from published trials and discuss the tentative conclusions that can be drawn regarding the efficacy of the new agents. Finally, we provide suggestions for the future of treatment for SLE, including new therapeutic strategies.

  20. Localization of cytokines in cholesteatoma tissue.

    PubMed

    Marenda, S A; Aufdemorte, T B

    1995-03-01

    Acquired cholesteatoma is associated with an intense inflammatory reaction with resultant tissue and bone destruction. Cytokines are molecules released by inflammatory cells at the site of infection and are potent mediators of inflammation and the immune response. Five cytokines, tumor necrosis factor-alpha, transforming growth factor-beta 1 and 2, and interleukin-1 and 6, were immunolocalized in human cholesteatoma epithelium and subepithelial stroma, with greater intensity of staining compared with noninflamed external auditory canal skin. Increased interleukin-6 activity in cholesteatoma epithelium and stroma correlated significantly with the presence of ossicular and bony erosion and granulation tissue noted intraoperatively. Transforming growth factor-beta 2 activity in cholesteatoma epithelium correlated significantly with bony erosion at surgery. Additionally, transforming growth factor-beta 1 activity in cholesteatoma epithelium correlated significantly with increased length of disease. Tumor necrosis factor-alpha, interleukin-1, and interleukin-6 appear to be involved in the inflammation and resultant remodeling associated with cholesteatoma. We hypothesized a protective function of transforming growth factor-beta 1 and 2 in the presence of cholesteatoma. The antiinflammatory and osteoclast and keratinocyte inhibitory actions of the transforming growth factor-beta s could potentially slow the proliferation and resultant tissue destructiveness associated with cholesteatoma.

  1. Hepatitis-related hepatocellular carcinoma: Insights into cytokine gene polymorphisms

    PubMed Central

    Dondeti, Mahmoud Fathy; El-Maadawy, Eman Anwar; Talaat, Roba Mohamed

    2016-01-01

    Hepatocellular carcinoma (HCC) is a primary liver cancer, which is one of the most prevalent cancers among humans. Many factors are involved in the liver carcinogenesis as lifestyle and environmental factors. Hepatitis virus infections are now recognized as the chief etiology of HCC; however, the precise mechanism is still enigmatic till now. The inflammation triggered by the cytokine-mediated immune response, was reported to be the closest factor of HCC development. Cytokines are immunoregulatory proteins produced by immune cells, functioning as orchestrators of the immune response. Genes of cytokines and their receptors are known to be polymorphic, which give rise to variations in their genes. These variations have a great impact on the expression levels of the secreted cytokines. Therefore, cytokine gene polymorphisms are involved in the molecular mechanisms of several diseases. This piece of work aims to shed much light on the role of cytokine gene polymorphisms as genetic host factor in hepatitis related HCC. PMID:27570418

  2. Hepatitis-related hepatocellular carcinoma: Insights into cytokine gene polymorphisms.

    PubMed

    Dondeti, Mahmoud Fathy; El-Maadawy, Eman Anwar; Talaat, Roba Mohamed

    2016-08-14

    Hepatocellular carcinoma (HCC) is a primary liver cancer, which is one of the most prevalent cancers among humans. Many factors are involved in the liver carcinogenesis as lifestyle and environmental factors. Hepatitis virus infections are now recognized as the chief etiology of HCC; however, the precise mechanism is still enigmatic till now. The inflammation triggered by the cytokine-mediated immune response, was reported to be the closest factor of HCC development. Cytokines are immunoregulatory proteins produced by immune cells, functioning as orchestrators of the immune response. Genes of cytokines and their receptors are known to be polymorphic, which give rise to variations in their genes. These variations have a great impact on the expression levels of the secreted cytokines. Therefore, cytokine gene polymorphisms are involved in the molecular mechanisms of several diseases. This piece of work aims to shed much light on the role of cytokine gene polymorphisms as genetic host factor in hepatitis related HCC. PMID:27570418

  3. THE BACTERICIDAL PROPERTIES OF ULTRAVIOLET IRRADIATED LIPIDS OF THE SKIN.

    PubMed

    Stevens, F A

    1937-01-01

    The lipids of the skin after exposure to ultraviolet light are bactericidal. Since other fats and oils which have been irradiated are bactericidal on account of the active oxygen released on contact with bacteria, the mechanism of the bactericidal action of irradiated lipids of the skin must be similar because the lipids have the properties of other irradiated fats and oils. Irradiation increases the active oxygen content of dried skin markedly but little increase occurs if the lipids have been extracted. Although the normal lipids extracted from the skin contain some active oxygen, the active oxygen content is much increased by irradiation. The vapor from lipids exposed to ultraviolet light fogs photographic plates intensely and retards the growth of hemolytic streptococcus. When emulsified in salt solution, the irradiated lipids kill hemolytic streptococcus promptly in comparison with emulsions of lipid which have not been irradiated. The addition of neutralized cysteine HCl to the emulsions of the lipid, normal or irradiated, prolongs the life of bacteria suspended in the emulsions. This protective effect is due to the reducing action of the cysteine, Normal non-irradiated lipid, extracted from the skin under conditions which permit oxidation, kills bacteria more quickly than that used in these experiments, where precautions were taken to prevent oxidation (unpublished data). Even though these precautions were taken some oxidation occurred, because lipid so extracted contained some active oxygen, and bacteria lived longer in emulsions of this normal lipid if cysteine were added.

  4. Effects of icariin on cytokine-induced ankylosing spondylitis with fibroblastic osteogenesis and its molecular mechanism.

    PubMed

    Jia, Chunrong; Liu, Hongxiao; Li, Min; Wu, Zhikui; Feng, Xinghua

    2014-01-01

    The aim of this study is to explore the effects of icariin on cytokine induced ankylosing spondylitis fibroblast osteogenesis type expression and its molecular mechanism. The normal fibroblasts were collected as normal control group, and the fibroblasts of hip joint capsule of AS patients were collected, which were respectively added in fetal bovine serum (group AS), fetal bovine serum and cytokines (BMP-2+TGF-beta 1) (group AS), and cell factor solution (icariin group), and observed of the osteogenic expression of fibroblast, to evaluate the impact of Icariin on it. The ALP activity, the content of collagen, osteocalcin content and cbfa1mRNA and OCmRNA of fibroblast of AS group increased compared to the normal control group and AS control group (P < 0.01), indicating that icariin can significantly inhibit the above changes (P < 0.01). Icariin can inhibit fibroblast further osteogenic differentiation through inhibiting the effect of cytokines on the fibroblast osteogenesis type markers and osteogenic gene expression and osteogenic differentiation.

  5. Triggering Dectin-1-Pathway Alone Is Not Sufficient to Induce Cytokine Production by Murine Macrophages

    PubMed Central

    Walachowski, Sarah

    2016-01-01

    β-glucans (BG) are abundant polysaccharides of the Saccharomyces cerevisiae cell wall (Sc CW), an industry byproduct. They have immuno-stimulatory properties upon engagement of dectin-1 (Clec7a), their main receptor on particular immune cells, and they actually become of great interest because of their preventive or therapeutic potentials. Zymosan, a crude extract of Sc CW was studied as a prototypic BG, despite its miscellaneous PAMPs content. Here, we examined the response of murine wild type or Clec7a-/- bone marrow-derived macrophages (BMDM) to products with increasing BG content (15, 65 or 75%) and compared their effects with those of other dectin-1 ligands. The enrichment process removed TLR ligands while preserving dectin-1 activity. The most enriched extracts have very low NFκB activity and triggered low amounts of cytokine production in contrast with crude products like zymosan and BG15. Furthermore, MyD88-/- BMDM did not produce TNFα in response to crude Sc CW extracts, whereas their response to BG-enriched extracts was unaffected, suggesting that BG alone are not able to initiate cytokine secretion. Although Sc CW-derived BG stimulated the late and strong expression of Csf2 in a dectin-1-dependent manner, they remain poor inducers of chemokine and cytokine production in murine macrophages. PMID:26840954

  6. Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines

    SciTech Connect

    Okunieff, Paul . E-mail: paul_okunieff@urmc.rochester.edu; Xu Jianhua; Hu Dongping; Liu Weimin; Zhang Lurong; Morrow, Gary; Pentland, Alice; Ryan, Julie L.; Ding, Ivan M.D.

    2006-07-01

    Purpose: To determine whether curcumin ameliorates acute and chronic radiation skin toxicity and to examine the expression of inflammatory cytokines (interleukin [IL]-1, IL-6, IL-18, IL-1Ra, tumor necrosis factor [TNF]-{alpha}, and lymphotoxin-{beta}) or fibrogenic cytokines (transforming growth factor [TGF]-{beta}) during the same acute and chronic phases. Methods and Materials: Curcumin was given intragastrically or intraperitoneally to C3H/HeN mice either: 5 days before radiation; 5 days after radiation; or both 5 days before and 5 days after radiation. The cutaneous damage was assessed at 15-21 days (acute) and 90 days (chronic) after a single 50 Gy radiation dose was given to the hind leg. Skin and muscle tissues were collected for measurement of cytokine mRNA. Results: Curcumin, administered before or after radiation, markedly reduced acute and chronic skin toxicity in mice (p < 0.05). Additionally, curcumin significantly decreased mRNA expression of early responding cytokines (IL-1 IL-6, IL-18, TNF-{alpha}, and lymphotoxin-{beta}) and the fibrogenic cytokine, TGF-{beta}, in cutaneous tissues at 21 days postradiation. Conclusion: Curcumin has a protective effect on radiation-induced cutaneous damage in mice, which is characterized by a downregulation of both inflammatory and fibrogenic cytokines in irradiated skin and muscle, particularly in the early phase after radiation. These results may provide the molecular basis for the application of curcumin in clinical radiation therapy.

  7. 3-aminobenzamide, a poly (ADP ribose) polymerase inhibitor, enhances wound healing in whole body gamma irradiated model.

    PubMed

    El-Hamoly, Tarek; El-Denshary, Ezzeddin S; Saad, Shokry Mohamed; El-Ghazaly, Mona A

    2015-09-01

    The custom use of radiotherapy was found to participate in the development of chronic unhealed wounds. In general, exposure to gamma radiation stimulates the production of reactive oxygen species (ROS) that eventually leads to damaging effect. Conversely, overexpression of a nuclear poly (ADP-ribose) polymerase enzyme (PARP) after oxidative insult extremely brings about cellular injury due to excessive consumption of NAD and ATP. Here, we dedicated our study to investigate the role of 3-aminobenzamide (3-AB), a PARP inhibitor, on pregamma irradiated wounds. Two full-thickness (6 mm diameter) wounds were created on the dorsum of Swiss albino mouse. The progression of wound contraction was monitored by capturing daily photo images. Exposure to gamma radiation (6Gy) exacerbated the normal healing of excisional wounds. Remarkably, topical application of 3-AB cream (50 µM) revealed a marked acceleration in the rate of wound contraction. Likewise, PARP inhibition ameliorated the unbalanced oxidative/nitrosative status of granulated skin tissues. Such effect was significantly revealed by the correction of the reduced antioxidant capacity and the enhanced lipid peroxidation, hydrogen peroxide, and myeloperoxidase contents. Moreover, application of 3-AB modified the cutaneous nitrite content throughout healing process. Conversely, the expressions of pro-inflammatory cytokines were down-regulated by PARP inhibition. The mitochondrial ATP content showed a lower consumption rate on 3-AB-treated wound bed as well. In parallel, the mRNA expressions of Sirt-1 and acyl-COA oxidase-2 (ACOX-2) were up-regulated; whom functions control the mitochondrial ATP synthesis and lipid metabolism. The current data suggested that inhibition of PARP-1 enzyme may accelerate the delayed wound healing in whole body gamma irradiated mice by early modifying the oxidative stress as well as the inflammatory response. PMID:26080614

  8. Effect of gamma irradiation on the physicochemical properties of alkali-extracted rice starch

    NASA Astrophysics Data System (ADS)

    Ashwar, Bilal Ahmad; Shah, Asima; Gani, Asir; Rather, Sajad Ahmad; Wani, Sajad Mohd.; Wani, Idrees Ahmed; Masoodi, Farooq Ahmad; Gani, Adil

    2014-06-01

    Starches isolated from two newly released rice varieties (K-322 and K-448) were subject to irradiation at 0, 5, 10, and 20 kGy doses. Comparative study between native (not irradiated) and irradiated starch samples was carried out to evaluate the changes in physicochemical, morphological and pasting properties due to gamma irradiation. Significant decrease was found in apparent amylose content, pH, swelling power, syneresis, and pasting properties, whereas carboxyl content, water absorption capacity, and transmittance were found to increase with the increase in irradiation dose. Granule morphology of native and irradiated starches under scanning electron microscope revealed that granules were polygonal or irregular in shape. The starch granules were somewhat deformed by gamma irradiation. X-ray diffraction pattern showed A type of pattern in native as well as irradiated starches.

  9. Thermal annealing as a method to predict results of high temperature irradiation embrittlement

    NASA Astrophysics Data System (ADS)

    Kryukov, A.; Debarberis, L.; Hähner, P.; Gillemot, F.; Oszvald, F.

    2013-01-01

    In order to assess the validity of post-irradiation annealing as a method to predict results of high temperature irradiation a new analysis of experimental data has been performed revealing the combined influence of annealing temperature and impurities content on residual embrittlement after annealing. For 2CrMoV (WWER-440 reactor pressure vessel) steel with low contents of copper and phosphorus, the comparison of two embrittlement dependencies has been done: on irradiation temperature and post-irradiation annealing temperature. It is demonstrated that data for both the transition temperature shift after irradiation, ΔTk, and the residual transition temperature shift after post-irradiation annealing, ΔTres, fall within the same scatter band. A similarly close correlation is observed by comparison of yield strength increases after irradiation and after post-irradiation annealing.

  10. Cytokine Patterns and Endotypes in Acute and Chronic Rhinosinusitis.

    PubMed

    Scheckenbach, Kathrin; Wagenmann, Martin

    2016-01-01

    Since rhinosinusitis is an inflammatory disease, cytokines as key regulators of inflammation play a central role in its pathophysiology. In acute rhinosinusitis, several proinflammatory cytokines of different types have been identified. Initial information about the involvement of the inflammasome in rhinosinusitis has been gained, but this area remains open for more detailed research. Although it has been accepted now that chronic rhinosinusitis (CRS) needs to be differentiated into CRS with and without nasal polyps, it has become clear that this distinction is insufficient to clearly define subgroups with uniform pathophysiology and cytokine patterns. While Th1-cytokines are mostly found in CRSsNP and Th2 cytokines in CRSwNP, there is a substantial overlap, and several other cytokines have also been detected. Attempts to identify CRS endotypes based on cytokines are ongoing but not yet generally accepted. Despite the central role of cytokines in rhinosinusitis, no specific cytokine-targeted therapies are currently available, and only very few studies have specifically addressed the effects of such biologicals in rhinosinusitis.

  11. Low and moderate doses of ionizing radiation up to 2 Gy modulate transmigration and chemotaxis of activated macrophages, provoke an anti-inflammatory cytokine milieu, but do not impact upon viability and phagocytic function.

    PubMed

    Wunderlich, R; Ernst, A; Rödel, F; Fietkau, R; Ott, O; Lauber, K; Frey, B; Gaipl, U S

    2015-01-01

    Benign painful and inflammatory diseases have been treated for decades with low/moderate doses of ionizing radiation (LD-X-irradiation). Tissue macrophages regulate initiation and resolution of inflammation by the secretion of cytokines and by acting as professional phagocytes. Having these pivotal functions, we were interested in how activated macrophages are modulated by LD-X-irradiation, also with regard to radiation protection issues and carcinogenesis. We set up an ex-vivo model in which lipopolysaccharide pre-activated peritoneal macrophages (pMΦ) of radiosensitive BALB/c mice, mimicking activated macrophages under inflammatory conditions, were exposed to X-irradiation from 0·01 Gy up to 2 Gy. Afterwards, the viability of the pMΦ, their transmigration and chemotaxis, the phagocytic behaviour, the secretion of inflammatory cytokines and underlying signalling pathways were determined. Exposure of pMΦ up to a single dose of 2 Gy did not influence their viability and phagocytic function, an important fact regarding radiation protection. However, significantly reduced migration, but increased chemotaxis of pMΦ after exposure to 0·1 or 0·5 Gy, was detected. Both might relate to the resolution of inflammation. Cytokine analyses revealed that, in particular, the moderate dose of 0·5 Gy applied in low-dose radiotherapy for inflammatory diseases results in an anti-inflammatory cytokine microenvironment of pMΦ, as the secretion of the proinflammatory cytokine interleukin (IL)-1β was reduced and that of the anti-inflammatory cytokine transforming growth factor (TGF)-β increased. Further, the reduced secretion of IL-1β correlated with reduced nuclear translocation of nuclear factor (NF)-κB p65, starting at exposure of pMΦ to 0·5 Gy of X-irradiation. We conclude that inflammation is modulated by LD-X-irradiation via changing the inflammatory phenotype of macrophages.

  12. Safety evaluation of irradiated foods in China: A condensed report

    SciTech Connect

    Yin, D. )

    1989-03-01

    Eight trials, with 439 human volunteers who consumed irradiated foods including rice, potatoes, mushrooms, peanuts, and Chinese sausages, as well as diets composed of multiple irradiated foods (irradiated at dosages of 0.2 to 8 kGy) that accounted for 60-66% of the entire diet, were carried out for 2-3 months according to a unified protocol. No adverse effects on body weight, blood pressure, ECG, hematology, blood enzyme activities, serum lipids or blood or urine 17-hydroxycortisol contents and no chromosomal aberration of peripheral blood lymphocytes were found. It is especially worthwhile to note that there was no change in the polyploidy after consumption of irradiated diets. On the basis of these results and a comprehensive analysis of the physical and chemical characteristics of irradiated foods, temporary hygienic standards for irradiated rice, potatoes, onions, garlic, Chinese sausages, peanuts, and mushrooms were promulgated by the Chinese Ministry of Public Health.

  13. Inflammatory cytokines in pediatric obstructive sleep apnea

    PubMed Central

    Huang, Yu-Shu; Guilleminault, Christian; Hwang, Fang-Ming; Cheng, Chuan; Lin, Cheng-Hui; Li, Hsueh-Yu; Lee, Li-Ang

    2016-01-01

    Abstract Pediatric obstructive sleep apnea (OSA) is associated with chronic systemic inflammation and with cognitive impairments. This study aimed to investigate the status of proinflammatory cytokines, particularly interleukin 17 (IL-17) and interleukin 23 (IL-23) and cognition in pediatric OSA. Controls and OSA children participated in the study. Exclusion criteria were adenotonsillectomy, heart, neurological and severe psychiatric diseases, craniofacial syndromes, and obesity. Polysomnogram was followed by serum testing for inflammatory markers and neurocognitive tests such as continuous performance task (CPT) and Wisconsin card sorting test, questionnaires, analyses of plasma high-sensitivity C-reactive protein (HS-CRP), tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1), interleukin 6 (IL-6), IL-17, and IL-23. Seventy-nine, 4 to 12-year-old subjects in 2 groups ended the study: 47 nonobese OSA children (mean age = 7.84 ± 0.56 years, body mass index [BMI] = 16.95 ± 0.47 kg/m2, BMI z-score = 0.15 ± 0.21, and mean apnea–hypopnea index [AHI] = 9.13 ± 1.67 events/h) and 32 healthy control children (mean age = 7.02 ± 0.65 years, with BMI = 16.55 ± 0.58 kg/m2, BMI z-score = −0.12 ± 0.27, and mean AHI = 0.41 ± 0.07 event/h) were enrolled. Serum cytokine analyses showed significantly higher levels of HS-CRP, IL-17, and IL-23 in OSA children (P = 0.002, P = 0.024, and P = 0.047). Regression test showed significant influence of HS-CRP, TNF-α, IL-6, IL-17, and specifically IL-23, with the continuous performance test and Wisconsin card sorting test. OSA children have abnormal levels of IL-17, an interleukin related to T helper 17 cells, a T helper cell involved in development of autoimmunity and inflammation. This high expression level may contribute to the complications of pediatric OSA; we also found a significant influence of inflammatory cytokines, particularly IL-23, on abnormal neurocognitive testing. PMID

  14. [Cytokine regulation of immune response in patients with chronic hepatitis C].

    PubMed

    Korochkina, O V; Sobchak, D M; Mikhaĭlova, E A; Monakova, E A

    2003-01-01

    To evaluate content of interleukines (IL-1, IL-2, IL-4 and IL-6) and tumor necrosis factor (TNF) in patients with chronic hepatitis C (CHC), 72 CHC patients (37 males and 35 females, mean age 37.2 +/- 4.8 years) were examined. The control group consisted of 20 healthy donors (mean age 25.5 +/- 2.3 years). It was found that low levels of IL-1, IL-2, IL-6, TNF evidence for weak immune response which means long-term virus circulation and active replication. The highest concentrations of the above cytokines correspond to low replicative activity while high IL-4 levels point to active virus replication. IL-1, IL-2, IL-4, IL-6, TNF were high in patients with high cytolysis. Cytokine regulation of immune response can be used for assessment of the effectiveness of antiviral and immunocorrective therapy.

  15. Low-level laser therapy on skeletal muscle inflammation: evaluation of irradiation parameters

    NASA Astrophysics Data System (ADS)

    Mantineo, Matías; Pinheiro, João P.; Morgado, António M.

    2014-09-01

    We evaluated the effect of different irradiation parameters in low-level laser therapy (LLLT) for treating inflammation induced in the gastrocnemius muscle of rats through cytokines concentration in systemic blood and analysis of muscle tissue. We used continuous (830 and 980 nm) and pulsed illuminations (830 nm). Animals were divided into five groups per wavelength (10, 20, 30, 40, and 50 mW), and a control group. LLLT was applied during 5 days with a constant irradiation time and area. TNF-α, IL-1β, IL-2, and IL-6 cytokines were quantified by ELISA. Inflammatory cells were counted using microscopy. Identical methodology was used with pulsed illumination. Average power (40 mW) and duty cycle were kept constant (80%) at five frequencies (5, 25, 50, 100, and 200 Hz). For continuous irradiation, treatment effects occurred for all doses, with a reduction of TNF-α, IL-1β, and IL-6 cytokines and inflammatory cells. Continuous irradiation at 830 nm was more effective, a result explained by the action spectrum of cytochrome c oxidase (CCO). Best results were obtained for 40 mW, with data suggesting a biphasic dose response. Pulsed wave irradiation was only effective for higher frequencies, a result that might be related to the rate constants of the CCO internal electron transfer process.

  16. Elevated specific peripheral cytokines found in major depressive disorder patients with childhood trauma exposure: a cytokine antibody array analysis.

    PubMed

    Lu, Shaojia; Peng, Hongjun; Wang, Lifeng; Vasish, Seewoobudul; Zhang, Yan; Gao, Weijia; Wu, Weiwei; Liao, Mei; Wang, Mi; Tang, Hao; Li, Wenping; Li, Weihui; Li, Zexuan; Zhou, Jiansong; Zhang, Zhijun; Li, Lingjiang

    2013-10-01

    Taking into consideration the previous evidence of revealing the relationship of early life adversity, major depressive disorder (MDD), and stress-linked immunological changes, we recruited 22 MDD patients with childhood trauma exposures (CTE), 21 MDD patients without CTE, and 22 healthy controls without CTE, and then utilized a novel cytokine antibody array methodology to detect potential biomarkers underlying MDD in 120 peripheral cytokines and to evaluate the effect of CTE on cytokine changes in MDD patients. Although 13 cytokines were identified with highly significant differences in expressions between MDD patients and normal controls, this relationship was significantly attenuated and no longer significant after consideration of the effect of CTE in MDD patients. Depressed individuals with CTE (TD patients) were more likely to have higher peripheral levels of those cytokines. Severity of depression was associated with plasma levels of certain increased cytokines; meanwhile, the increased cytokines led to a proper separation of TD patients from normal controls during clustering analyses. Our research outcomes add great strength to the relationship between depression and cytokine changes and suggest that childhood trauma may play a vital role in the co-appearance of cytokine changes and depression.

  17. Modulation of Cytokine and Cytokine Receptor/Antagonist by Treatment with Doxycycline and Tetracycline in Patients with Dengue Fever

    PubMed Central

    Castro, J. E. Z.; Vado-Solis, I.; Perez-Osorio, C.; Fredeking, T. M.

    2011-01-01

    Dengue virus infection can lead to dengue fever (DF) or dengue hemorrhagic fever (DHF). Disease severity has been linked to an increase in various cytokine levels. In this study, we evaluated the effectiveness of doxycycline and tetracycline to modulate serum levels of IL-6, IL-1B, and TNF and cytokine receptor/receptor antagonist TNF-R1 and IL-1RA in patients with DF or DHF. Hospitalized patients were randomized to receive standard supportive care or supportive care combined with doxycycline or tetracycline therapy. Serum cytokine and cytokine receptor/antagonist levels were determined at the onset of therapy and after 3 and 7 days. Cytokine and cytokine receptor/antagonist levels were substantially elevated at day 0. IL-6, IL-1β, and TNF remained at or above day 0 levels throughout the study period in untreated patients. Treatment with tetracycline or doxycycline resulted in a significant decline in cytokine levels. Similarly, IL-1RA and TNF-R1 serum concentrations were elevated at baseline and showed a moderate increase among untreated patients. Both drugs resulted in a significant rise in IL-1Ra levels by day 3 in patients. In contrast, treatment did not affect a similar result for TNF-R1. When compared to the control group, however, a significant rise post-treatment was seen upon intragroup analysis. Further analysis demonstrated that doxycycline was significantly more effective at modulating cytokine and cytokine receptor/antagonist levels than tetracycline. PMID:21461372

  18. Elevated specific peripheral cytokines found in major depressive disorder patients with childhood trauma exposure: a cytokine antibody array analysis.

    PubMed

    Lu, Shaojia; Peng, Hongjun; Wang, Lifeng; Vasish, Seewoobudul; Zhang, Yan; Gao, Weijia; Wu, Weiwei; Liao, Mei; Wang, Mi; Tang, Hao; Li, Wenping; Li, Weihui; Li, Zexuan; Zhou, Jiansong; Zhang, Zhijun; Li, Lingjiang

    2013-10-01

    Taking into consideration the previous evidence of revealing the relationship of early life adversity, major depressive disorder (MDD), and stress-linked immunological changes, we recruited 22 MDD patients with childhood trauma exposures (CTE), 21 MDD patients without CTE, and 22 healthy controls without CTE, and then utilized a novel cytokine antibody array methodology to detect potential biomarkers underlying MDD in 120 peripheral cytokines and to evaluate the effect of CTE on cytokine changes in MDD patients. Although 13 cytokines were identified with highly significant differences in expressions between MDD patients and normal controls, this relationship was significantly attenuated and no longer significant after consideration of the effect of CTE in MDD patients. Depressed individuals with CTE (TD patients) were more likely to have higher peripheral levels of those cytokines. Severity of depression was associated with plasma levels of certain increased cytokines; meanwhile, the increased cytokines led to a proper separation of TD patients from normal controls during clustering analyses. Our research outcomes add great strength to the relationship between depression and cytokine changes and suggest that childhood trauma may play a vital role in the co-appearance of cytokine changes and depression. PMID:23639406

  19. Commercial sunscreen formulations: UVB irradiation stability and effect on UVB irradiation-induced skin oxidative stress and inflammation.

    PubMed

    Vilela, Fernanda M P; Oliveira, Franciane M; Vicentini, Fabiana T M C; Casagrande, Rubia; Verri, Waldiceu A; Cunha, Thiago M; Fonseca, Maria J V

    2016-10-01

    Evidence shows that sunscreens undergo degradation processes induced by UV irradiation forming free radicals, which reduces skin protection. In this regard, the biological effects of three commercial sunscreen formulations upon UVB irradiation in the skin were investigated. The three formulations had in common the presence of benzophenone-3 added with octyl methoxycinnamate or octyl salycilate or both, which are regular UV filters in sunscreens. The results show that formulations F1 and F2 presented partial degradation upon UVB irradiation. Formulations F1 and F2 presented higher skin penetration profiles than F3. None of the formulations avoided UVB irradiation-induced GSH depletion, but inhibited reduction of SOD activity, suggesting the tested formulations did not present as a major mechanism inhibiting all UVB irradiation-triggered oxidative stress pathways. The formulations avoided the increase of myeloperoxidase activity and cytokine production (IL-1β and TNF-α), but with different levels of protection in relation to the IL-1β release. Concluding, UVB irradiation can reduce the stability of sunscreens, which in turn, present the undesirable properties of reaching viable skin. Additionally, the same SPF does not mean that different sunscreens will present the same biological effects as SPF is solely based on a skin erythema response. This found opens up perspectives to consider additional studies to reach highly safe sunscreens.

  20. Commercial sunscreen formulations: UVB irradiation stability and effect on UVB irradiation-induced skin oxidative stress and inflammation.

    PubMed

    Vilela, Fernanda M P; Oliveira, Franciane M; Vicentini, Fabiana T M C; Casagrande, Rubia; Verri, Waldiceu A; Cunha, Thiago M; Fonseca, Maria J V

    2016-10-01

    Evidence shows that sunscreens undergo degradation processes induced by UV irradiation forming free radicals, which reduces skin protection. In this regard, the biological effects of three commercial sunscreen formulations upon UVB irradiation in the skin were investigated. The three formulations had in common the presence of benzophenone-3 added with octyl methoxycinnamate or octyl salycilate or both, which are regular UV filters in sunscreens. The results show that formulations F1 and F2 presented partial degradation upon UVB irradiation. Formulations F1 and F2 presented higher skin penetration profiles than F3. None of the formulations avoided UVB irradiation-induced GSH depletion, but inhibited reduction of SOD activity, suggesting the tested formulations did not present as a major mechanism inhibiting all UVB irradiation-triggered oxidative stress pathways. The formulations avoided the increase of myeloperoxidase activity and cytokine production (IL-1β and TNF-α), but with different levels of protection in relation to the IL-1β release. Concluding, UVB irradiation can reduce the stability of sunscreens, which in turn, present the undesirable properties of reaching viable skin. Additionally, the same SPF does not mean that different sunscreens will present the same biological effects as SPF is solely based on a skin erythema response. This found opens up perspectives to consider additional studies to reach highly safe sunscreens. PMID:27627683

  1. Molecular structure and physicochemical properties of potato and bean starches as affected by gamma-irradiation.

    PubMed

    Chung, Hyun-Jung; Liu, Qiang

    2010-08-01

    In this study, potato and bean starches were treated by gamma-irradiation up to 50kGy. Molecular structure and physicochemical properties of irradiated potato and bean starches were investigated. Microscopic observation under scanning electron microscope (SEM) and polarized microscope showed that some of potato and bean starch granules were destroyed by gamma-irradiation and the breakage was much greater at a higher dose (50 kGy). Carboxyl content and amylose leaching increased, whereas the swelling factor and apparent amylose content decreased after irradiation in both potato and bean starches. The proportions of short (DP 6-12) and long (DP > or = 37) amylopectin chains as well as average chain length increased with increasing irradiation dose. However, the proportion of DP 13-24 decreased by irradiation. The relative crystallinity, the degree of granule surface order, and gelatinization enthalpy decreased with an increase in irradiation dose. The extent of decrease in potato starch was greater than that in bean starch. The exothermic peak around 90-110 degrees C was observed in DSC thermogram when the potato starch was irradiated at 50 kGy. The pasting viscosity significantly decreased with an increase in irradiation dose. The proportion of slowly digestible starch (SDS) decreased and resistant starch (RS) content increased by irradiation in both potato and bean starches. However, the rapidly digestible starch (RDS) of potato starch increased with increasing irradiation dose, whereas the bean starch showed the opposite trend to potato starch in RDS content.

  2. Production of hemo- and immunoregulatory cytokines by erythroblast antigen+ and glycophorin A+ cells from human bone marrow

    PubMed Central

    Sennikov, Sergey V; Injelevskaya, Tatyana V; Krysov, Sergey V; Silkov, Alexandr N; Kovinev, Igor B; Dyachkova, Natalya J; Zenkov, Anton N; Loseva, Mary I; Kozlov, Vladimir A

    2004-01-01

    Background Erythroid nuclear cells (ENC) of the bone marrow (BM) have not previously been considered as important producers of wide spectrum of haemo- and immunoregulatory cytokines. The aim of the current work was to confirm the production of the main hemo- and immunoregulatory cytokines in human ENC from BM. Results We used native human BM ENC in our experiments. We for the first time have shown, that the unstimulated erythroblasts (Gl A+ or AG-EB+) produced a wide spectrum of immunoregulatory cytokines. Human BM ENC produce cytokines such as interleukn (IL)-1β, IL-2, IL-4, IL-6, interferon (IFN)-γ, transforming growth factor (TGF)-β1, tumor necrosis factor (TNF)-α and IL-10. They can be sub-divided into glycophorin A positive (Gl A+) and erythroblast antigen positive (AG-EB+) cells. To study potential differences in cytokine expression between these subsets, ENC were isolated and purified using specific antibodies to Gl A and AG-EB and the separated cells were cultivated for 24 hours. The cytokine contents of the supernatant were measured by electrochemiluminescence immunoassay. Quantitative differences in TGF-β1 and TNF-α production were found between Gl A+ and AG-EB+ BM ENC. Furthermore, in vitro addition of erythropoietin (EPO) reduced IFN-γ and IL-2 production specifically by the AG-EB+ ENC. Thus, Gl A+ and AG-EB+ ENC produce IL-1β, IL-2, IL-4, IL-6, IFN-γ, TGF-β1 and TNF-α. Gl A+ ENC also produce IL-10. Conclusion Cytokine production by erythroid nuclear cells suggests that these cells might be involved in regulating the proliferation and differentiation of hematopoietic and immunocompetent cells in human BM. PMID:15488155

  3. Comminuting irradiated ferritic steel

    DOEpatents

    Bauer, Roger E.; Straalsund, Jerry L.; Chin, Bryan A.

    1985-01-01

    Disclosed is a method of comminuting irradiated ferritic steel by placing the steel in a solution of a compound selected from the group consisting of sulfamic acid, bisulfate, and mixtures thereof. The ferritic steel is used as cladding on nuclear fuel rods or other irradiated components.

  4. MASSIVE LEAKAGE IRRADIATOR

    DOEpatents

    Wigner, E.P.; Szilard, L.; Christy, R.F.; Friedman, F.L.

    1961-05-30

    An irradiator designed to utilize the neutrons that leak out of a reactor around its periphery is described. It avoids wasting neutron energy and reduces interference with the core flux to a minimum. This is done by surrounding all or most of the core with removable segments of the material to be irradiated within a matrix of reflecting material.

  5. Perspective on food irradiation

    SciTech Connect

    Not Available

    1987-02-01

    Recent US Food and Drug Administration approval of irradiation treatment for fruit, vegetables and pork has stimulated considerable discussion in the popular press on the safety and efficacy of irradiation processing of food. This perspective is designed to summarize the current scientific information available on this issue.

  6. Morphogen and proinflammatory cytokine release kinetics from PRGF-Endoret fibrin scaffolds: evaluation of the effect of leukocyte inclusion.

    PubMed

    Anitua, E; Zalduendo, M M; Prado, R; Alkhraisat, M H; Orive, G

    2015-03-01

    The potential influence of leukocyte incorporation in the kinetic release of growth factors from platelet-rich plasma (PRP) may explain the conflicting efficiency of leukocyte platelet-rich plasma (L-PRP) scaffolds in tissue regeneration. To assess this hypothesis, leukocyte-free (PRGF-Endoret) and L-PRP fibrin scaffolds were prepared, and both morphogen and proinflammatory cytokine release kinetics were analyzed. Clots were incubated with culture medium to monitor protein release over 8 days. Furthermore, the different fibrin scaffolds were morphologically characterized. Results show that leukocyte-free fibrin matrices were homogenous while leukocyte-containing ones were heterogeneous, loose and cellular. Leukocyte incorporation produced a significant increase in the contents of proinflammatory cytokines interleukin (IL)-1β and IL-16 but not in the platelet-derived growth factors release (<1.5-fold). Surprisingly, the availability of vascular endothelial growth factor suffered an important decrease after 3 days of incubation in the case of L-PRP matrices. While the release of proinflammatory cytokines was almost absent or very low from PRGF-Endoret, the inclusion of leukocytes induced a major increase in these cytokines, which was characterized by the presence of a latent period. The PRGF-Endoret matrices were stable during the 8 days of incubation. The inclusion of leukocytes alters the growth factors release profile and also increased the dose of proinflammatory cytokines.

  7. Cortisol modulates the expression of cytokines and suppressors of cytokine signaling (SOCS) in rainbow trout hepatocytes.

    PubMed

    Philip, Anju M; Daniel Kim, S; Vijayan, Mathilakath M

    2012-10-01

    Although liver is a key target for corticosteroid action, its role in immune function is largely unknown. We tested the hypothesis that stress levels of cortisol down regulate immune-relevant genes in rainbow trout (Oncorhynchus mykiss) liver. Hepatocytes were treated with lipopolysaccharide (LPS) for 24h either in the presence or absence of cortisol. LPS stimulated heat shock protein 70 expression, enhanced glycolytic capacity, and reduced glucose output. LPS stimulated mRNA abundance of cytokines and serum amyloid protein A (SAA), while suppressors of cytokine signaling (SOCS)-3 was reduced. Cortisol increased mRNA abundances of IL-1β, SOCS-1 and SOCS-2, while inhibiting either basal or LPS-stimulated IL-8, TNF α2 and SAA. These cortisol-mediated effects were rescued by Mifepristone, a glucocorticoid receptor antagonist. Altogether, cortisol modulates the molecular immune response in trout hepatocytes. The upregulation of SOCS-1 and SOCS-2 by cortisol may be playing a key role in suppressing cytokine signaling and the associated inflammatory response.

  8. Absence of CCL2 is sufficient to restore hippocampal neurogenesis following cranial irradiation

    PubMed Central

    Lee, Star W.; Haditsch, Ursula; Cord, Branden J.; Guzman, Raphael; Kim, Soo Jeong; Boettcher, Chotima; Priller, Josef; Ormerod, Brandi K.; Palmer, Theo D.

    2012-01-01

    Cranial irradiation for the treatment of brain tumors causes a delayed and progressive cognitive decline that is pronounced in young patients. Dysregulation of neural stem and progenitor cells is thought to contribute to these effects by altering early childhood brain development. Earlier work has shown that irradiation creates a chronic neuroinflammatory state that severely and selectively impairs postnatal and adult neurogenesis. Here we show that irradiation induces a transient non-classical cytokine response with selective upregulation of CCL2/monocyte chemoattractant protein–1(MCP-1). Absence of CCL2 signaling in the hours after irradiation is alone sufficient to attenuate chronic microglia activation and allow the recovery of neurogenesis in the weeks following irradiation. This identifies CCL2 signaling as a potential clinical target for moderating the long-term defects in neural stem cell function following cranial radiation in children. PMID:23041279

  9. Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors

    PubMed Central

    2013-01-01

    Introduction Platelet-rich plasma (PRP) is nowadays widely applied in different clinical scenarios, such as orthopedics, ophthalmology and healing therapies, as a growth factor pool for improving tissue regeneration. Studies into its clinical efficiency are not conclusive and one of the main reasons for this is that different PRP preparations are used, eliciting different responses that cannot be compared. Platelet quantification and the growth factor content definition must be defined in order to understand molecular mechanisms behind PRP regenerative strength. Standardization of PRP preparations is thus urgently needed. Methods PRP was prepared by centrifugation varying the relative centrifugal force, temperature, and time. Having quantified platelet recovery and yield, the two-step procedure that rendered the highest output was chosen and further analyzed. Cytokine content was determined in different fractions obtained throughout the whole centrifugation procedure. Results Our method showed reproducibility when applied to different blood donors. We recovered 46.9 to 69.5% of total initial platelets and the procedure resulted in a 5.4-fold to 7.3-fold increase in platelet concentration (1.4 × 106 to 1.9 × 106 platelets/μl). Platelets were highly purified, because only <0.3% from the initial red blood cells and leukocytes was present in the final PRP preparation. We also quantified growth factors, cytokines and chemokines secreted by the concentrated platelets after activation with calcium and calcium/thrombin. High concentrations of platelet-derived growth factor, endothelial growth factor and transforming growth factor (TGF) were secreted, together with the anti-inflammatory and proinflammatory cytokines interleukin (IL)-4, IL-8, IL-13, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-α. No cytokines were secreted before platelet activation. TGF-β3 and IFNγ were not detected in any studied fraction. Clots obtained after platelet coagulation

  10. Irradiation Creep in Graphite

    SciTech Connect

    Ubic, Rick; Butt, Darryl; Windes, William

    2014-03-13

    An understanding of the underlying mechanisms of irradiation creep in graphite material is required to correctly interpret experimental data, explain micromechanical modeling results, and predict whole-core behavior. This project will focus on experimental microscopic data to demonstrate the mechanism of irradiation creep. High-resolution transmission electron microscopy should be able to image both the dislocations in graphite and the irradiation-induced interstitial clusters that pin those dislocations. The team will first prepare and characterize nanoscale samples of virgin nuclear graphite in a transmission electron microscope. Additional samples will be irradiated to varying degrees at the Advanced Test Reactor (ATR) facility and similarly characterized. Researchers will record microstructures and crystal defects and suggest a mechanism for irradiation creep based on the results. In addition, the purchase of a tensile holder for a transmission electron microscope will allow, for the first time, in situ observation of creep behavior on the microstructure and crystallographic defects.

  11. Vitamin D and Inflammatory Cytokines in Healthy and Preeclamptic Pregnancies.

    PubMed

    Barrera, David; Díaz, Lorenza; Noyola-Martínez, Nancy; Halhali, Ali

    2015-08-04

    Preeclampsia is a pregnancy disease characterized by hypertension and proteinuria. Among several disorders, the imbalance of inflammatory cytokines and the alteration of vitamin D metabolism have been reported in preeclampsia. The effects of calcitriol upon inflammatory cytokines has been demonstrated. In healthy pregnant women there is a shift toward a Th2 cytokine profile, which is necessary for an adequate pregnancy outcome. As compared with normal pregnancy, high pro-inflammatory and low anti-inflammatory cytokine levels have been observed in preeclamptic women. Preeclampsia has been associated with low calcitriol levels and vitamin D deficiency is correlated with a higher risk of the development of this disease. It has been demonstrated that placenta is a source as well as the target of calcitriol and cytokines and placental dysfunction has been associated with preeclampsia. Therefore, the present manuscript includes a review about serum calcitriol levels in non-pregnant, pregnant, and preeclamptic women as well as a review on the fetoplacental vitamin D metabolism in healthy and preeclamptic pregnancies. In addition, circulating and fetoplacental inflammatory cytokines in healthy and preeclamptic pregnancies are reviewed. Finally, the effects of calcitriol upon placental pro-inflammatory cytokines are also explored. In conclusion, maternal and placental calcitriol levels are low in preeclampsia which may explain, at least in part, high pro-inflammatory cytokine levels in this disease.

  12. Vitamin D and Inflammatory Cytokines in Healthy and Preeclamptic Pregnancies

    PubMed Central

    Barrera, David; Díaz, Lorenza; Noyola-Martínez, Nancy; Halhali, Ali

    2015-01-01

    Preeclampsia is a pregnancy disease characterized by hypertension and proteinuria. Among several disorders, the imbalance of inflammatory cytokines and the alteration of vitamin D metabolism have been reported in preeclampsia. The effects of calcitriol upon inflammatory cytokines has been demonstrated. In healthy pregnant women there is a shift toward a Th2 cytokine profile, which is necessary for an adequate pregnancy outcome. As compared with normal pregnancy, high pro-inflammatory and low anti-inflammatory cytokine levels have been observed in preeclamptic women. Preeclampsia has been associated with low calcitriol levels and vitamin D deficiency is correlated with a higher risk of the development of this disease. It has been demonstrated that placenta is a source as well as the target of calcitriol and cytokines and placental dysfunction has been associated with preeclampsia. Therefore, the present manuscript includes a review about serum calcitriol levels in non-pregnant, pregnant, and preeclamptic women as well as a review on the fetoplacental vitamin D metabolism in healthy and preeclamptic pregnancies. In addition, circulating and fetoplacental inflammatory cytokines in healthy and preeclamptic pregnancies are reviewed. Finally, the effects of calcitriol upon placental pro-inflammatory cytokines are also explored. In conclusion, maternal and placental calcitriol levels are low in preeclampsia which may explain, at least in part, high pro-inflammatory cytokine levels in this disease. PMID:26247971

  13. Effects of selected herbicides on cytokine production in vitro.

    PubMed

    Hooghe, R J; Devos, S; Hooghe-Peters, E L

    2000-05-19

    To evaluate possible deleterious effects of commonly used herbicides on leukocytes, cytokine production was selected as a sensitive indicator. After in vitro exposure of human peripheral blood mononuclear cells from normal donors, the production of all 3 cytokines tested--interferon-gamma (a type 1 cytokine), interleukin-5 (a type 2 cytokine) and tumor necrosis factor-alpha (an inflammatory cytokine)--was impaired by up to 70, 50 and 70% respectively in a concentration-dependent manner in cultures exposed to atrazine (0.03-3 microM in 1% dimethylsulfoxide, DMSO). The effect paralleled that seen with dexamethasone, a known immunosuppressive agent. Other pesticides also dissolved in DMSO--mecoprop, simazine or MCPA (each up to 1 microM)--or dissolved in phosphate-buffered saline--diuron (up to 1 microM), isoproturon (up to 3 microM), metoxuron (up to 8 microM) or metamitron (up to 80 microM)--showed no concentration-related effects on cytokine production. There was, however, an inhibition of IFN-gamma and TNF-alpha production by simazine, metoxuron and mecoprop and of all three cytokines tested by diuron. MCPA (0.01 and 0.1 microM) stimulated the production of TNF-alpha. Thus, exposure to herbicides leading to plasma levels in the micromolar range induces imbalance in cytokine production.

  14. Cytokine Signaling Modulates Blood-Brain Barrier Function

    PubMed Central

    Pan, Weihong; Stone, Kirsten P.; Hsuchou, Hung; Manda, Vamshi K.; Zhang, Yan; Kastin, Abba J.

    2014-01-01

    The blood-brain barrier (BBB) provides a vast interface for cytokines to affect CNS function. The BBB is a target for therapeutic intervention. It is essential, therefore, to understand how cytokines interact with each other at the level of the BBB and how secondary signals modulate CNS functions beyond the BBB. The interactions between cytokines and lipids, however, have not been fully addressed at the level of the BBB. Here, we summarize current understanding of the localization of cytokine receptors and transporters in specific membrane microdomains, particularly lipid rafts, on the luminal (apical) surface of the microvascular endothelial cells composing the BBB. We then illustrate the clinical context of cytokine effects on the BBB by neuroendocrine regulation and amplification of inflammatory signals. Two unusual aspects discussed are signaling crosstalk by different classes of cytokines and genetic regulation of drug efflux transporters. We also introduce a novel area of focus on how cytokines may act through nuclear hormone receptors to modulate efflux transporters and other targets. A specific example discussed is the ATP-binding cassette transporter-1 (ABCA-1) that regulates lipid metabolism. Overall, cytokine signaling at the level of the BBB is a crucial feature of the dynamic regulation that can rapidly change BBB function and affect brain health and disease. PMID:21834767

  15. Cytokines, Graves' Disease, and Thyroid-Associated Ophthalmopathy

    PubMed Central

    Khadavi, Nicole; Smith, Terry J.

    2008-01-01

    Graves' disease, an autoimmune process associated with thyroid dysfunction, can also manifest as remodeling of orbital connective tissue. Affected tissues exhibit immune responses that appear to be orchestrated by resident cells and those recruited from the bone marrow through their expression and release of cytokines and surface display of cytokine receptors. Cytokines are small molecules produced by many types of cells, including those of the “professional” immune system. Aberrant cytokine expression appears to play an important role in the pathogenesis of many human diseases, including thyroid autoimmunity. The skewed pattern of cytokine expression in the thyroid, including the T helper cell bias, may condition the response to apoptotic signals and determine the characteristics of an autoimmune reaction. Furthermore, chemoattractant cytokines, including IL16, RANTES, and CXCL10, elaborated by resident cells in the thyroid and orbit may provoke mononuclear cell infiltration. Other cytokines may drive cell activation and tissue remodeling. Thus cytokines and the signaling pathways they activate represent attractive therapeutic targets. Interruption of these might alter the natural course of Graves' disease and its orbital manifestations. PMID:18713026

  16. Cytokines, Graves' disease, and thyroid-associated ophthalmopathy.

    PubMed

    Gianoukakis, Andrew G; Khadavi, Nicole; Smith, Terry J

    2008-09-01

    Graves' disease, an autoimmune process associated with thyroid dysfunction, can also manifest as remodeling of orbital connective tissue. Affected tissues exhibit immune responses that appear to be orchestrated by resident cells and those recruited from the bone marrow through their expression and release of cytokines and surface display of cytokine receptors. Cytokines are small molecules produced by many types of cells, including those of the "professional" immune system. Aberrant cytokine expression appears to play an important role in the pathogenesis of many human diseases, including thyroid autoimmunity. The skewed pattern of cytokine expression in the thyroid, including the T helper cell bias, may condition the response to apoptotic signals and determine the characteristics of an autoimmune reaction. Furthermore, chemoattractant cytokines, including IL16, RANTES, and CXCL10, elaborated by resident cells in the thyroid and orbit may provoke mononuclear cell infiltration. Other cytokines may drive cell activation and tissue remodeling. Thus cytokines and the signaling pathways they activate represent attractive therapeutic targets. Interruption of these might alter the natural course of Graves' disease and its orbital manifestations. PMID:18713026

  17. Vitamin D and Inflammatory Cytokines in Healthy and Preeclamptic Pregnancies.

    PubMed

    Barrera, David; Díaz, Lorenza; Noyola-Martínez, Nancy; Halhali, Ali

    2015-08-01

    Preeclampsia is a pregnancy disease characterized by hypertension and proteinuria. Among several disorders, the imbalance of inflammatory cytokines and the alteration of vitamin D metabolism have been reported in preeclampsia. The effects of calcitriol upon inflammatory cytokines has been demonstrated. In healthy pregnant women there is a shift toward a Th2 cytokine profile, which is necessary for an adequate pregnancy outcome. As compared with normal pregnancy, high pro-inflammatory and low anti-inflammatory cytokine levels have been observed in preeclamptic women. Preeclampsia has been associated with low calcitriol levels and vitamin D deficiency is correlated with a higher risk of the development of this disease. It has been demonstrated that placenta is a source as well as the target of calcitriol and cytokines and placental dysfunction has been associated with preeclampsia. Therefore, the present manuscript includes a review about serum calcitriol levels in non-pregnant, pregnant, and preeclamptic women as well as a review on the fetoplacental vitamin D metabolism in healthy and preeclamptic pregnancies. In addition, circulating and fetoplacental inflammatory cytokines in healthy and preeclamptic pregnancies are reviewed. Finally, the effects of calcitriol upon placental pro-inflammatory cytokines are also explored. In conclusion, maternal and placental calcitriol levels are low in preeclampsia which may explain, at least in part, high pro-inflammatory cytokine levels in this disease. PMID:26247971

  18. Transgenic models for cytokine-induced neurological disease

    PubMed Central

    Campbell, Iain L.; Hofer, Markus J.; Pagenstecher, Axel

    2009-01-01

    Considerable evidence supports the idea that cytokines are important mediators of pathophysiologic processes within the central nervous system (CNS). Numerous studies have documented the increased production of various cytokines in the human CNS in a variety of neurological and neuropsychiatric disorders. Deciphering cytokine actions in the intact CNS has important implications for our understanding of the pathogenesis and treatment of these disorders. One approach to address this problem that has been used widely employs transgenic mice with CNS-targeted production of different cytokines. Transgenic production of cytokines in the CNS of mice allows not only for the investigation of complex cellular responses at a localized level in the intact brain, but also more closely recapitulates the expression of these mediators as found in disease states. As discussed in this review, the findings show that these transgenic animals exhibit wide-ranging structural and functional deficits that are linked to the development of distinct neuroinflammatory responses which are relatively specific for each cytokine. These cytokine-induced alterations often recapitulate those found in various human neurological disorders not only underscoring the relevance of these models but also reinforcing the clinicopathogenetic significance of cytokines in diseases of the CNS. PMID:19835956

  19. Neutrophil myeloperoxidase destruction by ultraviolet irradiation

    SciTech Connect

    Hanker, J.; Giammara, B.; Strauss, G.

    1988-01-01

    The peroxidase activity of enriched leukocyte preparations on coverslips was determined cytochemically with a newly developed method. The techniques utilizes diaminobenzidine medium and cupric nitrate intensification and is suitable for analysis with light microscopy, SEM, and TEM. Blood specimens from control individuals were studied with and without in vitro UV irradiation and compared with those from psoriasis patients exposed therapeutically to various types of UV in phototherapy. All UV irradiated samples showed diminished neutrophil myeloperoxidase (MP) activity although that of the principal eosinophil peroxidase was unaffected. The SEMs supported the contention that decreased neutrophil MP activity might be related to UV induced degranulation. It is believed to be possible, eventually, to equate the observed MP degranulation effect after UV irradiation with diminished ability to fight bacterial infections.

  20. The role of cytokines in immune changes induced by spaceflight

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, G.; Miller, E. S.

    1993-01-01

    It has become apparent that spaceflight alters many immune responses. Among the regulatory components of the immune response that have been shown to be affected by spaceflight is the cytokine network. Spaceflight, as well as model systems of spaceflight, have been shown to affect the production and action of various cytokines including interferons, interleukins, colony stimulating factors, and tumor necrosis factors. These changes have been shown not to involve a general shutdown of the cytokine network but, rather, to involve selective alterations of specific cytokine functions by spaceflight. The full breadth of changes in cytokines induced by spaceflight, as well as mechanisms, duration, adaptation, reversibility, and significance to resistance to infection and neoplastic diseases, remains to be established.

  1. Kitasato Symposium 2009: New Prospects for Cytokine Inhibition

    PubMed Central

    2009-01-01

    The Kitasato Symposium 2009: New Prospects for Cytokine Inhibition was held in Berlin, Germany from 7 to 9 May 2009. The key aims of this meeting were to bring together a group of front-line researchers and rheumatologists to evaluate the use of cytokine blockade and to examine the role of certain cytokines in the pathogenesis of rheumatoid arthritis and other autoimmune diseases. A keynote lecture delivered by Professor Jean-Michel Dayer provided an up-to-date overview of the interactions occurring between the immune system and acute phase proteins. Other speakers discussed the role of cytokines in rheumatoid arthritis, including their role in joint destruction, as well as their regulatory role upon T cells and B cells. The involvement of cytokines in other autoimmune diseases was also addressed. PMID:20067593

  2. The role of cytokines in immunological tolerance: potential for therapy.

    PubMed

    Harber, M; Sundstedt, A; Wraith, D

    2000-11-27

    Current immunosuppression protocols, although often effective, are nonspecific and therefore hazardous. Consequently, immunological tolerance that is antigen specific and does not globally depress the patient's immune system has become one of the Holy Grails of immunology. Since the discovery that cytokines have immunomodulatory effects, extensive research has investigated the potential of these molecules to induce and maintain specific immunological tolerance in the context of transplantation, allergy and autoimmunity. In this article, we review the possible mechanisms by which cytokines can modulate the immune response and the animal models that frequently confound the theory that a single cytokine, or group of cytokines, can induce tolerance in a predictable manner. Finally, we discuss the role of cytokines at a paracrine level, particularly in the context of inducing and maintaining antigen-specific, regulatory T cells with the clinical potential to suppress specific immune responses.

  3. Cytokines as potential biomarkers for Parkinson's disease: a multiplex approach.

    PubMed

    Litteljohn, Darcy; Hayley, Shawn

    2012-01-01

    Cytokines, which are immunological messengers facilitating both intra- and inter-system communication, are considered central players in the neuroinflammatory cascades associated with the neurodegenerative process in Parkinson's disease (PD) and other neurological disorders. They have also been implicated in depression and other cognitive (e.g., memory impairment, dementia) and affective disturbances (e.g., anxiety) that show high co-morbidity with neurodegenerative diseases. As such, cytokines may hold great promise as serological biomarkers in PD, with potential applications ranging from early diagnosis and disease staging, to prognosis, drug discovery, and tracking the response to treatment. Subclassification or risk stratification in PD could be based (among other things) on reliably determined cytokine panel profiles or "signatures" of particular co-morbid disease states or at-risk groups (e.g., PD alone, PD with depression and/or dementia). Researchers and clinicians seeking to describe cytokine variations in health vs. disease will benefit greatly from technologies that allow a high degree of multiplexing and thus permit the simultaneous determination of a large roster of cytokines in single small-volume samples. The need for such highly paralleled assays is underscored by the fact that cytokines do not act in isolation but rather against a backdrop of complementary and antagonistic cytokine effects; ascribing valence to the actions of any one cytokine thus requires specific knowledge about the larger cytokine milieu. This chapter provides a technological overview of the major cytokine multiplex assay platforms before discussing the implications of such tools for biomarker discovery and related applications in PD and its depressive and cognitive co-morbidities.

  4. Reconstitution of SCID mice with human lymphoid and myeloid cells after transplantation with human fetal bone marrow without the requirement for exogenous human cytokines.

    PubMed

    Kollmann, T R; Kim, A; Zhuang, X; Hachamovitch, M; Goldstein, H

    1994-08-16

    Investigation of human hematopoietic maturation has been hampered by the lack of in vivo models. Although engraftment of irradiated C.B-17 scid/scid (SCID) mice with human progenitor cells occurred after infusion with human pediatric bone marrow cells, significant engraftment of the mouse bone marrow with human cells was dependent upon continuous treatment with exogenous human cytokines. Furthermore, despite cytokine treatment, only minimal peripheral engraftment of these mice with human cells was observed. In the present study, after infusion of irradiated SCID mice with pre-cultured human fetal bone marrow cells (BM-SCID-hu mice), their bone marrow became significantly engrafted with human precursor cells and their peripheral lymphoid compartment became populated with human B cells and monocytes independently of the administration of extraneous human cytokines. Examination of the bone marrow of the BM-SCID-hu mice for human cytokine mRNA gene expression demonstrated human leukemia inhibitory factor mRNA and interleukin 7 mRNA in nine of nine BM-SCID-hu mice and macrophage-colony-stimulating factor mRNA in seven of eight BM-SCID-hu mice. This was an intriguing observation because these cytokines regulate different stages of human hematopoiesis. Since engraftment occurs in the absence of exogenous cytokine treatment, the BM-SCID-hu mouse model described should provide a useful in vivo system for studying factors important in the maturation of human myeloid and lymphoid cells in the bone marrow and the behavior of the mature human cells after dissemination into the peripheral lymphoid tissue.

  5. Reconstitution of SCID mice with human lymphoid and myeloid cells after transplantation with human fetal bone marrow without the requirement for exogenous human cytokines.

    PubMed Central

    Kollmann, T R; Kim, A; Zhuang, X; Hachamovitch, M; Goldstein, H

    1994-01-01

    Investigation of human hematopoietic maturation has been hampered by the lack of in vivo models. Although engraftment of irradiated C.B-17 scid/scid (SCID) mice with human progenitor cells occurred after infusion with human pediatric bone marrow cells, significant engraftment of the mouse bone marrow with human cells was dependent upon continuous treatment with exogenous human cytokines. Furthermore, despite cytokine treatment, only minimal peripheral engraftment of these mice with human cells was observed. In the present study, after infusion of irradiated SCID mice with pre-cultured human fetal bone marrow cells (BM-SCID-hu mice), their bone marrow became significantly engrafted with human precursor cells and their peripheral lymphoid compartment became populated with human B cells and monocytes independently of the administration of extraneous human cytokines. Examination of the bone marrow of the BM-SCID-hu mice for human cytokine mRNA gene expression demonstrated human leukemia inhibitory factor mRNA and interleukin 7 mRNA in nine of nine BM-SCID-hu mice and macrophage-colony-stimulating factor mRNA in seven of eight BM-SCID-hu mice. This was an intriguing observation because these cytokines regulate different stages of human hematopoiesis. Since engraftment occurs in the absence of exogenous cytokine treatment, the BM-SCID-hu mouse model described should provide a useful in vivo system for studying factors important in the maturation of human myeloid and lymphoid cells in the bone marrow and the behavior of the mature human cells after dissemination into the peripheral lymphoid tissue. Images PMID:7914701

  6. Test reactor irradiation coordination

    SciTech Connect

    Heartherly, D.W.; Siman Tov, I.I.; Sparks, D.W.

    1995-10-01

    This task was established to supply and coordinate irradiation services needed by NRC contractors other than ORNL. These services include the design and assembly of irradiation capsules as well as arranging for their exposure, disassembly, and return of specimens. During this period, the final design of the facility and specimen baskets was determined through an iterative process involving the designers and thermal analysts. The resulting design should permit the irradiation of all test specimens to within 5{degrees}C of their desired temperature. Detailing of all parts is ongoing and should be completed during the next reporting period. Procurement of the facility will also be initiated during the next review period.

  7. Alaskan Commodities Irradiation Project

    SciTech Connect

    Zarling, J.P.; Swanson, R.B.; Logan, R.R.; Das, D.K.; Lewis, C.E.; Workman, W.G.; Tumeo, M.A.; Hok, C.I.; Birklid, C.A.; Bennett, F.L.

    1988-12-01

    The ninety-ninth US Congress commissioned a six-state food irradiation research and development program to evaluate the commercial potential of this technology. Hawaii, Washington, Iowa, Oklahoma and Florida as well as Alaska have participated in the national program; various food products including fishery products, red meats, tropical and citrus fruits and vegetables have been studied. The purpose of the Alaskan study was to review and evaluate those factors related to the technical and economic feasibility of an irradiator in Alaska. This options analysis study will serve as a basis for determining the state's further involvement in the development of food irradiation technology. 40 refs., 50 figs., 53 tabs.

  8. Neuroprotective properties of tianeptine: interactions with cytokines.

    PubMed

    Plaisant, F; Dommergues, M-A; Spedding, M; Cecchelli, R; Brillault, J; Kato, G; Muñoz, C; Gressens, P

    2003-05-01

    Tianeptine is an antidepressant with proven clinical efficacy and effects on hippocampal plasticity. Hypoxia increased lactate dehydrogenase (LDH) release from cortical neuronal cultures, and tianeptine (1, 10 and 100 microM) inhibited LDH release as efficiently as the N-methyl-D-aspartate (NMDA) antagonist, MK-801. However, tianeptine did not block apoptosis in cultured cortical neurones caused by NMDA, but reduced apoptosis when interleukin-1beta (IL-1beta) was included with NMDA. In 5-day old mice, intracerebral injection of ibotenate induced reproducible lesions in cortex and white matter. Lesion size was markedly reduced by co-administration of MK-801 (1 mg/kg i.p.) but neither by tianeptine or its enantiomers administered acutely (1, 3 or 10 mg/kg i.p.) nor by tianeptine administered chronically (10 mg/kg i.p. for 5 days). Chronic administration of IL-1beta (10 ng/kg i.p. for 5 days) prior to ibotenate injection exacerbated lesion size in cortex and white matter, and this exacerbation was prevented by chronic pre-treatment with tianeptine (10 mg/kg i.p.) or by acute administration of tianeptine (10 mg/kg i.p.) concomitantly with ibotenate. Thus tianeptine has neuroprotective effects against hypoxia in tissue culture and against the deleterious effects of cytokines in cortex and white matter, but not against NMDA receptor-mediated excitotoxicity.

  9. Obligate Ordered Binding of Human Lactogenic Cytokines*

    PubMed Central

    Voorhees, Jeffery L.; Brooks, Charles L.

    2010-01-01

    Class 1 cytokines bind two receptors to create an active heterotrimeric complex. It has been argued that ligand binding to their receptors is an ordered process, but a structural mechanism describing this process has not been determined. We have previously described an obligate ordered binding mechanism for the human prolactin/prolactin receptor heterotrimeric complex. In this work we expand this conceptual understanding of ordered binding to include three human lactogenic hormones: prolactin, growth hormone, and placental lactogen. We independently blocked either of the two receptor binding sites of each hormone and used surface plasmon resonance to measure human prolactin receptor binding kinetics and stoichiometries to the remaining binding surface. When site 1 of any of the three hormones was blocked, site 2 could not bind the receptor. But blocking site 2 did not affect receptor binding at site 1, indicating a requirement for receptor binding to site 1 before site 2 binding. In addition we noted variable responses to the presence of zinc in hormone-receptor interaction. Finally, we performed Förster resonance energy transfer (FRET) analyses where receptor binding at subsaturating stoichiometries induced changes in FRET signaling, indicative of binding-induced changes in hormone conformation, whereas at receptor:hormone ratios in excess of 2:1 no additional changes in FRET signaling were observed. These results strongly support a conformationally mediated obligate-ordered receptor binding for each of the three lactogenic hormones. PMID:20427283

  10. Phototherapy-treated apoptotic tumor cells induce pro-inflammatory cytokines production in macrophage

    NASA Astrophysics Data System (ADS)

    Lu, Cuixia; Wei, Yanchun; Xing, Da

    2014-09-01

    Our previous studies have demonstrated that as a mitochondria-targeting cancer phototherapy, high fluence low-power laser irradiation (HF-LPLI) induces mitochondrial superoxide anion burst, resulting in oxidative damage to tumor cells. In this study, we further explored the immunological effects of HF-LPLI-induced apoptotic tumor cells. When macrophages were co-incubated with apoptotic cells induced by HF-LPLI, we observed the increased levels of TNF-α secretion and NO production in macrophages. Further experiments showed that NF-κB was activated in macrophages after co-incubation with HF-LPLI-induced apoptotic cells, and inhibition of NF-κB activity by pyrrolidinedithiocarbamic acid (PDTC) reduced the elevated levels of TNF-α secretion and NO production. These data indicate that HF-LPLI-induced apoptotic tumor cells induce the secretion of pro-inflammatory cytokines in macrophages, which may be helpful for better understanding the biological effects of cancer phototherapy.

  11. [Cytokines profile and metabolic activity of neutrophils of peripheral blood when progressing neoplasma].

    PubMed

    Abakumova, T V; Antoneeva, I I; Gening, T P; Gening, S O; Dolgova, D R; Fomina, A V

    2014-01-01

    The neutrophil is considered as the peculiar monocelled sekretorny gland realizing the effector potential including by secretion of soluble products - cytokines and for today. Influence of a tumor on functional activity of neutrophils depends on type, localization and a stage of its development. In our research dynamics of metabolic and of neutrophils of peripheral blood, the contents in a lysate and serums of blood of cytokines of IL-1β, 1Ra, 2, 6, 10, 18, TNF-α, IFN-γ and is studied when progressing a cervical cancer. Cytokines and metabolism indicators - activity of, determined by an immunofermental method, level of cationic proteins, a share of active cages in the spontaneous NST-test were cytochemical. It is shown that when progressing cervical cancer against increase in total of neutrophils significant decrease in their, aerobic and anaerobic bacterial action, decrease in the IL-1β and IL-1 Ra level, and also IFN-γ takes place at TNF-α increase, increase of production of matrix metalloproteinas-2 on Ib-IIa of a stage of a disease that allows to assume emergence at this stage of cervical cancer of pro-tumoral effect of neutrophils.

  12. [Time course of changes in serum cytokine levels and the erysipelas clinical pattern].

    PubMed

    Zhukova, L I; Kovtun, E A; Manaeva, D A; Kulbuzheva, M I

    2010-02-01

    The time course of changes in the values of proinflammatory tumor necrosis factor-alpha (TNF-alpha) and IL-8 and the anti-inflammatory cytokine IL-4 has been studied in 78 patients with erysipelas of different frequencies and pathomorphological forms of the disease. In erysipelas and its erythematous form, there is an increase in the levels of TNF-alpha and IL-8 in early phase of the disease, a decrease in these indices during convalescence, and a rise in the content of the cytokine IL-4, which are typical of an acute cyclic infectious process with a good outcome. In recurrent erysipelas and its most severe bullous-hemorrhagic form, there is imbalance in the production of cytokines that are suggestive of that there might be a disease recurrence. In erysipelas patients with a TNF-alpha value of 2.5 pg/ml or less at the onset of the disease, the relative risk for prolonged signs of systemic and local inflammatory reactions increases as compared with those who have a TNF-alpha level of more than 2.5 pg/ml.

  13. Effect of gamma irradiation on the conversion of ginsenoside Rb1 to Rg3

    NASA Astrophysics Data System (ADS)

    Kim, Jae-Hun; Kwon, Sun-Kyu; Sung, Nak-Yun; Jung, Pil-Mun; Choi, Jong-il; Kim, Jae-Kyung; Sharma, Arun K.; Lee, Ju-Woon

    2012-08-01

    Ginsenosides, the most important secondary metabolites in ginseng, have various biological activities. Many studies have focused on the conversion of one of the major ginsenosides, Rb1, to the more active minor ginsenoside, Rg3. This study was carried out to investigate the effect of gamma irradiation on the conversion of Rb1 to Rg3. Rb1 solutions were gamma-irradiated at doses of 10 and 30 kGy and analyzed by high performance liquid chromatography (HPLC). HPLC chromatograms showed a decreased content of Rb1 with increasing irradiation dose, but the content of Rg3 was increased. The highest content of Rg3 was present in the 30 kGy-irradiated Rb1 sample. The cytotoxic effects tested in cancer cell lines were increased in the gamma-irradiated group. Therefore, these results suggest that gamma irradiation can be an effective method for the conversion of the ginsenoside Rb1 to Rg3.

  14. Plant responses to UV-B irradiation are modified by UV-A irradiation

    SciTech Connect

    Middleton, E.M.; Teramura, A.H. Univ. of Maryland, College Park )

    1993-06-01

    The increasing UV-B radiation (0.28-0.32 [mu]m) reaching the earth's surface is an important concern. Plant response in artificial UV-B irradiation studies has been difficult to assess, especially regarding photosynthetic pigments, because the fluorescent lamps also produce UV-A (0.32-0.40[mu]m) radiation which is involved with blue light in pigment synthesis. Both UV-A and UV-B irradiances were controlled in two glasshouse experiments conducted under relatively high PPFD (> 1300[mu]mol m[sup [minus]2] s[sup [minus]1]) at two biologically effective daily UV-B irradiances (10.7 and 14.1 kJ m[sup [minus]2]); UV-A irradiances were matched in Controls ([approximately]5, 9 kJ m[sup [minus]2]). Normal, chlorophyll-deficient, and flavonoid-deficient isolines of soybean cultivar, Clark, were utilized. Many growth/ pigment variables exhibited a statistically significant interaction between light quality and quantity: in general, UV-A radiation moderated the damaging effects of UV-B radiation. Regression analyses demonstrated that a single negative function related photosynthetic efficiency to carotenoid Content (r[sup 2] =0.73, P[le]0.001), implying a [open quotes]cost[close quotes] in maintaining carotenoids for photoprotection. A stomatal limitation to photosynthesis was verified and carotenoid content was correlated with UV-B absorbing compound levels, in UV-B irradiated plants.

  15. Divergent T-Cell Cytokine Patterns in Inflammatory Arthritis

    NASA Astrophysics Data System (ADS)

    Simon, A. K.; Seipelt, E.; Sieper, J.

    1994-08-01

    A major immunoregulatory mechanism in inflammatory infections and allergic diseases is the control of the balance of cytokines secreted by Th1/Th2 subsets of T helper (Th) cells. This might also be true in autoimmune diseases; a Th2 pattern that prevents an effective immune response in infections with intracellular bacteria may favor immunosuppression in autoimmune diseases. The pattern of cytokine expression was compared in the synovial tissue from patients with a typical autoimmune disease, rheumatoid arthritis, and with a disorder with similar synovial pathology but driven by persisting exogenous antigen, reactive arthritis. We screened 12 rheumatoid and 9 reactive arthritis synovial tissues by PCR and in situ hybridization for their expression of T-cell cytokines. The cytokine pattern differs significantly between the two diseases; rheumatoid arthritis samples express a Th1-like pattern whereas in reactive arthritis interferon γ expression is accompanied by that of interleukin 4. Studying the expression of cytokines by in situ hybridization confirmed the results found by PCR; they also show an extremely low frequency of cytokine-transcribing cells. In a double-staining experiment, it was demonstrated that interleukin 4 is made by CD4 cells. These experiments favor the possibility of therapeutic intervention in inflammatory rheumatic diseases by means of inhibitory cytokines.

  16. Cytokines: Names and Numbers You Should Care About

    PubMed Central

    Gan, Poh-Yi

    2015-01-01

    Cytokines play an important role in host defense against microorganisms. They orchestrate innate immunity by inducing protective local inflammation and systemic acute phase responses. Cytokines are important in initiating, amplifying, directing, mediating, and regulating adaptive immunity. Unfortunately, they may also direct tissue damage if excessive responses occur or if they are involved in directing and mediating autoimmunity. Under these circumstances, cytokines are potential therapeutic targets. Over the last 20 years, we have seen the successful development and clinical implementation of biologic strategies that target key cytokines in specific inflammatory diseases with efficacy, specificity, and toxicity profiles challenging conventional drug therapies. These therapies are finding new applications and many new agents show promise. Unfortunately, these new cytokine-based therapies have had little effect on renal disease. This review provides evidence that common renal diseases, including those causing AKI and the autoimmune proliferative and crescentic forms of GN, have cytokine mediation profiles that suggest they would be susceptible to cytokine-targeting therapeutic strategies. PMID:25941193

  17. Cytokines: Names and Numbers You Should Care About.

    PubMed

    Holdsworth, Stephen R; Gan, Poh-Yi

    2015-12-01

    Cytokines play an important role in host defense against microorganisms. They orchestrate innate immunity by inducing protective local inflammation and systemic acute phase responses. Cytokines are important in initiating, amplifying, directing, mediating, and regulating adaptive immunity. Unfortunately, they may also direct tissue damage if excessive responses occur or if they are involved in directing and mediating autoimmunity. Under these circumstances, cytokines are potential therapeutic targets. Over the last 20 years, we have seen the successful development and clinical implementation of biologic strategies that target key cytokines in specific inflammatory diseases with efficacy, specificity, and toxicity profiles challenging conventional drug therapies. These therapies are finding new applications and many new agents show promise. Unfortunately, these new cytokine-based therapies have had little effect on renal disease. This review provides evidence that common renal diseases, including those causing AKI and the autoimmune proliferative and crescentic forms of GN, have cytokine mediation profiles that suggest they would be susceptible to cytokine-targeting therapeutic strategies. PMID:25941193

  18. Modulation of Cytokines in Cancer Patients by Intravenous Ascorbate Therapy

    PubMed Central

    Mikirova, Nina; Riordan, Neil; Casciari, Joseph

    2016-01-01

    Background Cytokines play an important role in tumor angiogenesis and inflammation. There is evidence in the literature that high doses of ascorbate can reduce inflammatory cytokine levels in cancer patients. The objective of this study was to investigate the effect of treatment by intravenous vitamin C (IVC) on cytokines and tumor markers. Material/Methods With the availability of protein array kits allowing assessment of many cytokines in a single sample, we measured 174 cytokines and additional 54 proteins and tumor markers in 12 cancer patients before and after a series of IVC treatments. Results Presented results show for our 12 patients the effect of treatment resulted in normalization of many cytokine levels. Cytokines that were most consistently elevated prior to treatments included M-CSF-R, Leptin, EGF, FGF-6, TNF-α, β, TARC, MCP-1,4, MIP, IL-4, 10, IL-4, and TGF-β. Cytokine levels tended to decrease during the course of treatment. These include mitogens (EGF, Fit-3 ligand, HGF, IGF-1, IL-21R) and chemo-attractants (CTAC, Eotaxin, E-selectin, Lymphotactin, MIP-1, MCP-1, TARC, SDF-1), as well as inflammation and angiogenesis factors (FGF-6, IL-1β, TGF-1). Conclusions We are able to show that average z-scores for several inflammatory and angiogenesis promoting cytokines are positive, indicating that they are higher than averages for healthy controls, and that their levels decreased over the course of treatment. In addition, serum concentrations of tumor markers decreased during the time period of IVC treatment and there were reductions in cMyc and Ras, 2 proteins implicated in being upregulated in cancer. PMID:26724916

  19. Cytokine changes in tears and relationship to contact lens discomfort

    PubMed Central

    Zhao, Zhenjun; Naduvilath, Thomas; Lazon de la Jara, Percy

    2015-01-01

    Purpose To determine the reproducibility of a multiplex bead assay for measuring cytokines in tears and correlations between ocular discomfort with or without contact lens wear and the concentration of cytokines in tears. Methods Ninety participants (divided into two groups) were enrolled in this prospective study. They were asked to rate their ocular comfort and collect their tears in the morning and just before sleep for 10 days with or without contact lenses. The participants collected their tears using a glass microcapillary tube for both stages. Galyfilcon A lenses were worn on a daily disposable basis during the contact lens stage, and comfort scores and tears were collected before lens insertion and prior to lens removal at the end of the day. Tears were analyzed for cytokine concentrations using a 27-plex multibead assay. Correlations were sought between cytokine concentrations and comfort. Results There was a significant (p<0.022) decrease in ocular comfort over the day with or without lens wear. The magnitude of ocular discomfort was significantly greater (p<0.009) with lens wear. The concentrations of 12 cytokines differed significantly between the groups; thus, these cytokines were not analyzed further. For the remaining 15 cytokines, interleukin-8 (IL-8) was the only cytokine that changed in both groups during the day without (reduced by >-0.5 Log pg/ml, p<0.001) or with lens wear (reduced by >-0.2 Log pg/ml, p<0.001). The change in the vascular endothelial growth factor (VEGF) concentration only in tears was correlated to ocular comfort, but this was not changed by contact lens wear. Conclusions Ocular comfort during the day is magnified by contact lens wear. However, the increase in the change in comfort during lens wear was not associated with changes in 15 cytokines in the tear film. PMID:25814827

  20. Ionoluminescence of fused silica under swift ion irradiation

    NASA Astrophysics Data System (ADS)

    Saavedra, R.; Jiménez-Rey, D.; Martin, P.; Vila, R.

    2016-09-01

    Ion beam induced luminescence spectra have been in-situ recorded during He+ (2.5 MeV), O4+ (13.5 MeV) and Si4+ (24.4 MeV) irradiations for three vitreous silica grades with different OH content (KU1, KS-4V and Infrasil 301). Remarkable changes in the ionoluminescence spectra of the three silica grades were observed for low ion fluences. He+ irradiated samples exhibited higher luminescence than equivalent ones irradiated with heavier O4+ and Si4+ ions. KU1 samples with the highest OH content showed the lowest blue luminescence. Blue luminescence maximum during ion irradiations with O4+ and Si4+ ions is correlated with structural changes.

  1. Economics of food irradiation

    SciTech Connect

    Deitch, J.

    1982-01-01

    This article examines the cost competitiveness of the food irradiation process. An analysis of the principal factors--the product, physical plant, irradiation source, and financing--that impact on cost is made. Equations are developed and used to calculate the size of the source for planned product throughput, efficiency factors, power requirements, and operating costs of sources, radionuclides, and accelerators. Methods of financing and capital investment are discussed. A series of tables show cost breakdowns of sources, buildings, equipment, and essential support facilities for both a cobalt-60 and a 10-MeV electron accelerator facility. Additional tables present irradiation costs as functions of a number of parameters--power input, source size, dose, and hours of annual operation. The use of the numbers in the tables are explained by examples of calculations of the irradiation costs for disinfestation of grains and radicidation of feed.

  2. Electron Irradiation Damage in Quartz

    NASA Astrophysics Data System (ADS)

    Ayensu, Akwasi; Ocran, John

    2002-03-01

    Transmission electron microscopy for observing highly beam sensitive materials had been used to study the microstructure of deformed quartz crystals. At 100 kV accelerating voltage and electron flux of 3 x 10^8 e/cm2/s, beam spots damage appeared within five minutes of exposure to the electron beam. The rate of damage was found to depend on the crystal type; in particular, on the OH content and initial defect density, since these factors controlled the plasticity of quartz. The electron irradiation damage was manifested as black spots, prismatic dislocation loops, defect clusters, hairpin shaped images of dislocations and long segements of dislocation loops. The observed microstructure indicate that during electron beam irradiation, the primary defects in quartz attained sufficiently high mobilities permitting large-scale recombination and clustering leading to rapid creation of secondary defects from the clustering processes. The number of electrons that are lost by the recombination process is determined by the density of the recombination centres and the probability that an electron will interact with the centre.

  3. LPS-induced cytokine production in human dendritic cells is regulated by sialidase activity

    PubMed Central

    Stamatos, Nicholas M.; Carubelli, Ivan; van de Vlekkert, Diantha; Bonten, Erik J.; Papini, Nadia; Feng, Chiguang; Venerando, Bruno; d'Azzo, Alessandra; Cross, Alan S.; Wang, Lai-Xi; Gomatos, Peter J.

    2010-01-01

    Removal of sialic acid from glycoconjugates on the surface of monocytes enhances their response to bacterial LPS. We tested the hypothesis that endogenous sialidase activity creates a permissive state for LPS-induced cytokine production in human monocyte-derived DCs. Of the four genetically distinct sialidases (Neu1–4), Neu1, Neu3, and Neu4 are expressed in human monocytes, but only Neu1 and Neu3 are up-regulated as cells differentiate into DCs. Neu1 and Neu3 are present on the surface of monocytes and DCs and are also present intracellularly. DCs contain a greater amount of sialic acid than monocytes, but the amount of sialic acid/mg total protein declines during differentiation to DCs. This relative hyposialylation of cells does not occur in mature DCs grown in the presence of zanamivir, a pharmacologic inhibitor of Neu3 but not Neu1, or DANA, an inhibitor of Neu1 and Neu3. Inhibition of sialidase activity during differentiation to DCs causes no detectable change in cell viability or expression of DC surface markers. Differentiation of monocytes into DCs in the presence of zanamivir results in reduced LPS- induced expression of IL-6, IL-12p40, and TNF-α by mature DCs, demonstrating a role for Neu3 in cytokine production. A role for Neu3 is supported by inhibition of cytokine production by DANA in DCs from Neu1–/– and WT mice. We conclude that sialidase-mediated change in sialic acid content of specific cell surface glycoconjugates in DCs regulates LPS-induced cytokine production, thereby contributing to development of adaptive immune responses. PMID:20826611

  4. Multiparameter screening reveals a role for Na+ channels in cytokine-induced β-cell death.

    PubMed

    Yang, Yu Hsuan Carol; Vilin, Yury Y; Roberge, Michel; Kurata, Harley T; Johnson, James D

    2014-03-01

    Pancreatic β-cell death plays a role in both type 1 and type 2 diabetes, but clinical treatments that specifically target β-cell survival have not yet been developed. We have recently developed live-cell imaging-based, high-throughput screening methods capable of identifying factors that modulate pancreatic β-cell death, with the hope of finding drugs that can intervene in this process. In the present study, we used a high-content screen and the Prestwick Chemical Library of small molecules to identify drugs that block cell death resulting from exposure to a cocktail of cytotoxic cytokines (25 ng/mL TNF-α, 10 ng/mL IL-1β, and 10 ng/mL IFN-γ). Data analysis with self-organizing maps revealed that 19 drugs had profiles similar to that of the no cytokine condition, indicating protection. Carbamazepine, an antiepileptic Na(+) channel inhibitor, was particularly interesting because Na(+) channels are not generally considered targets for antiapoptotic therapy in diabetes and because the function of these channels in β-cells has not been well studied. We analyzed the expression and characteristics of Na(+) currents in mature β-cells from MIP-GFP mice. We confirmed the dose-dependent protective effects of carbamazepine and another use-dependent Na(+) channel blocker in cytokine-treated mouse islet cells. Carbamazepine down-regulated the proapoptotic and endoplasmic reticulum stress signaling induced by cytokines. Together, these studies point to Na(+) channels as a novel therapeutic target in diabetes. PMID:24438339

  5. Nature versus nurture in T cell cytokine production.

    PubMed

    Fitzpatrick, D R; Kelso, A

    1999-12-01

    Both extrinsic and intrinsic factors influence the development of cytokine expression patterns in T lymphocytes. The models proposed to accommodate these factors are often separated into two types: deterministic (or instructional) and probabilistic (or stochastic). In this review we compare these two types of models and examine how they account for different stages of T cell cytokine responses to antigen stimulation. We conclude by showing how a reconciliation of the two types of models may be possible, perhaps through the regulatory potential of heritable epigenetic mechanisms. This type of reconciliation may open up new avenues for manipulating T cell cytokine expression and redirecting immune responses. PMID:10614767

  6. The Role of Suppressors of Cytokine Signalling in Human Neoplasms

    PubMed Central

    Sharma, Anup K.; Mokbel, Kefah

    2014-01-01

    Suppressors of cytokine signalling 1–7 (SOCS1–7) and cytokine-inducible SH2-containing protein (CIS) are a group of intracellular proteins that are well known as JAK-STAT and several other signalling pathways negative feedback regulators. More recently several members have been identified as tumour suppressors and dysregulation of their biological roles in controlling cytokine and growth factor signalling may contribute to the development of many solid organ and haematological malignancies. This review explores their biological functions and their possible tumour suppressing role in human neoplasms. PMID:24757565

  7. Role of Sucrose in Gamma-irradiated Chrysanthemum Cut Flowers.

    PubMed

    Nakahara, K; Kikuchi, O K; Todoriki, S; Hosoda, H; Hayashi, T

    1998-01-01

    Vase solution containing 2% sucrose prevented the deterioration of chrysanthemum (Dendranthema grandiflorum Kitamura) cut flowers induced by gamma-rays at 750 Gy. Glucose, fructose, and sucrose in florets and leaves of irradiated chrysanthemums decreased more rapidly than those of unirradiated ones, when the cut chrysanthemums were held in a vase solution without sucrose. The sugar contents of florets and leaves and the respiratory rate of irradiated chrysanthemums held with sucrose remained at higher levels than those of unirradiated ones. Incorporation of (14)C from [(14)C]sucrose into CO2 was increased by irradiation. Incorporation of [α-(32)P]dTTP into trichloroacetic acid (TCA) insoluble substances in florets was increased by irradiation and by exogenous sucrose supply. These results suggest that sucrose in a vase solution was used as a respiratory substrate and facilitated the repair of radiation-induced damage, resulting in the extension of longevity of irradiated chrysanthemums.

  8. Gamma irradiation of corn starches with different amylose-to-amylopectin ratio.

    PubMed

    Chung, Kok-Heung; Othman, Zainon; Lee, Jau-Shya

    2015-10-01

    Corn starches with different amylose-to-amylopectin ratio (waxy, normal, Hylon V, and Hylon VII) were treated with five doses of gamma irradiation (1, 5, 10, 25, and 50 kGy). The effects of gamma irradiation on the physicochemical properties of starch samples were investigated. Waxy samples showed an increase of amylose-like fractions when irradiated at 10 kGy. The reduction in apparent amylose content increased with amylose content when underwent irradiation at 25 and 50 kGy. Low amylose starches lost their pasting ability when irradiated at 25 and 50 kGy. Results from thermal behavior and pasting profile suggested that low level of cross-linking occurred in Hylon VII samples irradiated at 5 kGy. Severe reduction in pasting properties, gelatinization temperatures and relative crystallinity with increasing irradiation intensity revealed that waxy samples were affected more by gamma irradiation; this also indicated amylopectin was the starch fraction most affected by gamma irradiation. Alteration level was portrayed differently when different kind of physicochemical properties were investigated, in which the pasting properties and crystallinity of starches were more immensely influenced by gamma irradiation while thermal behavior was less affected. Despite the irradiation level, the morphology and crystal pattern of starch granules were found remain unchanged by irradiation. PMID:26396368

  9. Reactivation of Herpes Simplex Virus Type 1 in the Mouse Trigeminal Ganglion: an In Vivo Study of Virus Antigen and Cytokines

    PubMed Central

    Shimeld, Carolyn; Easty, David L.; Hill, Terry J.

    1999-01-01

    Reactivation of herpes simplex virus type 1 (HSV-1) in the trigeminal ganglion (TG) was induced by UV irradiation of the corneas of latently infected mice. Immunocytochemistry was used to monitor the dynamics of cytokine (interleukin-2 [IL-2], IL-4, IL-6, IL-10, gamma interferon [IFN-γ], and tumor necrosis factor alpha [TNF-α]) and viral antigen production in the TG and the adjacent central nervous system on days 1 to 4, 6, 7, and 10 after irradiation. UV irradiation induced increased expression of IL-6 and TNF-α from satellite cells in uninfected TG. In latently infected TG, prior to reactivation, all satellite cells were TNF-α+ and most were also IL-6+. Reactivation, evidenced by HSV-1 antigens and/or infiltrating immune cells, occurred in 28 of 45 (62%) TG samples. Viral antigens were present in the TG in neurons, often disintegrating on days 2 to 6 after irradiation. Infected neurons were usually surrounded by satellite cells and the foci of immune cells producing TNF-α and/or IL-6. IL-4+ cells were detected as early as day 3 and were more numerous by day 10 (a very few IL-2+ and/or IFN-γ+ cells were seen at this time). No IL-10 was detected at any time. Our observations indicate that UV irradiation of the cornea may modulate cytokine production by satellite cells. We confirm that neurons are the site of reactivation and that they probably do not survive this event. The predominance of TNF-α and IL-6 following reactivation parallels primary infection in the TG and suggests a role in viral clearance. The presence of Th2-type cytokines (IL-4 and IL-6) indicates a role for antibody. Thus, several clearance mechanisms may be at work. PMID:9971753

  10. Total lymphoid irradiation

    SciTech Connect

    Sutherland, D.E.; Ferguson, R.M.; Simmons, R.L.; Kim, T.H.; Slavin, S.; Najarian, J.S.

    1983-05-01

    Total lymphoid irradiation by itself can produce sufficient immunosuppression to prolong the survival of a variety of organ allografts in experimental animals. The degree of prolongation is dose-dependent and is limited by the toxicity that occurs with higher doses. Total lymphoid irradiation is more effective before transplantation than after, but when used after transplantation can be combined with pharmacologic immunosuppression to achieve a positive effect. In some animal models, total lymphoid irradiation induces an environment in which fully allogeneic bone marrow will engraft and induce permanent chimerism in the recipients who are then tolerant to organ allografts from the donor strain. If total lymphoid irradiation is ever to have clinical applicability on a large scale, it would seem that it would have to be under circumstances in which tolerance can be induced. However, in some animal models graft-versus-host disease occurs following bone marrow transplantation, and methods to obviate its occurrence probably will be needed if this approach is to be applied clinically. In recent years, patient and graft survival rates in renal allograft recipients treated with conventional immunosuppression have improved considerably, and thus the impetus to utilize total lymphoid irradiation for its immunosuppressive effect alone is less compelling. The future of total lymphoid irradiation probably lies in devising protocols in which maintenance immunosuppression can be eliminated, or nearly eliminated, altogether. Such protocols are effective in rodents. Whether they can be applied to clinical transplantation remains to be seen.

  11. IL-35 is a novel responsive anti-inflammatory cytokine--a new system of categorizing anti-inflammatory cytokines.

    PubMed

    Li, Xinyuan; Mai, Jietang; Virtue, Anthony; Yin, Ying; Gong, Ren; Sha, Xiaojin; Gutchigian, Stefanie; Frisch, Andrew; Hodge, Imani; Jiang, Xiaohua; Wang, Hong; Yang, Xiao-Feng

    2012-01-01

    It remains unknown whether newly identified anti-inflammatory/immunosuppressive cytokine interleukin-35 (IL-35) is different from other anti-inflammatory cytokines such as IL-10 and transforming growth factor (TGF)-β in terms of inhibition of inflammation initiation and suppression of full-blown inflammation. Using experimental database mining and statistical analysis methods we developed, we examined the tissue expression profiles and regulatory mechanisms of IL-35 in comparison to other anti-inflammatory cytokines. Our results suggest that in contrast to TGF-β, IL-35 is not constitutively expressed in human tissues but it is inducible in response to inflammatory stimuli. We also provide structural evidence that AU-rich element (ARE) binding proteins and microRNAs target IL-35 subunit transcripts, by which IL-35 may achieve non-constitutive expression status. Furthermore, we propose a new system to categorize anti-inflammatory cytokines into two groups: (1) the house-keeping cytokines, such as TGF-β, inhibit the initiation of inflammation whereas (2) the responsive cytokines including IL-35 suppress inflammation in full-blown stage. Our in-depth analyses of molecular events that regulate the production of IL-35 as well as the new categorization system of anti-inflammatory cytokines are important for the design of new strategies of immune therapies.

  12. TREK-1 Regulates Cytokine Secretion from Cultured Human Alveolar Epithelial Cells Independently of Cytoskeletal Rearrangements

    PubMed Central

    Schwingshackl, Andreas; Roan, Esra; Teng, Bin; Waters, Christopher M.

    2015-01-01

    Background TREK-1 deficient alveolar epithelial cells (AECs) secrete less IL-6, more MCP-1, and contain less F-actin. Whether these alterations in cytokine secretion and F-actin content are related remains unknown. We now hypothesized that cytokine secretion from TREK-1-deficient AECs was regulated by cytoskeletal rearrangements. Methods We determined F-actin and α-tubulin contents of control, TREK-1-deficient and TREK-1-overexpressing human A549 cells by confocal microscopy and western blotting, and measured IL-6 and MCP-1 levels using real-time PCR and ELISA. Results Cytochalasin D decreased the F-actin content of control cells. Jasplakinolide increased the F-actin content of TREK-1 deficient cells, similar to the effect of TREK-1 overexpression in control cells. Treatment of control and TREK-1 deficient cells with TNF-α, a strong stimulus for IL-6 and MCP-1 secretion, had no effect on F-actin structures. The combination of TNF-α+cytochalasin D or TNF-α+jasplakinolide had no additional effect on the F-actin content or architecture when compared to cytochalasin D or jasplakinolide alone. Although TREK-1 deficient AECs contained less F-actin at baseline, quantified biochemically, they contained more α-tubulin. Exposure to nocodazole disrupted α-tubulin filaments in control and TREK-1 deficient cells, but left the overall amount of α-tubulin unchanged. Although TNF-α had no effect on the F-actin or α-tubulin contents, it increased IL-6 and MCP-1 production and secretion from control and TREK-1 deficient cells. IL-6 and MCP-1 secretions from control and TREK-1 deficient cells after TNF-α+jasplakinolide or TNF-α+nocodazole treatment was similar to the effect of TNF-α alone. Interestingly, cytochalasin D decreased TNF-α-induced IL-6 but not MCP-1 secretion from control but not TREK-1 deficient cells. Conclusion Although cytochalasin D, jasplakinolide and nocodazole altered the F-actin and α-tubulin structures of control and TREK-1 deficient AEC, the

  13. Study on dehydrochlorination of waste poly (vinyl chloride) resins by microwave irradiation

    NASA Astrophysics Data System (ADS)

    Moriwaki, Saburo; Qian, Qingrong; Sunohara, Satoshi; Machida, Motoi; Tatsumoto, Hideki

    Waste poly (vinyl chloride: PVC) resins are experimentally dehydrochlorinated by microwave irradiation. The following unique results are obtained: (1) plasticizer in PVC resin absorbs microwave power more effectively than PVC polymer. The higher the plasticizer content in PVC resin, the higher is the dehydrochlorination reaction (2) low PVC polymer content materials such as cushion floor require high microwave irradiation power to secure a high dehydrochlorination yield, (3) calcium carbonate in PVC resin reacts with released hydrochloric acid gas and results calcium chloride during microwave irradiation, (4) additives in PVC resin strongly influence dehydrochlorination yield, (5) it is evidenced that the PVC copolymer is also dehydrochlorinated by microwave irradiation.

  14. Effect of heavy ion irradiation on C 60

    NASA Astrophysics Data System (ADS)

    Lotha, S.; Ingale, A.; Avasthi, D. K.; Mittal, V. K.; Mishra, S.; Rustagi, K. C.; Gupta, A.; Kulkarni, V. N.; Khathing, D. T.

    1999-06-01

    Thin films of C 60 were subjected to swift heavy ion irradiation spanning the region from 2 to 11 keV/nm of electronic excitation. Studies of the irradiated films by Raman spectroscopy indicated polymerization and damage of the film with an ion fluence. The ion track radii are estimated for various ions using the Raman data. Photoluminescence spectroscopy of the irradiated film indicated a decrease in the C 60 phase with a dose, and an increase in the intensity at the 590 nm wavelength, which is attributed to an increase in the oxygen content.

  15. High efficiency cell-specific targeting of cytokine activity

    NASA Astrophysics Data System (ADS)

    Garcin, Geneviève; Paul, Franciane; Staufenbiel, Markus; Bordat, Yann; van der Heyden, José; Wilmes, Stephan; Cartron, Guillaume; Apparailly, Florence; de Koker, Stefaan; Piehler, Jacob; Tavernier, Jan; Uzé, Gilles

    2014-01-01

    Systemic toxicity currently prevents exploiting the huge potential of many cytokines for medical applications. Here we present a novel strategy to engineer immunocytokines with very high targeting efficacies. The method lies in the use of mutants of toxic cytokines that markedly reduce their receptor-binding affinities, and that are thus rendered essentially inactive. Upon fusion to nanobodies specifically binding to marker proteins, activity of these cytokines is selectively restored for cell populations expressing this marker. This ‘activity-by-targeting’ concept was validated for type I interferons and leptin. In the case of interferon, activity can be directed to target cells in vitro and to selected cell populations in mice, with up to 1,000-fold increased specific activity. This targeting strategy holds promise to revitalize the clinical potential of many cytokines.

  16. AMBIENT PARTICULATE MATTER DECREASED IN HUMAN ALVEOLAR MACHROPHAGE CYTOKINE RELEASE

    EPA Science Inventory

    Human exposure to ambient airborne particulate matter (PM) is associated with cardiopulmonary mortality and morbidity, including increased hospitalizations for lung infection. Normal lung immune responses to bacterial infection include alveolar macrophage cytokine production and...

  17. Dendritic cells and cytokines in immune rejection of cancer.

    PubMed

    Ferrantini, Maria; Capone, Imerio; Belardelli, Filippo

    2008-02-01

    Dendritic cells (DCs) play a crucial role in linking innate and adaptive immunity and, thus, in the generation of a protective immune response against both infectious diseases and tumors. The ability of DCs to prime and expand an immune response is regulated by signals acting through soluble mediators, mainly cytokines and chemokines. Understanding how cytokines influence DC functions and orchestrate the interactions of DCs with other immune cells is strictly instrumental to the progress in cancer immunotherapy. Herein, we will illustrate how certain cytokines and immune stimulating molecules can induce and sustain the antitumor immune response by acting on DCs. We will also discuss these cytokine-DC interactions in the light of clinical results in cancer patients. PMID:18054517

  18. Helper T cells and atherosclerosis: the cytokine web

    PubMed Central

    Baidya, S; Zeng, Q

    2005-01-01

    There is growing evidence regarding the importance of inflammation in the pathogenesis of atherosclerosis and its ultimate progression to the clinical syndromes. Recently there has been an increasing interest in the role of helper T (Th) cells in atherosclerosis. The Th cells act with the macrophages and the dendritic cells via the various cytokines in bringing about a variety of changes thus leading to the progression of atherosclerosis. Atherosclerotic lesions have been seen to have increased expression of type 1 helper T (TH1) cells together with increased levels of the Th1 related cytokines. It is mainly the cytokines involved with Th1 functioning that seem to show a prominent effect, with the whole process centred around interferon gamma, making it seem like every pathway and the cytokines involved lead to a final common pathway of interferon gamma secretion; the increase or decrease of which dictates the progression of atherosclerosis and its final manifestation as the clinical syndromes. PMID:16344296

  19. Irradiation and food processing.

    PubMed

    Sigurbjörnsson, B; Loaharanu, P

    1989-01-01

    After more than four decades of research and development, food irradiation has been demonstrated to be safe, effective and versatile as a process of food preservation, decontamination or disinfection. Its various applications cover: inhibition of sprouting of root crops; insect disinfestation of stored products, fresh and dried food; shelf-life extension of fresh fruits, vegetables, meat and fish; destruction of parasites and pathogenic micro-organisms in food of animal origin; decontamination of spices and food ingredients, etc. Such applications provide consumers with the increase in variety, volume and value of food. Although regulations on food irradiation in different countries are largely unharmonized, national authorities have shown increasing recognition and acceptance of this technology based on the Codex Standard for Irradiated Foods and its associated Code of Practice. Harmonization of national legislations represents an important prerequisite to international trade in irradiated food. Consumers at large are still not aware of the safety and benefits that food irradiation has to offer. Thus, national and international organizations, food industry, trade associations and consumer unions have important roles to play in introducing this technology based on its scientific values. Public acceptance of food irradiation may be slow at the beginning, but should increase at a faster rate in the foreseeable future when consumers are well informed of the safety and benefits of this technology in comparison with existing ones. Commercial applications of food irradiation has already started in 18 countries at present. The volume of food or ingredients treated on a commercial scale varies from country to country ranging from several tons of spices to hundreds of thousands of tons of grains per annum. With the increasing interest of national authorities and the food industry in applying the process, it is anticipated that some 25 countries will use some 55 commercial

  20. Quantitative analysis of cytokine-induced vascular toxicity and vascular leak in the mouse brain.

    PubMed

    Irwan, Yetty Y; Feng, Yi; Gach, H Michael; Symanowski, James T; McGregor, John R; Veni, Gopalkrishna; Schabel, Matthias; Samlowski, Wolfram E

    2009-09-30

    A storm of inflammatory cytokines is released during treatment with pro-inflammatory cytokines, such as interleukin-2 (IL-2), closely approximating changes initially observed during sepsis. These signals induce profound changes in neurologic function and cognition. Little is known about the mechanisms involved. We evaluated a number of experimental methods to quantify changes in brain blood vessel integrity in a well-characterized IL-2 treatment mouse model. Measurement of wet versus dry weight and direct measurement of small molecule accumulation (e.g. [(3)H]-H(2)O, sodium fluorescein) were not sensitive or reliable enough to detect small changes in mouse brain vascular permeability. Estimation of brain water content using proton density magnetic resonance imaging (MRI) measurements using a 7T mouse MRI system was sensitive to 1-2% changes in brain water content, but was difficult to reproduce in replicate experiments. Successful techniques included use of immunohistochemistry using specific endothelial markers to identify vasodilation in carefully matched regions of brain parenchyma and dynamic contrast enhanced (DCE) MRI. Both techniques indicated that IL-2 treatment induced vasodilation of the brain blood vessels. DCE MRI further showed a 2-fold increase in the brain blood vessel permeability to gadolinium in IL-2 treated mice compared to controls. Both immunohistochemistry and DCE MRI data suggested that IL-2 induced toxicity in the brain results from vasodilation of the brain blood vessels and increased microvascular permeability, resulting in perivascular edema. These experimental techniques provide us with the tools to further characterize the mechanism responsible for cytokine-induced neuropsychiatric toxicity.

  1. A genetically encoded bioluminescent indicator for illuminating proinflammatory cytokines.

    PubMed

    Kim, Sung Bae; Ozawa, Takeaki; Umezawa, Yoshio

    2016-01-01

    We introduce a method to evaluate the activities of cytokines based on the nuclear transport of NF-κB. A pair of bioluminescent indicators was made for conferring cytokine sensitivity to cervical carcinoma-derived HeLa cells. The principle is based on reconstitution of split fragments of Renilla reniformis luciferase (RLuc) by protein splicing with a DnaE intein from Synechocystis sp. PCC6803. The bioluminescence intensity of thus reconstituted RLuc in the HeLa cells was used as a measure of the activities for cytokines. With the present method, we evaluated the activities of various cytokines based on the nuclear transport of NF-κB in human cervical carcinoma-derived HeLa cells carrying the indicators. The present approach to evaluating the activities of cytokines may provide a potential clinical value in monitoring drug activity and directing treatment for various diseases related with NF-κB. The method highlights the experimental procedure from our original publications, Anal. Biochem. 2006, 359, 147-149 and Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 11542. The summary of the method is: •Cytokine activities are determined within 2 h after stimulation.•Temporarily inactivated split-luciferase fragments are reconstituted by protein splicing.•Nucleartrafficking of NF-κB was illuminated for gauging the ligand-driven activity. PMID:27489781

  2. Multidimensional scaling of multiplex data: human milk cytokines.

    PubMed

    Groer, Maureen W; Beckstead, Jason W

    2011-07-01

    The purpose of this study was to use multidimensional scaling (MDS) and cluster-analytic techniques to examine how cytokine levels from a large multiplex assay of human milk samples covary. Milk samples were collected at 4-6 weeks postpartum from 57 women and were assayed by Luminex multiplex technology for 20 cytokines, chemokines, and growth factors. The MDS was applied to a proximity-score matrix based on these values. A three-dimensional (3D) space was sufficient to accommodate the configuration of relationships. Cytokines that covaried in their concentrations were assigned similar coordinates and plotted close together in 3D space. Several clusters of cytokines were identified. Since very little is known about the origins and functions of cytokines in milk, this approach may provide new clues that will guide future explorations of origins and functional relationships of the separate clusters. This analytical tool may provide a new approach to understanding the physiology of milk cytokines and may be generalizable to multiplex data in general.

  3. Cerebrospinal Fluid Inflammatory Cytokines and Aggression in Personality Disordered Subjects

    PubMed Central

    Lee, Royce; Coussons-Read, Mary

    2015-01-01

    Background: Neurochemical studies have pointed to a modulatory role in human aggression for a variety of central neurotransmitters and neuromodulators such as cytokines. While animal studies of cytokines suggest an aggression-facilitating role for central cytokines, especially for interleukin-1β and other cytokines, no cerebrospinal fluid studies of cytokines have yet been reported in regard to human aggression. Methods: Basal lumbar cerebrospinal fluid samples were obtained from 38 physically healthy subjects with DSM-5 Personality Disorder and assayed for cerebrospinal fluid interleukin-6 (log IL-6) and cerebrospinal fluid soluble IL-1 Receptor II protein in the context of their relationship with measures of aggression. Results: Cerebrospinal fluid soluble interleukin-1 Receptor II (r=.35, r2 = .12, P= .03), but not log interleukin-6 (r = -.05, r2 = .00, P= .76), levels were positively correlated with a composite measure of aggression. Adding relevant covariates, including cerebrospinal fluid levels of serotonin and dopamine metabolites, to the statistical model doubled the strength of this relationship (partial r = .54, r2 = .29, P= .002). No relationship was seen with history of suicidal behavior or with any measure of impulsivity, negative affectivity, or of general dimensions of personality. Conclusion: These data suggest a positive relationship between at least one inflammatory cytokine in the central nervous system and aggression in human subjects. This finding adds to the complex picture of the central neurochemistry of impulsive aggression in human subjects. PMID:25650410

  4. Effects of antidepressants on cytokine production and actions.

    PubMed

    Castanon, Nathalie; Leonard, Brian E; Neveu, Pierre J; Yirmiya, Raz

    2002-10-01

    There are intriguing analogies between many features of depression and physiological and behavioral responses to infection, which are mediated by the brain effects of cytokines. These observations suggest that depression can be considered as a psychoneuroimmunological disorder where a central increase of pro-inflammatory cytokines, may have adverse consequences on the functional activity of the neurochemical and neuroendocrine systems implicated in the symptoms of the disorder. According to this hypothesis, the therapeutic effects of antidepressants should be at least partly exerted by attenuating the brain expression and/or actions of pro-inflammatory cytokines. Despite their inherent limitations, animal models of depression that are based on behavioral and pharmacological analogies with the symptoms observed in humans, represent the best available tool to test this hypothesis and to investigate the action mechanisms of the immune effects of antidepressants. Treatment with different classes of antidepressants indeed conferred protection against cytokine-induced depressive-like biological and behavioral changes. This 'anti-inflammatory' profile may be due to alterations of the pro-/anti-inflammatory cytokine balance. The mechanisms underlying these effects of antidepressants are presently unknown, but the available literature suggests several possibilities, including actions on different molecules representing potential mediators of mood disorders induced by cytokines. The studies summarized in this review have opened up new vistas in both the pathophysiology of depression and the pharmacology of antidepressants. Whether their demonstrated immune effects are a side effect or a significant part of their clinical activity still remains to be elucidated.

  5. Cardiac oxidative stress and inflammatory cytokines response after myocardial infarction.

    PubMed

    Neri, Margherita; Fineschi, Vittorio; Di Paolo, Marco; Pomara, Cristoforo; Riezzo, Irene; Turillazzi, Emanuela; Cerretani, Daniela

    2015-01-01

    Oxidative stress in heart failure or during ischemia/reperfusion occurs as a result of the excessive generation or accumulation of free radicals or their oxidation products. Free radicals formed during oxidative stress can initiate lipid peroxidation, oxidize proteins to inactive states and cause DNA strand breaks. Oxidative stress is a condition in which oxidant metabolites exert toxic effects because of their increased production or an altered cellular mechanism of protection. In the early phase of acute heart ischemia cytokines have the feature to be functional pleiotropy and redundancy, moreover, several cytokines exert similar and overlapping actions on the same cell type and one cytokine shows a wide range of biological effects on various cell types. Activation of cytokine cascades in the infarcted myocardium was established in numerous studies. In experimental models of myocardial infarction, induction and release of the pro-inflammatory cytokines like TNF-α (Tumor Necrosis Factor α), IL-1β (Interleukin- 1β) and IL-6 (Interleukin-6) and chemokines are steadily described. The current review examines the role of oxidative stress and pro-inflammatory cytokines response following acute myocardial infarction and explores the inflammatory mechanisms of cardiac injury.

  6. Ultraviolet irradiation in transplantation biology. Manipulation of immunity and immunogenicity

    SciTech Connect

    Deeg, H.J.

    1988-05-01

    Ultraviolet irradiation, particularly in the UVB range, has profound effects on immunological mechanisms. Optimum and tolerable doses of exposure vary from species to species, and from organ to organ. As a result of limited depth penetration and possibly significant energy absorption in nontargeted cells, every model requires diligent determination of an effective nontoxic approach. Nevertheless, it is clear that UVB and UVC irradiation can abolish proliferative and stimulatory ability as well as accessory/antigen-presenting ability of leukocytes in vitro. UV treatment alters cell-surface properties, calcium mobilization, cytokine production and release, and other subcellular processes. Preliminary data suggest that these manipulations also suppress immunity and reduce immunogenicity in vivo. Exposure of solid organs and of large volumes of blood is difficult due to technical problems--in particular poor depth penetration and absorption of UV energy in generally available transfusion bags. 111 references.

  7. Inhibition of Ultraviolet B-Induced Expression of the Proinflammatory Cytokines TNF-α and VEGF in the Cornea by Fucoxanthin Treatment in a Rat Model

    PubMed Central

    Chen, Shiu-Jau; Lee, Ching-Ju; Lin, Tzer-Bin; Liu, Hsiang-Jui; Huang, Shuan-Yu; Chen, Jia-Zeng; Tseng, Kuang-Wen

    2016-01-01

    Ultraviolet B (UVB) irradiation is the most common cause of radiation damage to the eyeball and is a risk factor for human corneal damage. We determined the protective effect of fucoxanthin, which is a carotenoid found in common edible seaweed, on ocular tissues against oxidative UVB-induced corneal injury. The experimental rats were intravenously injected with fucoxanthin at doses of 0.5, 5 mg/kg body weight/day or with a vehicle before UVB irradiation. Lissamine green for corneal surface staining showed that UVB irradiation caused serious damage on the corneal surface, including severe epithelial exfoliation and deteriorated epithelial smoothness. Histopathological lesion examination revealed that levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF), significantly increased. However, pretreatment with fucoxanthin inhibited UVB radiation-induced corneal disorders including evident preservation of corneal surface smoothness, downregulation of proinflammatory cytokine expression, and decrease of infiltrated polymorphonuclear leukocytes from UVB-induced damage. Moreover, significant preservation of the epithelial integrity and inhibition of stromal swelling were also observed after UVB irradiation in fucoxanthin-treated groups. Pretreatment with fucoxanthin may protect against UVB radiation-induced corneal disorders by inhibiting expression of proinflammatory factors, TNF-α, and VEGF and by blocking polymorphonuclear leukocyte infiltration. PMID:26751458

  8. Effect of gamma irradiation on mistletoe (Viscum album) lectin-mediated toxicity and immunomodulatory activity☆

    PubMed Central

    Sung, Nak-Yun; Byun, Eui-Baek; Song, Du-Sup; Jin, Yeung-Bae; Kim, Jae-Kyung; Park, Jong-Heum; Song, Beom-Seok; Jung, Pil-Mun; Byun, Myung-Woo; Lee, Ju-Woon; Park, Sang-Hyun; Kim, Jae-Hun

    2013-01-01

    This study evaluated the effect of gamma irradiation on the reduction of the toxicity of mistletoe lectin using both in vitro and in vivo models. To extract the lectin from mistletoe, an (NH4)2SO4 precipitation method was employed and the precipitant purified using a Sepharose 4B column to obtain the pure lectin fraction. Purified lectin was then gamma-irradiated at doses of 0, 5, 10, 15, and 20 kGy, or heated at 100 °C for 30 min. Toxic effects of non-irradiated, irradiated, and heat-treated lectins were tested using hemagglutination assays, cytotoxicity assays, hepatotoxicity, and a mouse survival test and immunological response was tested using cytokine production activity. Hemagglutination of lectin was remarkably decreased (P < 0.05) by irradiation at doses exceeding 10 kGy and with heat treatment. However, lectin irradiated with 5 kGy maintained its hemagglutination activity. The cytotoxicity of lectin was decreased by irradiation at doses over 5 kGy and with heat treatment. In experiments using mouse model, glutamate oxaloacetate transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels were decreased in the group treated with the 5 kGy irradiated and heat-treated lectins as compared to the intact lectin, and it was also shown that 5 kGy irradiated and heat-treated lectins did not cause damage in liver tissue or mortality. In the result of immunological response, tumor necrosis factor (TNF-α) and interleukin (IL-6) levels were significantly (P < 0.05) increased in the 5 kGy gamma-irradiated lectin treated group. These results indicate that 5 kGy irradiated lectin still maintained the immunological response with reduction of toxicity. Therefore, gamma-irradiation may be an effective method for reducing the toxicity of lectin maintaining the immune response. PMID:23847758

  9. ORNL irradiation creep facility

    SciTech Connect

    Reiley, T.C.; Auble, R.L.; Beckers, R.M.; Bloom, E.E.; Duncan, M.G.; Saltmarsh, M.J.; Shannon, R.H.

    1980-09-01

    A machine was developed at ORNL to measure the rates of elongation observed under irradiation in stressed materials. The source of radiation is a beam of 60 MeV alpha particles from the Oak Ridge Isochronous Cyclotron (ORIC). This choice allows experiments to be performed which simulate the effects of fast neutrons. A brief review of irradiation creep and experimental constraints associated with each measurement technique is given. Factors are presented which lead to the experimental choices made for the Irradiation Creep Facility (ICF). The ICF consists of a helium-filled chamber which houses a high-precision mechanical testing device. The specimen to be tested must be thermally stabilized with respect to the temperature fluctuations imposed by the particle beam which passes through the specimen. Electrical resistance of the specimen is the temperature control parameter chosen. Very high precision in length measurement and temperature control are required to detect the small elongation rates relevant to irradiation creep in the test periods available (approx. 1 day). The apparatus components and features required for the above are presented in some detail, along with the experimental procedures. The damage processes associated with light ions are discussed and displacement rates are calculated. Recent irradiation creep results are given, demonstrating the suitability of the apparatus for high resolution experiments. Also discussed is the suitability of the ICF for making high precision thermal creep measurements.

  10. Effect of gamma irradiation on physical characteristics of Jordanian durum wheat and quality of semolina and lasagna products

    NASA Astrophysics Data System (ADS)

    Azzeh, F. S.; Amr, A. S.

    2009-09-01

    This study was conducted to determine the effect of using varying gamma irradiation doses on the physiochemical and rheological properties of semolina and its products. Ash, protein and water content were not influenced with gamma irradiation, while falling number and fungi counts decreased with increasing irradiation dose. Irradiation adversely affected wet gluten at 5 kGy dose. Dough stability was deteriorated vigorously with increasing irradiation dose. Sensory evaluation showed that lasagna produced from 0.25- and 1 kGy-irradiated semolina did not show any significant differences as compared with the control sample.

  11. Cytokines Induced Neutrophil Extracellular Traps Formation: Implication for the Inflammatory Disease Condition

    PubMed Central

    Keshari, Ravi S.; Jyoti, Anupam; Dubey, Megha; Kothari, Nikhil; Kohli, Monica; Bogra, Jaishri; Barthwal, Manoj K.; Dikshit, Madhu

    2012-01-01

    Neutrophils (PMNs) and cytokines have a critical role to play in host defense and systemic inflammatory response syndrome (SIRS). Neutrophil extracellular traps (NETs) have been shown to extracellularly kill pathogens, and inflammatory potential of NETs has been shown. Microbial killing inside the phagosomes or by NETs is mediated by reactive oxygen and nitrogen species (ROS/RNS). The present study was undertaken to assess circulating NETs contents and frequency of NETs generation by isolated PMNs from SIRS patients. These patients displayed significant augmentation in the circulating myeloperoxidase (MPO) activity and DNA content, while PMA stimulated PMNs from these patients, generated more free radicals and NETs. Plasma obtained from SIRS patients, if added to the PMNs isolated from healthy subjects, enhanced NETs release and free radical formation. Expressions of inflammatory cytokines (IL-1β, TNFα and IL-8) in the PMNs as well as their circulating levels were significantly augmented in SIRS subjects. Treatment of neutrophils from healthy subjects with TNFα, IL-1β, or IL-8 enhanced free radicals generation and NETs formation, which was mediated through the activation of NADPH oxidase and MPO. Pre-incubation of plasma from SIRS with TNFα, IL-1β, or IL-8 antibodies reduced the NETs release. Role of IL-1β, TNFα and IL-8 thus seems to be involved in the enhanced release of NETs in SIRS subjects. PMID:23110185

  12. Cytokine polymorphisms in sickle cell disease and the relationship with cytokine expression.

    PubMed

    Olenscki Gilli, Simone Cristina; Pericole, Fernando Vieira; Benites, Bruno Deltreggia; Sippert, Emilia Ângela; Castilho, Lilian Maria; Addas-Carvalho, Marcelo; Olalla Saad, Sara Teresinha

    2016-07-01

    Sickle cell disease is a chronic inflammatory condition characterized by elevated levels of inflammatory cytokines, which may be regulated by genetic polymorphisms and could be associated with diverse disease presentations and alloimmunization. The aim of this study was to evaluate Treg and Th17 cell frequencies, cytokine gene polymorphisms, and their association with cytokine expression profile in patients with sickle cell disease. For that purpose, we evaluated the IL intron 3 variable number tandem repeat (VNTR, genotypes 1.1, 1.2, 2.2, and 2.3), IL4-T590C>T, IL6-174G>C, TNFα-308G>A, IL10-819T>C, IL10-592A>C, and IL10-1082A>G polymorphisms and their correlation with TGFβ, IL4, IL6, and IL10 gene expression in sickle cell patients. We observed a significant decrease in Treg frequency together with a substantial increase in Th17 response in patients with sickle cell disease compared with healthy controls (p < 0.001 and p = 0.014, respectively). There was also a higher prevalence of the IL4-590T/T genotype in patients with sickle cell disease than in Afro-Brazilian descendent controls (p < 0.001) and higher expression of IL4 in patients with the 1.1 genotype of IL4 intron 3 VNTR (p = 0.06). Significantly greater gene expression of TGFβ, IL6, and IL10 was observed in sickle cell patients when compared with controls (p = 0.01, 0.03, and <0.001, respectively). Moreover, higher levels of interleukin-6 and -10 were observed in the group of alloimmunized patients. These new data bring insights into the deregulation in the immune system affecting sickle cell patients and must be further investigated in larger cohorts to better characterize individual variations in immune responses and new markers for disease morbidity.

  13. Anti-photoaging effect of aaptamine in UVB-irradiated human dermal fibroblasts and epidermal keratinocytes.

    PubMed

    Kim, Min-Ji; Woo, Seon Wook; Kim, Myung-Suk; Park, Ji-Eun; Hwang, Jae-Kwan

    2014-12-01

    Chronic exposure to ultraviolet (UV) irradiation causes sunburn, inflammatory responses, skin cancer, and photoaging. Photoaging, in particular, generates reactive oxygen species (ROS) that stimulate mitogen-activated protein kinase (MAPK) signaling and transcription factors. UV irradiation also activates matrix metalloproteinases (MMPs) expression and inactivates collagen synthesis. Aaptamine, a marine alkaloid isolated from the marine sponge, has been reported to have antitumor, antimicrobial, antiviral, and antioxidant activities. However, the photo-protective effects of aaptamine have not been elucidated. In this study, our data demonstrated that aaptamine deactivated UVB-induced MAPK and activator protein-1 signaling by suppressing ROS, resulting in attenuating the expression of MMPs in UVB-irradiated human dermal fibroblasts. Aaptamine also decreased proinflammatory cytokines such as cyclooxygenase-2, tumor necrosis factor-α, interleukin-1β, and nuclear factor-kappa B subunits in UVB-irradiated human keratinocytes. In conclusion, we suggest that aaptamine represents a novel and effective strategy for treatment and prevention of photoaging.

  14. Defining an appropriate leucoreduction strategy by serial assessment of cytokine levels in platelet concentrates prepared by different methods

    PubMed Central

    Kaur, Daljit; Sharma, Ratti Ram; Marwaha, Neelam

    2015-01-01

    Background and Objectives: Different methods of platelet concentrate preparations leave behind certain number of residual leukocytes, accounting for most of the febrile nonhemolytic transfusion reactions, especially in multitransfused patients. Various inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 are generated during storage and have been implicated for these adverse effects. We have studied the levels of these cytokines and their correlation with leucocyte contents in platelet concentrates prepared by three different methods. Study Design and Methods: Five pools of platelet rich plasma platelet concentrates (PRP-PC) and buffy-coat platelet concentrates (BC-PC) each were prepared and divided into two halves. One half of the pool was leucofiltered (LF), whereas the other half was stored as such. Ten apheresis units were also included in the study. All the platelet concentrates were assessed for leucocyte load and cytokine content (IL-1β, IL-6, and TNF-α) on different days of storage (0, 3, and 5) using Nageotte chamber and commercially available immunoassays respectively. Results: There was a statistically significant rise in cytokine levels (IL-1β, IL-6, and TNF-α) in nonleucofiltered (NLF) random donor platelet concentrates (RDPs) (PRP-PC and BC-PC) during storage (day 3 and 5) whereas LF RDP concentrates (PRP-PC and BC-PC) and apheresis platelet concentrates (AP-PC) did not show any significant rise in cytokine levels (on day 3 and 5) over the baseline values at day 0. Conclusion: This data suggests that although AP-PCs are superior to PRP-PC (NLF) and BC-PC (NLF) in terms of in vitro quality control parameters and cytokine generation during storage, BC-PC mode of platelet preparation followed by leucofiltration is the best method to store platelets and minimise the cytokine accumulation. This strategy is best suited for transfusion in multitransfused hematooncologic patients, who cannot afford single

  15. Anti-inflammatory action of γ-irradiated genistein in murine peritoneal macrophage

    NASA Astrophysics Data System (ADS)

    Sung, Nak-Yun; Byun, Eui-Baek; Song, Du-Sup; Jin, Yeung-Bae; Park, Jae-Nam; Kim, Jae-Kyung; Park, Jong-Heum; Song, Beom-Seok; Park, Sang-Hyun; Lee, Ju-Woon; Kim, Jae-Hun

    2014-12-01

    This present study was to examine the cytotoxicity and anti-inflammatory activity of gamma (γ)-irradiated genistein in murine peritoneal macrophage. Inflammation to macrophage was induced by adding the lipopolysaccharide (LPS). γ-Irradiated genistein significantly decreased the cytotoxicity to murine peritoneal macrophage in dose ranges from 5 to 10 μM than that of non-irradiated genistein. Anti-inflammatory activity within the doses less than 2 μM showed that γ-irradiated genistein treatment remarkably reduced the lipopolysaccharide-induced inflammation by decreasing the nitric oxide (NO) and cytokines (TNF-α, IL-6) production. In a structural analysis through the high pressure liquid chromatography (HPLC), γ-irradiated genistein showed a new peak production distinguished from main peak of genistein (non-irradiated). Therefore, increase of anti-inflammatory activity may closely mediate with structural changes induced by γ irradiation exposure. Based on the above result, γ-irradiation could be an effective tool for reduction of toxicity and increase of physiological activity of biomolecules.

  16. Plasma cytokine expression in adolescent chronic fatigue syndrome.

    PubMed

    Wyller, Vegard Bruun; Sørensen, Øystein; Sulheim, Dag; Fagermoen, Even; Ueland, Thor; Mollnes, Tom Eirik

    2015-05-01

    Chronic fatigue syndrome (CFS) is a prevalent and disabling condition among adolescents. The pathophysiology is poorly understood, but low-grade systemic inflammation has been suggested as an important component. This study compared circulating levels of individual cytokines and parameters of cytokine networks in a large set of adolescent CFS patients and healthy controls, and explored associations between cytokines and symptoms in the CFS group. CFS patients (12-18years old) were recruited nation-wide to a single referral center as part of the NorCAPITAL project (ClinicalTrials ID: NCT01040429). A broad case definition of CFS was applied, requiring three months of unexplained, disabling chronic/relapsing fatigue of new onset, whereas no accompanying symptoms were necessary. Thus, the case definition was broader than the Fukuda-criteria of CFS. Healthy controls having comparable distribution of gender and age were recruited from local schools. Twenty-seven plasma cytokines, including interleukins, chemokines and growth factors were assayed using multiplex technology. The results were subjected to network analyses using the ARACNE algorithm. Symptoms were charted by a questionnaire, and patients were subgrouped according to the Fukuda-criteria. A total of 120 CFS patients and 68 healthy controls were included. CFS patients had higher scores for fatigue (p<0.001) and inflammatory symptoms (p<0.001) than healthy controls. All cytokine levels and cytokine network parameters were similar, and none of the differences were statistically different across the two groups, also when adjusting for adherence to the Fukuda criteria of CFS. Within the CFS group, there were no associations between aggregate cytokine network parameters and symptom scores. Adolescent CFS patients are burdened by symptoms that might suggest low-grade systemic inflammation, but plasma levels of individual cytokines as well as cytokine network measures were not different from healthy controls, and

  17. Effect of resistance exercise training on expression of Hsp70 and inflammatory cytokines in skeletal muscle and adipose tissue of STZ-induced diabetic rats.

    PubMed

    Molanouri Shamsi, M; Mahdavi, M; Quinn, L S; Gharakhanlou, R; Isanegad, A

    2016-09-01

    Impairment of adipose tissue and skeletal muscles accrued following type 1 diabetes is associated with protein misfolding and loss of adipose mass and skeletal muscle atrophy. Resistance training can maintain muscle mass by changing both inflammatory cytokines and stress factors in adipose tissue and skeletal muscle. The purpose of this study was to determine the effects of a 5-week ladder climbing resistance training program on the expression of Hsp70 and inflammatory cytokines in adipose tissue and fast-twitch flexor hallucis longus (FHL) and slow-twitch soleus muscles in healthy and streptozotocin-induced diabetic rats. Induction of diabetes reduced body mass, while resistance training preserved FHL muscle weight in diabetic rats without any changes in body mass. Diabetes increased Hsp70 protein content in skeletal muscles, adipose tissue, and serum. Hsp70 protein levels were decreased in normal and diabetic rats by resistance training in the FHL, but not soleus muscle. Furthermore, resistance training decreased inflammatory cytokines in FHL skeletal muscle. On the other hand, Hsp70 and inflammatory cytokine protein levels were increased by training in adipose tissue. Also, significant positive correlations between inflammatory cytokines in adipose tissue and skeletal muscles with Hsp70 protein levels were observed. In conclusion, we found that in diabetic rats, resistance training decreased inflammatory cytokines and Hsp70 protein levels in fast skeletal muscle, increased adipose tissue inflammatory cytokines and Hsp70, and preserved FHL muscle mass. These results suggest that resistance training can maintain skeletal muscle mass in diabetes by changing inflammatory cytokines and stress factors such as Hsp70 in skeletal muscle and adipose tissue. PMID:27245165

  18. Effect of resistance exercise training on expression of Hsp70 and inflammatory cytokines in skeletal muscle and adipose tissue of STZ-induced diabetic rats.

    PubMed

    Molanouri Shamsi, M; Mahdavi, M; Quinn, L S; Gharakhanlou, R; Isanegad, A

    2016-09-01

    Impairment of adipose tissue and skeletal muscles accrued following type 1 diabetes is associated with protein misfolding and loss of adipose mass and skeletal muscle atrophy. Resistance training can maintain muscle mass by changing both inflammatory cytokines and stress factors in adipose tissue and skeletal muscle. The purpose of this study was to determine the effects of a 5-week ladder climbing resistance training program on the expression of Hsp70 and inflammatory cytokines in adipose tissue and fast-twitch flexor hallucis longus (FHL) and slow-twitch soleus muscles in healthy and streptozotocin-induced diabetic rats. Induction of diabetes reduced body mass, while resistance training preserved FHL muscle weight in diabetic rats without any changes in body mass. Diabetes increased Hsp70 protein content in skeletal muscles, adipose tissue, and serum. Hsp70 protein levels were decreased in normal and diabetic rats by resistance training in the FHL, but not soleus muscle. Furthermore, resistance training decreased inflammatory cytokines in FHL skeletal muscle. On the other hand, Hsp70 and inflammatory cytokine protein levels were increased by training in adipose tissue. Also, significant positive correlations between inflammatory cytokines in adipose tissue and skeletal muscles with Hsp70 protein levels were observed. In conclusion, we found that in diabetic rats, resistance training decreased inflammatory cytokines and Hsp70 protein levels in fast skeletal muscle, increased adipose tissue inflammatory cytokines and Hsp70, and preserved FHL muscle mass. These results suggest that resistance training can maintain skeletal muscle mass in diabetes by changing inflammatory cytokines and stress factors such as Hsp70 in skeletal muscle and adipose tissue.

  19. Irradiation effect on mechanical properties in structural materials of fast breeder reactor plant

    NASA Astrophysics Data System (ADS)

    Nagae, Yuji; Takaya, Shigeru; Wakai, Eiichi; Aoto, Kazumi

    2011-07-01

    The effects of displacement per atom (dpa) level, helium content, and the ratio of helium content to dpa level on the tensile and creep properties have been investigated in the assumed irradiation damage range of FBR structural materials. The assumed irradiation damage range is up to about 1 dpa and about 30 appm for helium content. Austenitic stainless steel and high-chromium martensitic steel are considered as FBR structural materials. As a result, it is shown that the dpa level is a promising index for evaluating neutron irradiation damage.

  20. Docosahexaenoic diet supplementation, exercise and temperature affect cytokine production by lipopolysaccharide-stimulated mononuclear cells.

    PubMed

    Capó, Xavier; Martorell, Miquel; Sureda, Antoni; Batle, Juan Miguel; Tur, Josep Antoni; Pons, Antoni

    2016-09-01

    Acute exercise induces changes in peripheral mononuclear cells' (PBMCs) capabilities to produce cytokines. The aim was to investigate the effect of docosahexaenoic acid (DHA) diet supplementation on cytokine production, by lipopolysaccharide (LPS)-stimulated PBMCs after exercise, and the in vitro influence of temperature. Fifteen male soccer players were randomly assigned to a placebo or an experimental group. The experimental group consumed an almond-based beverage enriched with DHA (1.16 g DHA/day) for 8 weeks, whereas the placebo group consumed a similar non-enriched beverage. Blood samples were taken before and after the nutritional intervention in basal conditions and 2 h after acute exercise. Nutritional intervention significantly increased the DHA content in erythrocytes only in experimental group (from 34 ± 3.6 to 43 ± 3.6 nmols DHA/10(9) erythrocytes). Exercise significantly increased Toll-like receptor 4 (TLR4) in PBMCs but only in the placebo group (203 %). Exercise also significantly increased IL6, IL8, VEGF, INFγ, TNFα, IL1α, IL1β, MCP1, and EGG production rates by LPS-stimulated PBMCs, and this response was attenuated by DHA supplementation. Temperature but not DHA also affected the pattern of cytokine production increasing IL6, IL8, IL1β, and MCP1 synthesis. The higher change was evidenced in IL1β increasing the production rate at 39.5 °C from 3.19 ± 0.77 to 22.4 ± 6.1 pg/h 10(6) PBMC in placebo and from 2.36 ± 0.11 to 10.6 ± 0.38 pg/h 10(6) PBMC in the supplemented group. The profile of affected cytokines differs between temperature and exercise, suggesting a different PBMC activation pathway. DHA diet supplementation only attenuated cytokine production after exercise and not that induced by temperature. PMID:27139422

  1. Low level laser therapy on injured rat muscle: assessment of irradiation parameters

    NASA Astrophysics Data System (ADS)

    Mantineo, M.; Pinheiro, J. P.; Morgado, A. M.

    2013-11-01

    Although studies show the clinical effectiveness of low level laser therapy (LLLT) in facilitating the muscle healing process, scientific evidence is still required to prove the effectiveness of LLLT and to clarify the cellular and molecular mechanisms triggered by irradiation. Here we evaluate the effect of different LLLT wavelengths, using continuous coherent Laser illumination (830 nm and 980 nm) and non-coherent LED illumination (850 nm), in the treatment of inflammation induced in the gastrocnemius muscle of Wistar rats, through the quantification of cytokines in systemic blood. We verified that all applied doses of coherent radiation produce an effect on reducing the concentration of pro-inflammatory TNF-α and IL-1β cytokines, while no treatment effect was observed after irradiation with non-coherent radiation. The best results were obtained for 40 mW at 830 nm. The results may suggest an important role of coherence properties of laser in LLLT.

  2. Microwave Irradiation on Halloysite-Polypropylene Nanocomposites

    NASA Astrophysics Data System (ADS)

    Espino, Omar; Yust, Brian; Chipara, Dorina; Ajayan, Pullickel; Chipara, Alin; Chipara, Mircea; Utrgv Collaboration; Rice Collaboration

    Halloysite is an unique cyllindrical nanoclay characterized by poor electrical and thermal conductivity, which may become the filler of choice for the reinforcement of polymeric matrix, where electrical or thermal insulation are required. The main limits in the use of halloysite as replacement for carbon nanotube (CNT) are: 1. Smaller aspect ratio as halloysites are typically shorter than CNTs. 2. Smaller Young modulus of halloysites compared with CNTs. 3. Reduced thermal stability due to the loss of water upon heating. A research on halloysite dispersed within isotactic polypropylene is reported. To improve the interface between the halloysite and the polymeric matrix a microwave irradiation step has been considered. The local heating of the halloysite nanotubes is mediated by the absorbed/structural water content of the nanoclay. Nanocomposites loaded by various amounts of halloysite ranging from 0 % to 20 % wt. have been prepared by melt mixing by using a Haake RheoMixer. The as obtained nanocomposites have been subjected to microwave irradiation at 75 W in an Anton Paar Monowave 300 system and various irradiation times ranging from 5, 10, 15, 30, 45, and 60 minutes. The effect of microwave irradiation has been studied by Raman and FTIR spectroscopy

  3. Differential effects of irradiation with carbon ions and x-rays on macrophage function.

    PubMed

    Conrad, Sandro; Ritter, Sylvia; Fournier, Claudia; Nixdorff, Kathryn

    2009-05-01

    Macrophages are potent elicitors of inflammatory reactions that can play both positive and negative roles in radiotherapy. While several studies have investigated the effects of X-rays or gamma-rays on macrophages, virtually no work has been done on the responses of these cells to irradiation with carbon ions. Investigations into the effects of carbon ion irradiation are of particular interest in light of the fact that this type of radiation is being used increasingly for cancer therapy. In the present investigation we compared the effects of 250 kV X-rays with those of 9.8 MeV/u carbon ions on RAW 264.7 macrophages over a wide range of radiation doses. Macrophage functions including vitality, phagocytic activity, production of the proinflammatory cytokines IL-1beta and TNFalpha and production of nitric oxide (NO) were measured. In comparison to lymphocytes and fibroblasts, macrophages showed only a small decrease in vitality after irradiation with either X-rays or carbon ions. Proinflammatory cytokines and NO were induced in macrophages by LPS but not by irradiation alone. X-rays or carbon ions had little modulating effect on LPS-induced TNFalpha production. However, LPS-induced NO increased in a dose dependent manner up to 6-fold after carbon ion irradiation, while X-ray irradiation did not have this effect. Carbon ion irradiation mediated a concomitant decrease in IL-1beta production. Carbon ions also had a greater effect than X-rays in enhancing the phagocytic activity of macrophages. These results underscore the greater potential of carbon ion irradiation with regard to radiobiological effectiveness.

  4. Stimulation of Hepatoma Cell Invasiveness and Metastatic Potential by Proteins Secreted From Irradiated Nonparenchymal Cells

    SciTech Connect

    Zhou Leyuan; Wang Zhiming; Gao Yabo; Wang Lingyan; Zeng Zhaochong

    2012-11-01

    Purpose: To determine whether factors secreted by irradiated liver nonparenchymal cells (NPCs) may influence invasiveness and/or metastatic potential of hepatocellular carcinoma (HCC) cells and to elucidate a possible mechanism for such effect. Methods and Materials: Primary rat NPCs were cultured and divided into irradiated (10-Gy X-ray) and nonirradiated groups. Forty-eight hours after irradiation, conditioned medium from irradiated (SR) or nonirradiated (SnonR) cultures were collected and added to sublethally irradiated cultures of the hepatoma McA-RH7777 cell line. Then, hepatoma cells were continuously passaged for eight generations (RH10Gy-SR and RH10Gy-SnonR). The invasiveness and metastatic potential of McA-RH7777, RH10Gy-SnonR, and RH10Gy-SR cells were evaluated using an in vitro gelatinous protein (Matrigel) invasion and an in vivo metastasis assay. In addition, SR and SnonR were tested using rat cytokine antibody arrays and enzyme-linked immunosorbent assay (ELISA). Results: In vitro gelatinous protein invasion assay indicated that the numbers of invading cells was significantly higher in RH10Gy-SR (40 {+-} 4.74) than in RH10Gy-SnonR (30.6 {+-} 3.85) cells, and lowest in McA-RH7777 (11.4 {+-} 3.56) cells. The same pattern was observed in vivo in a lung metastasis assay, as evaluated by number of metastatic lung nodules seen with RH10Gy-SR (28.83 {+-} 5.38), RH10Gy-SnonR (22.17 {+-} 4.26), and McA-RH7777 (8.3 {+-} 3.8) cells. Rat cytokine antibody arrays and ELISA demonstrated that metastasis-promoting cytokines (tumor necrosis factor-{alpha} and interleukin-6), circulating growth factors (vascular endothelial growth factor and epidermal growth factor), and metalloproteinases (MMP-2 and MMP-9) were upregulated in SR compared with SnonR. Conclusions: Radiation can increase invasiveness and metastatic potential of sublethally irradiated hepatoma cells, and soluble mediators released from irradiated NPCs promote this potential. Increased secretion of

  5. Naringenin Inhibits UVB Irradiation-Induced Inflammation and Oxidative Stress in the Skin of Hairless Mice.

    PubMed

    Martinez, Renata M; Pinho-Ribeiro, Felipe A; Steffen, Vinicius S; Caviglione, Carla V; Vignoli, Josiane A; Barbosa, Décio S; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rubia

    2015-07-24

    Ultraviolet B (UVB) irradiation may cause inflammation- and oxidative-stress-dependent skin cancer and premature aging. Naringenin (1) has been reported to have anti-inflammatory and antioxidant properties, but its effects and mechanisms on UVB irradiation-induced inflammation and oxidative stress are still not known. Thus, the present study aimed to investigate the potential of naringenin to mitigate UVB irradiation-induced inflammation and oxidative damage in the skin of hairless mice. Skin edema, myeloperoxidase (neutrophil marker) and matrix metalloproteinase-9 (MMP-9) activity, and cytokine production were measured after UVB irradiation. Oxidative stress was evaluated by 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS) scavenging ability, ferric reducing antioxidant power (FRAP), reduced glutathione levels, catalase activity, lipid peroxidation products, superoxide anion production, and gp91phox (NADPH oxidase subunit) mRNA expression by quantitative PCR. The intraperitoneal treatment with naringenin reduced skin inflammation by inhibiting skin edema, neutrophil recruitment, MMP-9 activity, and pro-inflammatory (TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-12, IL-13, IL-17, IL-22, and IL-23) and anti-inflammatory (TGF-β and IL-10) cytokines. Naringenin also inhibited oxidative stress by reducing superoxide anion production and the mRNA expression of gp91phox. Therefore, naringenin inhibits UVB irradiation-induced skin damage and may be a promising therapeutic approach to control skin disease.

  6. Effects of Ligustrazine on DNA damage and apoptosis induced by irradiation.

    PubMed

    Zheng, Hong; Wang, Siying; Zhou, Pingkun; Liu, Wei; Ni, Fang

    2013-11-01

    Ligustrazine has been used to treat heart and blood vessel disease in China. In the present study, we investigated the potential action of Ligustrazine as a component of chuanxiong (a Chinese herb) in scavenging hydroxyl radical and superoxide radical as indicated in the ESR spin-trapping measurement. Treatment of Ligustrazine in mice decreased mortality after whole body γ-irradiation. The anti-radiation action of Ligustrazine was studied by measuring DNA damage (Comet assay and γ-H2AX formation) and apoptosis induced by irradiation. It was triggered by altering the level of DNA-PKcs protein, a critical component of DNA double-strand break (DSB) repair pathways in mice after irradiation. Consistently, the phosphorylation of Akt protein, a mediator of survival signaling, was concurrently increased by Ligustrazine treatment. Additionally, the cytokines along with the phosphorylation of the p38 protein which is activated by a variety of environmental stresses and inflammatory cytokines decreased in the Ligustrazine-treated group as compared to irradiation group. Our results suggest that Ligustrazine has radioprotective effect through its capabilities as a powerful antioxidant, in reducing reactive oxygen species (ROS) level induced by irradiation, minimizing DNA damage and apoptosis, and activating survival signal Akt pathways. This study will be of value in the development of novel radioprotective compounds. PMID:24184571

  7. Electroacupuncture Prevents Cognitive Impairments by Regulating the Early Changes after Brain Irradiation in Rats

    PubMed Central

    Fan, Xing-Wen; Chen, Fu; Chen, Yan; Chen, Guan-Hao; Liu, Huan-Huan; Guan, Shi-Kuo; Deng, Yun; Liu, Yong; Zhang, Sheng-Jian; Peng, Wei-Jun; Jiang, Guo-Liang; Wu, Kai-Liang

    2015-01-01

    Cognitive impairments severely affect the quality of life of patients who undergo brain irradiation, and there are no effective preventive strategies. In this study, we examined the therapeutic potential of electroacupuncture (EA) administered immediately after brain irradiation in rats. We detected changes in cognitive function, neurogenesis, and synaptic density at different time points after irradiation, but found that EA could protect the blood-brain barrier (BBB), inhibit neuroinflammatory cytokine expression, upregulate angiogenic cytokine expression, and modulate the levels of neurotransmitter receptors and neuropeptides in the early phase. Moreover, EA protected spatial memory and recognition in the delayed phase. At the cellular/molecular level, the preventative effect of EA on cognitive dysfunction was not dependent on hippocampal neurogenesis; rather, it was related to synaptophysin expression. Our results suggest that EA applied immediately after brain irradiation can prevent cognitive impairments by protecting against the early changes induced by irradiation and may be a novel approach for preventing or ameliorating cognitive impairments in patients with brain tumors who require radiotherapy. PMID:25830357

  8. FOOD IRRADIATION REACTOR

    DOEpatents

    Leyse, C.F.; Putnam, G.E.

    1961-05-01

    An irradiation apparatus is described. It comprises a pressure vessel, a neutronic reactor active portion having a substantially greater height than diameter in the pressure vessel, an annular tank surrounding and spaced from the pressure vessel containing an aqueous indium/sup 1//sup 1//sup 5/ sulfate solution of approximately 600 grams per liter concentration, means for circulating separate coolants through the active portion and the space between the annular tank and the pressure vessel, radiator means adapted to receive the materials to be irradiated, and means for flowing the indium/sup 1//sup 1//sup 5/ sulfate solution through the radiator means.

  9. Economics of food irradiation

    NASA Astrophysics Data System (ADS)

    Kunstadt, Peter; Eng, P.; Steeves, Colyn; Beaulieu, Daniel; Eng, P.

    1993-07-01

    The number of products being radiation processed worldwide is constantly increasing and today includes such diverse items as medical disposables, fruits and vegetables, spices, meats, seafoods and waste products. This range of products to be processed has resulted in a wide range of irradiator designs and capital and operating cost requirements. This paper discusses the economics of low dose food irradiation applications and the effects of various parameters on unit processing costs. It provides a model for calculating specific unit processing costs by correlating known capital costs with annual operating costs and annual throughputs. It is intended to provide the reader with a general knowledge of how unit processing costs are derived.

  10. Fuel or irradiation subassembly

    DOEpatents

    Seim, O.S.; Hutter, E.

    1975-12-23

    A subassembly for use in a nuclear reactor is described which incorporates a loose bundle of fuel or irradiation pins enclosed within an inner tube which in turn is enclosed within an outer coolant tube and includes a locking comb consisting of a head extending through one side of the inner sleeve and a plurality of teeth which extend through the other side of the inner sleeve while engaging annular undercut portions in the bottom portion of the fuel or irradiation pins to prevent movement of the pins.

  11. Effect of gamma irradiation on molecular structure and physicochemical properties of corn starch.

    PubMed

    Chung, H-J; Liu, Q

    2009-06-01

    Carboxyl content and amylose leaching of gamma-irradiated corn starch increased and swelling factor decreased with increasing radiation dose. The apparent amylose content decreased gradually from 28.7% for native starch to 20.9% for 50 kGy irradiated starch. The proportion of short amylopectin branch chains (DP 6 to 12) increased, while the proportion of longer branch chains (DP > or = 37) decreased with increasing radiation dose. The relative crystallinity and the degree of granule surface order decreased from 28.5% and 0.631 in native starch to 26.9% and 0.605 in 50 kGy irradiated starch, respectively. Pasting viscosity and gelatinization temperatures decreased with an increase in radiation dose. At a high dose (50 kGy), melting of amylose-lipid complex in DSC thermogram was not observed. The rapidly digestible starch (RDS) content slightly decreased up to 10 kGy but increased at 50 kGy. The resistant starch (RS) content slightly decreased at 2 kGy and then increased up to 50 kGy. The slowly digestible starch (SDS) content showed the opposite trend to RS content. Slower irradiation dose rate reduced carboxyl content, swelling factor, and amylose leaching. The apparent amylose content and amylopectin chain length distribution were not significantly affected by dose rate of gamma irradiation. However, the relative crystallinity and gelatinization enthalpy increased with slower dose rate. Slower dose rate decreased RDS and SDS contents, and increased RS content.

  12. Hepatotoxicants induce cytokine imbalance in response to innate immune system.

    PubMed

    Goto, Shima; Deguchi, Jiro; Nishio, Naoki; Nomura, Naruaki; Funabashi, Hitoshi

    2015-06-01

    In recent years, attention has been paid to innate immune systems as mechanisms to initiate or promote drug-induced liver injury (DILI). Kupffer cells are hepatic resident macrophages and might be involved in the pathogenesis of DILI by release of pro- and anti-inflammatory mediators such as cytokines, chemokines, reactive oxygen species, and/or nitric oxides. The purpose of this study was to investigate alterations in mediator levels induced by hepatotoxic compounds in isolated Kupffer cells and discuss the relation between balance of each cytokine or chemokine and potential of innate immune-mediated DILI. Primary cultured rat Kupffer cells were treated with hepatotoxic (acetaminophen, troglitazone, trovafloxacin) or non-hepatotoxic (pioglitazone, levofloxacin) compounds with or without lipopolysaccharide (LPS). After 24 hr treatment, cell supernatants were collected and various levels of mediators released by Kupffer cells were examined. Although hepatotoxicants had no effect on the LPS-induced tumor necrosis factor-alpha (TNF-α) secretion, they enhanced the release of pro-inflammatory cytokine interleukin-1 beta (IL-1β) and suppressed the anti-inflammatory cytokines interleukin-6 (IL-6) and interleukin-10 (IL-10) induced by LPS. These cytokine shifts were not associated with switching the phenotypes of M1 and M2 macrophages in Kupffer cells. In conclusion, the present study suggested that the levels of some specific cytokines are affected by DILI-related drugs with LPS stimulation, and imbalance between pro- and anti-inflammatory cytokines, induced by the up-regulation of IL-1β and the down-regulation of IL-6 or IL-10, plays a key role in innate immune-mediated DILI. PMID:25972199

  13. Therapeutic modulation of growth factors and cytokines in regenerative medicine.

    PubMed

    Ioannidou, Effie

    2006-01-01

    Regeneration that takes place in the human body is limited throughout life. Therefore, when organs are irreparably damaged, they are usually replaced with an artificial device or donor organ. The term "regenerative medicine" covers the restoration or replacement of cells, tissues, and organs. Stem cells play a major role in regenerative medicine by providing the way to repopulate organs damaged by disease. Stem cells have the ability to self renew and to regenerate cells of diverse lineages within the tissue in which they reside. Stem cells could originate from embryos or adult tissues. Growth factors are proteins that may act locally or systemically to affect the growth of cells in several ways. Various cell activities, including division, are influenced by growth factors. Cytokines are a family of low-molecular-weight proteins that are produced by numerous cell types and are responsible for regulating the immune response, inflammation, tissue remodeling and cellular differentiation. Target cells of growth factors and cytokines are mesenchymal, epithelial and endothelial cells. These molecules frequently have overlapping activities and can act in an autocrine or paracrine fashion. A complex network of growth factors and cytokines guides cellular differentiation and regeneration in all organs and tissues. The aim of this paper is to review the role of growth factors and cytokines in different organs or systems and explore their therapeutic application in regenerative medicine. The role of stem cells combined with growth factors and cytokines in the regeneration of vascular and hematopoietic, neural, skeletal, pancreatic, periodontal, and mucosal tissue is reviewed. There is evidence that supports the use of growth factors and cytokines in the treatment of neurological diseases, diabetes, cardiovascular disease, periodontal disease, cancer and its complication, oral mucositis. After solving the ethical issues and establishing clear and reasonable regulations

  14. Collection of Aerosolized Human Cytokines Using Teflon® Filters

    PubMed Central

    McKenzie, Jennifer H.; McDevitt, James J.; Fabian, M. Patricia; Hwang, Grace M.; Milton, Donald K.

    2012-01-01

    Background Collection of exhaled breath samples for the analysis of inflammatory biomarkers is an important area of research aimed at improving our ability to diagnose, treat and understand the mechanisms of chronic pulmonary disease. Current collection methods based on condensation of water vapor from exhaled breath yield biomarker levels at or near the detection limits of immunoassays contributing to problems with reproducibility and validity of biomarker measurements. In this study, we compare the collection efficiency of two aerosol-to-liquid sampling devices to a filter-based collection method for recovery of dilute laboratory generated aerosols of human cytokines so as to identify potential alternatives to exhaled breath condensate collection. Methodology/Principal Findings Two aerosol-to-liquid sampling devices, the SKC® Biosampler and Omni 3000™, as well as Teflon® filters were used to collect aerosols of human cytokines generated using a HEART nebulizer and single-pass aerosol chamber setup in order to compare the collection efficiencies of these sampling methods. Additionally, methods for the use of Teflon® filters to collect and measure cytokines recovered from aerosols were developed and evaluated through use of a high-sensitivity multiplex immunoassay. Our results show successful collection of cytokines from pg/m3 aerosol concentrations using Teflon® filters and measurement of cytokine levels in the sub-picogram/mL concentration range using a multiplex immunoassay with sampling times less than 30 minutes. Significant degradation of cytokines was observed due to storage of cytokines in concentrated filter extract solutions as compared to storage of dry filters. Conclusions Use of filter collection methods resulted in significantly higher efficiency of collection than the two aerosol-to-liquid samplers evaluated in our study. The results of this study provide the foundation for a potential new technique to evaluate biomarkers of inflammation in

  15. Plasma Cytokine Levels in Astronauts Before and after Spaceflight

    NASA Technical Reports Server (NTRS)

    Mehta, Satish K.; Aggarwal, Barat B.; Feiveson, Alan H.; Hammond, Dinne K.; Castro, Victoria A.; Stowe, Raymond; Pierson Duane L.

    2008-01-01

    Space flight is a unique experience and results in adverse effects on human physiology. Changes have been reported in various physiological systems, including musculoskeletal, neurovestibular, cardiovascular, endocrine, immunity and increased latent viral reactivation as well as others. The potential mechanisms behind these changes are not fully understood. Various cytokines such as IL-1, IL-6, TNF and chemokines have been linked to several of these changes, like muscle loss, bone loss, fatigue, sleep deprivation and viral reactivation. Eighteen astronauts (15 M and 3 F) from 8 spaceflights and 10 healthy age-matched adults (6 M, 4 F) were included in the present study. A panel of 21 plasma cytokines was analyzed with the Luminex 100 to measure the cytokines in these subjects 10 days before the flight (L-10), 2-3 hour after landing (R+0), 3 days after landing (R+3), and at their annual medical exam (AME). IL-10, IL-1, IFN-alpha, MCP-1 and IP-10 increased significantly at L-10 as compared with AME levels. IL-6 and IFN-alpha showed significant increases at R + 0 (P less than .05) over their baseline levels (AME). Cytokine levels at R+3 were not significantly different from R+0. IL-10 and IL-6 have been reported to increase in during viral reactivation. These data show that there was a shift from TH1 to TH2 cytokines L-10 and R+0. We also studied viral reactivation in 10 of the 18 subjects included in the present study before, during, and after space flight. Increased salivary varicella zoster virus (VZV) shedding in these subjects was found either during or after the mission. VZV shedding correlated with the increased levels of cytokines especially IL-10 and IL-6. Overall, our data suggests that cytokines may play an important role in regulating adverse changes in astronauts, and further studies are needed to fully understand the mechanism.

  16. Identification of irradiated pepper with the level of hydrogen gas as a probe

    SciTech Connect

    Dohmaru, T.; Furuta, M.; Katayama, T.; Toratani, H.; Takeda, A. )

    1989-12-01

    A novel method to detect whether or not a particular pepper has been irradiated has been developed which is based on the fact that H2 is formed in organic substances irradiated with ionizing radiation. Following gamma irradiation, black and white peppers were ground to powder in a gastight ceramic mill. By gas-chromatographic analysis of the gas in the mill, we observed that H2 had been released from the irradiated pepper grains. Curves plotting the H2 content vs storage time at storage temperatures of 7, 22, and 30 degrees C showed that the higher the temperatures, the smaller the H2 content, and that identification of irradiated pepper was possible for 2-4 months after 10 kGy irradiation.

  17. Effect of gamma irradiation on viscosity reduction of cereal porridges for improving energy density

    NASA Astrophysics Data System (ADS)

    Lee, Ju-Woon; Kim, Jae-Hun; Oh, Sang-Hee; Byun, Eui-Hong; Yook, Hong-Sun; Kim, Mee-Ree; Kim, Kwan-Soo; Byun, Myung-Woo

    2008-03-01

    Cereal porridges have low energy and nutrient density because of its viscosity. The objective of the present study was to evaluate the effect of irradiation on the reduction of viscosity and on the increasing solid content of cereal porridge. Four cereals, wheat, rice, maize (the normal starchy type) and waxy rice, were used in this study. The porridge with 3000 cP was individually prepared from cereal flour, gamma-irradiated at 20 kGy and tested. Gamma irradiation of 20 kGy was allowed that the high viscous and rigid cereal porridges turned into semi-liquid consistencies. The solid contents of all porridges could increase by irradiation, compared with non-irradiated ones. No significant differences of starch digestibility were observed in all cereal porridge samples. The results indicated that gamma irradiation might be helpful for improving energy density of cereal porridge with acceptable consistency.

  18. The 10Be contents of SNC meteorites

    NASA Technical Reports Server (NTRS)

    Pal, D. K.; Tuniz, C.; Moniot, R. K.; Savin, W.; Vajda, S.; Kruse, T.; Herzog, G. F.

    1986-01-01

    Several authors have explored the possibility that the Shergottites, Nakhlites, and Chassigny (SNC) came from Mars. The spallogenic gas contents of the SNC meteorites have been used to: constrain the sizes of the SNC's during the last few million years; to establish groupings independent of the geochemical ones; and to estimate the likelihood of certain entries in the catalog of all conceivable passages from Mars to Earth. The particular shielding dependence of Be-10 makes the isotope a good probe of the irradiation conditions experienced by the SNC meteorites. The Be-10 contents of nine members of the group were measured using the technique of accelerator mass spectrometry. The Be-10 contents of Nakhla, Governador Valadares, Chassigny, and probably Lafayette, about 20 dpm/kg, exceed the values expected from irradiation of the surface of a large body. The Be-10 data therfore do not support scenario III of Bogard et al., one in which most of the Be-10 in the SNC meteorites would have formed on the Martian surface; they resemble rather the Be-10 contents found in many ordinary chondrites subjected to 4 Pi exposures. The uncertainties of the Be-10 contents lead to appreciable errors in the Be-10 ages, t(1) = -1/lambda ln(1 Be-10/Be-10). Nonetheless, the Be-10 ages are consistent with the Ne-21 ages calculated assuming conventional, small-body production rates and short terrestrial ages for the finds. It is believed that this concordance strengthens the case for at least 3 different irradiation ages for the SNC meteorites. Given the similar half-thicknesses of the Be-10 and Ne-21 production rates, the ratios of the Be-10 and Ne-21 contents do not appear consistent with common ages for any of the groups. In view of the general agreement between the Be-10 and Ne-21 ages it does not seem useful at this time to construct multiple-stage irradiation histories for the SNC meteorites.

  19. Vanillin protects human keratinocyte stem cells against ultraviolet B irradiation.

    PubMed

    Lee, Jienny; Cho, Jae Youl; Lee, Sang Yeol; Lee, Kyung-Woo; Lee, Jongsung; Song, Jae-Young

    2014-01-01

    Ultraviolet-B (UVB) irradiation is one of major factors which induce cellular damages in the epidermis. We investigated protective effects and mechanisms of vanillin, a main constituent of vanilla beans, against UVB-induced cellular damages in keratinocyte stem cells (KSC). Here, vanillin significantly attenuated UVB irradiation-induced cytotoxicity. The vanillin effects were also demonstrated by the results of the senescence-associated β-galactosidase and alkaline comet assays. In addition, vanillin induced production of pro-inflammatory cytokines. Attempts to elucidate a possible mechanism underlying the vanillin-mediated effects revealed that vanillin significantly reduced UVB-induced phosphorylation of ataxia telangiectasia mutated (ATM), serine threonine kinase checkpoint kinase 2 (Chk2), tumor suppressor protein 53 (p53), p38/mitogen-activated protein kinase (p38), c-Jun N-terminal kinase/stress-activated protein kinase (JNK), S6 ribosomal protein (S6RP), and histone 2A family member X (H2A.X). UVB-induced activation of p53 luciferase reporter was also significantly inhibited by vanillin. In addition, while ATM inhibitor had no effect on the vanillin effects, mouse double minute 2 homolog (MDM2) inhibitor significantly attenuated suppressive effects of vanillin on UVB-induced activation of p53 reporter in KSC. Taken together, these findings suggest that vanillin protects KSC from UVB irradiation and its effects may occur through the suppression of downstream step of MDM2 in UVB irradiation-induced p53 activation.

  20. Effects of gamma irradiation on deteriorated paper

    NASA Astrophysics Data System (ADS)

    Bicchieri, Marina; Monti, Michela; Piantanida, Giovanna; Sodo, Armida

    2016-08-01

    Even though gamma radiation application, also at the minimum dosage required for disinfection, causes depolymerization and degradation of the paper substrate, recently published papers seemed, instead, to suggest that γ-rays application could be envisaged in some conditions for Cultural Heritage original documents and books. In some of the published papers, the possible application of γ-rays was evaluated mainly by using mechanical tests that scarcely reflect the chemical modifications induced in the cellulosic support. In the present article the effect of low dosage γ-irradiation on cellulosic substrates was studied and monitored applying different techniques: colorimetry, spectroscopic measurements, carbonyl content and average viscometric degree of polymerization. Two different papers were investigated, a non-sized, non-filled cotton paper, and a commercial permanent paper. To simulate a real deteriorated document, which could need γ-rays irradiation, some samples were submitted to a hydrolysis treatment. We developed a treatment based on the exposition of paper to hydrochloric acid vapors, avoiding any contact of the samples with water. This method induces a degradation similar to that observed on original documents. The samples were then irradiated with 3 kGy γ-rays at a 5258 Gy/h rate. The aforementioned analyses were performed on the samples just irradiated and after artificial ageing. All tests showed negative effects of gamma irradiation on paper. Non-irradiated paper preserves better its appearance and chemical properties both in the short term and after ageing, while the irradiated samples show appreciable color change and higher oxidation extent. Since the Istituto centrale restauro e conservazione patrimonio archivistico e librario is responsible for the choice of all restoration treatments that could be applied on library and archival materials under the protection of the Italian State (http://www.icpal.beniculturali.it/allegati/DM-7

  1. HDAC inhibitor reduces cytokine storm and facilitates induction of chimerism that reverses lupus in anti-CD3 conditioning regimen.

    PubMed

    Li, Nainong; Zhao, Dongchang; Kirschbaum, Mark; Zhang, Chunyan; Lin, Chia-Lei; Todorov, Ivan; Kandeel, Fouad; Forman, Stephen; Zeng, Defu

    2008-03-25

    In allogeneic hematopoietic cell transplantation (HCT), donor T cell-mediated graft versus host leukemia (GVL) and graft versus autoimmune (GVA) activity play critical roles in treatment of hematological malignancies and refractory autoimmune diseases. However, graft versus host disease (GVHD), which sometimes can be fatal, remains a major obstacle in classical HCT, where recipients are conditioned with total body irradiation or high-dose chemotherapy. We previously reported that anti-CD3 conditioning allows donor CD8(+) T cells to facilitate engraftment and mediate GVL without causing GVHD. However, the clinical application of this radiation-free and GVHD preventative conditioning regimen is hindered by the cytokine storm syndrome triggered by anti-CD3 and the high-dose donor bone marrow (BM) cells required for induction of chimerism. Histone deacetylase (HDAC) inhibitors such as suberoylanilide hydroxamic acid (SAHA) are known to induce apoptosis of cancer cells and reduce production of proinflammatory cytokines by nonmalignant cells. Here, we report that SAHA inhibits the proliferative and cytotoxic activity of anti-CD3-activated T cells. Administration of low-dose SAHA reduces cytokine production and ameliorates the cytokine storm syndrome triggered by anti-CD3. Conditioning with anti-CD3 and SAHA allows induction of chimerism with lower doses of donor BM cells in old nonautoimmune and autoimmune lupus mice. In addition, conditioning with anti-CD3 and SAHA allows donor CD8(+) T cell-mediated GVA activity to reverse lupus glomerulonephritis without causing GVHD. These results indicate that conditioning with anti-CD3 and HDAC inhibitors represent a radiation-free and GVHD-preventative regimen with clinical application potential.

  2. Intraocular inflammation after proton beam irradiation for uveal melanoma

    PubMed Central

    Lumbroso, L.; Desjardins, L.; Levy, C.; Plancher, C.; Frau, E.; D'Hermies, F.; Schlienger, P.; Mammar, H.; Delacroix, S.; Nauraye, C.; Ferrand, R.; Desblancs, C.; Mazal, A.; Asselain, B.

    2001-01-01

    AIM—To describe the inflammatory reaction that can occur following proton beam irradiation of uveal melanomas based on a large series of patients and to try to determine the risk factors for this reaction.
METHODS—Data from a cohort of patients with uveal melanoma treated by proton beam irradiation between 1991 and 1994 were analysed. The presence of inflammation was recorded and evaluated. Kaplan-Meier estimates and statistical analysis of general and tumour related risk factors were performed.
RESULTS—28% of patients treated during this period presented with ocular inflammation (median follow up 62 months). Risks factors were essentially tumour related and were correlated with larger lesions (height > 5 mm, diameter > 12 mm, volume > 0.4 cm3). Multivariate analysis identified initial tumour height and irradiation of a large volume of the eye as the two most important risk factors. Ocular inflammation usually consisted of mild anterior uveitis, resolving rapidly after topical steroids and cycloplegics. The incidence of inflammation after proton beam irradiation of melanomas seems higher than previously reported and is related to larger lesions. Evidence of inflammation associated with uveal melanoma has been described and seems to be associated with tumour necrosis (spontaneous or after irradiation). The appearance of transient inflammation during the follow up of these patients may be related to the release of inflammatory cytokines during tumour necrosis.
CONCLUSION—Inflammation following proton beam irradiation is not unusual. It is correlated with larger initial tumours and may be related to tumour necrosis.

 PMID:11673294

  3. NSUF Irradiated Materials Library

    SciTech Connect

    Cole, James Irvin

    2015-09-01

    The Nuclear Science User Facilities has been in the process of establishing an innovative Irradiated Materials Library concept for maximizing the value of previous and on-going materials and nuclear fuels irradiation test campaigns, including utilization of real-world components retrieved from current and decommissioned reactors. When the ATR national scientific user facility was established in 2007 one of the goals of the program was to establish a library of irradiated samples for users to access and conduct research through competitively reviewed proposal process. As part of the initial effort, staff at the user facility identified legacy materials from previous programs that are still being stored in laboratories and hot-cell facilities at the INL. In addition other materials of interest were identified that are being stored outside the INL that the current owners have volunteered to enter into the library. Finally, over the course of the last several years, the ATR NSUF has irradiated more than 3500 specimens as part of NSUF competitively awarded research projects. The Logistics of managing this large inventory of highly radioactive poses unique challenges. This document will describe materials in the library, outline the policy for accessing these materials and put forth a strategy for making new additions to the library as well as establishing guidelines for minimum pedigree needed to be included in the library to limit the amount of material stored indefinitely without identified value.

  4. Update on meat irradiation

    SciTech Connect

    Olson, D.G.

    1997-12-01

    The irradiation of meat and poultry in the United States is intended to eliminate pathogenic bacteria from raw product, preferably after packaging to prevent recontamination. Irradiation will also increase the shelf life of raw meat and poultry products approximately two to three times the normal shelf life. Current clearances in the United States are for poultry (fresh or frozen) at doses from 1.5 to 3.0 kGy and for fresh pork at doses from 0.3 to 1.0 kGy. A petition for the clearance of all red meat was submitted to the Food and Drug Administration (FDA) in July 1994. The petition is for clearances of fresh meat at doses from 1.5 to 4.5 kGy and for frozen meat at {approximately}2.5 to 7.5 kGy. Clearance for red meat is expected before the end of 1997. There are 28 countries that have food irradiation clearances, of which 18 countries have clearances for meat or poultry. However, there are no uniform categories or approved doses for meat and poultry among the countries that could hamper international trade of irradiated meat and poultry.

  5. Irradiating insect pests

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This is a non-technical article focusing on phytosanitary uses of irradiation. In a series of interview questions, I present information on the scope of the invasive species problem and the contribution of international trade in agricultural products to the movement of invasive insects. This is foll...

  6. Predictive value of cytokines for developing complications after polytrauma

    PubMed Central

    Dekker, Anne-Britt E; Krijnen, Pieta; Schipper, Inger B

    2016-01-01

    AIM: To investigate posttraumatic cytokine alterations and their value for predicting complications and mortality in polytraumatized patients. METHODS: Studies on the use of specific cytokines to predict the development of complications and mortality were identified in MEDLINE, EMBASE, Web of Science and the Cochrane Library. Of included studies, relevant data were extracted and study quality was scored. RESULTS: Forty-two studies published between 1988 and 2015 were identified, including 28 cohort studies and 14 “nested” case-control studies. Most studies investigated the cytokines interleukin (IL)-6, IL-8, IL-10 and tumor necrosis factor (TNF-α). IL-6 seems related to muliorgan dysfunction syndrome, multiorgan failure (MOF) and mortality; IL-8 appears altered in acute respiratory distress syndrome, MOF and mortality; IL-10 alterations seem to precede sepsis and MOF; and TNF-α seems related to MOF. CONCLUSION: Cytokine secretion patterns appear to be different for patients developing complications when compared to patients with uneventful posttraumatic course. More research is needed to strengthen the evidence for clinical relevance of these cytokines.

  7. The effect of inflammatory cytokines in alcoholic liver disease.

    PubMed

    Kawaratani, Hideto; Tsujimoto, Tatsuhiro; Douhara, Akitoshi; Takaya, Hiroaki; Moriya, Kei; Namisaki, Tadashi; Noguchi, Ryuichi; Yoshiji, Hitoshi; Fujimoto, Masao; Fukui, Hiroshi

    2013-01-01

    Alcohol is the most common cause of liver disease in the world. Chronic alcohol consumption leads to hepatocellular injury and liver inflammation. Inflammatory cytokines, such as TNF-α and IFN-γ, induce liver injury in the rat model of alcoholic liver disease (ALD). Hepatoprotective cytokines, such as IL-6, and anti-inflammatory cytokines, such as IL-10, are also associated with ALD. IL-6 improves ALD via activation of the signal transducer and activator of transcription 3 (STAT3) and the subsequent induction of a variety of hepatoprotective genes in hepatocytes. IL-10 inhibits alcoholic liver inflammation via activation of STAT3 in Kupffer cells and the subsequent inhibition of liver inflammation. Alcohol consumption promotes liver inflammation by increasing translocation of gut-derived endotoxins to the portal circulation and activating Kupffer cells through the LPS/Toll-like receptor (TLR) 4 pathways. Oxidative stress and microflora products are also associated with ALD. Interactions between pro- and anti-inflammatory cytokines and other cytokines and chemokines are likely to play important roles in the development of ALD. The present study aims to conduct a systemic review of ALD from the aspect of inflammation. PMID:24385684

  8. Discrimination, Racial Identity, and Cytokine Levels Among African American Adolescents

    PubMed Central

    Brody, Gene H.; Yu, Tianyi; Miller, Gregory E.; Chen, Edith

    2015-01-01

    Purpose Low-grade inflammation, measured by circulating levels of cytokines, is a pathogenic mechanism for several chronic diseases of aging. Identifying factors related to inflammation among African American youths may yield insights into mechanisms underlying racial disparities in health. The purpose of the study was to determine whether (a) reported racial discrimination from ages 17 to 19 forecast heightened cytokine levels at age 22, and (b) this association is lower for youths with positive racial identities. Methods A longitudinal research design was used with a community sample of 160 African Americans who were 17 at the beginning of the study. Discrimination and racial identity were measured with questionnaires, and blood was drawn to measure basal cytokine levels. Ordinary least squares regression analyses were used to examine the hypotheses. Results After controlling for socioeconomic risk, life stress, depressive symptoms, and body mass index, racial discrimination (β = .307, p < .01), racial identity (β = −.179, p < .05), and their interaction (β = −.180, p < .05) forecast cytokine levels. Youths exposed to high levels of racial discrimination evinced elevated cytokine levels 3 years later. This association was not significant for young adults with positive racial identities. Conclusions High levels of interpersonal racial discrimination and the development of a positive racial identity operate jointly to determine low-grade inflammation levels that have been found to forecast chronic diseases of aging, such as coronary disease and stroke. PMID:25907649

  9. Proinflammatory Cytokines and Potassium Channels in the Kidney

    PubMed Central

    Nakamura, Kazuyoshi; Hayashi, Hikaru; Kubokawa, Manabu

    2015-01-01

    Proinflammatory cytokines affect several cell functions via receptor-mediated processes. In the kidney, functions of transporters and ion channels along the nephron are also affected by some cytokines. Among these, alteration of activity of potassium ion (K+) channels induces changes in transepithelial transport of solutes and water in the kidney, since K+ channels in tubule cells are indispensable for formation of membrane potential which serves as a driving force for the transepithelial transport. Altered K+ channel activity may be involved in renal cell dysfunction during inflammation. Although little information was available regarding the effects of proinflammatory cytokines on renal K+ channels, reports have emerged during the last decade. In human proximal tubule cells, interferon-γ showed a time-dependent biphasic effect on a 40 pS K+ channel, that is, delayed suppression and acute stimulation, and interleukin-1β acutely suppressed the channel activity. Transforming growth factor-β1 activated KCa3.1 K+ channel in immortalized human proximal tubule cells, which would be involved in the pathogenesis of renal fibrosis. This review discusses the effects of proinflammatory cytokines on renal K+ channels and the causal relationship between the cytokine-induced changes in K+ channel activity and renal dysfunction. PMID:26508816

  10. Instruction of hematopoietic lineage choice by cytokine signaling

    SciTech Connect

    Endele, Max; Etzrodt, Martin; Schroeder, Timm

    2014-12-10

    Hematopoiesis is the cumulative consequence of finely tuned signaling pathways activated through extrinsic factors, such as local niche signals and systemic hematopoietic cytokines. Whether extrinsic factors actively instruct the lineage choice of hematopoietic stem and progenitor cells or are only selectively allowing survival and proliferation of already intrinsically lineage-committed cells has been debated over decades. Recent results demonstrated that cytokines can instruct lineage choice. However, the precise function of individual cytokine-triggered signaling molecules in inducing cellular events like proliferation, lineage choice, and differentiation remains largely elusive. Signal transduction pathways activated by different cytokine receptors are highly overlapping, but support the production of distinct hematopoietic lineages. Cellular context, signaling dynamics, and the crosstalk of different signaling pathways determine the cellular response of a given extrinsic signal. New tools to manipulate and continuously quantify signaling events at the single cell level are therefore required to thoroughly interrogate how dynamic signaling networks yield a specific cellular response. - Highlights: • Recent studies provided definite proof for lineage-instructive action of cytokines. • Signaling pathways involved in hematopoietic lineage instruction remain elusive. • New tools are emerging to quantitatively study dynamic signaling networks over time.

  11. Effects of cytokines on potassium channels in renal tubular epithelia.

    PubMed

    Nakamura, Kazuyoshi; Komagiri, You; Kubokawa, Manabu

    2012-02-01

    Renal tubular potassium (K(+)) channels play important roles in the formation of cell-negative potential, K(+) recycling, K(+) secretion, and cell volume regulation. In addition to these physiological roles, it was reported that changes in the activity of renal tubular K(+) channels were involved in exacerbation of renal cell injury during ischemia and endotoxemia. Because ischemia and endotoxemia stimulate production of cytokines in immune cells and renal tubular cells, it is possible that cytokines would affect K(+) channel activity. Although the regulatory mechanisms of renal tubular K(+) channels have extensively been studied, little information is available about the effects of cytokines on these K(+) channels. The first report was that tumor necrosis factor acutely stimulated the single channel activity of the 70 pS K(+) channel in the rat thick ascending limb through activation of tyrosine phosphatase. Recently, it was also reported that interferon-γ (IFN-γ) and interleukin-1β (IL-1β) modulated the activity of the 40 pS K(+) channel in cultured human proximal tubule cells. IFN-γ exhibited a delayed suppression and an acute stimulation of K(+) channel activity, whereas IL-1β acutely suppressed the channel activity. Furthermore, these cytokines suppressed gene expression of the renal outer medullary potassium channel. The renal tubular K(+) channels are functionally coupled to the coexisting transporters. Therefore, the effects of cytokines on renal tubular transporter activity should also be taken into account, when interpreting their effects on K(+) channel activity. PMID:22042037

  12. Genomic identification of chemokines and cytokines in opossum.

    PubMed

    Wong, Emily S W; Papenfuss, Anthony T; Belov, Katherine

    2011-03-01

    The cytokine repertoire of marsupials is largely unknown. The sequencing of the opossum genome has expedited the identification of many immune genes. However, many genes have not been identified using automated annotation pipelines because of high levels of sequence divergence. To fill gaps in our knowledge of the cytokine gene complement in marsupials, we searched the genome assembly of the gray short-tailed opossum for chemokine, interleukin, colony-stimulating factor, tumor necrosis factor, and transforming growth factor genes. In particular, we focused on genes that were not previously identified through Ensembl's automatic annotations. We report that the vast majority of cytokines are conserved, with direct orthologs between therian species. The major exceptions are chemokine genes, which show lineage-specific duplication/loss. Thirty-six chemokines were identified in opossum, including a lineage-specific expansion of macrophage inflammatory protein family genes. Divergent cytokines IL7, IL9, IL31, IL33, and CSF2 were identified. This is the first time IL31 and IL33 have been described outside of eutherian species. The high levels of similarities between the cytokine gene repertoires of therians suggest that the marsupial immune response is highly similar to eutherians.

  13. Integrative biology approach identifies cytokine targeting strategies for psoriasis.

    PubMed

    Perera, Gayathri K; Ainali, Chrysanthi; Semenova, Ekaterina; Hundhausen, Christian; Barinaga, Guillermo; Kassen, Deepika; Williams, Andrew E; Mirza, Muddassar M; Balazs, Mercedesz; Wang, Xiaoting; Rodriguez, Robert Sanchez; Alendar, Andrej; Barker, Jonathan; Tsoka, Sophia; Ouyang, Wenjun; Nestle, Frank O

    2014-02-12

    Cytokines are critical checkpoints of inflammation. The treatment of human autoimmune disease has been revolutionized by targeting inflammatory cytokines as key drivers of disease pathogenesis. Despite this, there exist numerous pitfalls when translating preclinical data into the clinic. We developed an integrative biology approach combining human disease transcriptome data sets with clinically relevant in vivo models in an attempt to bridge this translational gap. We chose interleukin-22 (IL-22) as a model cytokine because of its potentially important proinflammatory role in epithelial tissues. Injection of IL-22 into normal human skin grafts produced marked inflammatory skin changes resembling human psoriasis. Injection of anti-IL-22 monoclonal antibody in a human xenotransplant model of psoriasis, developed specifically to test potential therapeutic candidates, efficiently blocked skin inflammation. Bioinformatic analysis integrating both the IL-22 and anti-IL-22 cytokine transcriptomes and mapping them onto a psoriasis disease gene coexpression network identified key cytokine-dependent hub genes. Using knockout mice and small-molecule blockade, we show that one of these hub genes, the so far unexplored serine/threonine kinase PIM1, is a critical checkpoint for human skin inflammation and potential future therapeutic target in psoriasis. Using in silico integration of human data sets and biological models, we were able to identify a new target in the treatment of psoriasis.

  14. Integration of Cytokine Biology and Lipid Metabolism in Stroke**

    PubMed Central

    Adibhatla, Rao Muralikrishna; Dempsey, R.; Hatcher, J. F.

    2007-01-01

    Cytokines regulate the innate and adaptive immune responses and are pleiotropic, redundant and multifunctional. Expression of most cytokines, including TNF-α and IL-1α/ß, is very low in normal brain. Metabolism of lipids is of particular interest due to their high concentration in the brain. Inflammatory response after stroke suggests that cytokines (TNF-α, IL-1 α/ß, IL-6), affect the phospholipid metabolism and subsequent production of eicosanoids, ceramide, and ROS that may potentiate brain injury. Phosphatidylcholine and sphingomyelin are source for lipid messengers. Sphingomyelin synthase serves as a bridge between metabolism of glycerolipids and sphingolipids. TNF-α and IL-1 α/ß can induce phospholipases (A2, C, and D) and sphingomyelinases, and concomitantly proteolyse phosphatidylcholine and sphingomyelin synthesizing enzymes. Together, these alterations contribute to loss of phosphatidylcholine and sphingomyelin after stroke that can be attenuated by inhibiting TNF-α or IL-1 α/ß signaling. Inflammatory responses are instrumental in the formation and destabilization of atherosclerotic plaques. Secretory PLA2 IIA is found in human atherosclerotic lesions and is implicated in initiation, progression and maturation of atherosclerosis, a risk factor for stroke. Lipoprotein-PLA2, part of apolipoprotein B-100 of LDL, plays a role in vascular inflammation and coronary endothelial dysfunction. Cytokine antagonism attenuated secretory PLA2 IIA actions, suggesting cytokine-lipid integration studies will lead to new concepts contributing to bench-to-bedside transition for stroke therapy. PMID:17981627

  15. Predictive value of cytokines for developing complications after polytrauma

    PubMed Central

    Dekker, Anne-Britt E; Krijnen, Pieta; Schipper, Inger B

    2016-01-01

    AIM: To investigate posttraumatic cytokine alterations and their value for predicting complications and mortality in polytraumatized patients. METHODS: Studies on the use of specific cytokines to predict the development of complications and mortality were identified in MEDLINE, EMBASE, Web of Science and the Cochrane Library. Of included studies, relevant data were extracted and study quality was scored. RESULTS: Forty-two studies published between 1988 and 2015 were identified, including 28 cohort studies and 14 “nested” case-control studies. Most studies investigated the cytokines interleukin (IL)-6, IL-8, IL-10 and tumor necrosis factor (TNF-α). IL-6 seems related to muliorgan dysfunction syndrome, multiorgan failure (MOF) and mortality; IL-8 appears altered in acute respiratory distress syndrome, MOF and mortality; IL-10 alterations seem to precede sepsis and MOF; and TNF-α seems related to MOF. CONCLUSION: Cytokine secretion patterns appear to be different for patients developing complications when compared to patients with uneventful posttraumatic course. More research is needed to strengthen the evidence for clinical relevance of these cytokines. PMID:27652210

  16. Cytokine imbalance in pregnancy complications and its modulation.

    PubMed

    Raghupathy, Raj; Kalinka, Jaroslaw

    2008-01-01

    The phenomenon of pregnancy can be compromised by a number of complications, such as threatened abortion, recurrent spontaneous miscarriage, preeclampsia, and preterm delivery. Research conducted during the last decade has opened up the possibility that cellular immune effectors may underlie such pregnancy complications. Particularly interesting are the effects of pro-inflammatory and anti-inflammatory cytokines on the conceptus and thus on the success or failure of pregnancy. This review focuses on the association between cytokines and the different complications of pregnancy as well as on the possible pathways of the effector function of cytokines in pregnancy loss. This review also goes on to discuss the redirection of the cytokine profile towards one that is more conducive to pregnancy. Among the most promising agents for the modulation of the Th1/Th2 balance are progestogens such as progesterone and dydrogesterone. Recently published studies lead us to propose that a therapeutic approach worth pursuing would be to assess the individual cytokine profiles of women with pregnancy complications and then to adjust individual therapy using the most effective progestogen. PMID:17981605

  17. Low-fluence CO2 laser irradiation decreases enamel solubility

    NASA Astrophysics Data System (ADS)

    Esteves-Oliveira, M.; Apel, C.; Gutknecht, N.; Velloso, W. F.; Cotrim, M. E. B.; Eduardo, C. P.; Zezell, D. M.

    2008-04-01

    This study investigated whether subablative-pulsed CO2 laser (10.6 μm) irradiation, using fluences lower than 1 J/cm2, was capable of reducing enamel acid solubility. Fifty-one samples of bovine dental enamel were divided into three groups: control group, which was not irradiated (CG); group laser A (LA) irradiated with 0.3 J/cm2; and group laser B (LB) irradiated with 0.7 J/cm2. After irradiation, the samples were subjected to demineralization in an acetate buffer solution and were then analyzed by SEM. A finite-element model was used to calculate the temperature increase. The calcium and phosphorous content in the demineralization solution were measured with an ICP-OES. ANOVA and the t-test pairwise comparison ( p < 0.016) revealed that LB showed significantly lower mean Ca and P content values in the demineralization solution than other groups. A reduction in the enamel solubility can be obtained with pulsed CO2 laser irradiation (0.7 J/cm2, 135 mJ/pulse, 74 Hz, 100 μs) without any surface photomodification and a less than 2°C temperature increase at a 3-mm depth from the surface.

  18. Poly(lactide-co-glycolide) microspheres containing bupivacaine: comparison between gamma and beta irradiation effects.

    PubMed

    Montanari, L; Cilurzo, F; Selmin, F; Conti, B; Genta, I; Poletti, G; Orsini, F; Valvo, L

    2003-07-31

    The beta- and gamma-irradiation effects on stability of microspheres made of poly(lactide-co-glycolide) 50:50 copolymer (PLGA) containing bupivacaine (BU) were studied. Microspheres containing 10, 25, and 40% w/w, respectively, of BU were prepared by spray drying and irradiated in air with beta- and gamma-irradiation at a dose of 25 kGy. Morphology (atomic force microscopy, particle-size analysis), physico-chemical characteristics (DSC and FT-IR spectroscopy), drug content and in vitro dissolution profile of microspheres were all determined; the stability of irradiated microspheres was evaluated over a 9-month period. The decrease of BU content in gamma-irradiated microspheres was almost always constant independent of the amount of BU per sample, therefore it was in inverse proportion to drug loading (range between 5 and 15%). BU release rate increased immediately after irradiation and increased slightly until 90 days of storage. As far as beta-irradiated microspheres are concerned, BU content decreased in a significant way (approximately 3%) only in microspheres containing 10% w/w of BU. Immediately after irradiation, drug release rate in beta-irradiated microspheres increased less than in the corresponding gamma-irradiated microspheres, and it did not change further over the following storage period. BU-loaded microspheres have been shown to be more stable against beta- than gamma-irradiation. AFM revealed that the surface roughness of the irradiated microspheres increases depending on irradiation. As such, if a parameter is quantifiable, it is proposed as a marker of degradation due to ionizing radiation. PMID:12880695

  19. Role of gamma irradiation on the natural antioxidants in cumin seeds

    NASA Astrophysics Data System (ADS)

    Kim, Jae Hun; Shin, Mee-Hye; Hwang, Young-Jeong; Srinivasan, Periasamy; Kim, Jae Kyung; Park, Hyun Jin; Byun, Myung Woo; Lee, Ju Woon

    2009-02-01

    Antioxidants quench oxidation by transferring hydrogen atoms to free radicals. In the present investigation, the effect of gamma irradiation on the natural antioxidants of irradiated cumin was studied. Cumin samples were purchased from retailers and then irradiated in a cobalt-60 irradiator to 0, 1, 3, 5 and 10 kGy at ambient temperature. The effect of irradiation on the antioxidant properties of the cumin seed were investigated by evaluating the radical-scavenging effect on the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, determination of ferric reducing antioxidant power (FRAP), total polyphenol content (TPC) and the antioxidant index by β-carotene/linoleic acid co-oxidation. Electron spin resonance (ESR) was performed to assess ionization of cumin seeds by gamma irradiation. Irradiation was found to nonsignificantly increase and/or maintain all antioxidant parameters, TPC and the ESR signal intensity was found to be increased in cumin seeds.

  20. Enhancement of Antioxidant and Isoflavones Concentration in Gamma Irradiated Soybean

    PubMed Central

    Popović, Boris M.; Štajner, Dubravka; Mandić, Anamarija; Čanadanović-Brunet, Jasna; Kevrešan, Slavko

    2013-01-01

    Serbian soybean genotype Ana was gamma irradiated at doses of 1, 2, 4, and 10 kGy in order to evaluate the influence of gamma irradiation on isoflavone (genistein, daidzein, and their glycosides genistin and daidzin) contents and hydroxyl radical scavenging effect (HRSE). The increase in genistin and daidzin contents as well as antioxidant activities was observed especially at doses of 4 and 10 kGy. Results were also compared with our previous results relating to total phenol content (TPC), DPPH radical scavenger capacity (DPPH RSC), and ferric reducing antioxidant power (FRAP). Our results indicated that doses up to 10 kGy improve the antioxidant activities of soybean and also nutritional quality with respect to isoflavone content. All results were analyzed by multivariate techniques (correlation matrix calculation and autoscaling transformation of data). Significant positive correlations were observed between genistin, daidzin, DPPH RSC, and HRSE. PMID:24298214

  1. Low doses of gamma irradiation potentially modifies immunosuppressive tumor microenvironment by retuning tumor-associated macrophages: lesson from insulinoma.

    PubMed

    Prakash, Hridayesh; Klug, Felix; Nadella, Vinod; Mazumdar, Varadendra; Schmitz-Winnenthal, Hubertus; Umansky, Liudmila

    2016-03-01

    Tumor infiltrating iNOS+ macrophages under the influence of immunosuppressive tumor microenvironment gets polarized to tumor-promoting and immunosuppressive macrophages, known as tumor-associated macrophages (TAM). Their recruitment and increased density in the plethora of tumors has been associated with poor prognosis in cancer patients. Therefore, retuning of TAM to M1 phenotype would be a key for effective immunotherapy. Radiotherapy has been a potential non-invasive strategy to improve cancer immunotherapy and tumor immune rejection. Irradiation of late-stage tumor-bearing Rip1-Tag5 mice twice with 2 Gy dose resulted in profound changes in the inflammatory tumor micromilieu, characterized by induction of M1-associated effecter cytokines as well as reduction in protumorigenic and M2-associated effecter cytokines. Similarly, in vitro irradiation of macrophages with 2 Gy dose-induced expression of iNOS, NO, NFκBpp65, pSTAT3 and proinflammatory cytokines secretion while downregulating p38MAPK which are involved in iNOS translation and acquisition of an M1-like phenotype. Enhancement of various M2 effecter cytokines and angiogenic reprogramming in iNOs+ macrophage depleted tumors and their subsequent reduction by 2 Gy dose in Rip1-Tag5 transgenic mice furthermore demonstrated a critical role of peritumoral macrophages in the course of gamma irradiation mediated M1 retuning of insulinoma. PMID:26785731

  2. Reconfigurable microfluidic device with integrated antibody arrays for capture, multiplexed stimulation, and cytokine profiling of human monocytes

    PubMed Central

    Vu, Tam; Rahimian, Ali; Stybayeva, Gulnaz; Gao, Yandong; Kwa, Timothy; Van de Water, Judy; Revzin, Alexander

    2015-01-01

    Monocytes represent a class of immune cells that play a key role in the innate and adaptive immune response against infections. One mechanism employed by monocytes for sensing foreign antigens is via toll-like receptors (TLRs)—transmembrane proteins that distinguish classes of foreign pathogens, for example, bacteria (TLR4, 5, and 9) vs. fungi (TLR2) vs. viruses (TLR3, 7, and 8). Binding of antigens activates a signaling cascade through TLR receptors that culminate in secretion of inflammatory cytokines. Detection of these cytokines can provide valuable clinical data for drug developers and disease investigations, but this usually requires a large sample volume and can be technically inefficient with traditional techniques such as flow cytometry, enzyme-linked immunosorbent assay, or luminex. This paper describes an approach whereby antibody arrays for capturing cells and secreted cytokines are encapsulated within a microfluidic device that can be reconfigured to operate in serial or parallel mode. In serial mode, the device represents one long channel that may be perfused with a small volume of minimally processed blood. Once monocytes are captured onto antibody spots imprinted into the floor of the device, the straight channel is reconfigured to form nine individually perfusable chambers. To prove this concept, the microfluidic platform was used to capture monocytes from minimally processed human blood in serial mode and then to stimulate monocytes with different TLR agonists in parallel mode. Three cytokines, tumor necrosis factor-α, interleukin (IL)-6, and IL-10, were detected using anti-cytokine antibody arrays integrated into each of the six chambers. We foresee further use of this device in applications such as pediatric immunology or drug/vaccine testing where it is important to balance small sample volume with the need for high information content. PMID:26339315

  3. Adipose Tissue Promotes a Serum Cytokine Profile Related to Lower Insulin Sensitivity after Chronic Central Leptin Infusion

    PubMed Central

    Burgos-Ramos, Emma; Canelles, Sandra; Perianes-Cachero, Arancha; Arilla-Ferreiro, Eduardo; Argente, Jesús; Barrios, Vicente

    2012-01-01

    Obesity is an inflammatory state characterized by an augment in circulating inflammatory factors. Leptin may modulate the synthesis of these factors by white adipose tissue decreasing insulin sensitivity. We have examined the effect of chronic central administration of leptin on circulating levels of cytokines and the possible relationship with cytokine expression and protein content as well as with leptin and insulin signaling in subcutaneous and visceral adipose tissues. In addition, we analyzed the possible correlation between circulating levels of cytokines and peripheral insulin resistance. We studied 18 male Wistar rats divided into controls (C), those treated icv for 14 days with a daily dose of 12 μg of leptin (L) and a pair-fed group (PF) that received the same food amount consumed by the leptin group. Serum leptin and insulin were measured by ELISA, mRNA levels of interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-4, IL-6, IL-10 and tumor necrosis factor-α (TNF-α) by real time PCR and serum and adipose tissue levels of these cytokines by multiplexed bead immunoassay. Serum leptin, IL-2, IL-4, IFN-γ and HOMA-IR were increased in L and TNF-α was decreased in PF and L. Serum leptin and IL-2 levels correlate positively with HOMA-IR index and negatively with serum glucose levels during an ip insulin tolerance test. In L, an increase in mRNA levels of IL-2 was found in both adipose depots and IFN-γ only in visceral tissue. Activation of leptin signaling was increased and insulin signaling decreased in subcutaneous fat of L. In conclusion, leptin mediates the production of inflammatory cytokines by adipose tissue independent of its effects on food intake, decreasing insulin sensitivity. PMID:23056516

  4. Gamma irradiation of peanut kernel to control mold growth and to diminish aflatoxin contamination

    NASA Astrophysics Data System (ADS)

    Y.-Y. Chiou, R.

    1996-09-01

    Peanut kernel inoculated with Aspergillus parasiticus conidia were gamma irradiated with 0, 2.5, 5.0 and 10 kGy using Co60. Levels higher than 2.5 kGy were effective in retarding the outgrowth of A. parasiticus and reducing the population of natural mold contaminants. However, complete elimination of these molds was not achieved even at the dose of 10 kGy. After 4 wk incubation of the inoculated kernels in a humidified condition, aflatoxins produced by the surviving A. parasiticus were 69.12, 2.42, 57.36 and 22.28 μ/g, corresponding to the original irradiation levels. Peroxide content of peanut oils prepared from the irradiated peanuts increased with increased irradiation dosage. After storage, at each irradiation level, peroxide content in peanuts stored at -14°C was lower than that in peanuts stored at an ambient temperature. TBA values and CDHP contents of the oil increased with increased irradiation dosage and changed slightly after storage. However, fatty acid contents of the peanut oil varied in a limited range as affected by the irradiation dosage and storage temperature. The SDS-PAGE protein pattern of peanuts revealed no noticeable variation of protein subunits resulting from irradiation and storage.

  5. Cytokines and chemokines in neuromyelitis optica: pathogenetic and therapeutic implications.

    PubMed

    Uzawa, Akiyuki; Mori, Masahiro; Masahiro, Mori; Kuwabara, Satoshi

    2014-01-01

    Neuromyelitis optica (NMO) is characterized by severe optic neuritis and longitudinally extensive transverse myelitis. The discovery of an NMO-specific autoantibody to the aquaporin-4 (AQP4) water channel has improved knowledge of NMO pathogenesis. Many studies have focused on inflammatory and pathological biomarkers of NMO, including cytokines and chemokines. Increased concentrations of T helper (Th)17- and Th2-related cytokines and chemokines may be essential factors for developing NMO inflammatory lesions. For example, interleukin-6 could play important roles in NMO pathogenesis, as it is involved in the survival of plasmablasts that produce anti-AQP4 antibody in peripheral circulation and in the enhancement of inflammation in the central nervous system. Therefore, assessment of these useful biomarkers may become a supportive criterion for diagnosing NMO. Significant advances in the understanding of NMO pathogenesis will lead to the development of novel treatment strategies. This review focuses on the current advances in NMO immunological research, particularly that of cytokines and chemokines.

  6. Immunotherapeutic implications of IL-6 blockade for cytokine storm.

    PubMed

    Tanaka, Toshio; Narazaki, Masashi; Kishimoto, Tadamitsu

    2016-07-01

    IL-6 contributes to host defense against infections and tissue injuries. However, exaggerated, excessive synthesis of IL-6 while fighting environmental stress leads to an acute severe systemic inflammatory response known as 'cytokine storm', since high levels of IL-6 can activate the coagulation pathway and vascular endothelial cells but inhibit myocardial function. Remarkable beneficial effects of IL-6 blockade therapy using a humanized anti-IL-6 receptor antibody, tocilizumab were recently observed in patients with cytokine release syndrome complicated by T-cell engaged therapy. In this review we propose the possibility that IL-6 blockade may constitute a novel therapeutic strategy for other types of cytokine storm, such as the systemic inflammatory response syndrome including sepsis, macrophage activation syndrome and hemophagocytic lymphohistiocytosis. PMID:27381687

  7. Recent advances in cytokines in cutaneous and systemic lupus erythematosus.

    PubMed

    Mikita, Naoya; Ikeda, Takaharu; Ishiguro, Mariko; Furukawa, Fukumi

    2011-09-01

    Lupus erythematosus (LE) includes a broad spectrum of diseases from a cutaneous-limited type to a systemic type. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease which affects multiple organs. Cutaneous lupus erythematosus (CLE) includes skin symptoms seen in SLE and cutaneous-limited LE. Although immune abnormalities, as well as heritable, hormonal and environmental factors, are involved in the pathology of LE, the actual pathogenesis is still unclear. Recently, the involvement of various cytokines has been shown in the pathogenesis of LE. Moreover, some trials with biological agents targeted specific cytokines are also ongoing for SLE. In this article, we review the contributions of major cytokines such as interferon, tumor necrosis factor-α and interleukin-18 to LE, especially SLE and CLE.

  8. MicroRNA-Regulated Proinflammatory Cytokines in Sarcopenia

    PubMed Central

    Fan, Jingjing; Kou, Xianjuan; Yang, Yi; Chen, Ning

    2016-01-01

    Sarcopenia has been defined as the aging-related disease with the declined mass, strength, and function of skeletal muscle, which is the major cause of frailty and falls in elders. The activation of inflammatory signal pathways due to diseases and aging is suggested to reveal the critical impact on sarcopenia. Several proinflammatory cytokines, especially interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), play crucial roles in modulation of inflammatory signaling pathway during the aging-related loss of skeletal muscle. MicroRNAs (miRNAs) have emerged as the important regulators for the mass and functional maintenance of skeletal muscle through regulating gene expression of proinflammatory cytokines. In this paper, we have systematically discussed regulatory mechanisms of miRNAs for the expression and secretion of inflammatory cytokines during sarcopenia, which will provide some novel targets and therapeutic strategies for controlling aging-related atrophy of skeletal muscle and corresponding chronic inflammatory diseases. PMID:27382188

  9. Abnormal Growth Factor/Cytokine Network in Gastric Cancer

    PubMed Central

    2008-01-01

    Gastric cancer cells express a broad spectrum of the growth factor/cytokine receptor systems that organize the complex interaction between cancer cells and stromal cells in tumor microenvironment, which confers cell growth, apoptosis, morphogenesis, angiogenesis, progression and metastasis. However, these abnormal growth factor/cytokine networks differ in the two histological types of gastric cancer. Importantly, activation of nuclear factor-kB pathway by Helicobacter pylori infection may act as a key player for induction of growth factor/cytokine networks in gastritis and pathogenesis of gastric cancer. Better understanding of these events will no doubt provide new approaches for biomarkers of diagnosis and effective therapeutic targeting of gastric cancer. PMID:19308687

  10. Immunotherapeutic implications of IL-6 blockade for cytokine storm.

    PubMed

    Tanaka, Toshio; Narazaki, Masashi; Kishimoto, Tadamitsu

    2016-07-01

    IL-6 contributes to host defense against infections and tissue injuries. However, exaggerated, excessive synthesis of IL-6 while fighting environmental stress leads to an acute severe systemic inflammatory response known as 'cytokine storm', since high levels of IL-6 can activate the coagulation pathway and vascular endothelial cells but inhibit myocardial function. Remarkable beneficial effects of IL-6 blockade therapy using a humanized anti-IL-6 receptor antibody, tocilizumab were recently observed in patients with cytokine release syndrome complicated by T-cell engaged therapy. In this review we propose the possibility that IL-6 blockade may constitute a novel therapeutic strategy for other types of cytokine storm, such as the systemic inflammatory response syndrome including sepsis, macrophage activation syndrome and hemophagocytic lymphohistiocytosis.

  11. Immunoregulatory biological response modifiers: effect of cytokines on septic shock

    PubMed Central

    De Simone, Claudio

    1993-01-01

    Whole bacteria or bacterial components or their extracts were employed to restore or augment the immune system. Beneficial effects were attained with these agents in treating various diseases. These agents were named biological response modifiers (BRMs) because they regulated certain cellular components of the immune system. The cellular regulation induced by these BRMs was found to be due to cytokines. The cytokines were shown to act directly on the various cellular components and to provide therapeutic benefit in various autoimmune and immune deficiency diseases. Overproduction of specific cytokines however leads to a deleterious effect on the host. Overproduction of tumour necrosis factor (endotoxin, lipopolysaccharide) leads to septic shock. Bacteraemia is the leading cause of overproduction of tumour necrosis factor (TNF). Septic shock in many cases leads to death. Several monoclonal antibodies to lipopolysaccharide (LPS) and anticytokines have demonstrated protection against septic shock. PMID:18475571

  12. The Role of Cytokines in Breast Cancer Development and Progression

    PubMed Central

    Esquivel-Velázquez, Marcela; Ostoa-Saloma, Pedro; Palacios-Arreola, Margarita Isabel; Nava-Castro, Karen E.; Castro, Julieta Ivonne

    2015-01-01

    Cytokines are highly inducible, secretory proteins that mediate intercellular communication in the immune system. They are grouped into several protein families that are referred to as tumor necrosis factors, interleukins, interferons, and colony-stimulating factors. In recent years, it has become clear that some of these proteins as well as their receptors are produced in the organisms under physiological and pathological conditions. The exact initiation process of breast cancer is unknown, although several hypotheses have emerged. Inflammation has been proposed as an important player in tumor initiation, promotion, angiogenesis, and metastasis, all phenomena in which cytokines are prominent players. The data here suggest that cytokines play an important role in the regulation of both induction and protection in breast cancer. This knowledge could be fundamental for the proposal of new therapeutic approaches to particularly breast cancer and other cancer-related disorders. PMID:25068787

  13. Effect of gamma irradiation on the structure of fucoidan

    NASA Astrophysics Data System (ADS)

    Choi, Jong-il; Gu Lee, Sung; Jong Han, Se; Cho, Minho; Cheon Lee, Pyung

    2014-07-01

    The change of molecular structure of fucoidan by gamma irradiation was analyzed by spectral and chemical methods. Fucoidan samples with different molecular weights of 85, 30, 15, and 7 kDa were prepared by radiation degradation of 217 kDa fucoidan. In the molecular weight analysis, the polydispersity decreased by gamma radiation because of further degradation of higher weight molecules. Ultraviolet absorption and Fourier-transform infrared spectroscopy analyses were carried out to define the changes of the functional groups in fucoidan by gamma irradiation. Carboxyl groups and carbon double bonds increased by gamma irradiation; however, sulfate content remained unchanged. The granular fissures were observed from scanning electron microscopy in gamma-irradiated fucoidan.

  14. Improvement in properties of plastic teeth by electron beam irradiation

    NASA Astrophysics Data System (ADS)

    Sano, Yuko; Ishikawa, Shun-ichi; Seguchi, Tadao

    2011-11-01

    Improvement of the comfort and esthetics of artificial plastic teeth is desirable for the recently increasing numbers of elderly in society. Plastic teeth made of polycarbonate (PC) were modified by electron beam (EB) irradiation under specific conditions, and the change in the chemical properties of the PC was investigated. The water absorption, glucose attachment, level of bis-phenol-A (BPA) extraction, maltose adhesion, and mucin adhesion on the PC teeth were measured before and after EB irradiation. EB irradiation to a dose of 3.5 kGy at 150 °C in a nitrogen gas atmosphere reduced the water absorption by 20%, glucose absorption by 40%, maltose adhesion by 20%, and the amount of various amino acids, formed as the hydrolysis products of mucin, adhering on the PC teeth were reduced by 60-99%. The BPA content was lower than the detection limit for analysis of both the original and the EB irradiated PC teeth.

  15. Cytokine knockouts in reproduction: the use of gene ablation to dissect roles of cytokines in reproductive biology.

    PubMed

    Ingman, Wendy V; Jones, Rebecca L

    2008-01-01

    Cytokines play many diverse and important roles in reproductive biology, and dissecting the complex interactions between these proteins and the different reproductive organs is a difficult task. One approach is to use gene ablation, or 'knockout', to analyse the effect of deletion of a single cytokine on mouse reproductive function. This review summarizes the essential roles of cytokines in reproductive biology that have been revealed by gene knockout studies, including development and regulation of the hypothalamo-pituitary-gondal axis, ovarian folliculogenesis, implantation and immune system modulation during pregnancy. However, successful utilization of this approach must consider the caveats associated with gene ablation studies, e.g. embryonic lethality, systemic effects of cytokine ablation on local reproductive processes and the limited exposure to pathogens in mice housed in laboratory conditions. New sophisticated technology that temporally or spatially regulates gene ablation can overcome some of these limitations. Discoveries on the roles of cytokines in reproductive function uncovered by gene ablation studies can now be applied to improve in vitro fertilization for infertile couples and in the development of contraceptive therapies.

  16. Some microbial, chemical and sensorial properties of gamma irradiated sesame (Sesamum indicum L.) seeds.

    PubMed

    Al-Bachir, Mahfouz

    2016-04-15

    The effect on microbial, chemical and sensorial properties of sesame seeds was determined after irradiation and storage. The sesame seeds were analyzed before and after irradiation with 3, 6 and 9 kGy of gamma irradiation, and after 6 and 12 months of storage. The results showed that gamma irradiation had no significant (p>0.05) effect on the moisture, ash and fat content on sesame seeds. While, small differences, but sometimes significant (p<0.05), on protein and sugar contents were recorded between irradiated and non-irradiated samples. Total acidity percentage decreased significantly (p<0.05), while total volatile basic nitrogen (TVBN) increased significantly (p<0.05) due to irradiation. During storage, total acidity increased (p<0.05) and TVBN decreased (p<0.05). Gamma irradiation reduced the microorganisms of sesame seeds. Samples treated with 3 kGy or more remained completely free of fungi throughout the storage. While, only the samples treated with 9 kGy remained completely free of bacteria at the end of storage period (after 12 months). The scores for taste, flavor, color and texture of irradiated samples were higher, but not significantly (p>0.05) than those of non-irradiated samples. PMID:26616940

  17. Some microbial, chemical and sensorial properties of gamma irradiated sesame (Sesamum indicum L.) seeds.

    PubMed

    Al-Bachir, Mahfouz

    2016-04-15

    The effect on microbial, chemical and sensorial properties of sesame seeds was determined after irradiation and storage. The sesame seeds were analyzed before and after irradiation with 3, 6 and 9 kGy of gamma irradiation, and after 6 and 12 months of storage. The results showed that gamma irradiation had no significant (p>0.05) effect on the moisture, ash and fat content on sesame seeds. While, small differences, but sometimes significant (p<0.05), on protein and sugar contents were recorded between irradiated and non-irradiated samples. Total acidity percentage decreased significantly (p<0.05), while total volatile basic nitrogen (TVBN) increased significantly (p<0.05) due to irradiation. During storage, total acidity increased (p<0.05) and TVBN decreased (p<0.05). Gamma irradiation reduced the microorganisms of sesame seeds. Samples treated with 3 kGy or more remained completely free of fungi throughout the storage. While, only the samples treated with 9 kGy remained completely free of bacteria at the end of storage period (after 12 months). The scores for taste, flavor, color and texture of irradiated samples were higher, but not significantly (p>0.05) than those of non-irradiated samples.

  18. Nicotinamide is a potent inhibitor of proinflammatory cytokines

    PubMed Central

    UNGERSTEDT, J S; BLOMBÄCK, M; SöDERSTRÖM, T

    2003-01-01

    The present study investigates the modulating effects of nicotinamide on the cytokine response to endotoxin. In an in vitro model of endotoxaemia, human whole blood was stimulated for two hours with endotoxin at 1 ng/ml, achieving high levels of the proinflammatory cytokines IL-1β, IL-6, IL-8 and TNFα. When coincubating whole blood, endotoxin and the vitamin B3 derivative nicotinamide, all four cytokines measured were inhibited in a dose dependent manner. Inhibition was observed already at a nicotinamide concentration of 2 mmol/l. At a concentration of 40 mmol/l, the IL-1β, IL-6 and TNFα responses were reduced by more than 95% and the IL-8 levels reduced by 85%. Endotoxin stimulation activates poly(ADP-ribose)polymerase (PARP), a nuclear DNA repair enzyme. It has been hypothesized that the anti-inflammatory properties of nicotinamide are due to PARP inhibition. In the present study, the endotoxin induced PARP activation was dose dependently decreased with 4–40 mmol/l nicotinamide or 4–100 µmol/l 6(5H) phenanthridinone, a specific PARP inhibitor. 6(5H)phenanthridinone however, failed to inhibit the proinflammatory cytokines. Thus, the mechanism behind the cytokine inhibition in our model seems not to be due to PARP inhibition. In conclusion, the present study could not only confirm previous reports of a down-regulatory effect on TNFα, but demonstrates that nicotinamide is a potent modulator of several proinflammatory cytokines. These findings demonstrate that nicotinamide has a potent immunomodulatory effect in vitro, and may have great potential for treatment of human inflammatory disease. PMID:12519385

  19. [Behavior-immunity relationship: the role of cytokines].

    PubMed

    Espinosa, E; Bermúdez-Rattoni, F

    2001-01-01

    There are several phenomena in which the immune and the central nervous systems regulate each other. However, their mechanisms are poorly understood. Since cytokines have a central role in the regulation of the immune response, this review describes their participation in two forms of neuro-immune communication, immunomodulation by psychological stress and behavioral conditioning of immune response. The role of cytokines in the endocrine and behavioral effects of acute phase, where cytokines have an effect in functions of the central nervous system, is also reviewed. The effects of psychological stress are described as both immunosuppressing and immunoenhancing. Among them, a relevant immunosuppressing one is the reduction of IL-1, IL-2, and IFN-gamma levels. In contrast, some of the pro-inflammatory effects of stress are mediated by an increase in the levels of IL-6, IL-1, and TNF mediated by the neurotransmitter Substance P. A possible role for IL-1 and IFN-beta as possible messengers in immune regulation by behavioral conditioning is proposed. Pro-inflammatory cytokines in turn can activate the hypothalamus-pituitary-adrenal axis and induce sickness behavior during the acute phase response, during which the parasympathetic nervous system serves as pathway for their detection by the central nervous system. An account is given about recent findings on the regulation of cytokine expression by neurotransmitters from the sympathetic nervous system (epinephrine and norepinephrine), a key piece in all these mechanisms of brain-immune communication. Possible mechanisms and pathways of communication between the brain and the immune system, as well as the possible participation of other cytokines are discussed.

  20. Cytokines as Biomarkers of Pancreatic Ductal Adenocarcinoma: A Systematic Review

    PubMed Central

    Yako, Yandiswa Yolanda; Kruger, Deirdré; Smith, Martin; Brand, Martin

    2016-01-01

    Objectives A systematic review of the role of cytokines in clinical medicine as diagnostic, prognostic, or predictive biomarkers in pancreatic ductal adenocarcinoma was undertaken. Materials and Methods A systematic review was conducted according to the 2009 PRISMA guidelines. PubMed database was searched for all original articles on the topic of interest published until June 2015, and this was supplemented with references cited in relevant articles. Studies were evaluated for risk of bias using the Quality in Prognosis Studies tools. Results Forty one cytokines were investigated with relation to pancreatic ductal adenocarcinoma (PDAC) in 65 studies, ten of which were analyzed by more than three studies. Six cytokines (interleukin[IL]-1β, -6, -8, -10, vascular endothelial growth factor, and transforming growth factor) were consistently reported to be increased in PDAC by more than four studies; irrespective of sample type; method of measurement; or statistical analysis model used. When evaluated as part of distinct panels that included CA19-9, IL-1β, -6 and -8 improved the performance of CA19-9 alone in differentiating PDAC from healthy controls. For example, a panel comprising IL-1β, IL-8, and CA 19–9 had a sensitivity of 94.1% vs 85.9%, specificity of 100% vs 96.3%, and area under the curve of 0.984 vs 0.925. The above-mentioned cytokines were associated with the severity of PDAC. IL-2, -6, -10, VEGF, and TGF levels were reported to be altered after patients received therapy or surgery. However, studies did not show any evidence of their ability to predict treatment response. Conclusion Our review demonstrates that there is insufficient evidence to support the role of individual cytokines as diagnostic, predictive or prognostic biomarkers for PDAC. However, emerging evidence indicates that a panel of cytokines may be a better tool for discriminating PDAC from other non-malignant pancreatic diseases or healthy individuals. PMID:27170998

  1. EFFECT OF CYTOKINE AND PHARMACOGENOMIC GENETIC POLYMORPHISMS IN TRANSPLANTATION

    PubMed Central

    Girnita, Diana M; Burckart, Gilbert; Zeevi, Adriana

    2008-01-01

    Purpose of review Recent investigations related to the polymorphism of genes that affect drug therapy and the polymorphisms of cytokines and growth factors that control immune responses have been associated with outcomes following solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT). This review will provide a current update on the most recent findings and discuss the challenges for developing individualized therapeutic strategies based on clinical and genetic profiles. Recent Findings Single nucleotide polymorphisms (SNPs) of cytokine genes have been shown to have an impact in vitro or in vivo protein secretion, dividing the individuals into High, Low or Intermediate producers for a given molecule. Many studies have been performed to determine the contribution of single cytokine gene SNPs on SOT or HSCT outcomes and the reported results are still controversial. However, analysis of a combination of several cytokines and/or cytokine receptor polymorphisms adjusted for known clinical risk factors and ethnicity have resulted in significant clinical correlations. Furthermore, associations with gene polymorphisms that affect immunosuppressive drug therapy in solid organ transplantation have also been extensively studied. There is a continuous flow of new information regarding functional SNPs that may affect the immune response to the allograft or to drug therapy and their impact on clinical outcomes have yet to be validated in large cohorts SOT or HSCT Summary Consolidating the information that we have on pharmacogenetics and on cytokine genetics to produce patient-oriented individualized drug regimens is an important challenge in transplantation medicine. Using a multi-variant approach based on genetic profile and other relevant clinical factors a score system may be developed to predict the severity of rejection, infection or other complications associated with transplantation. The ultimate goal of these studies is to improve patient

  2. [Behavior-immunity relationship: the role of cytokines].

    PubMed

    Espinosa, E; Bermúdez-Rattoni, F

    2001-01-01

    There are several phenomena in which the immune and the central nervous systems regulate each other. However, their mechanisms are poorly understood. Since cytokines have a central role in the regulation of the immune response, this review describes their participation in two forms of neuro-immune communication, immunomodulation by psychological stress and behavioral conditioning of immune response. The role of cytokines in the endocrine and behavioral effects of acute phase, where cytokines have an effect in functions of the central nervous system, is also reviewed. The effects of psychological stress are described as both immunosuppressing and immunoenhancing. Among them, a relevant immunosuppressing one is the reduction of IL-1, IL-2, and IFN-gamma levels. In contrast, some of the pro-inflammatory effects of stress are mediated by an increase in the levels of IL-6, IL-1, and TNF mediated by the neurotransmitter Substance P. A possible role for IL-1 and IFN-beta as possible messengers in immune regulation by behavioral conditioning is proposed. Pro-inflammatory cytokines in turn can activate the hypothalamus-pituitary-adrenal axis and induce sickness behavior during the acute phase response, during which the parasympathetic nervous system serves as pathway for their detection by the central nervous system. An account is given about recent findings on the regulation of cytokine expression by neurotransmitters from the sympathetic nervous system (epinephrine and norepinephrine), a key piece in all these mechanisms of brain-immune communication. Possible mechanisms and pathways of communication between the brain and the immune system, as well as the possible participation of other cytokines are discussed. PMID:11496712

  3. Distribution of cytokine gene single nucleotide polymorphisms among a multi-ethnic Iranian population

    PubMed Central

    Kurdistani, Zana Karimi; Saberi, Samaneh; Talebkhan, Yeganeh; Oghalaie, Akbar; Esmaeili, Maryam; Mohajerani, Nazanin; Bababeik, Maryam; Hassanpour, Parisa; Barani, Shaghik; Farjaddoost, Ameneh; Ebrahimzadeh, Fatemeh; Trejaut, Jean; Mohammadi, Marjan

    2015-01-01

    Background: Cytokine gene single nucleotide polymorphisms (SNPs) are widely used to study susceptibility to complex diseases and as a tool for anthropological studies. Materials and Methods: To investigate cytokine SNPs in an Iranian multi-ethnic population, we have investigated 10 interleukin (IL) SNPs (IL-1β (C-511T, T-31C), IL-2 (G-384T), IL-4 (C-590T), IL-6 (G-174C), IL-8 (T-251A), IL-10 (G-1082A, C-819T, C-592A) and tumor necrosis factor-alpha (TNF-α) (G-308A) in 415 Iranian subjects comprising of 6 different ethnicities. Allelic and genotypic frequencies as well as Hardy-Weinberg equilibrium (HWE) were calculated by PyPop software. Population genetic indices including observed heterozygosity (Ho), expected heterozygosity (He), fixation index (FIS), the effective number of alleles (Ne) and polymorphism information content (PIC) were derived using Popgene 32 software. Multidimensional scaling (MDS) was constructed using Reynold's genetic distance obtained from the frequencies of cytokine gene polymorphism. Results: Genotypic distributions were consistent with the HWE assumptions, except for 3 loci (IL-4-590, IL-8-251 and IL-10-819) in Fars and 4 loci (IL-4-590, IL-6-174, IL-10-1082 and TNF-α-308) in Turks. Pairwise assessment of allelic frequencies, detected differences at the IL-4-590 locus in Gilakis versus Kurds (P = 0.028) and Lurs (P = 0.022). Mazanis and Gilakis displayed the highest (Ho= 0.50 ± 0.24) and lowest (Ho= 0.34 ± 0.16) mean observed heterozygosity, respectively. Conclusions: MDS analysis of our study population, in comparison with others, revealed that Iranian ethnicities except Kurds and Mazanis were tightly located within a single cluster with closest genetic affinity to Europeans. PMID:26436076

  4. The Role of Cytokines and Chemokines in Filovirus Infection

    PubMed Central

    Bixler, Sandra L.; Goff, Arthur J.

    2015-01-01

    Ebola- and marburgviruses are highly pathogenic filoviruses and causative agents of viral hemorrhagic fever. Filovirus disease is characterized by a dysregulated immune response, severe organ damage, and coagulation abnormalities. This includes modulation of cytokines, signaling mediators that regulate various components of the immune system as well as other biological processes. Here we examine the role of cytokines in filovirus infection, with an emphasis on understanding how these molecules affect development of the antiviral immune response and influence pathology. These proteins may present targets for immune modulation by therapeutic agents and vaccines in an effort to boost the natural immune response to infection and/or reduce immunopathology. PMID:26512687

  5. Tear cytokine response to multipurpose solutions for contact lenses

    PubMed Central

    Kalsow, Carolyn M; Reindel, William T; Merchea, Mohinder M; Bateman, Kirk M; Barr, Joseph T

    2013-01-01

    Purpose An increased risk of corneal infiltrative events has been noted with the use of certain contact lenses and multipurpose solutions (MPS). This study was designed to evaluate tear cytokine assay as a sensitive, objective, and quantitative measure of the ocular surface response to contact lens/MPS and to consider the assay’s clinical relevance in the context of other measures of ocular surface response. Methods Two MPS, ReNu® Fresh™ (RNF) and Opti-Free® RepleniSH (OFR), were used with daily wear silicone hydrogel contact lenses in a randomized, prospective crossover study involving 26 subjects. Clinical data collection (conjunctival hyperemia, ocular surface sensitivity, solution induced corneal staining (SICS) test score, and subjective responses) and tear cytokine assays were conducted masked. Responses were tracked as change from baseline throughout the experimental schedule. Results Similar response patterns for several inflammatory cytokines were seen throughout both phases: subjects who received OFR in Phase I had mean tear concentrations that were generally higher than those of the RNF Phase I group. OFR Phase I subjects had significant (P < 0.01) increases over baseline at day 1 and/or following washout for 13 cytokines (cc chemokine ligands [CCL] 3, CCL5, CCL11, granulocyte-macrophage colony-stimulating factor [GM-CSF], interferon [INF]-γ, interleukin [IL]-2, IL-4, IL-5, IL-6, IL-13, IL-15, IL-17, tumor necrosis factor [TNF]-α). These changes were not observed in RNF Phase I subjects, even though SICS test scores increased. Phase I OFR subjects also had increased dryness, while RNF Phase I subjects had decreased bulbar hyperemia. No changes were detected with respect to limbal hyperemia or surface sensitivity thresholds. Conclusion The tear cytokine assay can detect and differentiate contact lens/MPS induced increases in inflammatory cytokines. Changes in cytokine levels were consistent with measurement of hyperemia and dryness but not with

  6. Insights into pathogenesis and treatment of cytokines in cardiomyopathy.

    PubMed

    Vadlamani, L; Abraham, W T

    2000-03-01

    Our understanding of the pathophysiology of chronic heart failure is rapidly expanding. recent investigations suggest a role for various proinflammatory and vasoconstrictive cytokines in the development and progression of the disease. In particular, tumor necrosis factor-alpha, interlukin-6, and endothelin have all been implicated in heart failure desease progression. These cytokines appear to be activated in response to a remodeling, induction of programmed cell death, neurohormonal activation, and hemodynamics, these agents cause a variety of deleterious effects in the setting of ventricular dysfunction. Investigational inhibitors and antagonists of these substances show promise for the future treatment of heart failure. PMID:10980882

  7. Content identification: binary content fingerprinting versus binary content encoding

    NASA Astrophysics Data System (ADS)

    Ferdowsi, Sohrab; Voloshynovskiy, Svyatoslav; Kostadinov, Dimche

    2014-02-01

    In this work, we address the problem of content identification. We consider content identification as a special case of multiclass classification. The conventional approach towards identification is based on content fingerprinting where a short binary content description known as a fingerprint is extracted from the content. We propose an alternative solution based on elements of machine learning theory and digital communications. Similar to binary content fingerprinting, binary content representation is generated based on a set of trained binary classifiers. We consider several training/encoding strategies and demonstrate that the proposed system can achieve the upper theoretical performance limits of content identification. The experimental results were carried out both on a synthetic dataset with different parameters and the FAMOS dataset of microstructures from consumer packages.

  8. Alteration of cytokine profiles in mice exposed to chronic low-dose ionizing radiation

    SciTech Connect

    Shin, Suk Chul; Lee, Kyung-Mi; Kang, Yu Mi; Kim, Kwanghee; Kim, Cha Soon; Yang, Kwang Hee; Jin, Young-Woo; Kim, Chong Soon; Kim, Hee Sun

    2010-07-09

    While a high-dose of ionizing radiation is generally harmful and causes damage to living organisms, a low-dose of radiation has been shown to be beneficial in a variety of animal models. To understand the basis for the effect of low-dose radiation in vivo, we examined the cellular and immunological changes evoked in mice exposed to low-dose radiation at very low (0.7 mGy/h) and low (3.95 mGy/h) dose rate for the total dose of 0.2 and 2 Gy, respectively. Mice exposed to low-dose radiation, either at very low- or low-dose rate, demonstrated normal range of body weight and complete blood counts. Likewise, the number and percentage of peripheral lymphocyte populations, CD4{sup +} T, CD8{sup +} T, B, or NK cells, stayed unchanged following irradiation. Nonetheless, the sera from these mice exhibited elevated levels of IL-3, IL-4, leptin, MCP-1, MCP-5, MIP-1{alpha}, thrombopoietin, and VEGF along with slight reduction of IL-12p70, IL-13, IL-17, and IFN-{gamma}. This pattern of cytokine release suggests the stimulation of innate immunity facilitating myeloid differentiation and activation while suppressing pro-inflammatory responses and promoting differentiation of naive T cells into T-helper 2, not T-helper 1, types. Collectively, our data highlight the subtle changes of cytokine milieu by chronic low-dose {gamma}-radiation, which may be associated with the functional benefits observed in various experimental models.

  9. Hippocampal dysfunction during the chronic phase following a single exposure to cranial irradiation.

    PubMed

    Son, Yeonghoon; Yang, Miyoung; Kim, Joong-Sun; Kim, Juhwan; Kim, Sung-Ho; Kim, Jong-Choon; Shin, Taekyun; Wang, Hongbing; Jo, Sung-Kee; Jung, Uhee; Moon, Changjong

    2014-04-01

    Ionizing radiation can significantly affect brain functioning in adults. The present study assessed depression-like behaviors in adult C57BL/6 mice using the tail suspension test (TST) at 30 and 90days following a single cranial exposure to γ-rays (0, 1, or 10Gy) to evaluate hippocampus-related behavioral dysfunction during the chronic phase following cranial irradiation. Additionally, hippocampal neurogenesis, inflammatory cytokines, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF) were analyzed. At 30 and 90days following irradiation with 10Gy, mice displayed significant depression-like behaviors. We observed a persistent decrease in the number of cells positive for doublecortin, an immunohistochemical marker for neurogenesis, in the hippocampus from 1 to 90days after irradiation with 10Gy. Changes in the mRNA expression of inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor-α, IL-6, and interferon-γ, were not correlated with the decrease in hippocampal neurogenesis or the appearance of depression-like behavior during the chronic phase following irradiation. However, at 30 and 90days after irradiation with 10Gy, the number of microglia was significantly decreased compared with age-matched sham-irradiated controls. The reduction in the chronic phase was consistent with the significant down-regulation in the mRNA expression of iNOS, COX-2, BDNF, and GDNF in the hippocampus. Therefore, hippocampal dysfunction during the chronic phase following cranial irradiation may be associated with decreases in the neurogenesis- and synaptic plasticity-related signals, concomitant with microglial reduction in the hippocampus.

  10. [The pathogenic aspects of fat acids metabolism with short chain and production of cytokines in target affected areas of skin under psoriasis].

    PubMed

    fal'ko, E V; Khyshiktuev, B S; Karavaeva, T M; Tereshkov, P P; Gomboeva, A Ts

    2012-01-01

    The article deals with the results of analysis of specters of short-chained fat acids and cytokines in affected skin of patients with psoriasis. The study revealed the significant decrease of short-chained fat acids level, the shift of cytokine profile in the direction of anti-inflammatory factors (interleukins 1L-1beta, IL-8, tumor necrosis factor TNF-alpha, interferon IFN-alpha) and mytogenetic factors (EGF) on the background of stable values of anti-inflammatory cytokine IL-4. The direct pathogenically significant correlation relationships are established between the IL-4 level and the amount of most analyzed short-chained fat acids. The negative correlation relationships were established between content of C2 and IL-1beta.

  11. Plasma cytokine concentration and the cytokine producing ability of whole blood cell cultures from healthy females with pharmacologically induced hyperprolactinemia.

    PubMed

    Rovenský, J; Lackovic, V; Veselková, Z; Horváthová, M; Koska, J; Blazícková, S; Vigas, M

    1999-01-01

    We investigated the in vitro effect of domperidone-induced hyperprolactinemia on plasma cytokine concentration and blood leukocyte cytokine production in healthy female volunteers. No changes were found in the plasma concentration of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, IL-10, IL-6 and IL-13 during hyperprolactinemia when compared with control values. Using unseparated blood leukocytes, we found that the spontaneous production of IL-6 (4-8 h) and transforming growth factor (TGF)-beta 1 (2-4 h) was significantly decreased and that the in vitro stimulated production of IFN-gamma (2-8 h) and TNF (4 h) was significantly increased compared with control. Our data concerning the increased IFN-gamma and TNF producing capacity of unseparated leukocytes during pharmacologically induced hyperprolactinemia strongly support the possibility that the lymphocyte production of these cytokines can be rapidly amplified by prolactin via a priming mechanism. PMID:10568223

  12. Influence of the physical structure of irradiated starches on their electron spin resonance spectra kinetics

    SciTech Connect

    Raffi, J.J.; Agnel, J.P.L.

    1983-06-23

    This study deals with the shape and kinetic changes of the ESR spectra of eight irradiated starchs, from several hours to several months after ..gamma..-irradiation. Whatever the origin and water content of the starches two major radicals or groups of radicals are observed. The kinetic law depends on the water content; two main zones are pointed out which are relative to the amorphous and crystalline parts of starches.

  13. ELECTRON IRRADIATION OF SOLIDS

    DOEpatents

    Damask, A.C.

    1959-11-01

    A method is presented for altering physical properties of certain solids, such as enhancing the usefulness of solids, in which atomic interchange occurs through a vacancy mechanism, electron irradiation, and temperature control. In a centain class of metals, alloys, and semiconductors, diffusion or displacement of atoms occurs through a vacancy mechanism, i.e., an atom can only move when there exists a vacant atomic or lattice site in an adjacent position. In the process of the invention highenergy electron irradiation produces additional vacancies in a solid over those normally occurring at a given temperature and allows diffusion of the component atoms of the solid to proceed at temperatures at which it would not occur under thermal means alone in any reasonable length of time. The invention offers a precise way to increase the number of vacancies and thereby, to a controlled degree, change the physical properties of some materials, such as resistivity or hardness.

  14. Necrostatin-1 rescues mice from lethal irradiation.

    PubMed

    Huang, Zhentai; Epperly, Michael; Watkins, Simon C; Greenberger, Joel S; Kagan, Valerian E; Bayır, Hülya

    2016-04-01

    There is an emerging need in new medical products that can mitigate and/or treat the short- and long-term consequences of radiation exposure after a radiological or nuclear terroristic event. The direct effects of ionizing radiation are realized primarily via apoptotic death pathways in rapidly proliferating cells within the initial 1-2days after the exposure. However later in the course of the radiation disease necrotic cell death may ensue via direct and indirect pathways from increased generation of pro-inflammatory cytokines. Here we evaluated radiomitigative potential of necrostatin-1 after total body irradiation (TBI) and the contribution of necroptosis to cell death induced by radiation. Circulating TNFα levels were increased starting on d1 after TBI and associated with increased plasmalemma permeability in ileum of irradiated mice. Necrostatin-1 given iv. 48h after 9.5Gy TBI attenuated radiation-induced receptor interacting protein kinase 3 (RIPK3) serine phosphorylation in ileum and improved survival vs. vehicle. Utilizing apoptosis resistant cytochrome c(-/-) cells, we showed that radiation can induce necroptosis, which is attenuated by RNAi knock down of RIPK1 and RIPK3 or by treatment with necrostatin-1 or -1s whereas 1-methyl-L-tryptophan, an indoleamine-2,3-dioxygenase inhibitor, did not exhibit radiomitigative effect. This suggests that the beneficial effect of necrostatin-1 is likely through inhibition of RIPK1-mediated necroptotic pathway. Overall, our data indicate that necroptosis, a form of programmed necrosis, may play a significant role in cell death contributing to radiation disease and mortality. This study provides a proof of principle that necrostatin-1 and perhaps other RIPK1 inhibitors are promising therapeutic agents for radiomitigation after TBI. PMID:26802452

  15. BIOLOGICAL IRRADIATION FACILITY

    DOEpatents

    McCorkle, W.H.; Cern, H.S.

    1962-04-24

    A facility for irradiating biological specimens with neutrons is described. It includes a reactor wherein the core is off center in a reflector. A high-exposure room is located outside the reactor on the side nearest the core while a low-exposure room is located on the opposite side. Means for converting thermal neutrons to fast neutrons are movably disposed between the reactor core and the high and low-exposure rooms. (AEC)

  16. Characterization of Natural Killer Cells and Cytokines in Maternal Placenta and Fetus of Diabetic Mothers

    PubMed Central

    Hara, Cristiane de Castro Pernet; França, Eduardo Luzía; Fagundes, Danny Laura Gomes; de Queiroz, Adriele Ataides; Rudge, Marilza Vieira Cunha; Honorio-França, Adenilda Cristina; Calderon, Iracema de Mattos Paranhos

    2016-01-01

    The present study characterized natural killer cells and cytokines in diabetic mothers, their placenta, and fetus. In the maternal blood from the hyperglycemic groups, the CD16+CD56− NK cells increased, whereas that of CD16+CD56+ decreased in gestational diabetes mellitus [GDM] group. Cord blood from type 2 diabetes [DM-2] showed a higher proportion of CD16+CD56− and CD16−CD56+. The placental extravillous layer of GDM and DM-2 showed an increase of CD16+CD56− cells and, irrespective of region, the proportion of CD16−CD56+ cells was higher in mild gestational hyperglycemia [MGH] and GDM and lower in DM-2. IL-2 was lower in maternal blood and IFN-γ higher in maternal and cord blood from the GDM group. IL-17 was higher in maternal and cord blood from the DM-2 group. The placental extravillous layer of the MGH showed high levels of IL-4, IL-6, IL-10, IL-17, and IFN-γ and low levels of IL-1β and IL-8, whereas the placental villous layer contained high levels of IL-17 and IFN-γ. The GDM group, irrespective of region, showed higher levels of IL-8. The DM-2 group, irrespective of region, placenta showed high levels of TNF-α, IL-17, and IFN-γ. The hyperglycemia produces an inflammatory environment with a high content of inflammatory cytokines and cells expressing CD16+. PMID:27294162

  17. Isorhamnetin attenuates collagen-induced arthritis via modulating cytokines and oxidative stress in mice

    PubMed Central

    Wang, Xuewen; Zhong, Wei

    2015-01-01

    Inflammation and oxidative stress were involved in the development and progression of rheumatoid arthritis (RA). Isorhamnetin has anti-inflammatory and anti-oxidative activities, but its effects on RA have not been investigated. In order to observe the possible therapeutic effects of isorhamnetin on RA, we established a collagen-induced arthritis mouse model and treated the animal with isorhamnetin for 3 weeks. Besides, fibroblast-like synoviocytes (FLS) were treated with lipopolysaccharide (LPS) and isorhamnetin. The severity of arthritis was assessed by arthritis score, joint destruction score and inflammation score. Levels of cytokines TNF-α, IL-1β, IL-6, IL-17A, IL-17F, IL-10 and IL-35 in the joint tissue homogenate and cell culture medium as well as anti-type II collagen antibody in serum were measured using ELISA. Contents of H2O2 and malondialdehyde (MDA) in joint tissue homogenate were measured using assay kits. We found collagen immunization induced significant arthritis in mice and isorhamnetin at the dose of 10 and 20 mg/kg/day could significantly attenuate the collagen-induced arthritis. Isorhamnetin also modulated the production of cytokines and suppressed the oxidative stress in the mice with collagen-induced arthritis at the dose of 10 and 20 mg/kg/day. These data suggested that isorhamnetin might be a potential agent for the management of RA. PMID:26629181

  18. Role of cytokines and chemokines in non-alcoholic fatty liver disease

    PubMed Central

    Braunersreuther, Vincent; Viviani, Giorgio Luciano; Mach, François; Montecucco, Fabrizio

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) includes a variety of histological conditions (ranging from liver steatosis and steatohepatitis, to fibrosis and hepatocarcinoma) that are characterized by an increased fat content within the liver. The accumulation/deposition of fat within the liver is essential for diagnosis of NAFLD and might be associated with alterations in the hepatic and systemic inflammatory state. Although it is still unclear if each histological entity represents a different disease or rather steps of the same disease, inflammatory processes in NAFLD might influence its pathophysiology and prognosis. In particular, non-alcoholic steatohepatitis (the most inflamed condition in NAFLDs, which more frequently evolves towards chronic and serious liver diseases) is characterized by a marked activation of inflammatory cells and the upregulation of several soluble inflammatory mediators. Among several mediators, cytokines and chemokines might play a pivotal active role in NAFLD and are considered as potential therapeutic targets. In this review, we will update evidence from both basic research and clinical studies on the potential role of cytokines and chemokines in the pathophysiology of NAFLD. PMID:22371632

  19. Isorhamnetin attenuates collagen-induced arthritis via modulating cytokines and oxidative stress in mice.

    PubMed

    Wang, Xuewen; Zhong, Wei

    2015-01-01

    Inflammation and oxidative stress were involved in the development and progression of rheumatoid arthritis (RA). Isorhamnetin has anti-inflammatory and anti-oxidative activities, but its effects on RA have not been investigated. In order to observe the possible therapeutic effects of isorhamnetin on RA, we established a collagen-induced arthritis mouse model and treated the animal with isorhamnetin for 3 weeks. Besides, fibroblast-like synoviocytes (FLS) were treated with lipopolysaccharide (LPS) and isorhamnetin. The severity of arthritis was assessed by arthritis score, joint destruction score and inflammation score. Levels of cytokines TNF-α, IL-1β, IL-6, IL-17A, IL-17F, IL-10 and IL-35 in the joint tissue homogenate and cell culture medium as well as anti-type II collagen antibody in serum were measured using ELISA. Contents of H2O2 and malondialdehyde (MDA) in joint tissue homogenate were measured using assay kits. We found collagen immunization induced significant arthritis in mice and isorhamnetin at the dose of 10 and 20 mg/kg/day could significantly attenuate the collagen-induced arthritis. Isorhamnetin also modulated the production of cytokines and suppressed the oxidative stress in the mice with collagen-induced arthritis at the dose of 10 and 20 mg/kg/day. These data suggested that isorhamnetin might be a potential agent for the management of RA. PMID:26629181

  20. Hyperparathyroidism after neck irradiation.

    PubMed

    Christmas, T J; Chapple, C R; Noble, J G; Milroy, E J; Cowie, A G

    1988-09-01

    A retrospective review of 1550 cases of hyperparathyroidism (HPT) treated surgically over a 30-year period reveals a past history of exposure to neck irradiation in 10 cases (0.7 per cent). The indication for radiotherapy was benign disease in nine and papillary thyroid carcinoma in one case. The mean interval between radiation exposure and the detection of HPT was 32 years (range 3-63 years). Patients treated with radioactive iodine alone developed HPT after a mean of 5 years while the interval for those treated with external beam therapy alone was a mean of 44 years. The parathyroid histology was adenoma in six cases, carcinoma in three cases and nodular hyperplasia in one case. All patients had coincident benign thyroid disease apart from one that had previously had papillary carcinoma and another with follicular carcinoma. Neck irradiation has been shown to confer an increased risk of HPT due to parathyroid adenoma and carcinoma. Radiotherapy for benign disease has generally been abandoned and these cases demonstrate a further contra-indication for the use of neck irradiation.

  1. Long-term ultraviolet A irradiation of the eye induces photoaging of the skin in mice.

    PubMed

    Hiramoto, Keiichi; Yamate, Yurika; Kobayashi, Hiromi; Ishii, Masamitsu

    2012-01-01

    Irradiation by long-term ultraviolet (UV) A initiates the induction of photoaging. However, the mechanisms responsible for the structural changes of skin induced by UVA irradiation of the eye are still unknown. Male hairless mice were used in this study. The eye or dorsal skin was locally exposed to UVA after covering the remaining body surface with aluminum foil at a dose of 110 kJ/m(2) using a FL20SBLB-A lamp for 60 days. The plasma α-melanocyte stimulating hormone (α-MSH), nitrogen oxides (NO(2)/NO(3)), tumor necrosis factor-α (TNF-α), and the prostaglandin E(2) (PGE(2)) content all increased after UVA irradiation. The levels of NO(2)/NO(3), TNF-α, and PGE(2) also increased more after UVA skin irradiation than after UVA eye irradiation. However, the level of α-MSH increased more by eye irradiation than skin irradiation. In addition, UVA irradiation of the eye and dorsal skin increased the number of mast cells and fibroblasts. Furthermore, the expression of the melanocortin-1 receptor (MC1R) was increased on the fibroblast surface by UVA irradiation of the eye. These results indicate that the signal evoked by UVA irradiation of the eye, through the hypothalamo-pituitary proopiomelanocortin system, up-regulated the production of α-MSH. This hormone controls the collagen generation from fibroblasts, thus suggesting that photoaging was induced by UVA irradiation of the eye.

  2. Expression of interleukin-15 and inflammatory cytokines in skeletal muscles of STZ-induced diabetic rats: effect of resistance exercise training.

    PubMed

    Molanouri Shamsi, M; Hassan, Z H; Gharakhanlou, R; Quinn, L S; Azadmanesh, K; Baghersad, L; Isanejad, A; Mahdavi, M

    2014-05-01

    Skeletal muscle atrophy is associated with type-1 diabetes. Skeletal muscle is the source of pro- and anti-inflammatory cytokines that can mediate muscle hypertrophy and atrophy, while resistance exercise can modulate both muscle mass and muscle cytokine expression. This study determined the effects of a 5-week resistance exercise training regimen on the expression of muscle cytokines in healthy and streptozotocin-induced diabetic rats, with special emphasis on interleukin-15 (IL-15), a muscle-derived cytokine proposed to be involved in muscle hypertrophy or responses to stress. Induction of diabetes reduced muscle weight in both the fast flexor hallucis longus (FHL) and slow soleus muscles, while resistance training preserved FHL muscle weight in diabetic rats. IL-15 protein content was increased by training in both FHL and soleus muscles, as well as serum, in normal and diabetic rats. With regard to proinflammatory cytokines, muscle IL-6 levels were increased in diabetic rats, while training decreased muscle IL-6 levels in diabetic rats; training had no effect on FHL muscle IL-6 levels in healthy rats. Also, tumor necrosis factor-alpha (TNF-α) and IL-1β levels were increased by diabetes, but not changed by training. In conclusion, we found that in diabetic rats, resistance training increased muscle and serum IL-15 levels, decreased muscle IL-6 levels, and preserved FHL muscle mass.

  3. PCTAIRE1-knockdown sensitizes cancer cells to TNF family cytokines.

    PubMed

    Yanagi, Teruki; Shi, Ranxin; Aza-Blanc, Pedro; Reed, John C; Matsuzawa, Shu-ichi

    2015-01-01

    While PCTAIRE1/PCTK1/Cdk16 is overexpressed in malignant cells and is crucial in tumorigenesis, its function in apoptosis remains unclear. Here we investigated the role of PCTAIRE1 in apoptosis, especially in the extrinsic cell death pathway. Gene-knockdown of PCTAIRE1 sensitized prostate cancer PPC1 and Du145 cells, and breast cancer MDA-MB-468 cells to TNF-family cytokines, including TNF-related apoptosis-inducing ligand (TRAIL). Meanwhile, PCTAIRE1-knockdown did not sensitize non-malignant cells, including diploid fibroblasts IMR-90 and the immortalized prostate epithelial cell line 267B1. PCTAIRE1-knockdown did not up-regulate death receptor expression on the cell surface or affect caspase-8, FADD and FLIP expression levels. PCTAIRE1-knockdown did promote caspase-8 cleavage and RIPK1 degradation, while RIPK1 mRNA knockdown sensitized PPC1 cells to TNF-family cytokines. Furthermore, the kinase inhibitor SNS-032, which inhibits PCTAIRE1 kinase activity, sensitized PPC1 cells to TRAIL-induced apoptosis. Together these results suggest that PCTAIRE1 contributes to the resistance of cancer cell lines to apoptosis induced by TNF-family cytokines, which implies that PCTAIRE1 inhibitors could have synergistic effects with TNF-family cytokines for cytodestruction of cancer cells. PMID:25790448

  4. [Cytokine release after administration of endotoxin containing vaccines

    PubMed

    Ecker, Martina; Müller, Günter

    1998-01-01

    Endotoxins from gram negative bacteria are known to be potent inducers for the synthesis and the release of cytokines such as tumour necrosis factor (TNF) and interleukin 6 (IL-6). The amount of these proinflammatory mediators in plasma from animals and human patients suffering of an acute infection or sepsis, however, is well correlated with the outcome and the prognosis of such diseases (Hack et al., 1989; Ostermann et al., 1997; Rigato, 1996). In connection with regular testing of vaccine lots we determine the release and the kinetic of TNF and IL-6 in piglets after immunisation with different vaccines containing endotoxin. The current results suggest that the amounts of both cytokines increased with elevated endotoxin concentration given with the doses. TNF peaked in plasma after one hour, IL-6 peaked between two and four hours p.appl. We did not find any influence of the gender of the animals. In contrast, the body weight seems to affect the cytokine release in different ways. Determination of cytokine changes in plasma is a sensitive tool for the evaluation of systemic reactions and supports data about the clinical and haematological signs.

  5. Cytokine therapy: a natural alternative for disease control.

    PubMed

    Lowenthal, J W; O'Neil, T E; David, A; Strom, G; Andrew, M E

    1999-12-15

    Disease control in food production animals is normally mediated through the use of vaccines, chemicals and antibiotics. However, the extensive use of antibiotics and chemicals in livestock has resulted in environmental and human health concerns, particularly with regard to the emergence of drug-resistant bacteria in the food chain. In fact, the World Health Organisation (WHO) has now urged meat producers to use environmentally-friendly alternative methods to control disease. Cytokines, as natural mediators of the immune response, offer exciting alternatives to conventional therapeutics. The utilisation of cytokines is becoming more feasible with the recent cloning of a number of cytokine genes. Since the chicken's immune system is similar to that of mammals, they offer an attractive model system with which to study the effectiveness of cytokine therapy in the control of disease in intensive livestock. In this report we will review our recent studies on the therapeutic potential of chicken interferon gamma (ChIFN-gamma) as a vaccine adjuvant and a growth promoter. PMID:10614508

  6. TLR signals posttranscriptionally regulate the cytokine trafficking mediator sortilin

    PubMed Central

    Yabe-Wada, Toshiki; Matsuba, Shintaro; Takeda, Kazuya; Sato, Tetsuya; Suyama, Mikita; Ohkawa, Yasuyuki; Takai, Toshiyuki; Shi, Haifeng; Philpott, Caroline C.; Nakamura, Akira

    2016-01-01

    Regulating the transcription, translation and secretion of cytokines is crucial for controlling the appropriate balance of inflammation. Here we report that the sorting receptor sortilin plays a key role in cytokine production. We observed interactions of sortilin with multiple cytokines including IFN-α, and sortilin depletion in plasmacytoid dendritic cells (pDCs) led to a reduction of IFN-α secretion, suggesting a pivotal role of sortilin in the exocytic trafficking of IFN-α in pDCs. Moreover, sortilin mRNA was degraded posttranscriptionally upon stimulation with various TLR ligands. Poly-rC-binding protein 1 (PCBP1) recognized the C-rich element (CRE) in the 3′ UTR of sortilin mRNA, and depletion of PCBP1 enhanced the degradation of sortilin transcripts, suggesting that PCBP1 can act as a trans-acting factor to stabilize sortilin transcripts. The nucleotide-binding ability of PCBP1 was impaired by zinc ions and alterations of intracellular zinc affect sortilin expression. PCBP1 may therefore control the stability of sortilin transcripts by sensing intracellular zinc levels. Collectively, our findings provide insights into the posttranslational regulation of cytokine production through the posttranscriptional control of sortilin expression by TLR signals. PMID:27220277

  7. Selective suppression of endothelial cytokine production by progesterone receptor.

    PubMed

    Goddard, Lauren M; Ton, Amy N; Org, Tõnis; Mikkola, Hanna K A; Iruela-Arispe, M Luisa

    2013-01-01

    Steroid hormones are well-recognized suppressors of the inflammatory response, however, their cell- and tissue-specific effects in the regulation of inflammation are far less understood, particularly for the sex-related steroids. To determine the contribution of progesterone in the endothelium, we have characterized and validated an in vitro culture system in which human umbilical vein endothelial cells constitutively express human progesterone receptor (PR). Using next generation RNA-sequencing, we identified a selective group of cytokines that are suppressed by progesterone both under physiological conditions and during pathological activation by lipopolysaccharide. In particular, IL-6, IL-8, CXCL2/3, and CXCL1 were found to be direct targets of PR, as determined by ChIP-sequencing. Regulation of these cytokines by progesterone was also confirmed by bead-based multiplex cytokine assays and quantitative PCR. These findings provide a novel role for PR in the direct regulation of cytokine levels secreted by the endothelium. They also suggest that progesterone-PR signaling in the endothelium directly impacts leukocyte trafficking in PR-expressing tissues. PMID:23747964

  8. Cytokines in thyroid eye disease: potential for anticytokine therapy.

    PubMed

    Bahn, R S

    1998-05-01

    Interactions between between orbital fibroblasts and immunocompetent cells that infiltrate or reside within the orbit are thought to be important in the pathogenesis of thyroid eye disease (TED). These interactions are mediated primarily by cytokines; interferon-gamma, tumor necrosis factor-alpha, interleukin-1alpha and leukoregulin are of particular interest in this regard. These mediators induce or enhance the in vitro expression of immunomodulatory proteins in orbital fibroblasts, and stimulate proliferative and metabolic activities of these cells. The stimulation by particular cytokines of glycosaminoglycan synthesis in orbital fibroblasts is an important factor in the development of the clinical disease. A similarly important pathophysiological role for cytokines has been defined in rheumatoid arthritis. In this disease, the chronic erosive changes in the cartilage and bone of the joints result from cytokine-stimulated production of collegenases and other neutral proteases by synovial cells and articular chondrocytes. Advances in the understanding of the pathogenesis of rheumatologic joint disease has led to treatment trials aimed at immune-modulation, including trials of anticytokine therapy. Lessons learned in early clinical trials using these biological therapies in the treatment of rheumatoid arthritis can be applied to studies of similar agents in the treatment of TED. PMID:9623733

  9. Cytokine responses in the common cold and otitis media.

    PubMed

    Wine, Todd M; Alper, Cuneyt M

    2012-12-01

    Cytokines are a group of diverse molecules that influence the function of every organ system. They are most well studied in their effects on the immune system and their integral role in mediating inflammation. The common cold and otitis media are two such disease states, and much has been learned about the various effects of cytokines in each disease. Most often the viruses isolated include rhinovirus (RV), respiratory syncytial virus (RSV), adenovirus, coronavirus, and picornavirus. Otitis media, sinusitis, bronchiolitis, pneumonia, and asthma exacerbation are commonly accepted as complications of viral upper respiratory tract infections. Furthermore, otitis media and upper respiratory infections are inextricably linked in that the majority (>70 %) of cases of acute otitis media occur as complications of the common cold. Cytokine polymorphisms have been associated with the severity of colds as well as the frequency of otitis media. This article attempts to update the reader on various studies that have recently been published regarding the role of cytokines in these two disease entities.

  10. Human malarial disease: a consequence of inflammatory cytokine release

    PubMed Central

    Clark, Ian A; Budd, Alison C; Alleva, Lisa M; Cowden, William B

    2006-01-01

    Malaria causes an acute systemic human disease that bears many similarities, both clinically and mechanistically, to those caused by bacteria, rickettsia, and viruses. Over the past few decades, a literature has emerged that argues for most of the pathology seen in all of these infectious diseases being explained by activation of the inflammatory system, with the balance between the pro and anti-inflammatory cytokines being tipped towards the onset of systemic inflammation. Although not often expressed in energy terms, there is, when reduced to biochemical essentials, wide agreement that infection with falciparum malaria is often fatal because mitochondria are unable to generate enough ATP to maintain normal cellular function. Most, however, would contend that this largely occurs because sequestered parasitized red cells prevent sufficient oxygen getting to where it is needed. This review considers the evidence that an equally or more important way ATP deficency arises in malaria, as well as these other infectious diseases, is an inability of mitochondria, through the effects of inflammatory cytokines on their function, to utilise available oxygen. This activity of these cytokines, plus their capacity to control the pathways through which oxygen supply to mitochondria are restricted (particularly through directing sequestration and driving anaemia), combine to make falciparum malaria primarily an inflammatory cytokine-driven disease. PMID:17029647

  11. Transcriptional regulation of cytokine function in airway smooth muscle cells

    PubMed Central

    Clarke, Deborah; Damera, Gautam; Sukkar, Maria B.; Tliba, Omar

    2009-01-01

    The immuno-modulatory properties of airway smooth muscle have become of increasing importance in our understanding of the mechanisms underlying chronic inflammation and structural remodeling of the airway wall in asthma and chronic obstructive pulmonary disease (COPD). ASM cells respond to many cytokines, growth factors and lipid mediators to produce a wide array of immuno-modulatory molecules which may in turn orchestrate and perpetuate the disease process in asthma and COPD. Despite numerous studies of the cellular effects of cytokines on cultured ASM, few have identified intracellular signaling pathways by which cytokines modulate or induce these cellular responses. In this review we provide an overview of the transcriptional mechanisms as well as intracellular signaling pathways regulating cytokine functions in ASM cells. The recent discovery of toll-like receptors in ASM cells represents a significant development in our understanding of the immuno-modulatory capabilities of ASM cells. Thus, we also review emerging evidence of the inflammatory response to toll-like receptor activation in ASM cells. PMID:19393330

  12. Micropatterning of Aptamer Beacons to Create Cytokine-Sensing Surfaces.

    PubMed

    Tuleuova, Nazgul; Revzin, Alexander

    2010-12-01

    Aptamer beacons are DNA or RNA probes that bind proteins or small molecules of interest and emit signal directly upon interaction with the target analyte. This paper describes micropatterning of aptamer beacons for detection of IFN-γ-an important inflammatory cytokine. The beacon consisted of a fluorophore-labeled aptamer strand hybridized with a shorter, quencher-carrying complementary strand. Cytokine molecules were expected to displace quenching strands of the beacon, disrupting FRET effect and resulting in fluorescence signal. The glass substrate was first micropatterned with poly(ethylene glycol) (PEG) hydrogel microwells (35 μm diameter individual wells) so as to define sites for attachment of beacon molecules. PEG microwell arrays were then incubated with avidin followed by biotin-aptamer-fluorophore constructs. Subsequent incubation with quencher-carrying complementary strands resulted in formation of DNA duplex and caused quenching of fluorescence due to FRET effect. When exposed to IFN-γ, microwells changed fluorescence from low (quencher hybridized with fluorophore-carrying strand) to high (quenching strand displaced by cytokine molecules). The fluorescence signal was confined to microwells, was changing in real-time and was dependent on the concentration of IFN-γ. In the future, we plan to co-localize aptamer beacons and cells on micropatterned surfaces in order to monitor in real-time cytokine secretion from immune cells in microwells.

  13. Genetic modification of cytotoxic T lymphocytes to express cytokine receptors.

    PubMed

    Perna, Serena K; Savoldo, Barbara; Dotti, Gianpietro

    2014-01-01

    Adoptive transfer of tumor-infiltrating lymphocytes (TIL) or antigen-specific cytotoxic T lymphocytes (CTL) is safe and can be effective in cancer patients. Achievement of clinical responses in these patients is associated with the in vivo expansion and persistence of the transferred T lymphocytes. For this reason, recombinant human interleukin-2 (IL-2) is frequently used to support the in vivo survival of T lymphocytes infused into patients. However, IL-2 also causes important side effects. Thus, alternative strategies are highly demanded to limit cytokine-related off-target effects and to redirect the responsiveness of specific T-cell subsets to selected cytokines. Interleukin-7 (IL-7) is a promising alternative cytokine as it possesses the above mentioned properties. However, because its receptor is downregulated in ex vivo-expanded T cells, methods are required to restore their responsiveness to this homeostatic cytokine. In this chapter, we describe the methodology to obtain the ectopic expression of IL-7 receptor alpha (IL-7Rα) in antigen-specific CTL, using Epstein-Barr virus-specific CTL (EBV-CTL), as a model.

  14. Clinical application of growth factors and cytokines in wound healing.

    PubMed

    Barrientos, Stephan; Brem, Harold; Stojadinovic, Olivera; Tomic-Canic, Marjana

    2014-01-01

    Wound healing is a complex and dynamic biological process that involves the coordinated efforts of multiple cell types and is executed and regulated by numerous growth factors and cytokines. There has been a drive in the past two decades to study the therapeutic effects of various growth factors in the clinical management of nonhealing wounds (e.g., pressure ulcers, chronic venous ulcers, diabetic foot ulcers). For this review, we conducted an online search of Medline/PubMed and critically analyzed the literature regarding the role of growth factors and cytokines in the management of these wounds. We focused on currently approved therapies, emerging therapies, and future research possibilities. In this review, we discuss four growth factors and cytokines currently being used on and off label for the healing of wounds. These include granulocyte-macrophage colony-stimulating factor, platelet-derived growth factor, vascular endothelial growth factor, and basic fibroblast growth factor. While the clinical results of using growth factors and cytokines are encouraging, many studies involved a small sample size and are disparate in measured endpoints. Therefore, further research is required to provide definitive evidence of efficacy.

  15. Induction of Cytokines by Glucosyltransferases of Streptococcus mutans

    PubMed Central

    Chia, Jean-San; Lien, Huei-Ting; Hsueh, Po-Ren; Chen, Pei-Min; Sun, Andy; Chen, Jen-Yang

    2002-01-01

    Production of proinflammatory cytokines is implicated in the pathogenesis of viridans streptococcus-induced α-streptococcal shock syndrome and infective endocarditis. Streptococcus mutans, one of the opportunistic pathogens causing infective endocarditis, was reported previously to stimulate monocytes and epithelial and endothelial cells in vitro to produce various cytokines. We found that glucosyltransferases (GTFs) GtfC and GtfD of S. mutans stimulated predominantly the production of interleukin-6 (IL-6) from T cells cultured in vitro. The level of IL-6 but not of tumor necrosis factor alpha in blood was significantly elevated when rats were injected intravenously with S. mutans GS-5, whereas IL-6 was detected at a much lower level when rats were challenged with NHS1DD, an isogenic mutant defective in the expression of GTFs. The serum IL-6 level was elevated in patients with endocarditis caused by different species of viridans streptococci which express GTF homologues. Affinity column-purified GTFs reduced the levels of detectable IL-2 of T cells stimulated by another bacterial antigen, tetanus toxoid. These results suggested that GTFs might modulate the production of Th1-type cytokines and that GTFs of S. mutans play a significant role in stimulating the production of the proinflammatory cytokine IL-6 in vivo. PMID:12093691

  16. Circulating Cytokines as Biomarkers of Alcohol Abuse and Alcoholism

    PubMed Central

    Achur, Rajeshwara N.; Freeman, Willard M.; Vrana, Kent E.

    2010-01-01

    There are currently no consistent objective biochemical markers of alcohol abuse and alcoholism. Development of reliable diagnostic biomarkers that permit accurate assessment of alcohol intake and patterns of drinking is of prime importance to treatment and research fields. Diagnostic biomarker development in other diseases has demonstrated the utility of both open, systems biology, screening for biomarkers and more rational focused efforts on specific biomolecules or families of biomolecules. Long term alcohol consumption leads to altered inflammatory cell and adaptive immune responses with associated pathologies and increased incidence of infections. This has led researchers to focus attention on identifying cytokine biomarkers in models of alcohol abuse. Alcohol is known to alter cytokine levels in plasma and a variety of tissues including lung, liver, and very importantly brain. A number of cytokine biomarker candidates have been identified, including: TNF alpha, IL1-alpha, IL1-beta, IL6, IL8, IL12 and MCP-1. This is an emerging and potentially exciting avenue of research in that circulating cytokines may contribute to diagnostic biomarker panels and a combination of multiple biomarkers may significantly increase the sensitivity and specificity of the biochemical tests aiding reliable and accurate detection of excessive alcohol intake. PMID:20020329

  17. Analysis of the cell surface expression of cytokine receptors using the surface protein biotinylation method.

    PubMed

    Pavel, Mahmud Arif; Lam, Clarissa; Kashyap, Parul; Salehi-Najafabadi, Zahra; Singh, Gurpreet; Yu, Yong

    2014-01-01

    Cytokines are pleiotropic, low-molecular-weight proteins that regulate the immune responses to infection and inflammation. They stimulate the immune responses by binding to cytokine receptors on the cell plasma membrane. Thus, knowledge of the expression level of particular cytokine receptors on cell surface is crucial for understanding the cytokine function and regulation. One of the techniques to explore the membrane embedded cytokine receptors is cell surface biotinylation. Biotinylated surface proteins can be rapidly purified through the strong interaction between biotin and streptavidin. Here, we describe the procedure for surface biotinylation and purification of biotinylated cytokine receptors for further downstream analysis. PMID:24908305

  18. Analysis of the cell surface expression of cytokine receptors using the surface protein biotinylation method.

    PubMed

    Pavel, Mahmud Arif; Lam, Clarissa; Kashyap, Parul; Salehi-Najafabadi, Zahra; Singh, Gurpreet; Yu, Yong

    2014-01-01

    Cytokines are pleiotropic, low-molecular-weight proteins that regulate the immune responses to infection and inflammation. They stimulate the immune responses by binding to cytokine receptors on the cell plasma membrane. Thus, knowledge of the expression level of particular cytokine receptors on cell surface is crucial for understanding the cytokine function and regulation. One of the techniques to explore the membrane embedded cytokine receptors is cell surface biotinylation. Biotinylated surface proteins can be rapidly purified through the strong interaction between biotin and streptavidin. Here, we describe the procedure for surface biotinylation and purification of biotinylated cytokine receptors for further downstream analysis.

  19. Prostaglandin E2 in tick saliva regulates macrophage cell migration and cytokine profile

    PubMed Central

    2013-01-01

    Background Ticks are obligate hematophagous ectoparasites that suppress the host’s immune and inflammatory responses by secreting immuno-modulatory and anti-inflammatory molecules in their saliva. In previous studies we have shown that tick salivary gland extract (SGE) and saliva from Dermacentor variabilis have distinct effects on platelet-derived growth factor (PDGF)-stimulated IC-21 macrophage and NIH3T3-L1 fibroblast migration. Since tick saliva contains a high concentration of prostaglandin E2 (PGE2), a potent modulator of inflammation, we used a PGE2 receptor antagonist to evaluate the role of PGE2 in the different migratory responses induced by saliva and its impact on macrophage cytokine profile. Methods Adult ticks were fed on female New Zealand white rabbits for 5-8 days. Female ticks were stimulated with dopamine/theophylline to induce salivation and saliva was pooled. Competitive enzyme immunoassays (EIA) were used to measure saliva PGE2 content and the changes in macrophage intracellular cyclic adenosine monophosphate (cAMP) levels. The effects of tick saliva on macrophage and fibroblast migration were assessed in the absence and presence of the PGE2 receptor antagonist, AH 6809, using blind well chamber assays. A cytokine antibody array was used to examine the effects of tick saliva on macrophage cytokine secretion. Statistical significance was determined by one-way ANOVA; Student Newman-Kuels post-test was used for multiple comparisons. Results The saliva-induced increase in PDGF-stimulated macrophage migration was reversed by AH 6809. The inhibition of PDGF-stimulated fibroblast migration by saliva was also antagonist-sensitive. Tick saliva induced macrophages to secrete copious amounts of PGE2, and conditioned medium from these cells caused an AH 6809-sensitive inhibition of stimulated fibroblast migration, showing that macrophages can regulate fibroblast activity. We show that tick saliva decreased the secretion of the pro

  20. In situ expression of cytokines in human heart allografts.

    PubMed Central

    Van Hoffen, E.; Van Wichen, D.; Stuij, I.; De Jonge, N.; Klöpping, C.; Lahpor, J.; Van Den Tweel, J.; Gmelig-Meyling, F.; De Weger, R.

    1996-01-01

    Although allograft rejection, the major complication of human organ transplantation, has been extensively studied, little is known about the exact cellular localization of the cytokine expression inside the graft during rejection. Therefore, we used in situ hybridization and immunohistochemistry to study local cytokine mRNA and protein expression in human heart allografts, in relation to the phenotypical characteristics of the cellular infiltrate. Clear expression of mRNA for interleukin (IL)-6, IL-8, IL-9, and IL-10 and weak expression for IL-2, IL-4, IL-5, and tumor necrosis factor (TNF)-alpha was detected in biopsies exhibiting high rejection grades (grade 3A/B). Also at lower grades of rejection, mRNA for IL-6 and IL-9 was present. Some mRNA for IL-1 beta, TNF-beta, and interferon (IFN)-gamma was detected in only a few biopsies. Using immunohistochemistry, IL-2, IL-3, and IL-10 protein was detected in biopsies with high rejection grades, whereas few cells expressed IL-6, IL-8, and IFN-gamma. In biopsies with lower grades of rejection, a weaker expression of these cytokines was observed. IL-4 was hardly detected in any of the biopsies. The level of IL-12 expression was equal in all biopsies. Although mRNA expression of several cytokines was expressed at a low level compared with the protein level of those cytokines, there was a good correlation between localization of cytokine mRNA and protein. Expression of IL-2, IL-4, IL-5, TNF-alpha, and IFN-gamma was mainly detected in lymphocytes. IL-3, IL-6, IL-10, and IL-12 were not detected or not only detected in lymphocytes but also in other stromal elements (eg, macrophages). Macrophage production of IL-3 and IL-12 was confirmed by immunofluorescent double labeling with CD68. We conclude that cardiac allograft rejection is not simply regulated by T helper cell cytokine production, but other intragraft elements contribute considerably to this process. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8952534

  1. FDA perspective on food irradiation

    SciTech Connect

    Pauli, G.H.

    1994-12-31

    The Center for Food Safety and Applied Nutrition (CFSAN) monitors the safety of food irradiation. A few limited uses are regulated, and occasionally CFSAN receives a petition for a new use. Despite extensive studies (more than 400) showing the safety of food irradiation, a cloud of suspicion continues to hang over this issue in the mind of the public. People perceive food irradiation and direct body irradiation as having similar implications. Food irradiation is banned in two states in the United States. Food is irradiated for the following purposes: delay of ripening, prevention of sprouting, eradication of pests and sterilization, and allowing commodities to be stored unrefrigerated for long periods of time. The dosage depends on the purpose of the irradiation. Radiolytic products are formed during irradiation and during storage afterward. Most of these products are also formed during conventional preservation. In 1980, CFSAN, then the Bureau of Foods, introduced the term unique radiolytic products for compounds not identified in foods after conventional processing. Although the existence of URPs was never proven chemically, the term has caused anxiety. Irradiation of foods in the commercially useful range does not generate radioactivity above natural background. Because radiolytic products formed from beef, chicken, and pork are primarily the same, irradiated foods of similar food groups may be evaluated generically.

  2. Cytokine-induced alterations of gastrointestinal motility in gastrointestinal disorders

    PubMed Central

    Akiho, Hirotada; Ihara, Eikichi; Motomura, Yasuaki; Nakamura, Kazuhiko

    2011-01-01

    Inflammation and immune activation in the gut are usually accompanied by alteration of gastrointestinal (GI) motility. In infection, changes in motor function have been linked to host defense by enhancing the expulsion of the infectious agents. In this review, we describe the evidence for inflammation and immune activation in GI infection, inflammatory bowel disease, ileus, achalasia, eosinophilic esophagitis, microscopic colitis, celiac disease, pseudo-obstruction and functional GI disorders. We also describe the possible mechanisms by which inflammation and immune activation in the gut affect GI motility. GI motility disorder is a broad spectrum disturbance of GI physiology. Although several systems including central nerves, enteric nerves, interstitial cells of Cajal and smooth muscles contribute to a coordinated regulation of GI motility, smooth muscle probably plays the most important role. Thus, we focus on the relationship between activation of cytokines induced by adaptive immune response and alteration of GI smooth muscle contractility. Accumulated evidence has shown that Th1 and Th2 cytokines cause hypocontractility and hypercontractility of inflamed intestinal smooth muscle. Th1 cytokines downregulate CPI-17 and L-type Ca2+ channels and upregulate regulators of G protein signaling 4, which contributes to hypocontractility of inflamed intestinal smooth muscle. Conversely, Th2 cytokines cause hypercontractilty via signal transducer and activator of transcription 6 or mitogen-activated protein kinase signaling pathways. Th1 and Th2 cytokines have opposing effects on intestinal smooth muscle contraction via 5-hydroxytryptamine signaling. Understanding the immunological basis of altered GI motor function could lead to new therapeutic strategies for GI functional and inflammatory disorders. PMID:22013552

  3. Dissecting innate immune signaling in viral evasion of cytokine production.

    PubMed

    Zhang, Junjie; Zhu, Lining; Feng, Pinghui

    2014-03-02

    In response to a viral infection, the host innate immune response is activated to up-regulate gene expression and production of antiviral cytokines. Conversely, viruses have evolved intricate strategies to evade and exploit host immune signaling for survival and propagation. Viral immune evasion, entailing host defense and viral evasion, provides one of the most fascinating and dynamic interfaces to discern the host-virus interaction. These studies advance our understanding in innate immune regulation and pave our way to develop novel antiviral therapies. Murine γHV68 is a natural pathogen of murine rodents. γHV68 infection of mice provides a tractable small animal model to examine the antiviral response to human KSHV and EBV of which perturbation of in vivo virus-host interactions is not applicable. Here we describe a protocol to determine the antiviral cytokine production. This protocol can be adapted to other viruses and signaling pathways. Recently, we have discovered that γHV68 hijacks MAVS and IKKβ, key innate immune signaling components downstream of the cytosolic RIG-I and MDA5, to abrogate NFΚB activation and antiviral cytokine production. Specifically, γHV68 infection activates IKKβ and that activated IKKβ phosphorylates RelA to accelerate RelA degradation. As such, γHV68 efficiently uncouples NFΚB activation from its upstream activated IKKβ, negating antiviral cytokine gene expression. This study elucidates an intricate strategy whereby the upstream innate immune activation is intercepted by a viral pathogen to nullify the immediate downstream transcriptional activation and evade antiviral cytokine production.

  4. Biochemical and immunological properties of cytokines conjugated to dendritic polymers.

    PubMed

    Lee, S C; Parthasarathy, R; Botwin, K; Kunneman, D; Rowold, E; Lange, G; Klover, J; Abegg, A; Zobel, J; Beck, T; Miller, T; Hood, W; Monahan, J; McKearn, J P; Jansson, R; Voliva, C F

    2004-09-01

    Here we describe a post-translational modification of SC-63032, a variant of the species restricted, multi-lineage hematopoeitic factor human interleukin-3 (hIL-3). We have made two new dendritic polymer (polyamidoamine or PAMAM dendrimers, generation 5)-SC-63032 bioconjugates. Using two distinct chemistries (one of which is novel to this work), we achieved site-specific conjugation with respect to the amino acid in the proteins ligated to the dendrimers. In both bioconjugates, conjugated cytokine maintains its ability to bind the hIL-3 alpha receptor subunit, but is significantly (about 10-fold) less potent in inducing hIL-3 dependent in vitro cell proliferation than is the free cytokine. In vivo data indicates that conjugation decreases the immunogenicity of the conjugated cytokine modestly. In the absence of pharmacokinetic or biodistribution effects associated with the bioconjugates that increase their potency in vivo (which can only be tested in a higher primate, due to the species restriction of hIL-3 and its derivatives), these immune mitigation effects may be too small to be therapeutically significant. Though unmodified PAMAM dendrimers fail to elicit an antibody response in mice, protein conjugation to dendrimers haptenizes them, and a dendrimer-specific antibody response is produced. In toto, the principal limitation of the dendrimer-cytokine bioconjugates herein is in their reduced receptor affinity and potency in vitro. Were the in vivo potency of the bioconjugates to parallel the in vitro potency of the conjugates reported here, it is likely that particular dendrimer bioconjugates could not justify their higher costs of goods relative to the parent SC-63032 molecule, though retention of SC-63032 biological activities in conjugates suggests that other cytokine-dendrimer bioconjugates may be bioactive. This is good news to the nanotechnology community, in as much as PAMAM dendrimers are among the monodisperse polymeric nanomaterials available, and these

  5. T-Helper Cytokine Profiles in Patients with Kawasaki Disease

    PubMed Central

    Lee, Sang Bum; Kim, Young Hyun; Hyun, Myung Chul; Kim, Yeo Hyang; Kim, Hee Sun

    2015-01-01

    Background and Objectives Kawasaki disease is an acute systemic vasculitis of which pathogenesis suspected is caused by immune dysregulation. The goal of this study is to evaluate the activation pattern of T helper cell type 1 (Th1) and T helper cell type 2 (Th2) in patients with Kawasaki disease. Subjects and Methods Prospective study of 60 patients (male 36, female 24) with diagnosis of Kawasaki disease were enrolled. One hundred and eighty blood samples from these patients were collected according to the different clinical stages {before initial intravenous immunoglobulin (IVIG), 5 days after initial IVIG, 2 months after initial IVIG}. The plasma level of Th1 cytokines; interferon-gamma (IFN-γ) & interleukin (IL)-2 and Th2 cytokines; IL-4 & IL-10 were measured by enzyme-liked immunosorbent assay. Results In all patients, the plasma level of Th1 cytokines (IFN-γ, IL-2) and Th2 cytokines (IL-4 and IL-10) were markedly elevated during the acute stage of Kawasaki disease. Since then, the plasma level of all these cytokines decreased significantly along with the process of clinical stages. Regardless of the existence of coronary artery lesion or no response to initial IVIG treatment, there were no significant differences between them. Conclusion These data suggest that both Th1 and Th2 cells may be activated simultaneously during the acute stage of Kawasaki disease. Further studies are therefore required to establish the difference of activation pattern of T helper cells between Kawasaki disease and other inflammatory diseases. PMID:26617655

  6. Post-irradiation effects in polyethylenes irradiated under various atmospheres

    NASA Astrophysics Data System (ADS)

    Suljovrujic, E.

    2013-08-01

    If a large amount of polymer free radicals remain trapped after irradiation of polymers, the post-irradiation effects may result in a significant alteration of physical properties during long-term shelf storage and use. In the case of polyethylenes (PEs) some failures are attributed to the post-irradiation oxidative degradation initiated by the reaction of residual free radicals (mainly trapped in crystal phase) with oxygen. Oxidation products such as carbonyl groups act as deep traps and introduce changes in carrier mobility and significant deterioration in the PEs electrical insulating properties. The post-irradiation behaviour of three different PEs, low density polyethylene (LDPE), linear low density polyethylene (LLDPE) and high density polyethylene (HDPE) was studied; previously, the post-irradiation behaviour of the PEs was investigated after the irradiation in air (Suljovrujic, 2010). In this paper, in order to investigate the influence of different irradiation media on the post-irradiation behaviour, the samples were irradiated in air and nitrogen gas, to an absorbed dose of 300 kGy. The annealing treatment of irradiated PEs, which can substantially reduce the concentration of free radicals, is used in this study, too. Dielectric relaxation behaviour is related to the difference in the initial structure of PEs (such as branching, crystallinity etc.), to the changes induced by irradiation in different media and to the post-irradiation changes induced by storage of the samples in air. Electron spin resonance (ESR), differential scanning calorimetry (DSC), infra-red (IR) spectroscopy and gel measurements were used to determine the changes in the free radical concentration, crystal fraction, oxidation and degree of network formation, respectively.

  7. Effect of gamma irradiation on curcuminoids and volatile oils of fresh turmeric ( Curcuma longa)

    NASA Astrophysics Data System (ADS)

    Dhanya, R.; Mishra, B. B.; Khaleel, K. M.

    2011-11-01

    In our earlier study a radiation dose of 5 kGy was reported to be suitable for microbial decontamination and shelf life extension of fresh turmeric ( Curcuma longa), while maintaining its quality attributes. In continuation of that work, the effect of gamma radiation on curcuminoids and volatile oil constituents in fresh turmeric was studied. Fresh peeled turmeric rhizomes were gamma irradiated at doses of 1, 3 and 5 kGy. Curcuminoid content and volatile oils were analyzed by reverse phase HPLC and GC-MS, respectively. The curcuminoid content was slightly increased by gamma irradiation. No statistically significant changes were observed due to irradiation in majority of the volatile oil constituents.

  8. Protein Quality of Irradiated Brazilian Beans

    NASA Astrophysics Data System (ADS)

    Delincée, Henry; Villavicencio, Anna-Lucia C. H.; Mancini-Filho, Jorge

    1998-06-01

    Beans are a major source of dietary protein in Brazil. However, high losses due to insect infestation occur after each harvest. To combat these losses, radiation processing of beans offers promise as an alternative to chemical treatment, provided the nutritional quality of beans is not impaired by the radiation treatment. Conflicting results have been published about the effect of radiation on the biological value of legume proteins. Therefore, two varieties of Brazilian beans were studied: 1) Phaseolus vulgaris L., var. carioca and 2) Vigna unguiculata (L.) Walp, var. macaçar. The beans were irradiated with doses of 0, 0.5, 1.0, 2.5, 5.0 and 10 kGy. Since irradiated beans will be consumed after appropriate storage, the beans under study were stored for 6 months at ambient temperature. Protein quality was measured by a biological assay employing the nitrogen balance approach in weanling rats. The animals were fed with optimally cooked beans, which were the only source of protein (˜10%). Nitrogen contents of legumes, diets, animal urine and faeces were determined by Kjeldahl analysis. The indices for apparent protein quality: net protein utilisation, digestibility and biological value were not influenced by irradiation. Thus, radiation treatment of Brazilian beans offers considerable promise as an effective insect disinfection process, without impairing the biological quality of the valuable bean protein.

  9. Cytokine Profiles during Invasive Nontyphoidal Salmonella Disease Predict Outcome in African Children.

    PubMed

    Gilchrist, James J; Heath, Jennifer N; Msefula, Chisomo L; Gondwe, Esther N; Naranbhai, Vivek; Mandala, Wilson; MacLennan, Jenny M; Molyneux, Elizabeth M; Graham, Stephen M; Drayson, Mark T; Molyneux, Malcolm E; MacLennan, Calman A

    2016-07-01

    Nontyphoidal Salmonella is a leading cause of sepsis in African children. Cytokine responses are central to the pathophysiology of sepsis and predict sepsis outcome in other settings. In this study, we investigated cytokine responses to invasive nontyphoidal Salmonella (iNTS) disease in Malawian children. We determined serum concentrations of 48 cytokines with multiplexed immunoassays in Malawian children during acute iNTS disease (n = 111) and in convalescence (n = 77). Principal component analysis and logistic regression were used to identify cytokine signatures of acute iNTS disease. We further investigated whether these responses are altered by HIV coinfection or severe malnutrition and whether cytokine responses predict inpatient mortality. Cytokine changes in acute iNTS disease were associated with two distinct cytokine signatures. The first is characterized by increased concentrations of mediators known to be associated with macrophage function, and the second is characterized by raised pro- and anti-inflammatory cytokines typical of responses reported in sepsis secondary to diverse pathogens. These cytokine responses were largely unaltered by either severe malnutrition or HIV coinfection. Children with fatal disease had a distinctive cytokine profile, characterized by raised mediators known to be associated with neutrophil function. In conclusion, cytokine responses to acute iNTS infection in Malawian children are reflective of both the cytokine storm typical of sepsis secondary to diverse pathogens and the intramacrophage replicative niche of NTS. The cytokine profile predictive of fatal disease supports a key role of neutrophils in the pathogenesis of NTS sepsis. PMID:27170644

  10. Cytokine Profiles during Invasive Nontyphoidal Salmonella Disease Predict Outcome in African Children

    PubMed Central

    Gilchrist, James J.; Heath, Jennifer N.; Msefula, Chisomo L.; Gondwe, Esther N.; Naranbhai, Vivek; Mandala, Wilson; MacLennan, Jenny M.; Molyneux, Elizabeth M.; Graham, Stephen M.; Drayson, Mark T.; Molyneux, Malcolm E.

    2016-01-01

    Nontyphoidal Salmonella is a leading cause of sepsis in African children. Cytokine responses are central to the pathophysiology of sepsis and predict sepsis outcome in other settings. In this study, we investigated cytokine responses to invasive nontyphoidal Salmonella (iNTS) disease in Malawian children. We determined serum concentrations of 48 cytokines with multiplexed immunoassays in Malawian children during acute iNTS disease (n = 111) and in convalescence (n = 77). Principal component analysis and logistic regression were used to identify cytokine signatures of acute iNTS disease. We further investigated whether these responses are altered by HIV coinfection or severe malnutrition and whether cytokine responses predict inpatient mortality. Cytokine changes in acute iNTS disease were associated with two distinct cytokine signatures. The first is characterized by increased concentrations of mediators known to be associated with macrophage function, and the second is characterized by raised pro- and anti-inflammatory cytokines typical of responses reported in sepsis secondary to diverse pathogens. These cytokine responses were largely unaltered by either severe malnutrition or HIV coinfection. Children with fatal disease had a distinctive cytokine profile, characterized by raised mediators known to be associated with neutrophil function. In conclusion, cytokine responses to acute iNTS infection in Malawian children are reflective of both the cytokine storm typical of sepsis secondary to diverse pathogens and the intramacrophage replicative niche of NTS. The cytokine profile predictive of fatal disease supports a key role of neutrophils in the pathogenesis of NTS sepsis. PMID:27170644

  11. Cytokine Profiles during Invasive Nontyphoidal Salmonella Disease Predict Outcome in African Children.

    PubMed

    Gilchrist, James J; Heath, Jennifer N; Msefula, Chisomo L; Gondwe, Esther N; Naranbhai, Vivek; Mandala, Wilson; MacLennan, Jenny M; Molyneux, Elizabeth M; Graham, Stephen M; Drayson, Mark T; Molyneux, Malcolm E; MacLennan, Calman A

    2016-07-01

    Nontyphoidal Salmonella is a leading cause of sepsis in African children. Cytokine responses are central to the pathophysiology of sepsis and predict sepsis outcome in other settings. In this study, we investigated cytokine responses to invasive nontyphoidal Salmonella (iNTS) disease in Malawian children. We determined serum concentrations of 48 cytokines with multiplexed immunoassays in Malawian children during acute iNTS disease (n = 111) and in convalescence (n = 77). Principal component analysis and logistic regression were used to identify cytokine signatures of acute iNTS disease. We further investigated whether these responses are altered by HIV coinfection or severe malnutrition and whether cytokine responses predict inpatient mortality. Cytokine changes in acute iNTS disease were associated with two distinct cytokine signatures. The first is characterized by increased concentrations of mediators known to be associated with macrophage function, and the second is characterized by raised pro- and anti-inflammatory cytokines typical of responses reported in sepsis secondary to diverse pathogens. These cytokine responses were largely unaltered by either severe malnutrition or HIV coinfection. Children with fatal disease had a distinctive cytokine profile, characterized by raised mediators known to be associated with neutrophil function. In conclusion, cytokine responses to acute iNTS infection in Malawian children are reflective of both the cytokine storm typical of sepsis secondary to diverse pathogens and the intramacrophage replicative niche of NTS. The cytokine profile predictive of fatal disease supports a key role of neutrophils in the pathogenesis of NTS sepsis.

  12. Effect of electron irradiation and heat on the structure of hairtail surimi

    NASA Astrophysics Data System (ADS)

    Lin, Xianping; Yang, Wenge; Xu, Dalun; Wang, Lili

    2015-09-01

    Hairtail surimi was treated with electron radiation and heat, the chemical interactions, thermal properties and the structural changes were determined. The chemical interaction data indicate that the contribution of disulfide bonds to heat-induced gel formation was decisive. Irradiation promoted the formation of disulfide bonds during the cooking. Differential scanning calorimetry showed that the myosin and actin thermal transitions of irradiated surimi shifted to lower temperatures. And the myosin thermal stability of irradiated surimi was lower than unirradiated surimi. The Fourier transform infrared and Raman results showed the irradiation and heat treatments decreased the α-helix structure content and increased β-sheet structure content. This study may provide useful information for the effect of irradiation on the surimi gel properties.

  13. Identification of gamma-irradiated fruit juices by EPR spectroscopy

    NASA Astrophysics Data System (ADS)

    Aleksieva, K. I.; Dimov, K. G.; Yordanov, N. D.

    2014-10-01

    The results of electron paramagnetic resonance (EPR) study on commercially available juices from various fruits and different fruit contents: 25%, 40%, 50%, and 100%, homemade juices, nectars and concentrated fruit syrups, before and after gamma-irradiation are reported. In order to remove water from non- and irradiated samples all juices and nectars were filtered; the solid residue was washed with alcohol and dried at room temperature. Only concentrated fruit syrups were dried for 60 min at 40 °C in a standard laboratory oven. All samples under study show a singlet EPR line with g=2.0025 before irradiation with exception of concentrated fruit syrups, which are EPR silent. Irradiation of juice samples gives rise to complex EPR spectra which gradually transferred to “cellulose-like” EPR spectrum from 25% to 100% fruit content. Concentrated fruit syrups show typical “sugar-like“ spectra due to added saccharides. All EPR spectra are characteristic and can prove radiation treatment. The fading kinetics of radiation-induced EPR signals were studied for a period of 60 days after irradiation.

  14. Effect of γ-irradiation on structure and physico-chemical properties of Amorphophallus paeoniifolius starch.

    PubMed

    Reddy, Chagam Koteswara; Suriya, M; Vidya, P V; Vijina, K; Haripriya, Sundaramoorthy

    2015-08-01

    Gamma irradiation is one of the effective techniques able to alter structure and its properties of starch. In this research, the effect of modification in terms of molecular structure and physico-chemical properties of Amorphophallus paeoniifolius starch by γ-irradiation using (60)Co as γ-source at doses of 5, 10, 15, 20 and 25 kGy with dose rate 2 kGy/h was studied. Morphology of native and irradiated starches under scanning electron microscope revealed that granules are round, elliptical and polygonal in shape with smooth surfaces; no cracking or roughness was noted on irradiated starches. Amylose content, pH, swelling power of the starches and syneresis of the gelatinized starch were significantly decreased by irradiation; while carboxyl content, solubility, light transmittance and water absorption capacity of the starch granules were raised with increased dose of irradiation. Reduced pasting parameters and changes in FTIR spectrum significantly differed from each other. XRD pattern of irradiated starches showed C-type pattern with intermediate peaks of 2θ at 16.92° and 18.12°, strong peaks of 2θ at 23.05° and weak peaks of 2θ at 14.7°, displaying slight decreased in the intensity of peaks in irradiated starches. Irradiation of starches increased gelatinization temperatures and enthalpy value was measured using DSC.

  15. The effect of gamma irradiation on curcumin component of Curcuma domestica

    NASA Astrophysics Data System (ADS)

    Chosdu, R.; Erizal; Iriawan, T.; Hilmy, N.

    1995-02-01

    The effect of gamma irradiation on curcumin component of Curcuma domestica rhizome were investigated. Pure curcumin, sliced and powdered rhizome with 10% of moisture content were irradiated at 0, 10, 30 and 50 kGy (dose rate of 6 kGy/h). Curcumin content was analysed using HPLC method and ESR spectra. Results show that free radicals are already present in unirradiated rhizome. Gamma irradiation at the doses of 10, 30 and 50 kGy induced the free radicals formation of pure curcumin and Curcuma domestica rhizome. The ESR spectra of irradiated rhizome gave a very similar spectra to the signal of irradiated pure curcumin. The percentage of free radicals intensity from pure curcumin was very stable at room temperature up to 670 hours of storage. However, the percentage intensity of free radicals in the irradiated rhizome were decay during storage. Irradiation treatment and storage time did not give a significant change on curcumin content, water activity, pH and moisture content of rhizome investigated.

  16. Controlled release of cytokines using silk-biomaterials for macrophage polarization.

    PubMed

    Reeves, Andrew R D; Spiller, Kara L; Freytes, Donald O; Vunjak-Novakovic, Gordana; Kaplan, David L

    2015-12-01

    Polarization of macrophages into an inflammatory (M1) or anti-inflammatory (M2) phenotype is important for clearing pathogens and wound repair, however chronic activation of either type of macrophage has been implicated in several diseases. Methods to locally control the polarization of macrophages is of great interest for biomedical implants and tissue engineering. To that end, silk protein was used to form biopolymer films that release either IFN-γ or IL-4 to control the polarization of macrophages. Modulation of the solubility of the silk films through regulation of β-sheet (crystalline) content enabled a short-term release (4-8 h) of either cytokine, with smaller amounts released out to 24 h. Altering the solubility of the films was accomplished by varying the time that the films were exposed to water vapor. The released IFN-γ or IL-4 induced polarization of THP-1 derived macrophages into the M1 or M2 phenotypes, respectively. The silk biomaterials were able to release enough IFN-γ or IL-4 to repolarize the macrophage from M1 to M2 and vice versa, demonstrating the well-established plasticity of macrophages. High β-sheet content films that are not soluble and do not release the trapped cytokines were also able to polarize macrophages that adhered to the surface through degradation of the silk protein. Chemically conjugating IFN-γ to silk films through disulfide bonds allowed for longer-term release to 10 days. The release of covalently attached IFN-γ from the films was also able to polarize M1 macrophages in vitro. Thus, the strategy described here offers new approaches to utilizing biomaterials for directing the polarization of macrophages.

  17. Polymorphisms at Cytokine Genes May Determine the Effect of Vitamin E on Cytokine Production in the Elderly1–3

    PubMed Central

    Belisle, Sarah E.; Leka, Lynette S.; Delgado-Lista, Javier; Jacques, Paul F.; Ordovas, Jose M.; Meydani, Simin Nikbin

    2009-01-01

    Vitamin E has been shown to affect cytokine production. However, individual response to vitamin E supplementation varies. Previous studies indicate that cytokine production is heritable and common single nucleotide polymorphisms (SNP) may explain differences in cytokine production between individuals. We hypothesize that the differential response to the immunomodulatory actions of vitamin E reflects genetic differences among individuals, including SNP at cytokine genes that modulate cytokine production. We used data from a double-blind, placebo-controlled 1-y vitamin E (182 mg d,l-α-tocopherol) intervention study in elderly men and women (mean age 83 y) to test this hypothesis (vitamin E, n = 47; placebo, n = 63). We found that the effect of vitamin E on tumor necrosis factor (TNF)-α production in whole blood stimulated for 24 h with lipopolysaccharide (1.0 mg/L) is dependent on TNFα -308G > A. Participants with the A/A and A/G genotypes at TNFα -308G > A who were treated with vitamin E had lower TNFα production than those with the A allele treated with placebo. These observations suggest that individual immune responses to vitamin E supplementation are in part mediated by genetic factors. Because the A allele at TNFα has been previously associated with higher TNFα levels in whole blood and isolated immune cells, our observations suggest that the antiinflammatory effect of vitamin E is specific to those genetically predisposed to higher inflammation. Further studies are needed to determine the biological mechanism driving the interaction between vitamin E treatment and TNFα -308G > A and its implications for disease resistance. PMID:19710156

  18. Polymorphisms at cytokine genes may determine the effect of vitamin E on cytokine production in the elderly.

    PubMed

    Belisle, Sarah E; Leka, Lynette S; Delgado-Lista, Javier; Jacques, Paul F; Ordovas, Jose M; Meydani, Simin Nikbin

    2009-10-01

    Vitamin E has been shown to affect cytokine production. However, individual response to vitamin E supplementation varies. Previous studies indicate that cytokine production is heritable and common single nucleotide polymorphisms (SNP) may explain differences in cytokine production between individuals. We hypothesize that the differential response to the immunomodulatory actions of vitamin E reflects genetic differences among individuals, including SNP at cytokine genes that modulate cytokine production. We used data from a double-blind, placebo-controlled 1-y vitamin E (182 mg d,l-alpha-tocopherol) intervention study in elderly men and women (mean age 83 y) to test this hypothesis (vitamin E, n = 47; placebo, n = 63). We found that the effect of vitamin E on tumor necrosis factor (TNF)-alpha production in whole blood stimulated for 24 h with lipopolysaccharide (1.0 mg/L) is dependent on TNFalpha -308G > A. Participants with the A/A and A/G genotypes at TNFalpha -308G > A who were treated with vitamin E had lower TNFalpha production than those with the A allele treated with placebo. These observations suggest that individual immune responses to vitamin E supplementation are in part mediated by genetic factors. Because the A allele at TNFalpha has been previously associated with higher TNFalpha levels in whole blood and isolated immune cells, our observations suggest that the antiinflammatory effect of vitamin E is specific to those genetically predisposed to higher inflammation. Further studies are needed to determine the biological mechanism driving the interaction between vitamin E treatment and TNFalpha -308G > A and its implications for disease resistance.

  19. Craniospinal irradiation techniques

    SciTech Connect

    Scarlatescu, Ioana Avram, Calin N.; Virag, Vasile

    2015-12-07

    In this paper we present one treatment plan for irradiation cases which involve a complex technique with multiple beams, using the 3D conformational technique. As the main purpose of radiotherapy is to administrate a precise dose into the tumor volume and protect as much as possible all the healthy tissues around it, for a case diagnosed with a primitive neuro ectoderm tumor, we have developed a new treatment plan, by controlling one of the two adjacent fields used at spinal field, in a way that avoids the fields superposition. Therefore, the risk of overdose is reduced by eliminating the field divergence.

  20. Craniospinal irradiation techniques

    NASA Astrophysics Data System (ADS)

    Scarlatescu, Ioana; Virag, Vasile; Avram, Calin N.

    2015-12-01

    In this paper we present one treatment plan for irradiation cases which involve a complex technique with multiple beams, using the 3D conformational technique. As the main purpose of radiotherapy is to administrate a precise dose into the tumor volume and protect as much as possible all the healthy tissues around it, for a case diagnosed with a primitive neuro ectoderm tumor, we have developed a new treatment plan, by controlling one of the two adjacent fields used at spinal field, in a way that avoids the fields superposition. Therefore, the risk of overdose is reduced by eliminating the field divergence.

  1. Taxonomic applicability of inflammatory cytokines in adverse outcome pathway (AOP) development

    EPA Science Inventory

    Cytokines, low-molecular-weight messenger proteins that act as intercellular immunomodulatory signals, have become a mainstream preclinical marker for assessing the systemic inflammatory response to external stressors. The challenge is to quantitate from healthy subjects cytokine...

  2. Dose-rate effects of protons on in vivo activation of nuclear factor-kappa B and cytokines in mouse bone marrow cells

    SciTech Connect

    Rithidech, K.N.; Rusek, A.; Reungpatthanaphong, P.; Honikel, L.; Simon, S.R.

    2010-05-28

    The objective of this study was to determine the kinetics of nuclear factor-kappa B (NF-{kappa}B) activation and cytokine expression in bone marrow (BM) cells of exposed mice as a function of the dose rate of protons. The cytokines included in this study are pro-inflammatory [i.e., tumor necrosis factor-alpha (TNF-{alpha}), interleukin-1beta (IL-1{beta}), and IL-6] and anti-inflammatory cytokines (i.e., IL-4 and IL-10). We gave male BALB/cJ mice a whole-body exposure to 0 (sham-controls) or 1.0 Gy of 100 MeV protons, delivered at 5 or 10 mGy min{sup -1}, the dose and dose rates found during solar particle events in space. As a reference radiation, groups of mice were exposed to 0 (sham-controls) or 1 Gy of {sup 137}Cs {gamma} rays (10 mGy min{sup -1}). After irradiation, BM cells were collected at 1.5, 3, 24 h, and 1 month for analyses (five mice per treatment group per harvest time). The results indicated that the in vivo time course of effects induced by a single dose of 1 Gy of 100 MeV protons or {sup 137}Cs {gamma} rays, delivered at 10 mGy min{sup -1}, was similar. Although statistically significant levels of NF-{kappa}B activation and pro-inflammatory cytokines in BM cells of exposed mice when compared to those in the corresponding sham controls (Student's t-test, p < 0.05 or < 0.01) were induced by either dose rate, these levels varied over time for each protein. Further, only a dose rate of 5 mGy min{sup -1} induced significant levels of anti-inflammatory cytokines. The results indicate dose-rate effects of protons.

  3. A feasibility study of gamma irradiation on Thailand frozen shrimps ( PENEAUS MONODON)

    NASA Astrophysics Data System (ADS)

    Lacroix, M. L.; Charbonneau, R.; Jobin, M.; Thibault, C.; Nouchpramool, K.; Charoen, S.; Gagnon, M.

    1995-02-01

    Two lots of frozen precooked shrimps from Thaïland "PENAEUS MONODON" Black tiger variety were irradiated at 1.8 to 3.6 kGy. This way, it was hoped to compare the effects of gamma irradiation on the microbiological quality and the organoleptic properties of frozen precooked shrimps after transportation from Thailand to Canada. The results indicated that the extension of shelf-life based on mesophiles content was from 33 days for the control to more than 47 days for the irradiated shrimps stored at 3 ± 1 °C. The results of sensory evaluation gave slightly fresher odor for the control than the irradiated shrimps. On day one, this effect was more apparent. The results of hedonic tests showed that the irradiated shrimps were acceptable during storage. In conclusion, the results demonstrate that the combined treatments (freezing plus irradiation) of precooked shrimps are useful for increasing the storage life of shrimps without affecting consumer acceptability.

  4. Effects of gamma irradiation on physicochemical properties of Korean red ginseng powder

    NASA Astrophysics Data System (ADS)

    Byun, Myung-Woo; Yook, Hong-Sun; Kwon, Oh-Jin; Kang, Il-Jun

    1997-04-01

    Gamma irradiation was applied to Korean red ginseng powder to improve its quality. Major physicochemical properties (approximate composition, pH, acidity, browning pigment, hydrogen donating activity, fatty acids, minerals and saponin) were not significantly changed by gamma irradiation up to 10 kGy. The TBA value was increased depending on the increment of irradiation dose level. In free amino acids, threonine was increased while, serine and glutamic acid were decreased by gamma irradiation. In total amino acids, total contents were not significantly changed by gamma irradiation though tyrosine was slightly decreased P ⩽ 0.05. In free sugar, glucose, sucrose and maltose were significantly increased by 7.5 and 10 kGy gamma irradiation P ⩽ 0.05

  5. Improved dynamic properties of natural rubber filled with irradiation-modified carbon black

    NASA Astrophysics Data System (ADS)

    Wu, Yongpeng; Wen, Shipeng; Shen, Jing; Jiang, Jian; Hu, Shui; Zhang, Liqun; Liu, Li

    2015-06-01

    In this work, carbon black particles (CBs) were modified by high-energy electron beam (EB) irradiation at different doses. The influence of EB irradiation on the surface and particle size of CBs was investigated. Then, the CBs were compounded with natural rubber (NR), and the mechanical properties and dynamic properties of CBs/NR composite were further researched. The results showed that the irradiated CBs had more oxygen-containing groups and smaller particle sizes than original CBs. After irradiation, the content of bound rubber around the irradiated CBs increased, and the mechanical properties of CBs/NR composite were improved. Most importantly, NR filled with irradiated CBs has lower abrasion, higher wet skid resistance, and lower rolling resistance than NR filled with untreated CBs.

  6. Irradiation of northwest agricultural products

    NASA Astrophysics Data System (ADS)

    Eakin, D. E.; Tingey, G. I.

    1985-02-01

    Irradiation of food for disinfestation and preservation is increasing in importance because of increasing restrictions on various chemical treatments. Irradiation treatment is of particular interest in the Northwest because of a growing supply of agricultural products and the need to develop new export markets. Several products have, or could potentially have, significant export markets if stringent insect ocntrol procedures are developed and followed. Due to the recognized potential benefits of irradiation, this program was conducted to evaluate the benefits of using irradiation on Northwest agricultural products. Commodities currently included in the program are cherries, apples, asparagus, spices, hay, and hides.

  7. Cytokines in Machado Joseph Disease/Spinocerebellar Ataxia 3.

    PubMed

    da Silva Carvalho, Gerson; Saute, Jonas Alex Morales; Haas, Clarissa Branco; Torrez, Vitor Rocco; Brochier, Andressa Wigner; Souza, Gabriele Nunes; Furtado, Gabriel Vasata; Gheno, Tailise; Russo, Aline; Monte, Thais Lampert; Schumacher-Schuh, Artur; D'Avila, Rui; Donis, Karina Carvalho; Castilhos, Raphael Machado; Souza, Diogo Onofre; Saraiva-Pereira, Maria Luiza; Torman, Vanessa Leotti; Camey, Suzi; Portela, Luis Valmor; Jardim, Laura Bannach

    2016-08-01

    The aim of the present study is to describe the serum concentrations of a broad spectrum of cytokines in symptomatic and asymptomatic carriers of Machado Joseph disease (SCA3/MJD) CAG expansions. Molecularly confirmed carriers and controls were studied. Age at onset, disease duration, and clinical scales Scale for the Assessment and Rating of Ataxia (SARA), Neurological Examination Score for Spinocerebellar Ataxias (NESSCA), SCA Functional Index (SCAFI), and Composite Cerebellar Functional Score (CCFS) were obtained from the symptomatic carriers. Serum was obtained from all individuals and a cytokine panel "consisted of" eotaxin, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-α, IFN-γ, interleukin (IL)-1β, IL-1RA, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, interferon gamma-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, monokine induced by gamma interferon (MIG), macrophage inflammatory protein (MIP)-a, MIP-b, regulated on activation, normal T cell expressed and secreted (RANTES) and tumor necrosis factor (TNF)-α was analyzed. In a subgroup of symptomatic carriers, the cytokine panel was repeated after 360 days. Cytokine distribution among groups was studied by discriminant analysis; changes in serum levels after 360 days were studied by generalized estimation equation. Sixty-six symptomatic carriers, 13 asymptomatic carriers, and 43 controls were studied. No differences in cytokine patterns were found between controls and carriers of the CAG expansions or between controls and symptomatic carriers only. In contrast, eotaxin concentrations were significantly higher in asymptomatic than in symptomatic carriers or in controls (p = 0.001, ANCOVA). Eotaxin did not correlate with age, disease duration, CAG expansion, NESSCA score, and SARA score. Among symptomatic carriers, eotaxin dropped after 360 days (p = 0.039, GEE). SCA3/MJD patients presented a benign pattern of

  8. A competitive RT-PCR method for the quantitative analysis of cytokine mRNAs in mouse tissues.

    PubMed

    Zhou, N M; Matthys, P; Polacek, C; Fiten, P; Sato, A; Billiau, A; Froyen, G

    1997-03-01

    The authors describe the design and validation of a competitive RT-PCR method for the efficient and reproducible quantitation of mRNA molecules of IFN-gamma, TNF-alpha, IL-4 and IL-10 in mouse spleen RNA extracts. Before being subjected to RT-PCR, the RNA extracts were supplemented with internal control RNAs (IC-RNAs), which were constructed by inserting DNA fragments in the cDNA of the respective cytokines. The efficiency of amplification of the target and the IC-RNA was shown to remain equal over a wide range of cycle numbers. Reproducibility was such that differences in mRNA contents that were greater than 17% could be detected between two RNA samples run in parallel. Normal mouse spleen tissue was found to contain 10(7)-10(8) molecules of TNF-alpha, IFN-gamma, IL-4 and IL-10 mRNA per micrograms total RNA extracted. Injection of animals with anti-CD3 antibody, a well-known cytokine inducer, resulted in a moderate increase in TNF-alpha and IL-10 mRNA levels (14- and 24-fold, respectively), and in a substantially greater increase in the levels of mRNA for IL-4 and IFN-gamma (199- and 851-fold, respectively). These results demonstrate an accurate and reliable quantitation of cytokine mRNA levels in animal tissues.

  9. Weldability of neutron irradiated austenitic stainless steels

    NASA Astrophysics Data System (ADS)

    Asano, Kyoichi; Nishimura, Seiji; Saito, Yoshiaki; Sakamoto, Hiroshi; Yamada, Yuji; Kato, Takahiko; Hashimoto, Tsuneyuki

    1999-01-01

    Degradation of weldability in neutron irradiated austenitic stainless steel is an important issue to be addressed in the planning of proactive maintenance of light water reactor core internals. In this work, samples selected from reactor internal components which had been irradiated to fluence from 8.5 × 10 22 to 1.4 × 10 26 n/m 2 ( E > 1 MeV) corresponding to helium content from 0.11 to 103 appm, respectively, were subjected to tungsten inert gas arc (TIG) welding with heat input ranged 0.6-16 kJ/cm. The weld defects were characterized by penetrant test and cross-sectional metallography. The integrity of the weld was better when there were less helium and at lower heat input. Tensile properties of weld joint containing 0.6 appm of helium fulfilled the requirement for unirradiated base metal. Repeated thermal cycles were found to be very hazardous. The results showed the combination of material helium content and weld heat input where materials can be welded with little concern to invite cracking. Also, the importance of using properly selected welding procedures to minimize thermal cycling was recognized.

  10. Effect of gamma irradiation on the change of solubility and anti-inflammation activity of chrysin in macrophage cells and LPS-injected endotoxemic mice

    NASA Astrophysics Data System (ADS)

    Byun, Eui-Baek; Jang, Beom-Su; Byun, Eui-Hong; Sung, Nak-Yun

    2016-10-01

    This study evaluated the changes of solubility and anti-inflammatory properties of structurally modified gamma-irradiated chrysin. Chrysin was irradiated at various doses for a physical analysis and determining any structural changes and solubility. As shown through the physical analysis, the main peak of the chrysin was decreased as the irradiation dose increased, and it was concomitant with the appearance of several new peaks, which were highly increased in 50 kGy gamma-irradiated chrysin. The solubility was markedly increased in the gamma-irradiated groups. As shown through a physiological analysis, both gamma-irradiated- (15-50 kGy) and intact-chrysin (0 kGy) did not exert cytotoxicity to bone-marrow derived macrophages. The treatment of LPS-stimulated macrophages with 50 kGy gamma-irradiated chrysin resulted in a dose-dependent decrease in pro-inflammatory mediators, such as iNOS-mediated NO, PGE2, COX-2, and cell surface marker (CD80 and CD86), as well as pro-inflammatory cytokines (TNF-α and IL-6), when compared to the intact-chrysin treated group. Mechanically, we found that the inhibition of these pro-inflammatory mediators induced by gamma-irradiated chrysin occurred through an inhibition of MAPKs (ERK1/2 and p38) and the NF-κB signaling pathways. Furthermore, the anti-inflammatory activity remained in the LPS-injected animal model. In this model, gamma-irradiated chrysin treatment highly increased the mouse survival, and significantly decreased the serum cytokine (TNF-α, IL-6 and IL-1β) levels. From these findings, the anti-inflammatory action by gamma-irradiated chrysin may be closely mediated with structural modification. It seems likely that gamma irradiation can be an effective tool for improvement of the physical and physiological properties of polyphenols.

  11. Lung Irradiation Increases Mortality After Influenza A Virus Challenge Occurring Late After Exposure

    SciTech Connect

    Manning, Casey M.; Johnston, Carl J.; Reed, Christina K.; Lawrence, B. Paige; Williams, Jacqueline P.; Finkelstein, Jacob N.

    2013-05-01

    Purpose: To address whether irradiation-induced changes in the lung environment alter responses to a viral challenge delivered late after exposure but before the appearance of late lung radiation injury. Methods and Materials: C57BL/6J mice received either lung alone or combined lung and whole-body irradiation (0-15 Gy). At 10 weeks after irradiation, animals were infected with 120 HAU influenza virus strain A/HKx31. Innate and adaptive immune cell recruitment was determined using flow cytometry. Cytokine and chemokine production and protein leakage into the lung after infection were assessed. Results: Prior irradiation led to a dose-dependent failure to regain body weight after infection and exacerbated mortality, but it did not affect virus-specific immune responses or virus clearance. Surviving irradiated animals displayed a persistent increase in total protein in bronchoalveolar lavage fluid and edema. Conclusions: Lung irradiation increased susceptibility to death after infection with influenza virus and impaired the ability to complete recovery. This altered response does not seem to be due to a radiation effect on the immune response, but it may possibly be an effect on epithelial repair.

  12. Whole-body irradiation transiently diminishes the adrenocorticotropin response to recombinant human interleukin-1{alpha}

    SciTech Connect

    Perlstein, R.S.; Mehta, N.R.; Neta, R.; Whitnall, M.H.; Mougey, E.H.

    1995-03-01

    Recombinant human interleukin-1{alpha} (rhIL-1{alpha}) has significant potential as a radioprotector and/or treatment for radiation-induced hematopoietic injury. Both IL-1 and whole-body ionizing irradiation acutely stimulate the hypothalamic-pituitary-adrenal axis. We therefore assessed the interaction of whole-body irradiation and rhIL-1{alpha} in altering the functioning of the axis in mice. Specifically, we determined the adrenocorticotropin (ACTH) and corticosterone responses to rhIL-1{alpha} administered just before and hours to days after whole-body or sham irradiation. Our results indicate that whole-body irradiation does not potentiate the rhIL-1{alpha}-induced increase in ACTH levels at the doses used. In fact, the rhIL-1{alpha}-induced increase in plasma ACTH is transiently impaired when the cytokine is administered 5 h after, but not 1 h before, exposure to whole-body irradiation. The ACTH response may be inhibited by elevated corticosterone levels after whole-body irradiation, or by other radiation-induced effects on the pituitary gland and hypothalamus. 36 refs., 3 figs.

  13. Single-Cell Cytokine Profiling to Investigate Cellular Functional Diversity in Hematopoietic Malignancies.

    PubMed

    Chen, Jonathan J; Kwak, Minsuk; Fan, Rong

    2016-01-01

    Single-cell analysis of cytokine production is increasingly recognized as an important method to understand the inflammatory microenvironment and hematopoietic disease state. Certain cytokines are critical to the regulation of lineage specification, and the aberrant production of these cytokines can contribute to lineage reprogramming. Here, we describe of a platform combining subnanoliter microchambers and a high-density antibody barcode array for the study of single-cell cytokine secretions in hematopoietic cancer cell populations. PMID:27581152

  14. Cross-talk between apoptosis and cytokines in the regulation of parasitic infection.

    PubMed

    DosReis, George A; Ribeiro-Gomes, Flavia L; Guillermo, Landi V C; Lopes, Marcela F

    2007-01-01

    Parasitic diseases have worldwide medical and economical impact. Host T lymphocytes and the cytokines they produce determine the outcome of parasitic infections. Programmed cell death by apoptosis is induced in the course of parasitic infections, and affects cytokine production by removing activated effector T and B cells. In addition, engulfment of apoptotic cells promotes the secretion of cytokines that regulate intracellular replication of protozoan parasites. In this review, we discuss how the cross-talk between apoptosis and cytokines regulates parasitic infection.

  15. Jeju ground water containing vanadium induced immune activation on splenocytes of low dose γ-rays-irradiated mice.

    PubMed

    Ha, Danbee; Joo, Haejin; Ahn, Ginnae; Kim, Min Ju; Bing, So Jin; An, Subin; Kim, Hyunki; Kang, Kyung-goo; Lim, Yoon-Kyu; Jee, Youngheun

    2012-06-01

    Vanadium, an essential micronutrient, has been implicated in controlling diabetes and carcinogenesis and in impeding reactive oxygen species (ROS) generation. γ-ray irradiation triggers DNA damage by inducing ROS production and causes diminution in radiosensitive immunocytes. In this study, we elucidate the immune activation capacities of Jeju water containing vanadium on immunosuppression caused by γ-ray irradiation, and identify its mechanism using various low doses of NaVO(3). We examined the intracellular ROS generation, DNA damage, cell proliferation, population of splenocytes, and cytokine/antibody profiles in irradiated mice drinking Jeju water for 180 days and in non-irradiated and in irradiated splenocytes both of which were treated with NaVO(3). Both Jeju water and 0.245 μM NaVO(3) attenuated the intracellular ROS generation and DNA damage in splenocytes against γ-ray irradiation. Splenocytes were significantly proliferated by the long-term intake of Jeju water and by 0.245 μM NaVO(3) treatment, and the expansion of B cells accounted for the increased number of splenocytes. Also, 0.245 μM NaVO(3) treatment showed the potency to amplify the production of IFN-γ and total IgG in irradiated splenocytes, which correlated with the expansion of B cells. Collectively, Jeju water containing vanadium possesses the immune activation property against damages caused by γ-irradiation.

  16. Immunotherapy of prostate cancer in the Dunning rat model: use of cytokine gene modified tumor vaccines.

    PubMed

    Vieweg, J; Rosenthal, F M; Bannerji, R; Heston, W D; Fair, W R; Gansbacher, B; Gilboa, E

    1994-04-01

    Adenocarcinoma of the prostate is the most common cancer in men. The majority of cancers are discovered once they have already metastasized, and there is no effective therapy for prostatic cancer at this stage. The use of cytokine-secreting tumor cell preparations as therapeutic vaccines for the treatment of advanced prostate cancer was investigated in the Dunning rat R3327-MatLyLu prostatic tumor model. IL-2 secreting, irradiated, tumor cell preparations were capable of curing animals with s.c. established tumors, and induced immunological memory that protected animals from subsequent tumor challenge. Immunotherapy was less effective when tumors were induced orthotopically, but nevertheless led to improved outcome, significantly delaying, and occasionally preventing, recurrence of tumors after resection of the cancerous prostate. Granulocyte-macrophage colony stimulating factor secreting tumor cell preparations were less effective, and interferon-gamma secreting cells had only a marginal effect. Induction of a potent immune response in tumor bearing animals against the nonimmunogenic MatLyLu tumor supports the view that active immunotherapy warrants further investigation as a potential therapeutic approach to prostate cancer. PMID:8137291

  17. Food irradiation and sterilization

    NASA Astrophysics Data System (ADS)

    Josephson, Edward S.

    Radiation sterilization of food (radappertization) requires exposing food in sealed containers to ionizing radiation at absorbed doses high enough (25-70 kGy) to kill all organisms of food spoilage and public health significance. Radappertization is analogous to thermal canning is achieving shelf stability (long term storage without refrigeration). Except for dry products in which autolysis is negligible, the radappertization process also requires that the food be heated to an internal temperature of 70-80°C (bacon to 53°C) to inactivate autolytic enzymes which catalyze spoilage during storage without refrigeration. To minimize the occurence of irradiation induced off-flavors and odors, undesirable color changes, and textural and nutritional losses from exposure to the high doses required for radappertization, the foods are vacuum sealed and irradiated frozen (-40°C to -20°C). Radappertozed foods have the characteristic of fresh foods prepared for eating. Radappertization can substitute in whole or in part for some chemical food additives such as ethylene oxide and nitrites which are either toxic, carcinogenic, mutagenic, or teratogenic. After 27 years of testing for "wholesomeness" (safety for consumption) of radappertized foods, no confirmed evidence has been obtained of any adverse effecys of radappertization on the "wholesomeness" characteristics of these foods.

  18. Treatment by gamma or electron radiation decreases cell wall and gossypol content of cottonseed meal

    NASA Astrophysics Data System (ADS)

    Nayefi, M.; Salari, S.; Sari, M.; Behgar, M.

    2014-06-01

    The current study evaluated the effect of gamma and beam treatment (up to 40 kGy) on chemical composition and gossypol content of cottonseed meal. Irradiation decreased the crude fiber content. Gamma and electron treatment decreased total and free gossypol content.

  19. Research Review: The Role of Cytokines in Depression in Adolescents: A Systematic Review

    ERIC Educational Resources Information Center

    Mills, Natalie T.; Scott, James G.; Wray, Naomi R.; Cohen-Woods, Sarah; Baune, Bernhard T.

    2013-01-01

    Background: While cytokines have been implicated in the pathophysiology of depression in adults, the potential role in younger age groups such as adolescents is less clear. This article therefore reviews the literature (a) to explore the relationship between cytokines and depression in adolescents, and (b) to examine how cytokines may be related…

  20. Inter-individual variability and genetic influences on cytokine responses to bacteria and fungi.

    PubMed

    Li, Yang; Oosting, Marije; Deelen, Patrick; Ricaño-Ponce, Isis; Smeekens, Sanne; Jaeger, Martin; Matzaraki, Vasiliki; Swertz, Morris A; Xavier, Ramnik J; Franke, Lude; Wijmenga, Cisca; Joosten, Leo A B; Kumar, Vinod; Netea, Mihai G

    2016-08-01

    Little is known about the inter-individual variation of cytokine responses to different pathogens in healthy individuals. To systematically describe cytokine responses elicited by distinct pathogens and to determine the effect of genetic variation on cytokine production, we profiled cytokines produced by peripheral blood mononuclear cells from 197 individuals of European origin from the 200 Functional Genomics (200FG) cohort in the Human Functional Genomics Project (http://www.humanfunctionalgenomics.org), obtained over three different years. We compared bacteria- and fungi-induced cytokine profiles and found that most cytokine responses were organized around a physiological response to specific pathogens, rather than around a particular immune pathway or cytokine. We then correlated genome-wide single-nucleotide polymorphism (SNP) genotypes with cytokine abundance and identified six cytokine quantitative trait loci (QTLs). Among them, a cytokine QTL at the NAA35-GOLM1 locus markedly modulated interleukin (IL)-6 production in response to multiple pathogens and was associated with susceptibility to candidemia. Furthermore, the cytokine QTLs that we identified were enriched among SNPs previously associated with infectious diseases and heart diseases. These data reveal and begin to explain the variability in cytokine production by human immune cells in response to pathogens. PMID:27376574

  1. Cytokines and the hypothalamic-pituitary-ovarian-endometrial axis.

    PubMed

    Tabibzadeh, S

    1994-05-01

    Recently, the demarcating boundaries that allowed separation of the fields of reproductive biology, endocrinology, immunology and neurobiology have faded. The missing link that now ties these disciplines together is the understanding that the language by which cells communicate within these diverse systems is unanimous. This language is the network of products collectively called cytokines. The effect of these factors spans from the hypothalamus to the endometrium and is undoubtedly involved in the maintenance of the delicate balance within the hypothalamic-pituitary-gonadal-endometrial axis. Orchestrated networks of these cytokines also seem to be linked to the steroid hormone signals, an essential feature for maintenance of normal menstrual cycles. Evidence in favour of these emerging concepts is discussed. Major emphasis is placed on interferons, interleukins, tumour necrosis factor, transforming growth factors and colony-stimulating factors.

  2. Cytokines and the hypothalamic-pituitary-adrenal axis.

    PubMed

    Hermus, A R; Sweep, C G

    1990-12-20

    After administration of the cytokines interleukin 1 (IL1), tumor necrosis factor (TNF), interleukin 2 and interleukin 6 to laboratory animals or humans, plasma levels of glucocorticoids are elevated. This effect is mediated by activation of the hypothalamic-pituitary unit. IL1 and TNF inhibit aldosterone production by rat adrenocortical cells in vitro and stimulate renin release by rat renal cortical cells. Administration of IL1 or TNF in rats suppresses hypothalamic-pituitary-thyroid function, whereas IL1 acts at the level of the brain and the gonads to interfere with gonadotropin and sex steroid secretion. During stimulation of the immune system (e.g. during infectious diseases), peculiar alterations in hormone secretion occur (hypercortisolism, hyperreninemic hypoaldosteronism, euthyroid sick syndrome, hypogonadism). The role of cytokines in these alterations remains to be established.

  3. Foetal immune programming: hormones, cytokines, microbes and regulatory T cells.

    PubMed

    Hsu, Peter; Nanan, Ralph

    2014-10-01

    In addition to genetic factors, environmental cues play important roles in shaping the immune system. The first environment that the developing foetal immune system encounters is the uterus. Although physically the mother and the foetus are separated by the placental membranes, various factors such as hormones and cytokines may provide "environmental cues" to the foetal immune system. Additionally, increasing evidence suggests that prenatal maternal environmental factors, particularly microbial exposure, might significantly influence the foetal immune system, affecting long-term outcomes, a concept termed foetal immune programming. Here we discuss the potential mediators of foetal immune programming, focusing on the role of pregnancy-related hormones, cytokines and regulatory T cells, which play a critical role in immune tolerance.

  4. [Cytokine production in patients with systemic lupus erythematosus].

    PubMed

    Müzes, G; González-Cabello, R; Van Vien, C; Fehér, J; Gergely, P

    1991-09-01

    The production of different cytokines, namely interleukin-2, interleukin-1 and tumor necrosis factor-alpha produced by peripheral immunocompetent cells was evaluated in patients with systemic lupus erythematosus in active and inactive stage of the disease. The results obtained were compared to healthy controls. It has been found that lymphocytes from both groups of SLE patients produced similarly less interleukin-2 activity. Interleukin-1 activity of monocytes was significantly reduced only in patients with active stage of the disease, whereas tumor necrosis factor-alpha production was diminished even in cases of inactive SLE. The simultaneous detection of the above mentioned cytokines may indicate further details concerning immunoregulatory disturbances of systemic lupus erythematosus. PMID:1923468

  5. Systems biology of IL-6, IL-12 family cytokines.

    PubMed

    Dittrich, Anna; Hessenkemper, Wiebke; Schaper, Fred

    2015-10-01

    Interleukin-6-type cytokines play important roles in the communication between cells of multicellular organisms. They are involved in the regulation of complex cellular processes such as proliferation and differentiation and act as key player during inflammation and immune response. A major challenge is to understand how these complex non-linear processes are connected and regulated. Systems biology approaches are used to tackle this challenge in an iterative process of quantitative experimental and mathematical analyses. Here we review quantitative experimental studies and systems biology approaches dealing with the function of Interleukin-6-type cytokines in physiological and pathophysiological conditions. These approaches cover the analyses of signal transduction on a cellular level up to pharmacokinetic and pharmacodynamic studies on a whole organism level.

  6. Subversion of cytokine networks by virally encoded decoy receptors

    PubMed Central

    Epperson, Megan L.; Lee, Chung A.; Fremont, Daved H.

    2012-01-01

    Summary During the course of evolution, viruses have captured or created a diverse array of open reading frames that encode for proteins that serve to evade and sabotage the host innate and adaptive immune responses, which would otherwise lead to their elimination. These viral genomes are some of the best textbooks of immunology ever written. The established arsenal of immunomodulatory proteins encoded by viruses is large and growing and includes specificities for virtually all known inflammatory pathways and targets. The focus of this review is on herpes and poxvirus-encoded cytokine and chemokine binding proteins that serve to undermine the coordination of host immune surveillance. Structural and mechanistic studies of these decoy receptors have provided a wealth of information, not only about viral pathogenesis but also about the inner workings of cytokine signaling networks. PMID:23046131

  7. Chronic Inflammation and Cytokines in the Tumor Microenvironment

    PubMed Central

    Landskron, Glauben; De la Fuente, Marjorie; Thuwajit, Peti; Thuwajit, Chanitra; Hermoso, Marcela A.

    2014-01-01

    Acute inflammation is a response to an alteration induced by a pathogen or a physical or chemical insult, which functions to eliminate the source of the damage and restore homeostasis to the affected tissue. However, chronic inflammation triggers cellular events that can promote malignant transformation of cells and carcinogenesis. Several inflammatory mediators, such as TNF-α, IL-6, TGF-β, and IL-10, have been shown to participate in both the initiation and progression of cancer. In this review, we explore the role of these cytokines in important events of carcinogenesis, such as their capacity to generate reactive oxygen and nitrogen species, their potential mutagenic effect, and their involvement in mechanisms for epithelial mesenchymal transition, angiogenesis, and metastasis. Finally, we will provide an in-depth analysis of the participation of these cytokines in two types of cancer attributable to chronic inflammatory disease: colitis-associated colorectal cancer and cholangiocarcinoma. PMID:24901008

  8. Irradiation hardening of pure tungsten exposed to neutron irradiation

    NASA Astrophysics Data System (ADS)

    Hu, Xunxiang; Koyanagi, Takaaki; Fukuda, Makoto; Kumar, N. A. P. Kiran; Snead, Lance L.; Wirth, Brian D.; Katoh, Yutai

    2016-11-01

    Pure tungsten samples have been neutron irradiated in HFIR at 90-850 °C to 0.03-2.2 dpa. A dispersed barrier hardening model informed by the available microstructure data has been used to predict the hardness. Comparison of the model predictions and the measured Vickers hardness reveals the dominant hardening contribution at various irradiation conditions. For tungsten samples irradiated in HFIR, the results indicate that voids and dislocation loops contributed to the hardness increase in the low dose region (<0.3 dpa), while the formation of intermetallic second phase precipitation, resulting from transmutation, dominates the radiation-induced strengthening beginning with a relatively modest dose (>0.6 dpa). The precipitate contribution is most pronounced for the HFIR irradiations, whereas the radiation-induced defect cluster microstructure can rationalize the entirety of the hardness increase observed in tungsten irradiated in the fast neutron spectrum of Joyo and the mixed neutron spectrum of JMTR.

  9. Irradiation at 660 nm modulates different genes central to wound healing in wounded and diabetic wounded cell models

    NASA Astrophysics Data System (ADS)

    Houreld, Nicolette N.

    2014-02-01

    Wound healing is a highly orchestrated process and involves a wide variety of cellular components, chemokines and growth factors. Laser irradiation has influenced gene expression and release of various growth factors, cytokines and extracellular matrix proteins involved in wound healing. This study aimed to determine the expression profile of genes involved in wound healing in wounded and diabetic wounded fibroblast cells in response to irradiation at a wavelength of 660 nm. Human skin fibroblast cells (WS1) were irradiated with a diode laser (wavelength 660 nm; fluence 5 J/cm2; power output 100 mW; power density 11 mW/cm2; spot size 9.1 cm2; exposure duration 7 min 35 s). Total RNA was isolated and 1 μg reverse transcribed into cDNA which was used as a template in real-time qualitative polymerase chain reaction (qPCR). Eighty four genes involved in wound healing (extracellular matrix and cell adhesion; inflammatory cytokines and chemokines; growth factors; and signal transduction) were evaluated in wounded and diabetic wounded cell models. Forty eight hours post-irradiation, 6 genes were significantly upregulated and 8 genes were down-regulated in irradiated wounded cells, whereas 1 gene was up-regulated and 33 genes down-regulated in irradiated diabetic wounded cells. Irradiation of stressed fibroblast cells to a wavelength of 660 nm and a fluence of 5 J/cm2 modulated the expression of different genes involved in wound healing in different cell models. Modulation of these genes leads to the effects of laser irradiation seen both in vivo and in vitro, and facilitates the wound healing process.

  10. INDUCTION OF CYTOKINE PRODUCTION IN CHEETAH (ACINONYX JUBATUS) PERIPHERAL BLOOD MONONUCLEAR CELLS AND VALIDATION OF FELINE-SPECIFIC CYTOKINE ASSAYS FOR ANALYSIS OF CHEETAH SERUM.

    PubMed

    Franklin, Ashley D; Crosier, Adrienne E; Vansandt, Lindsey M; Mattson, Elliot; Xiao, Zhengguo

    2015-06-01

    Peripheral blood mononuclear cells (PBMCs) were isolated from the whole blood of cheetahs (Acinonyx jubatus ; n=3) and stimulated with lipopolysaccharides (LPS) to induce the production of proinflammatory cytokines TNF-α, IL-1β, and IL-6 for establishment of cross-reactivity between these cheetah cytokines and feline-specific cytokine antibodies provided in commercially available Feline DuoSet® ELISA kits (R&D Systems, Inc., Minneapolis, Minnesota 55413, USA). This study found that feline-specific cytokine antibodies bind specifically to cheetah proinflammatory cytokines TNF-α, IL-1β, and IL-6 from cell culture supernatants. The assays also revealed that cheetah PBMCs produce a measurable, cell concentration-dependent increase in proinflammatory cytokine production after LPS stimulation. To enable the use of these kits, which are designed for cell culture supernatants for analyzing cytokine concentrations in cheetah serum, percent recovery and parallelism of feline cytokine standards in cheetah serum were also evaluated. Cytokine concentrations in cheetah serum were approximated based on the use of domestic cat standards in the absence of cheetah standard material. In all cases (for cytokines TNF-α, IL-1β, and IL-6), percent recovery increased as the serum sample dilution increased, though percent recovery varied between cytokines at a given dilution factor. A 1:2 dilution of serum resulted in approximately 45, 82, and 7% recovery of TNF-α, IL-1β, and IL-6 standards, respectively. Adequate parallelism was observed across a large range of cytokine concentrations for TNF-α and IL-1β; however, a significant departure from parallelism was observed between the IL-6 standard and the serum samples (P=0.004). Therefore, based on our results, the Feline DuoSet ELISA (R&D Systems, Inc.) kits are valid assays for the measurement of TNF-α and IL-1β in cheetah serum but should not be used for accurate measurement of IL-6. PMID:26056884

  11. INDUCTION OF CYTOKINE PRODUCTION IN CHEETAH (ACINONYX JUBATUS) PERIPHERAL BLOOD MONONUCLEAR CELLS AND VALIDATION OF FELINE-SPECIFIC CYTOKINE ASSAYS FOR ANALYSIS OF CHEETAH SERUM.

    PubMed

    Franklin, Ashley D; Crosier, Adrienne E; Vansandt, Lindsey M; Mattson, Elliot; Xiao, Zhengguo

    2015-06-01

    Peripheral blood mononuclear cells (PBMCs) were isolated from the whole blood of cheetahs (Acinonyx jubatus ; n=3) and stimulated with lipopolysaccharides (LPS) to induce the production of proinflammatory cytokines TNF-α, IL-1β, and IL-6 for establishment of cross-reactivity between these cheetah cytokines and feline-specific cytokine antibodies provided in commercially available Feline DuoSet® ELISA kits (R&D Systems, Inc., Minneapolis, Minnesota 55413, USA). This study found that feline-specific cytokine antibodies bind specifically to cheetah proinflammatory cytokines TNF-α, IL-1β, and IL-6 from cell culture supernatants. The assays also revealed that cheetah PBMCs produce a measurable, cell concentration-dependent increase in proinflammatory cytokine production after LPS stimulation. To enable the use of these kits, which are designed for cell culture supernatants for analyzing cytokine concentrations in cheetah serum, percent recovery and parallelism of feline cytokine standards in cheetah serum were also evaluated. Cytokine concentrations in cheetah serum were approximated based on the use of domestic cat standards in the absence of cheetah standard material. In all cases (for cytokines TNF-α, IL-1β, and IL-6), percent recovery increased as the serum sample dilution increased, though percent recovery varied between cytokines at a given dilution factor. A 1:2 dilution of serum resulted in approximately 45, 82, and 7% recovery of TNF-α, IL-1β, and IL-6 standards, respectively. Adequate parallelism was observed across a large range of cytokine concentrations for TNF-α and IL-1β; however, a significant departure from parallelism was observed between the IL-6 standard and the serum samples (P=0.004). Therefore, based on our results, the Feline DuoSet ELISA (R&D Systems, Inc.) kits are valid assays for the measurement of TNF-α and IL-1β in cheetah serum but should not be used for accurate measurement of IL-6.

  12. Molecular detection of rabies encephalitis and correlation with cytokine expression.

    PubMed

    Nuovo, Gerard J; Defaria, Dulcelena L; Chanona-Vilchi, Juan G; Zhang, Yilan

    2005-01-01

    The purposes of this study were to elucidate the role of cytokine upregulation in the pathogenesis of rabies encephalitis and to compare the detection of Negri bodies with that of rabies protein by immunohistochemistry and rabies RNA by reverse transcriptase (RT) in situ PCR for its diagnosis. Negri bodies were evident in 4/7 of the documented rabies cases; viral protein and viral RNA were detected in each case. The average number of rabies-infected cells, determined by counting 150 neurons in serial sections in areas where viral protein was evident, with the three different detection methods was: Negri bodies (<1/150), immunohistochemistry (4/150), and RT in situ PCR (49/150). No rabies protein or RNA was detected in four control brain tissues that were read with the rabies cases in a blinded fashion. The ratio of cells expressing tumor necrosis factor alpha (TNFalpha) or inducible nitric oxide synthetase (iNOS) to 1 SSI-1/SOCS-1 (suppressors of cytokine signaling) expression, which is a novel class of negative feedback regulators of cytokine receptor signaling, was markedly increased only in the areas where many viral infected cells were present. Colabeling experiments showed that most of the cells expressing iNOS or TNFalpha were not virally infected, but rather adjacent to rabies-infected neurons. We conclude that RT in situ PCR for rabies virus is the most accurate test for the determination of viral load in rabies encephalitis. Further, the disease is characterized by massive viral infection of neurons in a markedly focal distribution in conjunction with a concomitant upregulation of cytokine expression in adjacent, noninfected cells that may be due, in part, to SOCS downregulation.

  13. Plasma Cytokine Levels During Long-Duration Spaceflight

    NASA Technical Reports Server (NTRS)

    Crucian, Brian E.; Zwart, Sara R.; Quiriarte, Heather A.; Smith, Scott M.; Sams, Clarence F.

    2011-01-01

    Reduced T cell, granulocyte, NK and monocyte function have all been reported following both long and short duration spaceflight, however these data indicate crews are generally not experiencing inflammatory or adaptive immune activation during spaceflight. There appear to be varied individual crew responses, and specific relationships between cytokines and markers of iron status and muscle turnover that warrant further evaluation. Increases in growth factors and chemokines may indicate other types of adaptation occurring during spaceflight, such as attempts to overcome diminished immunocyte function.

  14. Cytokine modulation of human blood viscosity from vivax malaria patients.

    PubMed

    Scherer, Edson Fredulin; Cantarini, Déborah Giovanna; Siqueira, Renan; Ribeiro, Elton Brito; Braga, Érika Martins; Honório-França, Adenilda Cristina; França, Eduardo Luzía

    2016-06-01

    Malaria is a major infectious disease in several countries and is caused by protozoa of the genus Plasmodium. In vivax malaria patients, inflammatory processes occur, as well as changes in cytokines and blood flow. The present study analyzed the cytokine modulation of blood viscosity from patients infected with Plasmodium vivax (P. vivax). Blood samples were collected from 42 non-infected individuals (control group) and 37 individuals infected with P. vivax. The IL-2, IL-4, IL-6, IL-10, TNFα, TGF-β and IL-17 cytokine concentrations in the serum were assessed, and the blood rheological properties were determined. The analysis of blood viscosity for shear rates revealed that the blood viscosity of the infected patients was significantly greater than that of the non-infected individuals. The viscosity of the blood was greater in the infected individuals than in the non-infected subjects. The serum from individuals with P. vivax infections exhibited higher IFN-γ and IL-17 concentrations and lower TGF-β levels. Incubation of the blood from infected individuals with IL-17 or IL-17 associated with IFN-γ reduced the viscosity to rates equivalent to the blood from non-infected individuals. Independently of cytokine modulation, no correlation was found between the parasitemia and blood viscosity of the infected patients. These data suggest that the alterations of blood viscosity are relevant as an auxiliary tool for the clinical diagnosis of disease. In malaria, erythrocytes are more sensitive to osmotic shock, and the reduction of viscosity by IL-17 may be related to a possible immunomodulator agent during infection.

  15. Cytokine and Chemokine Profile in Amicrobial Pustulosis of the Folds

    PubMed Central

    Marzano, Angelo V.; Tavecchio, Simona; Berti, Emilio; Gelmetti, Carlo; Cugno, Massimo

    2015-01-01

    Abstract Autoinflammation has recently been suggested in the pathogenesis of neutrophilic dermatoses but systematic studies on their cytokine profile are lacking. Notably, amicrobial pustulosis of the folds (APF), classified among neutrophilic dermatoses, has been studied only in small case series. In our University Hospital, we conducted an observational study on 15 APF patients, analyzing their clinical and laboratory features with a follow-up of 9 months to 20 years. Skin cytokine pattern of 9 of them was compared to that of 6 normal controls. In all patients, primary lesions were pustules symmetrically involving the skin folds and anogenital region with a chronic-relapsing course and responding to corticosteroids. Dapsone, cyclosporine, and tumor necrosis factor blockers were effective in refractory cases. In skin samples, the expressions of interleukin (IL)-1β, pivotal cytokine in autoinflammation, and its receptors I and II were significantly higher in APF (P = 0.005, 0.018, and 0.034, respectively) than in controls. Chemokines responsible for neutrophil recruitment such as IL-8 (P = 0.003), CXCL 1/2/3 (C-X-C motif ligand 1/2/3) (P = 0.010), CXCL 16 (P = 0.045), and RANTES (regulated on activation, normal T cell expressed and secreted) (P = 0.034) were overexpressed. Molecules involved in tissue damage like matrix metalloproteinase-2 (MMP-2) (P = 0.010) and MMP-9 (P = 0.003) were increased. APF is a pustular neutrophilic dermatosis with a typical distribution in all patients. The disorder may coexist with an underlying autoimmune/dysimmune disease but is often associated only with a few autoantibodies without a clear autoimmunity. The overexpression of cytokines/chemokines and molecules amplifying the inflammatory network supports the view that APF has an important autoinflammatory component. PMID:26683967

  16. Cytokine profile and lymphocyte subsets in type 2 diabetes

    PubMed Central

    Francisco, C.O.; Catai, A.M.; Moura-Tonello, S.C.G.; Arruda, L.C.M.; Lopes, S.L.B.; Benze, B.G.; Del Vale, A.M.; Malmegrim, K.C.R.; Leal, A.M.O.

    2016-01-01

    Type 2 diabetes mellitus (T2D) is a metabolic disease with inflammation as an important pathogenic background. However, the pattern of immune cell subsets and the cytokine profile associated with development of T2D are unclear. The objective of this study was to evaluate different components of the immune system in T2D patients' peripheral blood by quantifying the frequency of lymphocyte subsets and intracellular pro- and anti-inflammatory cytokine production by T cells. Clinical data and blood samples were collected from 22 men (51.6±6.3 years old) with T2D and 20 nonsmoking men (49.4±7.6 years old) who were matched for age and sex as control subjects. Glycated hemoglobin, high-sensitivity C-reactive protein concentrations, and the lipid profile were measured by a commercially available automated system. Frequencies of lymphocyte subsets in peripheral blood and intracellular production of interleukin (IL)-4, IL-10, IL-17, tumor necrosis factor-α, and interferon-γ cytokines by CD3+ T cells were assessed by flow cytometry. No differences were observed in the frequency of CD19+ B cells, CD3+CD8+ and CD3+CD4+ T cells, CD16+56+ NK cells, and CD4+CD25+Foxp3+ T regulatory cells in patients with T2D compared with controls. The numbers of IL-10- and IL-17-producing CD3+ T cells were significantly higher in patients with T2D than in controls (P<0.05). The frequency of interferon-γ-producing CD3+ T cells was positively correlated with body mass index (r=0.59; P=0.01). In conclusion, this study shows increased numbers of circulating IL-10- and IL-17-producing CD3+ T cells in patients with T2D, suggesting that these cytokines are involved in the immune pathology of this disease. PMID:27007651

  17. Immunomodulation of Skin Cytokine Secretion by House Dust Mite Extracts

    PubMed Central

    Arlian, Larry G.; Morgan, Marjorie S.

    2011-01-01

    Background Skin contact with house dust mites may contribute to atopic dermatitis and other skin diseases. We sought to determine if molecules from house dust mites could influence the release of proinflammatory cytokines and chemokines from epidermal keratinocytes and dermal fibroblasts grown in a human skin equivalent (HSE) model. Methods HSEs consisting of an epidermis of keratinocytes with stratum corneum over a dermis of fibroblasts in a collagen matrix were challenged with Dermatophagoides farinae, D. pteronyssinus and Euroglyphus maynei mite extracts. Results HSEs secreted interleukin (IL)-1α, IL-1 receptor antagonist, IL-6, IL-8, cutaneous T cell-attracting chemokine, transforming growth factor-α, granulocyte/macrophage and macrophage colony-stimulating factors and vascular endothelial cell growth factor in response to at least 1 mite extract. Extracts of different mite species stimulated HSEs to release different cytokines. Therefore, extracts of different species contained different molecules or different concentrations of similar molecules. The cytokine release profiles of cells in the HSEs were not the same as for monocultured keratinocytes and fibroblasts. Conclusions Molecules from house dust mites are capable of inducing the release of multiple proinflammatory cytokines and chemokines from epidermal keratinocytes and dermal fibroblasts. Avoiding skin contact with house dust mites would reduce the possibility of mite-induced inflammation in the skin. Therefore, measures to reduce contact with mite molecules such as frequent vacuuming of upholstered furniture and carpets and laundering of clothing and bedding to remove mite molecules and allergens could reduce skin contact with mite molecules and diminish exacerbations of skin inflammation in patients with atopic dermatitis and other skin diseases. PMID:21576987

  18. The cytokine network in asthma and chronic obstructive pulmonary disease

    PubMed Central

    Barnes, Peter J.

    2008-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) are very common inflammatory diseases of the airways. They both cause airway narrowing and are increasing in incidence throughout the world, imposing enormous burdens on health care. Cytokines play a key role in orchestrating the chronic inflammation and structural changes of the respiratory tract in both asthma and COPD and have become important targets for the development of new therapeutic strategies in these diseases. PMID:18982161

  19. Titanium surface hydrophilicity modulates the human macrophage inflammatory cytokine response.

    PubMed

    Alfarsi, Mohammed A; Hamlet, Stephen M; Ivanovski, Saso

    2014-01-01

    Increased titanium surface hydrophilicity has been shown to accelerate dental implant osseointegration. Macrophages are important in the early inflammatory response to surgical implant placement and influence the subsequent healing response. This study investigated the modulatory effect of a hydrophilic titanium surface on the inflammatory cytokine expression profile in a human macrophage cell line (THP-1). Genes for 84 cytokines, chemokines, and their receptors were analyzed following exposure to (1) polished (SMO), (2) micro-rough sand blasted, acid etched (SLA), and (3) hydrophilic-modified SLA (modSLA) titanium surfaces for 1 and 3 days. By day 3, the SLA surface elicited a pro-inflammatory response compared to the SMO surface with statistically significant up-regulation of 16 genes [Tumor necrosis factor (TNF) Interleukin (IL)-1β, Chemokine (C-C motif) ligand (CCL)-1, 2, 3, 4, 18, 19, and 20, Chemokine (C-X-C motif) ligand (CXCL)-1, 5, 8 and 12, Chemokine (C-C motif) receptor (CCR)-7, Lymphotoxin-beta (LTB), and Leukotriene B4 receptor (LTB4R)]. This effect was countered by the modSLA surface, which down-regulated the expression of 10 genes (TNF, IL-1α and β, CCL-1, 3, 19 and 20, CXCL-1 and 8, and IL-1 receptor type 1), while two were up-regulated (osteopontin and CCR5) compared to the SLA surface. These cytokine gene expression changes were confirmed by decreased levels of corresponding protein secretion in response to modSLA compared to SLA. These results show that a hydrophilic titanium surface can modulate human macrophage pro-inflammatory cytokine gene expression and protein secretion. An attenuated pro-inflammatory response may be an important molecular mechanism for faster and/or improved wound healing.

  20. Circulating levels of inflammatory cytokines and risk of colorectal adenomas

    PubMed Central

    Kim, Sangmi; Keku, Temitope O.; Martin, Christopher; Galanko, Joseph; Woosley, John T.; Schroeder, Jane C.; Satia, Jessie A.; Halabi, Susan; Sandler, Robert S.

    2009-01-01

    The association between obesity and colorectal neoplasia may be mediated by inflammation. Circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) are elevated in the obese. Adipose tissue can produce and release the inflammatory cytokines that are potentially procarcinogenic. We examined circulating levels of CRP, IL-6, and TNF-α in relation to risk factors and the prevalence of colorectal adenomas. Plasma levels of CRP, IL-6, and TNF-α were quantified in 873 participants (242 colorectal adenoma cases and 631 controls) in a colonoscopy-based cross-sectional study conducted between 1998 and 2002. Multivariable logistic regression was used to estimate associations between levels of inflammatory cytokines, colorectal adenomas, and known risk factors. Several known risk factors for colorectal neoplasia were associated with higher levels of inflammatory cytokines such as older age, current smoking, and increasing adiposity. The prevalence of colorectal adenomas was associated with higher concentrations of IL-6 and TNF-α, and to a lesser degree, with CRP. For IL-6, adjusted odds ratios for colorectal adenomas were 1.78 (95% confidence interval [CI]: 1.18–2.68) for the second highest plasma level, and 1.84 (95% CI: 1.24– 2.74) for the highest level compared with the reference level. A similar association was found with TNF-α, with adjusted odds ratios of 1.54 (95% CI: 1.02–2.33) and 1.65 (95% CI: 1.09–2.50), respectively. Our findings indicate that inflammation might be involved in the early development of colorectal neoplasia, and suggest that systemic inflammatory cytokines might be an indicator of obesity and other risk factors for colorectal neoplasia. PMID:18172326

  1. Secondhand Smoke Exposure and Serum Cytokine Levels in Healthy Children

    PubMed Central

    Wilson, Karen M.; Pier, Jennifer; Wesgate, Sarah C.; Weis, Emily; Love, Tanzy; Evans, Katie; Chhibber, Ashwani

    2013-01-01

    Background Exposure to secondhand smoke (SHS) is associated morbidity in children. Alterations in immune responses may explain this relationship, but have not been well-studied in children. Our objective was to determine the association between SHS exposure and serum cytokine levels in healthy children. Methods We recruited 1–6 year old patients undergoing routine procedures. A parent interview assessed medical history and SHS exposure. Children with asthma were excluded. Blood was collected under anesthesia. We used Luminex to test for a panel of cytokines; cotinine was determined using an enzyme-linked immunosorbent assay. Children were categorized as no, intermediate, or high exposure. A mixed-effects model was fit to determine differences in cytokines by exposure level. Results Of the 40 children recruited, 65% (N=26) had SHS exposure; 16 intermediate, and 10 high. There were no differences by demographics. In bivariate analyses, children exposed to SHS had lower concentrations of IL-1β, IL-4, IL-5, and IFN- γ than those with no exposure. In the mixed-effects model, children with any SHS exposure had significantly lower concentrations of IL-1β (0.554 pg/mL vs. 0.249 pg/mL) and IFN- γ (4.193 pg/mL vs. 0.816 pg/mL), and children with high exposure had significantly lower mean concentrations of IL-4 (8.141 pg/mL vs. 0.135 pg/mL) than children with no exposure. Conclusions This study suggests that SHS exposure decreases expression of some pro-inflammatory cytokines in SHS exposed children, including IFN-γ. Further research to describe the acute and chronic effects of SHS on the immune systems of children is needed. PMID:22805115

  2. Cytokine profile and lymphocyte subsets in type 2 diabetes.

    PubMed

    Francisco, C O; Catai, A M; Moura-Tonello, S C G; Arruda, L C M; Lopes, S L B; Benze, B G; Del Vale, A M; Malmegrim, K C R; Leal, A M O

    2016-01-01

    Type 2 diabetes mellitus (T2D) is a metabolic disease with inflammation as an important pathogenic background. However, the pattern of immune cell subsets and the cytokine profile associated with development of T2D are unclear. The objective of this study was to evaluate different components of the immune system in T2D patients' peripheral blood by quantifying the frequency of lymphocyte subsets and intracellular pro- and anti-inflammatory cytokine production by T cells. Clinical data and blood samples were collected from 22 men (51.6±6.3 years old) with T2D and 20 nonsmoking men (49.4±7.6 years old) who were matched for age and sex as control subjects. Glycated hemoglobin, high-sensitivity C-reactive protein concentrations, and the lipid profile were measured by a commercially available automated system. Frequencies of lymphocyte subsets in peripheral blood and intracellular production of interleukin (IL)-4, IL-10, IL-17, tumor necrosis factor-α, and interferon-γ cytokines by CD3+ T cells were assessed by flow cytometry. No differences were observed in the frequency of CD19+ B cells, CD3+CD8+ and CD3+CD4+ T cells, CD16+56+ NK cells, and CD4+CD25+Foxp3+ T regulatory cells in patients with T2D compared with controls. The numbers of IL-10- and IL-17-producing CD3+ T cells were significantly higher in patients with T2D than in controls (P<0.05). The frequency of interferon-γ-producing CD3+ T cells was positively correlated with body mass index (r=0.59; P=0.01). In conclusion, this study shows increased numbers of circulating IL-10- and IL-17-producing CD3+ T cells in patients with T2D, suggesting that these cytokines are involved in the immune pathology of this disease.

  3. Search for potent modulators of cytokine production by macrophages.

    PubMed

    Nikitin, A A; Abidov, M T; Kovalevskaya, E O; Kalyuzhin, O V

    2004-09-01

    We compared the effects of Tamerit, Polyoxidony, and Licopid on spontaneous and lipopolysaccharide-stimulated production of interleukin-1 and tumor necrosis factor by mouse peritoneal macrophages in vitro. The test preparations were equally potent in stimulating nonactivated cells. Licopid produced a costimulatory effect on macrophages primed with endotoxin. Tamerit in different doses suppressed cytokine production by cells. Polyoxidony in low doses activated, but in high doses suppressed this process. PMID:15665918

  4. Regulation of NF-κB by TNF Family Cytokines

    PubMed Central

    Hayden, Matthew S; Ghosh, Sankar

    2014-01-01

    The NF-κB family of inducible transcription factors is activated in response to a variety of stimuli. Amongst the best-characterized inducers of NF-κB are members of the TNF family of cytokines. Research on NF-κB and TNF have been tightly intertwined for more than 25 years. Perhaps the most compelling examples of the interconnectedness of NF-κB and the TNF have come from analysis of knock-out mice that are unable to activate NF-kB. Such mice die embryonically, however, deletion of TNF or TNFR1 can rescue the lethality thereby illustrating the important role of NF-κB as the key regulator of transcriptional responses to TNF. The physiological connections between NF-κB and TNF cytokines are numerous and best explored in articles focusing on a single TNF family member. Instead, in this review, we explore general mechanisms of TNF cytokine signaling, with a focus on the upstream signaling events leading to activation of the socalled canonical and noncanonical NF-κB pathways by TNFR1 and CD40 respectively. PMID:24958609

  5. [Methotrexate as inducer of proinflammatory cytokines by epithelial cells].

    PubMed

    Morón-Medina, Alejandra; Viera, Ninoska; de Morales, Thaís Rojas; Alcocer, Sirley; Bohorquez, Dinorath

    2014-03-01

    Methotrexate (MTX), a drug commonly used in childhood cancer, has also been indicated as a cytotoxic agent of the oral mucosa, which can trigger the inflammatory process and increase the vascularity of epithelial tissues during the early stages of oral mucositis. The aim of this study was to determine the production of proinflammatory cytokines IL-1beta, IL-6 y TNF-alpha in epithelial cell cultures treated with MTX. Epithelial cells of human larynx, obtained from the cell line Hep-2, were cultured with different doses of MTX during different incubation times. The drug cytotoxicity was analyzed by means of the colorimetric test, which is based on the metabolic reduction of the bromide of 3-(4, 5-dimetiltiazol-2-ilo)-2,5-difeniltetrazol (MTT); and the proinflammatory cytokines production by the test enzyme-linked immunosorbent assay (ELISA). Cultures of HEp-2 cells showed increased production of proinflammatory cytokines at 72 hours with 0.32 microM of MTX. These results suggest that depending on the dose and exposure time, MTX alters the physiology of human epithelial cells, which may play an important role during the phases of initiation and development of oral mucositis. PMID:24758098

  6. Cytokine Gene Polymorphisms and Outcome after Traumatic Brain Injury

    PubMed Central

    Waters, Ryan J.; Murray, Gordon D.; Teasdale, Graham M.; Stewart, Janice; Day, Ian; Lee, Robert J.

    2013-01-01

    Abstract Clinical outcome after traumatic brain injury (TBI) is variable and cannot easily be predicted. There is increasing evidence to suggest that there may be genetic influences on outcome. Cytokines play an important role in mediating the inflammatory response provoked within the central nervous system after TBI. This study was designed to identify associations between cytokine gene polymorphisms and clinical outcome 6 months after head injury. A prospectively identified cohort of patients (n=1096, age range 0–93 years, mean age 37) was used. Clinical outcome at 6 months was assessed using the Glasgow Outcome Scale. In an initial screen of 11 cytokine gene single nucleotide polymorphisms (SNPs) previously associated with disease susceptibility or outcome (TNFA −238 and −308, IL6 −174, −572 and −597, IL1A −889, IL1B −31, −511 and +3953, and TGFB −509 and −800), TNFA −308 was identified as having a likely association. The TNFA −308 SNP was further evaluated, and a significant association was identified, with 39% of allele 2 carriers having an unfavorable outcome compared with 31% of non-carriers (adjusted odds ratio 1.67, confidence interval 1.19–2.35, p=0.003). These findings are consistent with experimental and clinical data suggesting that neuroinflammation has an impact on clinical outcome after TBI and that tumor necrosis factor alpha plays an important role in this process. PMID:23768161

  7. Cytokine gene polymorphisms and outcome after traumatic brain injury.

    PubMed

    Waters, Ryan J; Murray, Gordon D; Teasdale, Graham M; Stewart, Janice; Day, Ian; Lee, Robert J; Nicoll, James A R

    2013-10-15

    Clinical outcome after traumatic brain injury (TBI) is variable and cannot easily be predicted. There is increasing evidence to suggest that there may be genetic influences on outcome. Cytokines play an important role in mediating the inflammatory response provoked within the central nervous system after TBI. This study was designed to identify associations between cytokine gene polymorphisms and clinical outcome 6 months after head injury. A prospectively identified cohort of patients (n=1096, age range 0-93 years, mean age 37) was used. Clinical outcome at 6 months was assessed using the Glasgow Outcome Scale. In an initial screen of 11 cytokine gene single nucleotide polymorphisms (SNPs) previously associated with disease susceptibility or outcome (TNFA -238 and -308, IL6 -174, -572 and -597, IL1A -889, IL1B -31, -511 and +3953, and TGFB -509 and -800), TNFA -308 was identified as having a likely association. The TNFA -308 SNP was further evaluated, and a significant association was identified, with 39% of allele 2 carriers having an unfavorable outcome compared with 31% of non-carriers (adjusted odds ratio 1.67, confidence interval 1.19-2.35, p=0.003). These findings are consistent with experimental and clinical data suggesting that neuroinflammation has an impact on clinical outcome after TBI and that tumor necrosis factor alpha plays an important role in this process.

  8. Human placental trophoblasts express the immunosuppressive cytokine IL-35.

    PubMed

    Mao, Haiting; Gao, Wenjuan; Ma, Chao; Sun, Jintang; Liu, Jia; Shao, Qianqian; Song, Bingfeng; Qu, Xun

    2013-07-01

    Studies of maternal-fetal tolerance focus on defining mechanisms for establishment of immunological privilege within the uterus during pregnancy. Fetal trophoblasts play a key role in maternal tolerance, in part through cytokines production. As a novel inhibitory cytokine, IL-35 is produced by Foxp3(+) regulatory T cells (Tregs) and mediates maximal suppression of Tregs. The purpose of the study is to analyze the expression of IL-35 in first-trimester human placental trophoblasts. IL-35 expression was detected at both protein and mRNA levels by immunohistochemical staining and quantitative real-time PCR method, respectively and secretion of IL-35 was measured by ELISA assay. Our results demonstrated that human trophoblasts constitutively expressed IL-35. Ebi3 and p35 (two subunits of IL-35) mRNA was shown to be co-expressed in trophoblast cells. Moreover, large amounts of secreted IL-35 were detected in the supernatants of trophoblast cells. But we did not detect the constitutive expression of IL-35 in decidual stromal cells. Our findings confirmed for the first time that first-trimester human trophoblast cells expressed and secreted IL-35, which might contribute to their suppressive capacity to maternal immune cells. Therefore, IL-35 may be an important factor of the cytokine network regulating local immune responses during human pregnancy.

  9. Changes in inflammatory cytokine networks in myasthenia gravis

    PubMed Central

    Uzawa, Akiyuki; Kanai, Tetsuya; Kawaguchi, Naoki; Oda, Fumiko; Himuro, Keiichi; Kuwabara, Satoshi

    2016-01-01

    Myasthenia gravis (MG) is an autoimmunological inflammatory disorder of the neuromuscular junction. Inflammation could be a key player for understanding the pathogenesis of MG. We measured the serum levels of 24 inflammatory cytokines in 43 patients with anti-acetylcholine receptor antibody-positive MG and 25 healthy controls. In patients with MG, serum levels of a proliferation-inducing ligand (APRIL), IL-19, IL-20, IL-28A and IL-35 were significantly increased as compared with controls (p < 0.05). Among them, IL-20, IL-28A and IL-35 were significantly decreased after treatment (p < 0.05). In clinical subtype analyses, APRIL and IL-20 were increased in patients with late-onset MG and IL-28A levels were increased in patients with thymoma-associated MG compared with healthy controls (p < 0.01). The results of the present study demonstrate both anti-inflammatory and inflammatory cytokines are upregulated in MG, reflecting the importance of cytokine-mediated inflammation and its regulation in MG pathophysiology. PMID:27172995

  10. Alterations in peripheral blood lymphocyte cytokine expression in obesity

    PubMed Central

    O'Rourke, R W; Kay, T; Lyle, E A; Traxler, S A; Deveney, C W; Jobe, B A; Roberts, C T; Marks, D; Rosenbaum, J T

    2006-01-01

    Obesity is characterized by alterations in immune and inflammatory function. In order to evaluate the potential role of cytokine expression by peripheral blood mononuclear cells (PBMC) in obesity-associated inflammation, we studied serum protein levels and mRNA levels in PBMC of interleukin (IL)-6, IL-1β, tumour necrosis factor (TNF)-α and IL-1Ra in nine lean and 10 obese subjects. Serum IL-1β was undetectable, IL-1Ra serum levels were elevated, serum levels of TNF-α were decreased and serum levels of IL-6 were similar in obese subjects compared to lean subjects, while transcript levels of IL-6, IL-1β and TNF-α, but not IL-1Ra, were decreased in PBMC from obese subjects. PBMC from obese subjects did, however, up-regulate cytokine expression in response to leptin. Thus, obesity-associated changes in IL-1Ra serum levels and IL-6 mRNA levels were not correlated with changes in cognate mRNA and serum levels, respectively, while TNF-α serum levels and PBMC mRNA levels were both decreased in obese patients. While immune alterations in obesity are manifest in peripheral blood lymphocytes, the general lack of correlation between altered serum levels and altered PBMC gene expression suggests that PBMC may not be the source of aberrant serum cytokine levels in obesity. PMID:16968396

  11. Cytokine production by peripheral blood mononuclear cells in recurrent miscarriage.

    PubMed

    Hossein, Hadinedoushan; Mahroo, Mirahmadian; Abbas, Aflatounian; Firouzeh, Akbari; Nadia, Hatmi

    2004-10-21

    It has been postulated that a proportion of recurrent miscarriage (RM) might be due to immune causes. The objective was to determine whether cytokine expression in peripheral blood mononuclear cell is altered in patients with a history of RM. We compared the levels of IL-2, IL-4, IL-10, IL-13, TGFbeta1 and IFNgamma in the supernatant of Phytohemagglutinin stimulated mononuclear cells in 21 women with RM at the time of 3rd or higher abortion (group I), 32 women who were at least 3 months past their 3rd or higher abortion (group II) and 32 pregnant women with no history of abortion (group III). Gestational age was matched between groups I and III. Group I had higher level of IL-2 than group III (P=0.001). Group II showed higher level of IL-2 (P=0.001) and IFNgamma (P=0.015) than group III. The production of IL-10 by mononuclear cells of group III was higher than both group I (P=0.002) and group II (P=0.001). There was no difference in the levels of IL-2, IL-10 and IFNgamma between groups I and II. Also, the levels of IL-4, IL-13, and TGFbeta1 were similar among the groups. The data indicate an elevation of Th1 cytokines in women with RM as compared to normal pregnant women, and IL-10 is an important cytokine in the maintenance of pregnancy.

  12. Cytokines as biomarkers of Crimean-Congo hemorrhagic fever.

    PubMed

    Papa, Anna; Tsergouli, Katerina; Çağlayık, Dilek Yağcı; Bino, Silvia; Como, Najada; Uyar, Yavuz; Korukluoglu, Gulay

    2016-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a potentially severe disease caused by CCHF virus. As in other viral hemorrhagic fevers, it is considered that the course and outcome of the disease depend on the viral load and the balance among the immune response mediators, and that a fatal outcome is the result of a "cytokine storm." The level of 27 cytokines was measured in serum samples taken from 29 patients during the acute phase of the disease. Two cases were fatal. Among survivors, significant differences between severe and non-severe cases were observed in the levels of IP-10, and MCP-1, while the levels of IL-1b, IL-5, IL-6, IL-8, IL-9, IL-10, IL-15, IP-10, MCP-1, TNF-α, and RANTES differed significantly between fatal and non-fatal cases (P < 0.05). RANTES was negatively correlated with the outcome of the disease. A striking similarity with the cytokine patterns seen in Ebola virus disease was observed. A weak Th1 immune response was seen. The viral load was positively correlated with IL-10, IP-10, and MCP-1 levels, and negatively correlated with the ratio IL-12/IL-10. Especially IP-10 and MCP-1 were significantly associated with the viral load, the severity and outcome of the disease, and they could act as biomarkers and, probably, as potential targets for treatment strategies design. PMID:26118413

  13. Cerebrospinal Fluid Cytokine Levels and Cognitive Impairment in Cerebral Malaria

    PubMed Central

    John, Chandy C.; Panoskaltsis-Mortari, Angela; Opoka, Robert O.; Park, Gregory S.; Orchard, Paul J.; Jurek, Anne M.; Idro, Richard; Byarugaba, Justus; Boivin, Michael J.

    2008-01-01

    Cerebrospinal fluid (CSF) and serum levels of 12 cytokines or chemokines important in central nervous system (CNS) infections were measured in 76 Ugandan children with cerebral malaria (CM) and 8 control children. As compared with control children, children with cerebral malaria had higher cerebrospinal fluid levels of interleukin (IL)-6, CXCL-8/IL-8, granulocyte-colony stimulating factor (G-CSF), tumor necrosis factor-α (TNF-α), and IL-1 receptor antagonist. There was no correlation between cerebrospinal and serum cytokine levels for any cytokine except G-CSF. Elevated cerebrospinal fluid but not serum TNF-α levels on admission were associated with an increased risk of neurologic deficits 3 months later (odds ratio 1.55, 95% CI: 1.10, 2.18, P = 0.01) and correlated negatively with age-adjusted scores for attention (Spearman rho, -0.34, P = 0.04) and working memory (Spearman rho, -0.32, P = 0.06) 6 months later. In children with cerebral malaria, central nervous system TNF-α production is associated with subsequent neurologic and cognitive morbidity. PMID:18256412

  14. Angiopoietin-2 is critical for cytokine-induced vascular leakage.

    PubMed

    Benest, Andrew V; Kruse, Karoline; Savant, Soniya; Thomas, Markus; Laib, Anna M; Loos, Elias K; Fiedler, Ulrike; Augustin, Hellmut G

    2013-01-01

    Genetic experiments (loss-of-function and gain-of-function) have established the role of Angiopoietin/Tie ligand/receptor tyrosine kinase system as a regulator of vessel maturation and quiescence. Angiopoietin-2 (Ang-2) acts on Tie2-expressing resting endothelial cells as an antagonistic ligand to negatively interfere with the vessel stabilizing effects of constitutive Ang-1/Tie-2 signaling. Ang-2 thereby controls the vascular response to inflammation-inducing as well as angiogenesis-inducing cytokines. This study was aimed at assessing the role of Ang-2 as an autocrine (i.e. endothelial-derived) regulator of rapid vascular responses (within minutes) caused by permeability-inducing agents. Employing two independent in vivo assays to quantitatively assess vascular leakage (tracheal microsphere assay, 1-5 min and Miles assay, 20 min), the immediate vascular response to histamine, bradykinin and VEGF was analyzed in Ang-2-deficient (Ang-2(-/-)) mice. In comparison to the wild type control mice, the Ang2(-/-) mice demonstrated a significantly attenuated response. The Ang-2(-/-) phenotype was rescued by systemic administration (paracrine) of an adenovirus encoding Ang-2. Furthermore, cytokine-induced intracellular calcium influx was impaired in Ang-2(-/-) endothelioma cells, consistent with reduced phospholipase activation in vivo. Additionally, recombinant human Ang-2 (rhAng-2) alone was unable to induce vascular leakage. In summary, we report here in a definite genetic setting that Ang-2 is critical for multiple vascular permeability-inducing cytokines. PMID:23940579

  15. Plasma Cytokine Profiles in Long-Term Strenuous Exercise

    PubMed Central

    Nielsen, Hilde G.; Øktedalen, Olav; Opstad, Per-Kristian; Lyberg, Torstein

    2016-01-01

    The open window theory indicates altered immunity 3 to 72 hours after exercise. The J-curve describes the risk of illness in response to exercise. The aim of this study was to examine the secretion of proinflammatory and anti-inflammatory cytokines before and after long-term strenuous exercise. Fourteen marathon and 16 half-marathon runners and 10 military cadets participating in a military ranger-training course were recruited to this study. Within-subject design was used measuring levels of plasma cytokines before, during, and after exercise. Plasma cytokines were measured using Luminex multiplex technology and ELISA. Comparing pre/post plasma levels both the marathon- and the half-marathon runners showed heavily increased levels of IL-6, IL-10, and IL-8 (P < 0.001). LPS stimulation among the half-marathon runners decreased the postrace levels of IL-6, IL-1b, and TNFα by 45%, 24%, and 43%, respectively (P < 0.01). During the ranger training course the spontaneous and LPS-stimulated levels of IL-6, IL-8, IL-10, IL-1b, and TNFα changed in a similar fashion as in the half-marathon runners although the fluctuations were smaller. Our study supports the open window and the J-curve theory; the immune system is more activated and the subjects are more threatened to infectious pathogens after intensive physical activity and in the period after exercise. PMID:27239554

  16. [The role of cytokines for the pathogenesis of psoriasis].

    PubMed

    Kapp, A

    1993-04-01

    Psoriasis is an inflammatory skin disorder characterized by marked hyperproliferation of keratinocytes in association with vascular expansion, fibroblast activation, leucocyte infiltration, and alterations of eicosanoid metabolism and of cytokine production. However, it is unclear at present whether these changes are the cause or the effect of the significantly increased keratinocyte turnover. More than one mechanism is involved in triggering active psoriasis; genetic predisposition and environmental factors affecting the immune system have a particularly important role. Most of the therapeutic regimens used for the treatment of psoriasis are immunosuppressive. Therefore, it is tempting to speculate that a specific defect of the immune system is the major pathogenic principle in psoriasis. There are several lines of evidence suggesting that changes in cytokine production by keratinocytes and immunocompetent cells in the skin of the patients, particularly of interleukin-6 and TGF alpha, may play an important part in propagation of the inflammatory response in psoriasis. Further studies are required to find how far local T-cell activation is involved as a basic mechanism of initiation and maintenance of the psoriatic inflammatory response. Accordingly, parameters such as the evaluation of cytokine production in vitro and in vivo and the measurement of cellular activation products may be useful in the diagnosis and monitoring of psoriasis.

  17. Interleukin-6, a Major Cytokine in the Central Nervous System

    PubMed Central

    Erta, María; Quintana, Albert; Hidalgo, Juan

    2012-01-01

    Interleukin-6 (IL-6) is a cytokine originally identified almost 30 years ago as a B-cell differentiation factor, capable of inducing the maturation of B cells into antibody-producing cells. As with many other cytokines, it was soon realized that IL-6 was not a factor only involved in the immune response, but with many critical roles in major physiological systems including the nervous system. IL-6 is now known to participate in neurogenesis (influencing both neurons and glial cells), and in the response of mature neurons and glial cells in normal conditions and following a wide arrange of injury models. In many respects, IL-6 behaves in a neurotrophin-like fashion, and seemingly makes understandable why the cytokine family that it belongs to is known as neuropoietins. Its expression is affected in several of the main brain diseases, and animal models strongly suggest that IL-6 could have a role in the observed neuropathology and that therefore it is a clear target of strategic therapies. PMID:23136554

  18. Structural design and molecular evolution of a cytokine receptor superfamily.

    PubMed Central

    Bazan, J F

    1990-01-01

    A family of cytokine receptors comprising molecules specific for a diverse group of hematopoietic factors and growth hormones has been principally defined by a striking homology of binding domains. This work proposes that the approximately 200-residue binding segment of the canonical cytokine receptor is composed of two discrete folding domains that share a significant sequence and structural resemblance. Analogous motifs are found in tandem approximately 100-amino acid domains in the extracellular segments of a receptor family formed by the interferon-alpha/beta and -gamma receptors and tissue factor, a membrane tether for a coagulation protease. Domains from the receptor supergroup reveal clear evolutionary links to fibronectin type III structures, approximately 90-amino acid modules that are typically found in cell surface molecules with adhesive functions. Predictive structural analysis of the shared receptor and fibronectin domains locates seven beta-strands in conserved regions of the chain; these strands are modeled to fold into antiparallel beta-sandwiches with a topology that is similar to immunoglobulin constant domains. These findings have strong implications for understanding the evolutionary emergence of an important class of regulatory molecules from primitive adhesive modules. In addition, the resulting double-barrel design of the receptors and the spatial clustering of conserved residues suggest a likely binding site for cytokine ligands. Images PMID:2169613

  19. Phytosanitary irradiation in south Asia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Irradiation has the potential to solve phytosanitary problems related to trade in south Asia. In general, it is the phytosanitary treatment most tolerated by fresh agricultural commodities. Irradiation technology is available in some countries of the region but is only used for phytosanitary purpos...

  20. Role of Pro-Inflammatory Cytokines and Biochemical Markers in the Pathogenesis of Type 1 Diabetes: Correlation with Age and Glycemic Condition in Diabetic Human Subjects

    PubMed Central

    Zubair, Swaleha; Ajmal, Mohd; Siddiqui, Sheelu Shafiq; Moin, Shagufta; Owais, Mohammad

    2016-01-01

    Background Type 1 diabetes mellitus is a chronic inflammatory disease involving insulin producing β-cells destroyed by the conjoined action of auto reactive T-cells, inflammatory cytokines and monocytic cells. The aim of this study was to elucidate the status of pro-inflammatory cytokines and biochemical markers and possible correlation of these factors towards outcome of the disease. Methods The study was carried out on 29 T1D subjects and 20 healthy subjects. Plasma levels of oxidative stress markers, enzymatic and non-enzymatic antioxidants were estimated employing biochemical assays. The levels of pro-inflammatory cytokines such as by IL-1β & IL-17 in the serum were determined by ELISA, while the expression of TNF-α, IL-23 & IFN-γ was ascertained by qRT-PCR. Results The onset of T1D disease was accompanied with elevation in levels of Plasma malondialdehyde, protein carbonyl content and nitric oxide while plasma vitamin C, reduced glutathione and erythrocyte sulfhydryl groups were found to be significantly decreased in T1D patients as compared to healthy control subjects. Activity of antioxidant enzymes, superoxide dismutase, catalase, glutathione reductase and glutathione-s-transferase showed a significant suppression in the erythrocytes of T1D patients as compared to healthy subjects. Nevertheless, the levels of pro-inflammatory cytokines IL-1β and IL-17A were significantly augmented (***p≤.001) on one hand, while expression of T cell based cytokines IFN-γ, TNF-α and IL-23 was also up-regulated (*p≤.05) as compared to healthy human subjects. Conclusion The level of pro-inflammatory cytokines and specific biochemical markers in the serum of the patient can be exploited as potential markers for type 1 diabetes pathogenesis. The study suggests that level of inflammatory markers is up-regulated in T1D patients in an age dependent manner. PMID:27575603