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Sample records for acute cytokine-induced inflammatory

  1. Requirement for C-X-C chemokines (macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant) in IgG immune complex-induced lung injury

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Warner, R L

    1997-01-01

    The C-X-C chemokines of the IL-8 family possess potent chemotactic activity for neutrophils, but their in vivo role in inflammatory responses is not well understood. In the IgG immune complex-induced model of acute lung inflammatory injury in the rat we have evaluated the roles of two rat...... chemokines, macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC). Both mRNA and protein for MIP-2 and CINC appeared in a time-dependent manner after initiation of IgG immune complex deposition in lung. There exists a 69% homology between the amino acid sequences...... by 125I-labeled albumin leakage from the pulmonary vasculature) and reduced neutrophil accumulation in the lung (as determined by myeloperoxidase (MPO content) and neutrophil counts in bronchoalveolar lavage (BAL) fluids); however, no change in TNF-alpha levels in BAL fluids was found. Chemotactic...

  2. Inflammatory Cytokines Induce Ubiquitination and Loss of the Prostate Suppressor Protein NKX3.1

    Science.gov (United States)

    2007-10-01

    foreign organisms. The inflammatory process is responsible for the removal of harmful stimuli and for cellular regeneration and healing. Acute...retinogenesis in zebrafish .(138) Regulation of Vsx-1 levels is mediated by C-terminal dependent ubiquitination.(139) In Kurtzman et al, truncation of the...FRANKS LM. Atrophy and hyperplasia in the prostate proper. J Pathol Bacteriol 1954; 68(2):617-621. (2) Liavag I. Atrophy and regeneration in the

  3. Viscum album exerts anti-inflammatory effect by selectively inhibiting cytokine-induced expression of cyclooxygenase-2.

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    Pushpa Hegde

    Full Text Available Viscum album (VA preparations are extensively used as complementary therapy in cancer and are shown to exert anti-tumor activities which involve the cytotoxic properties, induction of apoptosis, inhibition of angiogenesis and several other immunomodulatory mechanisms. In addition to their application in cancer therapy, VA preparations have also been successfully utilized in the treatment of several inflammatory pathologies. Owing to the intricate association of inflammation and cancer and in view of the fact that several anti-tumor phytotherapeutics also exert a potent anti-inflammatory effect, we hypothesized that VA exerts an anti-inflammatory effect that is responsible for its therapeutic benefit. Since, inflammatory cytokine-induced cyclo-oxygenase-2 (COX-2 and prostaglandin E2 (PGE2 play a critical role in the pathogenesis of inflammatory diseases, we investigated the anti-inflammatory effect of VA on regulation of cyclo-oxygenase expression and PGE2 biosynthesis by using human lung adenocarcinoma cells (A549 cells as a model. A549 cells were stimulated with IL-1β and treated with VA preparation (VA Qu Spez for 18 hours. PGE2 was analysed in the culture supernatants by enzyme immunoassay. Expression of COX-2 and COX-1 proteins was analyzed by immunoblotting and the expression of COX-2 mRNA was assessed by semi-quantitative RT-PCR. We found that VA Qu Spez inhibit the secretion of IL-1β-induced PGE2 in a dose-dependent manner. Further, we also show that this inhibitory action was associated with a reduced expression of COX-2 without modulating the COX-1 expression. Together these results demonstrate a novel anti-inflammatory mechanism of action of VA preparations wherein VA exerts an anti-inflammatory effect by inhibiting cytokine-induced PGE2 via selective inhibition of COX-2.

  4. The Effect of PSD-93 Deficiency on the Expression of Early Inflammatory Cytokines Induced by Ischemic Brain Injury.

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    Zhang, Qingxiu; Cheng, Hongyu; Rong, Rong; Yang, Hui; Ji, Qiuhong; Li, Qingjie; Rong, Liangqun; Hu, Gang; Xu, Yun

    2015-12-01

    The aim of the study was to explore the effect of PSD-93 deficiency on the expression of early inflammatory cytokines induced by cerebral ischemia/reperfusion injury. Ten- to twelve-week-old male PSD-93 knockout (PSD-93 KO) mice (C57BL/6 genetic background) and wild-type (WT) littermates were randomly divided into sham and ischemia/reperfusion (I/R) group. The focal cerebral I/R model was established by middle cerebral artery occlusion (MCAO) suture method. RT-PCR was used to detect the mRNA expression of IL-6, IL-10, Cox-2, iNOS, and TNF-α4h following reperfusion. Infarct volume at different time points after I/R was analyzed using 2,3,5-triphenyl tetrazolium staining, and neurological damage score (neurological severity scores, NSS) was used to evaluate the effect of PSD-93 gene knockout on the MCAO-induced neurological injury. In WT mice, early I/R injury led to the increase in the mRNA expression of proinflammatory cytokines IL-6, Cox-2, iNOS, and TNF-α that coincided with the decrease in the expression of anti-inflammatory cytokine IL-10, as compared to the sham group (P cytokines induced by cerebral ischemia.

  5. HSF-1 is involved in attenuating the release of inflammatory cytokines induced by LPS through regulating autophagy.

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    Tong, Zhongyi; Jiang, Bimei; Zhang, Lingli; Liu, Yanjuan; Gao, Min; Jiang, Yu; Li, Yuanbin; Lu, Qinglan; Yao, Yongming; Xiao, Xianzhong

    2014-05-01

    Autophagy plays a protective role in endotoxemic mice. Heat shock factor 1 (HSF-1) also plays a crucial protective role in endotoxemic mice by decreasing inflammatory cytokines. The purpose of this study was to determine whether HSF-1 is involved in attenuating the release of inflammatory cytokines in lipopolysaccharide (LPS)-stimulated mice and peritoneal macrophages (PMs) through regulating autophagy activity. Autophagosome formation in HSF-1(+/+) and HSF-1(-/-) mice and PMs stimulated by LPS was examined by Western blotting and immunofluorescence. Lipopolysaccharide-induced autophagy and inflammatory cytokines were examined in HSF-1(+/+) and HSF-1(-/-) PMs treated with 3-methyladenine (3-MA) or rapamycin. Results showed that LPS-induced autophagy was elevated transiently at 12 h but declined at 24 h in the livers and lungs of mice. Higher levels of inflammatory cytokines and lower autophagy activity were detected in HSF-1(-/-) mice and PMs compared with HSF-1(+/+) mice and PMs. Interestingly, LPS-induced release of inflammatory cytokines did not further increase in HSF-1(-/-) PMs treated with 3-MA but aggravated in HSF-1(+/+) PMs. Lipopolysaccharide-induced autophagy did not decrease in HSF-1(-/-) PMs treated with 3-MA but decreased in HSF-1 PMs(+/+). Taken together, our results suggested that HSF-1 attenuated the release of inflammatory cytokines induced by LPS by regulating autophagy activity.

  6. Rapamycin Maintains the Chondrocytic Phenotype and Interferes with Inflammatory Cytokine Induced Processes

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    Andrea De Luna-Preitschopf

    2017-07-01

    Full Text Available Osteoarthritis (OA is hallmarked by a progressive degradation of articular cartilage. Besides risk factors including trauma, obesity or genetic predisposition, inflammation has a major impact on the development of this chronic disease. During the course of inflammation, cytokines such as tumor necrosis factor-alpha(TNF-α and interleukin (IL-1β are secreted by activated chondrocytes as well as synovial cells and stimulate the production of other inflammatory cytokines and matrix degrading enzymes. The mTORC1 inhibitor rapamycin is a clinical approved immunosuppressant and several studies also verified its chondroprotective effects in OA. However, the effect of blocking the mechanistic target of rapamycin complex (mTORC1 on the inflammatory status within OA is not well studied. Therefore, we aimed to investigate if inhibition of mTORC1 by rapamycin can preserve and sustain chondrocytes in an inflammatory environment. Patient-derived chondrocytes were cultured in media supplemented with or without the mTORC1 inhibitor rapamycin. To establish an inflammatory environment, either TNF-α or IL-1β was added to the media (=OA-model. The chondroprotective and anti-inflammatory effects of rapamycin were evaluated using sulfated glycosaminoglycan (sGAG release assay, Caspase 3/7 activity assay, lactate dehydrogenase (LDH assay and quantitative real time polymerase chain reaction (PCR. Blocking mTORC1 by rapamycin reduced the release and therefore degradation of sGAGs, which are components of the extracellular matrix secreted by chondrocytes. Furthermore, blocking mTORC1 in OA chondrocytes resulted in an enhanced expression of the main chondrogenic markers. Rapamycin was able to protect chondrocytes from cell death in an OA-model shown by reduced Caspase 3/7 activity and diminished LDH release. Furthermore, inhibition of mTORC1 preserved the chondrogenic phenotype of OA chondrocytes, but also reduced inflammatory processes within the OA-model. This study

  7. Cytokines induced neutrophil extracellular traps formation: implication for the inflammatory disease condition.

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    Ravi S Keshari

    Full Text Available 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.

  8. Alteration of oxidative stress and inflammatory cytokines induces apoptosis in diabetic nephropathy.

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    Sha, Jibin; Sui, Bo; Su, Xiaoqing; Meng, Qingfang; Zhang, Chenggang

    2017-09-19

    Diabetic nephropathy (DN) is one of the most significant long‑term complications in terms of morbidity and mortality for diabetic patients; however, the exact cause remains unknown. To address this, the DN model was established, and oxidative stress indexes, including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH‑Px), and inflammatory cytokines, includinginterleukin‑6 (IL‑6), tumor necrosis factor‑alpha (TNF‑α) and transforming growth factor‑beta (TGF‑β), were examined by ELISA. Renal pathological alterations and cell apoptosis was examined by hematoxylin and eosin and terminal deoxynucleotidyl transferase mediated dUTP nick‑end labeling staining, respectively. The expression levels of B‑cell lymphoma‑2 (Bcl‑2), Bcl‑2 associated X (Bax) and caspase‑3 wereexamined by immunohistochemistry and western blotting. The DN model was correctly established, with lower body weight and the higher blood glucose in the diabetes model group. The expression levels of SOD and GSH‑Px were significantly decreased in the diabetes model group; however, MDA, IL‑6, TNF‑α and TGF‑β were significantly increased. The kidney was severely damaged in the diabetes model group, with inflammatory cell invasion, increasing amount of interstitial matrix and hypertrophy with vacuolar degeneration of renal tubular cells. Cell apoptosis levels were significantly increased, and Bcl‑2 was significantly decreased in the diabetes model group in contrast with that of the sham group; however, Bax and caspase‑3 were significantly increased. It suggested that increased oxidative stress and inflammatory cytokines may enhance the apoptosis levels in DN, and may provide a significant diagnostic reference for DN in diabetes patients.

  9. Effect of vitamin E succinate on inflammatory cytokines induced by high-intensity interval training

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    Hadi Sarir

    2015-01-01

    Full Text Available Aim and Scope: The anti-inflammatory effect of vitamin E under moderate exercises has been evaluated. However, the effect of vitamin E succinate, which has more potent anti-inflammatory effect than other isomers of vitamin E has not been evaluated. Therefore, the aim of the present study was to evaluate the effects of vitamin E succinate on tumor necrosis factor alpha (TNF-a and interleukin-6 (IL-6 production induced by high-intensity interval training (HIIT. Materials and Methods: In the present study, 24 rats were randomly divided into control (C, supplementation (S, HIIT, and HIIT + supplementation (HIIT+S groups. HIIT training protocol on a treadmill (at a speed of 40-54 m/min and vitamin E succinate supplementation (60 mg/kg/day was conducted for 6 weeks. Results: Serum IL-6 in the HIIT group significantly increased compared with the C group (350.42 ± 123.31 pg/mL vs 158.60 ± 41.96 pg/mL; P = 0.002. Also, serum TNF-a concentrations significantly enhanced (718.15 ± 133.42 pg/mL vs 350.87 ± 64.93 pg/mL; P = 0.001 in the HIIT group compared with the C group. Treatment of the training group with vitamin E numerically reduced IL-6 and TNF-a when compared with the HIIT group (217.31 ± 29.21 and 510.23 ± 217.88, respectively, P > 0.05. However, no significant changes were observed in serum TNF-a (P = 0.31 and IL-6 (P = 0.52 concentrations in the HIIT + S group compared with the C group. Conclusion: HIIT-induced IL-6 and TNF-α decreased by administration of Vitamin E succinate.

  10. [Curative effect of decitabine combined with cytokine-induced killer cells in two elderly patients with acute myeloid leukemia].

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    Chang, Cheng; Yang, Bo; Zhang, Lin; Zhu, Hong-Li; Lu, Xue-Chun; Guo, Bo; Cai, Li-Li; Han, Wei-Dong; Wang, Yao; Fan, Hui; Li, Su-Xia; Liu, Yang; Yang, Yang; Zhai, Bing; Ran, Hai-Hong; Lin, Jie; Zhang, Feng

    2013-02-01

    This study was aimed to evaluate the effectiveness and safety of low methylation drug decitabine combined with autologous cytokine induced killer cells (CIK) to treat the elderly patients with acute myeloid leukemia (AML). Two AML patients aged over 80 years old were diagnosed and treated in our department from 2006 to 2012; both company with MDS history, and one case was M4-type, another case was M6-type according to FAB classification. The changes in lymphocyte subsets, hematologic response, transfusion frequency, leukemic gene expression, obtaining CR or PR, quality of life and survival time of the patients with different treatment regimen (decitabine alone; CIK alone; decitabine combined with CIK) were systematically observed. The results showed that therapy of decitabine combined with CIK cells could reduce bone marrow suppression extent, decrease the frequency and volume of blood transfusion, and prolong the duration of partial remission, compared with the single use of CIK cell infusion and single use of decitabine treatment. Meanwhile, the kinds of expressed genes associated with leukemia decreased and the survival time was prolonged obviously. The patients' life quality significantly improved. It is concluded that decitabine combined with CIK for treatment of elderly patients with AML is safe and effective.

  11. Fasciola hepatica fatty acid binding protein inhibits TLR4 activation and suppresses the inflammatory cytokines induced by lipopolysaccharide in vitro and in vivo.

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    Martin, Ivelisse; Cabán-Hernández, Kimberly; Figueroa-Santiago, Olgary; Espino, Ana M

    2015-04-15

    TLR4, the innate immunity receptor for bacterial endotoxins, plays a pivotal role in the induction of inflammatory responses. There is a need to develop molecules that block either activation through TLR4 or the downstream signaling pathways to inhibit the storm of inflammation typically elicited by bacterial LPS, which is a major cause of the high mortality associated with bacterial sepsis. We report in this article that a single i.p. injection of 15 μg fatty acid binding protein from Fasciola hepatica (Fh12) 1 h before exposure to LPS suppressed significantly the expression of serum inflammatory cytokines in a model of septic shock using C57BL/6 mice. Because macrophages are a good source of IL-12p70 and TNF-α, and are critical in driving adaptive immunity, we investigated the effect of Fh12 on the function of mouse bone marrow-derived macrophages (bmMΦs). Although Fh12 alone did not induce cytokine expression, it significantly suppressed the expression of IL-12, TNF-α, IL-6, and IL-1β cytokines, as well as inducible NO synthase-2 in bmMΦs, and also impaired the phagocytic capacity of bmMΦs. Fh12 had a limited effect on the expression of inflammatory cytokines induced in response to other TLR ligands. One mechanism used by Fh12 to exert its anti-inflammatory effect is binding to the CD14 coreceptor. Moreover, it suppresses phosphorylation of ERK, p38, and JNK. The potent anti-inflammatory properties of Fh12 demonstrated in this study open doors to further studies directed at exploring the potential of this molecule as a new class of drug against septic shock or other inflammatory diseases.

  12. Lubricin/Proteoglycan 4 Binding to CD44 Receptor: A Mechanism of Lubricin’s suppression of Pro-inflammatory Cytokine Induced Synoviocyte Proliferation

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    Al-Sharif, Afnan; Jamal, Maha; Zhang, Ling; Larson, Katherine; Schmidt, Tannin; Jay, Gregory; Elsaid, Khaled

    2015-01-01

    Objective To evaluate recombinant human proteoglycan 4 (rhPRG4) binding to CD44 receptor and its consequence on cytokine induced synoviocyte proliferation. Methods rhPRG4 binding to CD44 and competition with high molecular weight hyaluronic acid (HMW HA) was evaluated using a direct enzyme linked immunosorbent assay (ELISA) and surface plasmon resonance. Sialidase-A and O-glycosidase digestion of rhPRG4 was performed and CD44 binding was evaluated using ELISA. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) were stimulated with interleukin-1 beta (IL-1β) or tumor necrosis factor alpha (TNF-α) for 48 hours in the presence or absence of rhPRG4 or HMW HA at 20, 40 and 80μg/ml and cell proliferation was measured. CD44 contribution was assessed by co-incubation with a CD44 antibody (IM7). The anti-proliferative effect of rhPRG4 was investigated following treatment of Prg4−/− synoviocytes with IL-1β or TNF-α in the presence or absence of IM7. Results rhPRG4 binds CD44 and interferes with HMW HA CD44 binding. Removal of sialic acid and O-glycosylations significantly increased CD44 binding by rhPRG4 (p<0.001). rhPRG4 and HMW HA at 40 and 80μg/ml significantly suppressed IL-1β induced RA-FLS proliferation (p<0.05). rhPRG4 at 20, 40 and 80μg/ml significantly suppressed TNF-α induced RA-FLS proliferation (p<0.05). CD44 neutralization reversed the effect of rhPRG4 on IL-1β and TNF-α stimulated RA-FLS and the effect of HMW HA on IL-1β stimulated RA-FLS. rhPRG4 inhibited cytokine-induced proliferation of Prg4−/− synoviocytes which could be prevented by blocking CD44. Conclusion Lubricin is a novel putative ligand for CD44 and may control synoviocyte overgrowth in inflammatory arthropathies via a CD44-mediated mechanism. PMID:25708025

  13. Inflammatory Cytokines Induce Expression of Chemokines by Human Retinal Cells: Role in Chemokine Receptor Mediated Age-related Macular Degeneration.

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    Nagineni, Chandrasekharam N; Kommineni, Vijay K; Ganjbaksh, Nader; Nagineni, Krishnasai K; Hooks, John J; Detrick, Barbara

    2015-11-01

    Chemokine reeptor-3 (CCR-3) was shown to be associated with choroidal neovascularization (CNV) in age-related macular degeneration (AMD). AMD is a vision threatening retinal disease that affects the aging population world-wide. Retinal pigment epithelium and choroid in the posterior part of the retina are the key tissues targeted in the pathogenesis of CNV in AMD. We used human retinal pigment epithelial (HRPE) and choroidal fibroblast (HCHF) cells, prepared from aged adult human donor eyes, to evaluate the expression of major CCR-3 ligands, CCL-5, CCL -7, CCL-11,CCL-24 and CCL-26. Microarray analysis of gene expression in HRPE cells treated with inflammatory cytokine mix (ICM= IFN-γ+TNF-α+IL-1β) revealed 75 and 23-fold increase in CCL-5 and CCL-7 respectively, but not CCL-11, CCL-24 and CCL-26. Chemokine secretion studies of the production of CCL5 and CCL7 by HRPE corroborated with the gene expression analysis data. When the HRPE cells were treated with either individual cytokines or the ICM, both CCL-5 and CCL-7 were produced in a dose dependent manner. Similar to the gene expression data, the ICM did not enhance HRPE production of CCL-11, CCL-24 and CCL-26. CCL-11 and CCL-26 were increased with IL-4 treatment and this HRPE production was augmented in the presence of TNF-α and IL1β. When HCHF cells were treated with either individual cytokines or the ICM, both CCL-5 and CCL-7 were produced in a dose dependent fashion. IL-4 induced low levels of CCL-11 and CCL-26 in HCHF and this production was significantly enhanced by TNF-α. Under these conditions, neither HRPE nor HCHF were demonstrated to produce CCL-24. These data demonstrate that chronic inflammation triggers CCL-5 and CCL-7 release by HRPE and HCHF and the subsequent interactions with CCR3 may participate in pathologic processes in AMD.

  14. Raman spectroscopic detection of rapid, reversible, early-stage inflammatory cytokine-induced apoptosis of adult hippocampal progenitors/stem cells

    CERN Document Server

    Ladiwala, Uma; Thakur, Bhushan; Santhosh, Chidangil; Mathur, Deepak

    2014-01-01

    The role of neuro-inflammation in diverse, acute and chronic brain pathologies is being increasingly recognized. Neuro-inflammation is accompanied by increased levels of both pro- and anti-inflammatory cytokines; these have deleterious as well as protective/reparative effects. Inflammation has varying effects on neurogenesis and is a subject of intense contemporary interest. We show that TNF-alpha and IFN-gamma, used concomitantly, cause apoptosis of adult rat hippocampal progenitor/stem cells in vitro as detected by the TUNEL and MTT assays on time scales of several hours. We have coupled Raman spectroscopy to an optical trap to probe early changes of apoptosis in single, live neural stem cells that have been treated with pro-inflammatory cytokines, TNF-alpha and IFN-gamma. Changes caused by inflammation-induced denaturation of DNA are observed in the Raman spectra that correspond to very early stages of apoptosis, occurring on very fast time scales: as short as 10 minutes. Addition of the anti-inflammatory ...

  15. Effects of dendritic cell-activated and cytokine-induced killer cell therapy on 22 children with acute myeloid leukemia after chemotherapy.

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    Bai, Yan; Zheng, Jin-e; Wang, Nan; Cai, He-hua; Zhai, Li-na; Wu, Yao-hui; Wang, Fang; Jin, Run-ming; Zhou, Dong-feng

    2015-10-01

    The efficiency of dendritic cell-activated and cytokine-induced killer cell (DC-CIK) therapy on children with acute myeloid leukemia (AML) after chemotherapy was investigated. Mononuclear cells were collected from children achieving complete remission after chemotherapy, cultured in vitro and transfused back into the same patient. Interleukin-2 (IL-2) was injected subcutaneously every other day 10 times at the dose of 1 × 10(6) units. Peripheral blood lymphocyte subsets and minimal residual disease (MRD) were detected by flow cytometry. Function of bone marrow was monitored by methods of morphology, immunology, cytogenetics and molecular biology. The side effects were also observed during the treatment. The average follow-up period for all the 22 patients was 71 months and relapse occurred in two AML patients (9.1%). The percentage of CD3(+)/CD8(+) cells in peripheral blood of 15 patients at the 3rd month after DC-CIK treatment (36.73% ± 12.51%) was dramatically higher than that before treatment (29.20% ± 8.34%, P 0.1% in 5 patients before the treatment, and became lower than 0.1% 3 months after the treatment. During the transfusion of DC-CIK, side effects including fever, chills and hives appeared in 7 out of 22 (31.82%) cases but disappeared quickly after symptomatic treatments. There were no changes in electrocardiography and liver-renal functions after the treatment. MRD in children with AML can be eliminated by DC-CIK therapy which is safe and has fewer side effects.

  16. Cytotoxic capacity of IL-15-stimulated cytokine-induced killer cells against human acute myeloid leukemia and rhabdomyosarcoma in humanized preclinical mouse models

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    Eva eRettinger

    2012-04-01

    Full Text Available Allogeneic stem cell transplantation (allo-SCT has become an important treatment modality for patients with high risk acute myeloid leukemia (AML and is also under investigation for soft tissue sarcomas. The therapeutic success is still limited by minimal residual disease (MRD status ultimately leading to patients’ relapse. Adoptive donor lymphocyte infusions (DLI based on MRD status using IL-15-expanded cytokine-induced killer (CIK cells may prevent relapse without causing graft-versus-host-disease (GvHD. To generate preclinical data we developed mouse models to study anti-leukemic- and anti-tumor-potential of CIK cells in vivo. Immunodeficient mice (NOD/SCID/IL2Rγc-, NSG were injected intravenously with human leukemic cell lines THP-1, SH-2 and with human rhabdomyosarcoma (RMS cell lines RH41 and RH30 at minimal doses required for leukemia or tumor engraftment. Mice transplanted with THP-1 or RH41 cells were randomly assigned for analysis of CIK cell treatment. Organs of mice were analyzed by flow cytometry as well as quantitative polymerase chain reaction (qPCR for engraftment of malignant cells and CIK cells. Potential of CIK cells to induce GvHD was determined by histological analysis. Tissues of the highest degree of THP-1 cell expansion included bone marrow (BM followed by liver, lung, spleen, peripheral blood (PB, and brain. RH30 and RH41 engraftment mainly took place in liver and lung, but was also detectable in spleen and PB. In spite of delayed CIK cell expansion compared with malignant cells, CIK cells injected at an effector to target cell (E:T ratio of 1:1 were sufficient for significant reduction of RH41 cells, whereas against fast-expanding THP-1 cells an E:T ratio of 250:1 was needed to achieve comparable results. Our preclinical in vivo mouse models showed a reliably 100% engraftment of malignant cells which is essential for analysis of anti-cancer therapy. Furthermore our data demonstrated that IL-15-activated CIK cells

  17. Phenolic compounds present in Sardinian wine extracts protect against the production of inflammatory cytokines induced by oxysterols in CaCo-2 human enterocyte-like cells.

    Science.gov (United States)

    Biasi, Fiorella; Guina, Tina; Maina, Marco; Cabboi, Barbara; Deiana, Monica; Tuberoso, Carlo I; Calfapietra, Simone; Chiarpotto, Elena; Sottero, Barbara; Gamba, Paola; Gargiulo, Simona; Brunetto, Vanessa; Testa, Gabriella; Dessì, Maria A; Poli, Giuseppe; Leonarduzzi, Gabriella

    2013-07-01

    Cholesterol auto-oxidation products, namely oxysterols, are widely present in cholesterol-rich foods. They are thought to potentially interfere with homeostasis of the human digestive tract, playing a role in intestinal mucosal damage. This report concerns the marked up-regulation in differentiated CaCo-2 colonic epithelial cells of two key inflammatory interleukins, IL-6 and IL-8, caused by a mixture of oxysterols representative of a high cholesterol diet. This strong pro-inflammatory effect appeared to be dependent on the net imbalance of red-ox equilibrium with the production of excessive levels of reactive oxygen species through the colonic NADPH-oxidase NOX1 activation. Induction of NOX1 was markedly while not fully inhibited by CaCo-2 cell pre-incubation with phenolic extracts obtained from well-selected wines from typical grape varieties grown in Sardinia. Oxysterol-dependent NOX1 activation, as well as interleukin synthesis, were completely prevented by Cannonau red wine extract that contains an abundant phenolic fraction, in particular phenolic acids and flavonoids. Conversely, cell pre-treatment with Vermentino white wine extract with smaller phenolic fraction showed only a partial NOX1 down-regulation and was ineffective in interleukin synthesis induced by dietary oxysterols. It is thus likely that the effects of Sardinian wine extracts against intestinal inflammation induced by dietary oxysterols are mainly due to their high phenolic content: low doses of phenolics would be responsible only for direct scavenging oxysterol-dependent ROS production. Besides this direct activity, an excess of phenolic compounds detectable in red wine, may exert an additional indirect action by blocking oxysterol-related NOX1 induction, thus totally preventing the pro-oxidant and pro-inflammatory events triggered by dietary oxysterols. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Acanthopanax koreanum roots inhibit the expression of pro-inflammatory cytokines, inducible nitric oxide synthase, and cyclooxygenase-2 in RAW 264.7 macrophages

    OpenAIRE

    2016-01-01

    Acanthopanax koreanum is a popular plant found on Jeju Island, Korea and is commonly used to prevent the side effects of consumption of alcoholic beverages. However, this plant has not been properly utilized as a medicinal material. In this study, we investigated the anti-inflammatory effects of the 70% ethanol extract of A. koreanum roots (AKR-E). The results indicated that the AKR-E (200 μg/mL) inhibited the lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and prostaglandin ...

  19. Acanthopanax koreanum roots inhibit the expression of pro-inflammatory cytokines, inducible nitric oxide synthase, and cyclooxygenase-2 in RAW 264.7 macrophages

    Directory of Open Access Journals (Sweden)

    Eun-Jin Yang

    2016-03-01

    Full Text Available Acanthopanax koreanum is a popular plant found on Jeju Island, Korea and is commonly used to prevent the side effects of consumption of alcoholic beverages. However, this plant has not been properly utilized as a medicinal material. In this study, we investigated the anti-inflammatory effects of the 70% ethanol extract of A. koreanum roots (AKR-E. The results indicated that the AKR-E (200 μg/mL inhibited the lipopolysaccharide (LPS-induced production of nitric oxide (NO and prostaglandin E2 (PGE2 in RAW 264.7 macrophages by 41.2% and 78.9%, respectively. These effects were accompanied by concentration-dependent decreases in the expression levels of inducible NO synthase (iNOS and cyclooxygenase-2 (COX-2 proteins. Additionally, the AKR-E inhibited the expression of pro-inflammatory cytokines, including interleukin (IL-6 (22.7% and IL-1β (74%. These data showed that the AKR-E had protective effects against the induction of LPS-induced inflammation in RAW 264.7 macrophages.

  20. The protein ATG16L1 suppresses inflammatory cytokines induced by the intracellular sensors Nod1 and Nod2 in an autophagy-independent manner.

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    Sorbara, Matthew T; Ellison, Lisa K; Ramjeet, Mahendrasingh; Travassos, Leonardo H; Jones, Nicola L; Girardin, Stephen E; Philpott, Dana J

    2013-11-14

    The peptidoglycan sensor Nod2 and the autophagy protein ATG16L1 have been linked to Crohn's disease (CD). Although Nod2 and the related sensor, Nod1, direct ATG16L1 to initiate anti-bacterial autophagy, whether ATG16L1 affects Nod-driven inflammation has not been examined. Here, we uncover an unanticipated autophagy-independent role for ATG16L1 in negatively regulating Nod-driven inflammatory responses. Knockdown of ATG16L1 expression, but not that of ATG5 or ATG9a, specifically enhanced Nod-driven cytokine production. In addition, autophagy-incompetent truncated forms of ATG16L1 regulated Nod-driven cytokine responses. Mechanistically, we demonstrated that ATG16L1 interfered with poly-ubiquitination of the Rip2 adaptor and recruitment of Rip2 into large signaling complexes. The CD-associated allele of ATG16L1 was impaired in its ability to regulate Nod-driven inflammatory responses. Overall, these results suggest that ATG16L1 is critical for Nod-dependent regulation of cytokine responses and that disruption of this Nod1- or Nod2-ATG16L1 signaling axis could contribute to the chronic inflammation associated with CD.

  1. Cytopathic changes and pro-inflammatory cytokines induced by Naegleria fowleri trophozoites in rat microglial cells and protective effects of an anti-Nfa1 antibody.

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    Oh, Y-H; Jeong, S-R; Kim, J-H; Song, K-J; Kim, K; Park, S; Sohn, S; Shin, H-J

    2005-12-01

    Naegleria fowleri, a free-living amoeba, causes fatal primary amoebic meningoencephalitis in experimental animals and humans. The nfa1 gene (360 bp) was previously cloned from a cDNA library of pathogenic N. fowleri by immunoscreening, and produced a 13.1-kDa recombinant protein that showed pseudopodia-specific localization by immunocytochemistry. On the basis of an idea that the pseudopodia-specific Nfa1 protein seems to be involved in the pathogenicity of N. fowleri, the cytopathic activity of N. fowleri trophozoites co-cultured with rat microglial cells was observed, and the effects of an anti-Nfa1 antibody in a co-culture system were elucidated. Using light, scanning and transmission electron microscopy, it was seen that N. fowleri trophozoites in contact with microglial cells produced vigorous pseudopodia and a food-cup structure. Microglial cells were destroyed by N. fowleri trophozoites as seen from necrotic cell death in a time-dependent manner. In a(51)Cr release assay, N. fowleri showed 17.8%, 24.9%, 54.6% and 98% cytotoxicity against microglial cells at 3, 6, 12 and 24 h post-incubation, respectively. However, when anti-Nfa1 antibody was added in a coculture system, N. fowleri cytotoxicity was reduced to 15.5%, 20.3%, 46.7% and 66.9%, respectively. Moreover, microglial cells co-cultured with N. fowleri trophozoites secreted the pro-inflammatory cytokines, TNF-alpha, IL-1beta and IL-6. In the presence of anti-Nfa1 antibody, the secretion of TNF-alpha was slightly, but not significantly, decreased.

  2. Seasonal trend of acute pelvic inflammatory disease.

    Science.gov (United States)

    Xholli, Anjeza; Cannoletta, Marianna; Cagnacci, Angelo

    2014-05-01

    Many infections follow a seasonal trend. Aim of our study was to check whether acute pelvic inflammatory disease (PID) follows a seasonal progress. In a retrospective study on 12,152 hospital records, 158 cases of acute pelvic inflammatory disease were identified. Periodogram analysis was applied to the date of pelvic inflammatory disease admission and to related environmental factors, such as temperature and photoperiod. Pelvic inflammatory disease follows a seasonal rhythm with mean to peak variation of 23 % and maximal values in September (±37.2 days). The rhythm, more evident in married women, is related to the rhythm of temperature advanced by 2 months and of photoperiod advanced by 3 months. Cases of pelvic inflammatory disease are more frequent than expected in unmarried (36 vs. 17.3/34,626, p = 0.015), particularly divorced women 30-40 years of age. Our study evidences a seasonal trend and confirms unmarried, particularly divorced status, as important risk factor for acute pelvic inflammatory disease.

  3. Systemic inflammatory response following acute myocardial infarction.

    Science.gov (United States)

    Fang, Lu; Moore, Xiao-Lei; Dart, Anthony M; Wang, Le-Min

    2015-05-01

    Acute cardiomyocyte necrosis in the infarcted heart generates damage-associated molecular patterns, activating complement and toll-like receptor/interleukin-1 signaling, and triggering an intense inflammatory response. Inflammasomes also recognize danger signals and mediate sterile inflammatory response following acute myocardial infarction (AMI). Inflammatory response serves to repair the heart, but excessive inflammation leads to adverse left ventricular remodeling and heart failure. In addition to local inflammation, profound systemic inflammation response has been documented in patients with AMI, which includes elevation of circulating inflammatory cytokines, chemokines and cell adhesion molecules, and activation of peripheral leukocytes and platelets. The excessive inflammatory response could be caused by a deregulated immune system. AMI is also associated with bone marrow activation and spleen monocytopoiesis, which sustains a continuous supply of monocytes at the site of inflammation. Accumulating evidence has shown that systemic inflammation aggravates atherosclerosis and markers for systemic inflammation are predictors of adverse clinical outcomes (such as death, recurrent myocardial infarction, and heart failure) in patients with AMI.

  4. Systemic inflammatory response following acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Lu FANG; Xiao-Lei Moore; Anthony M Dart; Le-Min WANG

    2015-01-01

    Acute cardiomyocyte necrosis in the infarcted heart generates damage-associated molecular patterns, activating complement and toll-like receptor/interleukin-1 signaling, and triggering an intense inflammatory response. Inflammasomes also recognize danger signals and mediate sterile inflammatory response following acute myocardial infarction (AMI). Inflammatory response serves to repair the heart, but excessive inflammation leads to adverse left ventricular remodeling and heart failure. In addition to local inflammation, profound systemic inflammation response has been documented in patients with AMI, which includes elevation of circulating inflammatory cytokines, chemokines and cell adhesion molecules, and activation of peripheral leukocytes and platelets. The excessive inflammatory response could be caused by a deregulated immune system. AMI is also associated with bone marrow activation and spleen monocytopoiesis, which sustains a continuous supply of monocytes at the site of inflammation. Accumulating evidence has shown that systemic inflammation aggravates atherosclerosis and markers for systemic inflammation are predictors of adverse clinical outcomes (such as death, recurrent myocardial in-farction, and heart failure) in patients with AMI.

  5. 小檗碱对脂多糖诱导的THP-1细胞相关炎性反应因子的影响%Effects of berberine on inflammatory cytokines induced by lipopolysaccharide in THP-1 cells

    Institute of Scientific and Technical Information of China (English)

    刘司漩; 刘云峰; 尹建红; 章毅; 许林鑫; 杨静

    2014-01-01

    Objective To observe the effects of berberine (BBR) on expression of inflammatory cytokines in THP-1 cells induced by lipopolysaccharide (LPS),and investigate the anti-inflammatory effects of BBR.Methods For analysing the toxicity of BBR on THP-1 cells,THP-1 cells were divided into control group,and different concentrations of BBR groups (BBR 5,10,20,50 μmol/L).After incubation for 6,24 and 48 hours,lactate dehydrogenase (LDH) released from THP-1 cells was used to assay the cytotoxicity of BBR.For analysis of the effects of BBR on inflammatory cytokines induced by LPS in THP-1 cells,THP-1 cells were divided into control group,LPS group (1 μg/mL LPS),and different concentrations of BBR with LPS groups (BBR 5,10 and 20 μmol/L + 1 μg/mL LPS).After 6,24 or 48 hours of incubation,the concentrations of inter4eukin (IL)-1 β,IL-6,IL-8 and tumor necrosis factor(TNF)-α in the culture medium were measured by enzyme-linked immunosorbent assay (ELISA).Results The survival rates of THP-1 cells were all over 90%after treated with BBR lower than 20 μmol/L for 6,24 and 48 hours.BBR decreased the release of IL-1β,IL-6,IL-8 and TNF-α from THP-1 cells in a dose-dependent manner.After 6 hours,20 μmol/L of BBR decreased the secretion of IL-1 β,IL-8 and TNF-α significantly compared with LPS group (P < 0.05).After 24 hours,the secretion of IL-8 and TNF-α was decreased significantly in 20 μmol/L of BBR + LPS group compared with those in LPS group (P < 0.05).After 48 hours,the secretion of TNF-α was decreased signifi-cantly (F=92.625,P < 0.05) in 5 μmol/L BBR + LPS group,the secrection of IL-1β、IL-6 and TNF-α were decreased (all P < 0.05) in 10 μmol/L BBR + LPS group,and the secretion of IL-1β,IL-6 and TNF-α were decreased in 20 μmol/L BBR + LPS group compared with those in LPS group (all P < 0.05).Conclusion BBR can decrease the secretion of inflammatory cytokines in THP-1 cells induced by LPS in a dose-dependent manner.%目的 通过观察小檗碱对

  6. Treatment of Acute Pelvic Inflammatory Disease

    Directory of Open Access Journals (Sweden)

    Richard L. Sweet

    2011-01-01

    Full Text Available Pelvic inflammatory disease (PID, one of the most common infections in nonpregnant women of reproductive age, remains an important public health problem. It is associated with major long-term sequelae, including tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. In addition, treatment of acute PID and its complications incurs substantial health care costs. Prevention of these long-term sequelae is dependent upon development of treatment strategies based on knowledge of the microbiologic etiology of acute PID. It is well accepted that acute PID is a polymicrobic infection. The sexually transmitted organisms, Neisseria gonorrhoeae and Chlamydia trachomatis, are present in many cases, and microorganisms comprising the endogenous vaginal and cervical flora are frequently associated with PID. This includes anaerobic and facultative bacteria, similar to those associated with bacterial vaginosis. Genital tract mycoplasmas, most importantly Mycoplasma genitalium, have recently also been implicated as a cause of acute PID. As a consequence, treatment regimens for acute PID should provide broad spectrum coverage that is effective against these microorganisms.

  7. [Acute-Onset Chronic Inflammatory Demyelinating Polyradiculoneuropathy].

    Science.gov (United States)

    Kanbayashi, Takamichi; Sonoo, Masahiro

    2015-11-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized by an insidious onset showing progression over two months. However, up to 16% of CIDP patients may show acute presentation similar to Guillain-Barré syndrome (GBS). Such cases are termed acute-onset CIDP (A-CIDP). Distinguishing A-CIDP from GBS, especially the acute inflammatory demyelinating polyneuropathy (AIDP) subtype, is critical because therapeutic strategies and outcomes may differ between the two syndromes. Regarding clinical features, A-CIDP is less likely to have autonomic nervous system involvement, facial weakness, a preceding infectious illness, or the need for mechanical ventilation, in comparison with AIDP. Electrophysiological features are usually quite similar between the two, although follow-up studies may elucidate key differences. Around 8%-16% of GBS patients may show clinical deterioration shortly after improvement or stabilization following initial immunological therapy. Such a situation is termed treatment-related fluctuation (TRF; GBS-TRF). The distinction between GBS-TRF and A-CIDP is an important clinical issue because maintenance treatment is often required in CIDP. The diagnosis of A-CIDP should be considered when the condition of a patient with GBS deteriorates after nine weeks from onset, or when deterioration occurs three times or more.

  8. CT findings of acute pelvic inflammatory disease.

    Science.gov (United States)

    Lee, Mi Hee; Moon, Min Hoan; Sung, Chang Kyu; Woo, Hyunsik; Oh, Sohee

    2014-12-01

    To determine the computed tomographic (CT) findings of acute pelvic inflammatory disease (PID). This retrospective, single-institution case-control study was approved by our institutional review board, and the informed consent was waived owing to the retrospective nature of the study. CT images of 32 women with clinically proven acute PID and 32 control subjects with other conditions of similar presentation were retrospectively reviewed. Analysis of CT findings included hepatic capsular enhancement, pelvic fat haziness, complicated ascites, uterine serosal enhancement, tubal thickening, endometritis, and oophoritis. Comparison of CT findings was performed with the Chi square test or the Fisher exact test and logistic regression analysis was used to determine significant CT findings in predicting PID. The CT findings that showed a statistically significant difference were hepatic capsular enhancement on late arterial phase (p = 0.003), pelvic fat haziness (p = 0.045), and tubal thickening (p = 0.001). Subsequent multivariate logistic regression analysis revealed that the presence of hepatic capsular enhancement on late arterial phase and tubal thickening were significant predictors of PID (hepatic capsular enhancement on late arterial phase, p = 0.015, odds ratio [OR] = 4.8; tubal thickening, p = 0.005, OR = 10.5). Diagnostic morphological CT findings in women with clinically proven PID and acute abdominal pain include hepatic capsular enhancement on late arterial phase and tubal thickening.

  9. Transvaginal sonography of acute pelvic inflammatory disease

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jin Soo; Kim, Young Hwa; Shin, Hyung Chul; Han, Gun Soo; Kim, Il Young [Chonan Hospital, Soonchunhyang University College of Medicine, Chonan (Korea, Republic of)

    1999-12-15

    To determine the value of transvaginal sonography in evaluating women with acute pelvic inflammatory disease (PID). Transvaginal sonography was performed in 25 patients with clinically suggested PID during recent 36 months. The sonographic findings of fallopian tubes and ovaries were analyzed and correlated with pathological findings of 2 fallopian tubes and 19 ovaries in 16 patients who had operations. The correct diagnosis of acute PID was made in 20/25 (80%) by transvaginal sonography. the abnormal sonographic findings of the fallopian tube include tubal thickening or dilatation with internal echo. The sensitivity, specificity, and accuracy for tubal abnormality were 88%, 96%, and 86% , respectively. Ovarian changes were seen on TVS in 14/19 (73%), which include multiple follicular enlargement in 5, tubo-ovarian complex in 9 (tubo-ovarian adhesion in 3, tubo-ovarian abscess in 6). At surgery, the ovay was not involved in all three women who showed tubo-ovarian adhesion on TVS. Among 6 women who showed tubo-ovarian abscess on TVS, tubo-ovarian abscess was confirmed in 3 and the remaining 3 had ovarian cysts. Trandvaginal sonography, a facilitative and accurate modality, is highly sensitive in detecting the abnormality of the tube and useful in differentiating the tubo-ovarian complex in patients with acute PID.

  10. Early identification of 'acute-onset' chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Sung, Jia-Ying; Tani, Jowy; Park, Susanna B; Kiernan, Matthew C; Lin, Cindy Shin-Yi

    2014-08-01

    Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P inflammatory demyelinating polyneuropathy and acute-onset chronic inflammatory demyelinating polyneuropathy could be clearly separated into two non-overlapping groups. Studies of nerve excitability may be able to

  11. Nitric oxide contributes to cytokine-induced apoptosis in pancreatic beta cells via potentiation of JNK activity and inhibition of Akt

    DEFF Research Database (Denmark)

    Størling, J; Binzer, J; Andersson, Annica;

    2005-01-01

    Pro-inflammatory cytokines cause beta cell secretory dysfunction and apoptosis--a process implicated in the pathogenesis of type 1 diabetes. Cytokines induce the expression of inducible nitric oxide (NO) synthase (iNOS) leading to NO production. NO contributes to cytokine-induced apoptosis, but t...

  12. Action of Antiproteases on the Inflammatory Response in Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Chun-Chia Chen

    2007-07-01

    Full Text Available The spectrum of acute pancreatitis ranges from mild edematous disease to a severe necrotizing process which is usually accompanied by local or systemic complications and even mortality. Early deaths (within the first week due to severe acute pancreatitis are generally caused by massive inflammatory responses which result in multiple organ failure. Although the exact mechanisms which trigger the inflammatory and necrotizing processes are not completely understood, it is generally accepted that autodigestion and activated leukocytes play important roles in the pathogenesis of acute pancreatitis. Proinflammatory cytokines are associated with systemic inflammatory response syndrome and multiple organ failure syndrome in acute pancreatitis. A compensatory anti-inflammatory response occurs in parallel with systemic inflammatory response syndrome. Trypsin secreted by the pancreatic acinar cells activates proteaseactivated receptor-2 which can result in the production of cytokines. Protease inhibitors such as aprotinin, gabexate mesilate, nafamostat mesilate, ulinastatin, etc. can inhibit the various enzymes and inflammatory response in experimental and clinical studies. Thus, protease inhibitors have been considered as a potential treatment to inhibit the pancreatic inflammation in acute pancreatitis. The beneficial effects of antiproteases on experimental severe acute pancreatitis may be, in part, due to the modulation of inflammatory cytokine responses. The effect of protease inhibitors on the inflammatory response in human acute pancreatitis deserves further study.

  13. Acute clinical onset chronic inflammatory demyelinating polyneuropathy in a dog.

    Science.gov (United States)

    Molín, Jéssica; Márquez, Mercedes; Raurell, Xavier; Matiasek, Kaspar; Ferrer, Isidre; Pumarola, Martí

    2011-09-01

    We report a case of acute-onset ambulatory paraparesis with electrophysiological abnormalities compatible with axonal and demyelinating lesions in a Rottweiler dog. Although the clinical findings were compatible with acute canine idiopathic polyneuropathy, postmortem investigations revealed a chronic demyelinating polyneuropathy affecting the nerve roots. Due to the combination of acute clinical presentation and chronic pathologic features, this case is consistent with the acute-onset form of chronic inflammatory demyelinating polyneuropathy (A-CIDP).

  14. Clinical and electrophysiological parameters distinguishing acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Dionne, Annie; Nicolle, Michael W; Hahn, Angelika F

    2010-02-01

    Up to 16% of chronic inflammatory demyelinating polyneuropathy (CIDP) patients may present acutely. We performed a retrospective chart review on 30 acute inflammatory demyelinating polyneuropathy (AIDP) and 15 acute-onset CIDP (A-CIDP) patients looking for any clinical or electrophysiological parameters that might differentiate AIDP from acutely presenting CIDP. A-CIDP patients were significantly more likely to have prominent sensory signs. They were significantly less likely to have autonomic nervous system involvement, facial weakness, a preceding infectious illness, or need for mechanical ventilation. With regard to electrophysiological features, neither sural-sparing pattern, sensory ratio >1, nor the presence of A-waves was different between the two groups. This study suggests that patients presenting acutely with a demyelinating polyneuropathy and the aforementioned clinical features should be closely monitored as they may be more likely to have CIDP at follow-up.

  15. The role of inflammatory stress in acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    沈成兴; 陈灏珠; 葛均波

    2004-01-01

    Objective To summarize current understanding of the roles of anti-inflammatory and proinflammatory mechanisms in the development of atherosclerosis and acute coronary syndrome and to postulate the novel concept of inflammation stress as the most important factor triggering acute coronary syndrome. Moreover, markers of inflammation stress and ways to block involved pathways are elucidated.Data sources A literature search (MEDLINE 1997 to 2002) was performed using the key words "inflammation and cardiovascular disease". Relevant book chapters were also reviewed.Study selection Well-controlled, prospective landmark studies and review articles on inflammation and acute coronary syndrome were selected.Data extraction Data and conclusions from the selected articles providing solid evidence to elucidate the mechanisms of inflammation and acute coronary syndrome were extracted and interpreted in the light of our own clinical and basic research.Data synthesis Inflammation is closely linked to atherosclerosis and acute coronary syndrome. Chronic and long-lasting inflammation stress, present both systemically or in the vascular walls, can trigger acute coronary syndrome.Conclusions Inflammation stress plays an important role in the process of acute coronary syndrome. Drugs which can modulate the balance of pro- and anti-inflammatory processes and attenuate inflammation stress, such as angiotensin-converting enzyme (ACE) inhibitors/angiotensin Ⅱ receptor blockers, statins, and cytokine antagonists may play active roles in the prevention and treatment of acute coronary syndrome when used in addition to conventional therapies (glycoprotein Ⅱb/Ⅲa receptor antagonists, mechanical intervention strategies, etc).

  16. Inflammatory role of the acinar cells during acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Isabel; De; Dios

    2010-01-01

    Pancreatic acinar cells are secretory cells whose main function is to synthesize, store and f inally release digestive enzymes into the duodenum. However, in response to noxious stimuli, acinar cells behave like real inflammatory cells because of their ability to activate signalling transduction pathways involved in the expression of inflammatory mediators. Mediated by the kinase cascade, activation of Nuclear factor-κB, Activating factor-1 and Signal transducers and activators of transcription transcription factors has been demonstrated in acinar cells, resulting in overexpression of inflammatory genes. In turn, kinase activity is down-regulated by protein phosphatases and the f inal balance between kinase and phosphatase activity will determine the capability of the acinar cells to produce inflammatory factors. The kinase/ phosphatase pair is a redox-sensitive system in which kinase activation overwhelms phosphatase activity under oxidant conditions. Thus, the oxidative stress developed within acinar cells at early stages of acute pancreatitis triggers the activation of signalling pathways involved in the up-regulation of cytokines, chemokines and adhesion molecules. In this way, acinar cells trigger the release of the f irst inflammatory signals which can mediate the activation and recruitment of circulating inflammatorycells into the injured pancreas. Accordingly, the role of acinar cells as promoters of the inflammatory response in acute pancreatitis may be considered. This concept leads to amplifying the focus from leukocyte to acinar cells themselves, to explain the local inflammation in early pancreatitis.

  17. Effect of Probiotic Administration on Acute Inflammatory Pain

    Directory of Open Access Journals (Sweden)

    Shadnoush

    2016-11-01

    Full Text Available Background Acute inflammatory pain causes by direct stimulation of nociceptors and release of inflammatory mediators and cytokines. Probiotics are capable to modulate the immune system, down regulate the inflammatory mediators, and increase regulatory and anti-inflammatory cytokines. Objectives The aim of this study was to examine the effect of oral administration of probiotics on behavioral, cellular and molecular aspects of acute inflammatory pain in male rats. Methods Adult male Wistar rats (200 - 220 g were selected and randomly divided into 7 experimental groups (CFA, CFA control, CFA + vehicle (distilled water, CFA + 3 doses of probiotics, CFA + indomethacin and each group was divided into 3 subgroups based on different time points (days 0, 3, and 7 (n = 6 rats, each group. Complete Freund’s adjuvant (CFA-induced arthritis (AA was caused by a single subcutaneous injection of CFA into the rats’ left hind paw on day 0. Different doses of probiotics (1/250, 1/500 and 1/1000 (109 CFU/g was administered daily (gavage after the CFA injection. Blood samples were taken from the vessel retro-orbital corners of rat’s eyes. After behavioral and inflammatory tests, the lumbar segments of rat’s spinal cord (L1 - L5 were removed. Hyperalgesia, edema, serum TNF-α and IL-1β levels and NF-κB expression were assessed on days 0, 3, and 7 of the study. Results The results of this study showed the role of effective dose of probiotics (1/500 in reducing edema (P = 0.0009, hyperalgesia (P = 0.0002, serum levels of TNF-α (P = 0.0004 and IL-1β (P = 0.0004 and NF-κB expression (P = 0.0007 during the acute phase of inflammatory pain caused by CFA. Conclusions It seems that an effective dose of probiotics due to its direct effects on inhibition of intracellular signaling pathways and pro-inflammatory cytokines can alleviate inflammatory symptoms and pain in the acute phase.

  18. Anti-inflammatory effect of Semecarpus anacardium Linn. Nut extract in acute and chronic inflammatory conditions.

    Science.gov (United States)

    Ramprasath, Vanu Ramkumar; Shanthi, Palanivelu; Sachdanandam, Panchanatham

    2004-12-01

    The article relates to investigation of the anti-inflammatory effects of Semecarpus anacardium LINN. nut extract (SA), and also an anti-inflammatory drug, indomethacin, on carrageenan-induced paw edema and cotton pellet granuloma tests for their effects on acute and chronic phases of inflammation, respectively. The effect of SA on developing and developed adjuvant arthritis was also evaluated. SA significantly decreased the carrageenan-induced paw edema and cotton pellet granuloma. Indomethacin also decreased the acute and chronic phases of inflammation. SA decreased the adjuvant induced (arthritis) paw edema after the treatment, in both developing and developed adjuvant arthritis. These results indicate that the potent anti-inflammatory effect and therapeutic efficacy of Semecarpus anacardium LINN. nut extract against all phases of inflammation, is comparable to that of indomethacin.

  19. Role of anaerobes in acute pelvic inflammatory disease

    OpenAIRE

    2003-01-01

    Pouch of Douglas aspirates were collected from 50 women with history and examination suggestive of acute pelvic inflammatory disease (PID) and 20 healthy women admitted for tubal ligation served as control. A total of 57 microorganisms were isolated from 37 patients out of 50 in study group. Of 37 positive cultures 21(56.7%) were monomicrobial and 16(43.2%) were polymicrobial. Most common symptom in study group was lower abdominal pain (90%), vaginal discharge (70%...

  20. Inhibition of histone deacetylases prevents cytokine-induced toxicity in beta cells

    DEFF Research Database (Denmark)

    Larsen, L; Tonnesen, M; Ronn, S G

    2007-01-01

    AIMS/HYPOTHESIS: The immune-mediated elimination of pancreatic beta cells in type 1 diabetes involves release of cytotoxic cytokines such as IL-1beta and IFNgamma, which induce beta cell death in vitro by mechanisms that are both dependent and independent of nitric oxide (NO). Nuclear factor kappa...... deacetylases (HDAC), and positive effects of HDAC inhibition have been obtained in several inflammatory diseases. Thus, the aim of this study was to investigate whether HDAC inhibition protects beta cells against cytokine-induced toxicity. MATERIALS AND METHODS: The beta cell line, INS-1, or intact rat islets...

  1. Cytokine-Induced Modulation of Colorectal Cancer.

    Science.gov (United States)

    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.

  2. Spontaneous and cytokine induced basophil adhesion evaluated by microtiter assay

    DEFF Research Database (Denmark)

    Quan, Sha; Poulsen, Lars K; Reimert, Claus Michael;

    2002-01-01

    We have developed a microtiter assay for evaluating basophil spontaneous adhesion to extracellular matrix (ECM) proteins exemplified by fibronectin and cytokine induced basophil adhesion to bovine serum albumin (BSA). The percentage of basophils adhering to either ECM or BSA was quantified...

  3. Peripheral nerve proteins as potential autoantigens in acute and chronic inflammatory demyelinating polyneuropathies.

    Science.gov (United States)

    Lim, Jia Pei; Devaux, Jérôme; Yuki, Nobuhiro

    2014-10-01

    Guillain-Barré syndrome is classified into acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy. Whereas autoantibodies to GM1 or GD1a induce the development of acute motor axonal neuropathy, pathogenic autoantibodies have yet to be identified in acute inflammatory demyelinating polyneuropathy and chronic inflammatory demyelinating polyneuropathy. This review highlights the importance of autoantibodies to peripheral nerve proteins in the physiopathology of acute and chronic inflammatory demyelinating polyneuropathies. Moreover, we listed up other potential antigens, which may become helpful biomarkers for acquired, dysimmune demyelinating neuropathies based on their critical functions during myelination and their implications in hereditary demyelinating neuropathies.

  4. Effects of gabapentin in acute inflammatory pain in humans

    DEFF Research Database (Denmark)

    Werner, M U; Perkins, F M; Holte, Kathrine;

    2001-01-01

    BACKGROUND AND OBJECTIVES: The aim of the study was to examine the analgesic effects of the anticonvulsant, gabapentin, in a validated model of acute inflammatory pain. METHODS: Twenty-two volunteers were investigated in a double-blind, randomized, placebo-controlled cross-over study. Gabapentin 1...... not significantly changed by gabapentin (P study indicates that gabapentin has no analgesic effect in normal skin, but may reduce primary mechanical allodynia in acute......,200 mg or placebo was given on 2 separate study days. Three hours after drug administration, a first-degree burn injury was produced on the medial aspect of the nondominant calf (12.5 cm(2), 47 degrees C for 7 minutes). Quantitative sensory testing (QST) included pain ratings to thermal and mechanical...

  5. Human immunodeficiency virus seroconversion presenting with acute inflammatory demyelinating polyneuropathy: a case report

    OpenAIRE

    Sloan Derek J; Nicolson Andrew; Miller Alastair RO; Beeching Nick J; Beadsworth Mike BJ

    2008-01-01

    Abstract Introduction Acute Human Immunodeficiency Virus infection is associated with a range of neurological conditions. Guillain-Barré syndrome is a rare presentation; acute inflammatory demyelinating polyneuropathy is the commonest form of Guillain-Barré syndrome. Acute inflammatory demyelinating polyneuropathy has occasionally been reported in acute Immunodeficiency Virus infection but little data exists on frequency, management and outcome. Case presentation We describe an episode of Gui...

  6. Role of anaerobes in acute pelvic inflammatory disease

    Directory of Open Access Journals (Sweden)

    Saini S

    2003-01-01

    Full Text Available Pouch of Douglas aspirates were collected from 50 women with history and examination suggestive of acute pelvic inflammatory disease (PID and 20 healthy women admitted for tubal ligation served as control. A total of 57 microorganisms were isolated from 37 patients out of 50 in study group. Of 37 positive cultures 21(56.7% were monomicrobial and 16(43.2% were polymicrobial. Most common symptom in study group was lower abdominal pain (90%, vaginal discharge (70% and irregular bleeding (40% and 30% patients had history of intrauterine contraceptive device (IUCD implantation. The predominant aerobic isolates were Escherichia coli, Coagulase Negative Staphylococcus (CONS, Staphylococcus aureus, Klebsiella pneumoniae while common anaerobes were Bacteroides fragilis, Prevotella melaninogenica, Fusobacterium nucleatum and Peptostreptococcus spp. Our study shows that cefotaxime, cefuroxime and gentamicin may be used for gram negative aerobic bacilli; cloxacillin, cephaloridine and erythromycin for aerobic gram positive cocci and amikacin and ceftazidime for Pseudomonas aeruginosa. Thus for optimum therapy of acute PID it is beneficial to keep in mind major conceptual changes and therapeutic realities that have influenced current understanding of acute PID and have affected the choice of therapy.

  7. Role of anaerobes in acute pelvic inflammatory disease.

    Science.gov (United States)

    Saini, S; Gupta, N; Batra, G; Arora, D R

    2003-01-01

    Pouch of Douglas aspirates were collected from 50 women with history and examination suggestive of acute pelvic inflammatory disease (PID) and 20 healthy women admitted for tubal ligation served as control. A total of 57 microorganisms were isolated from 37 patients out of 50 in study group. Of 37 positive cultures 21(56.7%) were monomicrobial and 16(43.2%) were polymicrobial. Most common symptom in study group was lower abdominal pain (90%), vaginal discharge (70%) and irregular bleeding (40%) and 30% patients had history of intrauterine contraceptive device (IUCD) implantation. The predominant aerobic isolates were Escherichia coli, Coagulase Negative Staphylococcus (CONS), Staphylococcus aureus, Klebsiella pneumoniae while common anaerobes were Bacteroides fragilis, Prevotella melaninogenica, Fusobacterium nucleatum and Peptostreptococcus spp. Our study shows that cefotaxime, cefuroxime and gentamicin may be used for gram negative aerobic bacilli; cloxacillin, cephaloridine and erythromycin for aerobic gram positive cocci and amikacin and ceftazidime for Pseudomonas aeruginosa. Thus for optimum therapy of acute PID it is beneficial to keep in mind major conceptual changes and therapeutic realities that have influenced current understanding of acute PID and have affected the choice of therapy.

  8. Is leptin related to systemic inflammatory response in acute pancreatitis?

    Institute of Scientific and Technical Information of China (English)

    Andrés Duarte-Rojo; Ana Lezama-Barreda; Mar(i)a Teresa Ram(i)rez-lglesias; Mario Peláez Luna; Guillermo Robles-Diaz

    2006-01-01

    AIM: To evaluate the relationship between leptin and systemic inflammation in acute pancreatitis.METHODS: Consecutive patients with acute pancreatitis were included. Body mass index and serum samples were obtained at admission. Leptin, TNF-α, IL-6, -8and -10 levels were determined by ELISA. Severity was defined according to Atlanta criteria.RESULTS: Fifty-two (29 females) patients were studied.Overall body mass index was similar between mild and severe cases, although women with severe pancreatitis had lower body mass index (P = 0.04) and men showed higher body mass index (P = 0.05). No difference was found in leptin levels regarding the severity of pancreatitis, but higher levels tended to appear in male patients with increased body mass index and severe pancreatitis (P = 0.1). A multivariate analysis showed no association between leptin levels and severity. The strongest cytokine associated with severity was IL-6.Correlations of leptin with another cytokines only showed a trend for IL-8 (P = 0.058).CONCLUSION: High body mass index was associated with severity only in males, which may be related to android fat distribution. Serum leptin seems not to play a role on the systemic inflammatory response in acute pancreatitis and its association with severe outcome in males might represent a marker of increased adiposity.

  9. Are inflammatory parameters predictors of amputation in acute arterial occlusions?

    Science.gov (United States)

    Saskin, Huseyin; Ozcan, Kazim S; Duzyol, Cagri; Baris, Ozgur; Koçoğulları, Uğur C

    2017-04-01

    Background The aim of the present study was to investigate the role of inflammatory markers to predict amputation following embolectomy in acute arterial occlusion. Methods A total of 123 patients operated for arterial thromboembolectomy due to acute embolism were included in the study. The patients without an extremity amputation following thromboembolectomy were classified as Group 1 ( n = 91) and the rest were classified as Group 2 ( n = 32). These groups were compared in terms of clinical and demographic characteristics, C-reactive protein, complete blood count parameters, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and red cell distribution width. Results The average age was 68.0 ± 11.7 years. The most common thromboembolism localization was femoral artery. When preoperative mean C-reactive protein ( p = 0.0001), mean platelet volume ( p = 0.0001), platelet-lymphocyte ratio ( p = 0.0001), neutrophil-lymphocyte ratio ( p = 0.0001) and red cell distribution width ( p = 0.0001) were compared, a statistically significant difference was observed between groups. In univariate and multivariate regression analysis, higher levels of preoperative C-reactive protein ( p = 0.009) and mean platelet volume ( p = 0.04) were detected as independent risk factors of early extremity amputation. Conclusion We observed that preoperative mean platelet volume and C-reactive protein were predictors of amputation after thromboembolectomy in acute arterial occlusion.

  10. Role of angiotensin Ⅱ type 1 receptor in the production of pro-inflammatory cytokines induced by lipopolysaccharide in RAW264.7 microphage%血管紧张素Ⅱ1型受体在脂多糖诱导RAW264.7巨噬细胞促炎性细胞因子产生中的作用

    Institute of Scientific and Technical Information of China (English)

    郭峰; 陈旭林; 王飞; 王永杰; 孙业祥

    2011-01-01

    Objective To investigate the role of angiotensin Ⅱ type 1receptor in the production of pro-inflammatory cytokines induced by lipopolysaccharide ( LPS ) in RAW264. 7 microphage and characterize the mechanism. Methods RAW264. 7 macrophages were randomly divided into four groups: control group,ZD7155 group, LPS group and ZD7155 + LPS group. The protein and mRNA expressions of tumor necrosis factor α ( TNF-α ) and interleukin-1β ( IL-1β ) in the cells were determined by enzyme-linked immunosorbent assay ( ELISA ) and reverse transcription polymerase chain reaction ( RT-PCR ) respectively. Electrophoretic mobility shift assay ( EMSA ) was preformed to determine the activities of nuclear factor kappaB ( NF-KB ) and activator protein 1 ( AP-1 ). Results Compared with control group,supernatant TNF-β and IL-1β of ZD7155 group were not found statistically significant difference ( P >0. 05 ). However, LPS stimulation increased the levels of TNF-α and IL-1β in the supernatant which were significantly higher than control group ( P <0. 01 ) and ZD7155 group ( P <0. 05 ). However, administration of LPS not only enhanced the mRNA expressions of TNF-αand IL-1β to 2. 19-fold ( P <0. 01 ) and 1. 77-fold ( P <0. 01 ) of control group, but also elevated the activities of NF-KB and AP-1 to 1. 43-fold ( P <0. 01 ) and 1. 90-fold ( P <0. 01 ) of control group. But compared with LPS group, the expression of TNF-α and IL-1β was inhibited significantly by the preincubation with ZD7155, intracellular TNF-α and IL-1β mRNA expression decreased by 34. 7% ( P <0. 01 ) and 49. 72% ( P <0. 01 ). Furthermore, compared with LPS group, the intracellular NF-KB and AP-1 activity of ZD7155 + LPS group decreased by 46. 15% ( P <0. 05 ) and 48. 42% ( P <0. 05 ). Conclusion Angiotensin n i receptor mediates the production and release of pro-inflammatory cytokines TNF-αand IL-1β in macrophages induced by LPS via the activation of transcription factor NF

  11. Dolichos biflorus exhibits anti-inflammatory and antioxidant properties in an acute inflammatory model

    Directory of Open Access Journals (Sweden)

    Limi Elizabeth Mathew

    2014-12-01

    Full Text Available Dolichos biflorus (Muthira is a branched, suberect, and downing herb, native to most parts of India, and found at altitudes of up to 1000 m, whose seeds can be cooked and eaten. Nutrition plays a key role in building immunity and preventing noncommunicable diseases to a certain extent. The purpose of this study was to evaluate the anti-inflammatory and antioxidant effects of 70% methanolic extract of seeds of D. biflorus (DME in carrageenan-induced inflammation. DME exhibited maximum percentage of oedema inhibition at a dose of 50 mg/kg at the 3rd hour of carrageenan induction. The effect was higher than that of the standard drug Voveran. The activities of cyclooxygenase, lipoxygenase, nitric oxide synthase, myeloperoxidase, and malondialdehyde showed significant (p < 0.05 reduction whereas the activities of antioxidant enzymes, vitamins C, and reduced glutathione level were increased significantly (p < 0.05 on treatment with DME. Also levels of the acute phase protein, ceruloplasmin, were brought to their normal range in DME-treated rats. Phytochemical analysis showed that the extract contains alkaloids, flavonoids, carbohydrates, proteins, and tannins, which may contribute to its anti-inflammatory and antioxidant activity. Thus the results demonstrate the potential beneficiary effect of DME on carrageenan-induced inflammation in rats.

  12. Curative Effect of Decitabine Combined with Cytokine-Induced Killer Cells in Two Elderly Patients with Acute Myeloid Leukemia%地西他滨联合自体CIK细胞治疗2例高龄急性髓系白血病的疗效观察

    Institute of Scientific and Technical Information of China (English)

    常城; 杨波; 张琳; 朱宏丽; 卢学春; 郭搏; 蔡力力; 韩为东; 王瑶

    2013-01-01

    本研究旨在观察低甲基化药物地西他滨联合自体细胞因子诱导的杀伤细胞(CIK)治疗老年急性髓系白血病(AML)的安全性及有效性.本科于2006-2012年收治2例80岁以上老年AML患者(M4型和M6型),均继发于骨髓增生异常综合征.对这2例患者先后采取单用自体CIK细胞输注、地西他滨或(和)自体CIK细胞方案治疗,系统观察了2例CIK治疗前后淋巴细胞亚群、临床相关指标(血液学反应、输血频率、白血病相关基因表达、缓解情况、生活质量)及生存期的变化.结果表明,与单用自体CIK细胞输注和单用地西他滨治疗相比,地西他滨联合自体CIK细胞治疗方案可减轻骨髓抑制程度,降低输血频率及输血量,延长部分缓解持续时间,同时表达的白血病相关基因减少,生存期显著延长,患者生活质量得到明显改善.结论:地西他滨联合自体CIK细胞治疗老年AML患者安全有效.%This study was aimed to evaluate the effectiveness and safety of low methylation drug decitabine combined with autologous cytokine induced killer cells (CIK) to treat the elderly patients with acute myeloid leukemia (AML). Two AML patients aged over 80 years old were diagnosed and treated in our department from 2006 to 2012; both companied with MDS history, and one case was M4-type, another case was M6-type according to FAB classification. The changes in lymphocyte subsets, hematologic response, transfusion frequency, leukemic gene expression, obtaining CRorPR, quality of life and survival time of the patients with different treatment regimen (decitabine alone; CIK alone; decitabine combined with CIK) were systematically observed. The results showed that therapy of decitabine combined with CIK cells could reduce bone marrow suppression extent, decrease the frequency and volume of blood transfusion, and prolong the duration of partial remission, compared with the single use of CIK cell infusion and single use of decitabine

  13. Diclofenac enhances proinflammatory cytokine-induced phagocytosis of cultured microglia via nitric oxide production

    Energy Technology Data Exchange (ETDEWEB)

    Kakita, Hiroki [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Aoyama, Mineyoshi, E-mail: ao.mine@med.nagoya-cu.ac.jp [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Nagaya, Yoshiaki; Asai, Hayato [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Hussein, Mohamed Hamed [Neonatal Intensive Care Unit, Pediatric Hospital, Cairo University, Cairo 11559 (Egypt); Maternal and Child Health Department, VACSERA, 51 Wizaret El-Zeraa-Agouza, Giza 22311 (Egypt); Suzuki, Mieko [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Kato, Shin [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Saitoh, Shinji [Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Asai, Kiyofumi [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan)

    2013-04-15

    Influenza-associated encephalopathy (IAE) is a central nervous system complication with a high mortality rate, which is increased significantly by the non-steroidal anti-inflammatory drug diclofenac sodium (DCF). In the present study, we investigated the effects of DCF on brain immune cells (i.e. microglia) stimulated with three proinflammatory cytokines, namely tumor necrosis factor-α, interleukin-1β, and interferon-γ. Similar to previous findings in astrocytes, all three cytokines induced the expression of inducible NO synthase (iNOS), as well as NO production, in microglia. The addition of DCF to the culture system augmented iNOS expression and NO production. Immunocytochemical analysis and the phagocytosis assay revealed that cytokine treatment induced morphological changes to and phagocytosis by the microglia. The addition of DCF to the culture system enhanced microglial activation, as well as the phagocytic activity of cytokine-stimulated microglia. Inhibitors of nuclear factor (NF)-κB inhibited iNOS gene expression in cytokine-stimulated microglia with or without DCF, suggesting that the NF-κB pathway is one of the main signaling pathways involved. The iNOS inhibitor N{sup G}-monomethyl-L-arginine (L-NMMA) reduced both cytokine-induced phagocytosis and phagocytosis induced by the combination of cytokines plus DCF. Furthermore, the NO donor sodium nitroprusside induced phagocytosis, indicating that NO production is a key regulator of microglial phagocytosis. In conclusion, DCF acts synergistically with proinflammatory cytokines to increase the production of NO in microglia, leading to phagocytic activity of the activated microglia. These findings, together with previous observations regarding astrocytes, may explain the significant increase in mortality of IAE patients treated with DCF. - Highlights: ► Influenza-associated encephalopathy (IAE) is associated with a high mortality rate. ► Hyperimmunization in the brain is believed to be responsible for

  14. Interplay between the acute inflammatory response and heart rate variability in healthy human volunteers.

    Science.gov (United States)

    Kox, Matthijs; Ramakers, Bart P; Pompe, Jan C; van der Hoeven, Johannes G; Hoedemaekers, Cornelia W; Pickkers, Peter

    2011-08-01

    The autonomic nervous system and the inflammatory response are intimately linked. Heart rate variability (HRV) analysis is a widely used method to assess cardiac autonomic nervous system activity, and changes in HRV indices may correlate with inflammatory markers. Here, we investigated whether baseline HRV predicts the acute inflammatory response to endotoxin. Second, we investigated whether the magnitude of the inflammatory response correlated with HRV alterations. Forty healthy volunteers received a single intravenous bolus of 2 ng/kg endotoxin (LPS, derived from Escherichia coli O:113). Of these, 12 healthy volunteers were administered LPS again 2 weeks later. Heart rate variability was determined at baseline (just before LPS administration) and hourly thereafter until 8 h after LPS administration. Plasma cytokine levels were determined at various time points. Baseline HRV indices did not correlate with the magnitude of the LPS-induced inflammatory response. Despite large alterations in HRV after LPS administration, the extent of the inflammatory response did not correlate with the magnitude of HRV changes. In subjects who were administered LPS twice, inflammatory cytokines were markedly attenuated after the second LPS administration, whereas LPS-induced HRV alterations were similar. Heart rate variability indices do not predict the acute inflammatory response in a standardized model of systemic inflammation. Although the acute inflammatory response results in HRV changes, no correlations with inflammatory cytokines were observed. Therefore, the magnitude of endotoxemia-related HRV changes does not reflect the extent of the inflammatory response.

  15. Acute, regional inflammatory response after traumatic brain injury: Implications for cellular therapy

    OpenAIRE

    Harting, Matthew T.; jimenez, fernando; Adams, Sasha D.; Mercer, David W.; Cox, Charles S.

    2008-01-01

    While cellular therapy has shown promise in the management of traumatic brain injury (TBI), microenvironment interactions between the intracerebral milieu and therapeutic stem cells are poorly understood. We sought to characterize the acute, regional inflammatory response after TBI.

  16. Acute-Phase Inflammatory Response in Idiopathic Sudden Deafness: Pathogenic Implications

    OpenAIRE

    López-González, Miguel A.; Antonio Abrante; Carmen López-Lorente; Antonio Gómez; Emilio Domínguez; Francisco Esteban

    2012-01-01

    The acute-phase inflammatory response in the peripheral bloodstream can be an expression of transient cerebral ischaemia in idiopathic sudden deafness. For this, a neurological and otorhinolaryngological examination of each patient, performing tests on audiometry, and tympanometry, haemogram, and cranial magnetic resonance were performed. The acute-phase inflammatory response manifests as an increased neutrophil/lymphocyte ratio that is detected 48–72 hours after the appearance of sudden deaf...

  17. Two opposite extremes of adiposity similarly reduce inflammatory response of antigen-induced acute joint inflammation

    NARCIS (Netherlands)

    Oliveira, M.C.; Silveira, A.L.; Tavares, L.P.; Rodrigues, D.F.; Loo, F.A.J. van de; Sousa, L.P.; Teixeira, M.M.; Amaral, F.A.; Ferreira, A.V.

    2017-01-01

    OBJECTIVE: Acute inflammation is a normal response of tissue to an injury. During this process, inflammatory mediators are produced and metabolic alterations occur. Adipose tissue is metabolically activated, and upon food consumption, it disrupts the inflammatory response. However, little is known a

  18. Peripheral analgesic effects of ketamine in acute inflammatory pain

    DEFF Research Database (Denmark)

    Pedersen, J L; Galle, T S; Kehlet, H

    1998-01-01

    BACKGROUND. This study examined the analgesic effect of local ketamine infiltration, compared with placebo and systemic ketamine, in a human model of inflammatory pain. METHODS: Inflammatory pain was induced by a burn (at 47 degrees C for 7 min; wound size, 2.5 x 5 cm) on the calf in 15 volunteer...

  19. Immune-Manipulation of the Inflammatory Response in Acute Pancreatitis. What Can Be Expected?

    Directory of Open Access Journals (Sweden)

    Corinaldesi R

    2004-05-01

    Full Text Available Severe acute pancreatitis still has a high mortality rate and multiple organ failure is considered to be a severe complication of the disease. Activated polymorphonuclear leukocytes have an important role in the development of multiple organ failure which may result from acute pancreatitis and they are an important pathogenetic factor in the severity of this disease. Therefore, a logical therapeutic approach is to limit the organ damage by selective suppression of inflammatory mediators involved in the systemic inflammatory response syndrome and protect against systemic complication. In this paper, we review the recent literature data on the possible manipulation of the immune response in acute pancreatitis.

  20. Angiopoietin-2 is critical for cytokine-induced vascular leakage.

    Directory of Open Access Journals (Sweden)

    Andrew V Benest

    Full Text Available 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.

  1. Natural product HTP screening for attenuation of cytokine-induced neutrophil chemo attractants (CINCs) and NO2- in LPS/IFNγ activated glioma cells.

    Science.gov (United States)

    Mazzio, Elizabeth A; Bauer, David; Mendonca, Patricia; Taka, Equar; Soliman, Karam F A

    2017-01-15

    Chronic and acute central nervous system (CNS) inflammation are contributors toward neurological injury associated with head trauma, stroke, infection, Parkinsons or Alzheimers disease. CNS inflammatory illnesses can also contribute toward risk of developing glioblastoma multiforme (GBM). With growing public interest in complementary and alternative medicines (CAMs), we conduct a high throughput (HTP) screening of >1400 natural herbs, plants and over the counter (OTC) products for anti-inflammatory effects on lipopolysaccharide (LPS)/interferon gamma (IFNγ) activated C6 glioma cells. Validation studies were performed showing a pro-inflammatory profile of [LPS 3 µg/ml/ IFNγ 3 ng/ml] consistent with greater release [>8.5 fold] of MCP-1, NO2-, cytokine-induced neutrophil chemo-attractants (CINC) 1, CINC 2a and CINC3. The data show no changes to the following, IL-13, TNF-a, fracktaline, leptin, LIX, GM-CSF, ICAM1, L-Selectin, activin A, agrin, IL-1α, MIP-3a, B72/CD86, NGF, IL-1b, MMP-8, IL-1 R6, PDGF-AA, IL-2, IL-4, prolactin R, RAGE, IL-6, Thymus Chemokine-1, CNTF,IL-10 or TIMP-1. A HTP screening was conducted, where we employ an in vitro efficacy index (iEI) defined as the ratio of toxicity (LC50)/anti-inflammatory potency (IC50). The iEI was precautionary to ensure biological effects were occurring in fully viable cells (ratio > 3.8) independent of toxicity. Using NO2- as a guideline molecule, the data show that 1.77% (25 of 1410 tested) had anti-inflammatory effects with iEI ratios >3.8 and IC50s 1750.0μg/ml, and the compound with the greatest iEI was quercetin where the IC50/LC50 was 10.0/>363.6μg/ml. These substances also downregulate the production of iNOS expression and attenuate CINC-3 release. In summary, this HTP screening provides guideline information about the efficacy of natural products that could prevent inflammatory processes associated with neurodegenerative disease and aggressive glioma tumor growth. Copyright © 2016 Elsevier B.V. All rights

  2. Investigation of inflammatory markers in horses with acute abdominal pain

    DEFF Research Database (Denmark)

    Pihl, Tina Holberg; Kjelgaard-Hansen, Mads; Andersen, Pia Haubro;

    Background The use of acute phase proteins as objective markers of underlying pathology may facilitate the decision-making regarding diagnosis, treatment and estimation of prognosis of colic horses in a referral hospital. Evaluation of acute phase proteins in both serum and peritoneal fluid of co...

  3. Divergent responses of inflammatory mediators within the amygdala and medial prefrontal cortex to acute psychological stress.

    Science.gov (United States)

    Vecchiarelli, Haley A; Gandhi, Chaitanya P; Gray, J Megan; Morena, Maria; Hassan, Kowther I; Hill, Matthew N

    2016-01-01

    There is now a growing body of literature that indicates that stress can initiate inflammatory processes, both in the periphery and brain; however, the spatiotemporal nature of this response is not well characterized. The aim of this study was to examine the effects of an acute psychological stress on changes in mRNA and protein levels of a wide range of inflammatory mediators across a broad temporal range, in key corticolimbic brain regions involved in the regulation of the stress response (amygdala, hippocampus, hypothalamus, medial prefrontal cortex). mRNA levels of inflammatory mediators were analyzed immediately following 30min or 120min of acute restraint stress and protein levels were examined 0h through 24h post-termination of 120min of acute restraint stress using both multiplex and ELISA methods. Our data demonstrate, for the first time, that exposure to acute psychological stress results in an increase in the protein level of several inflammatory mediators in the amygdala while concomitantly producing a decrease in the protein level of multiple inflammatory mediators within the medial prefrontal cortex. This pattern of changes seemed largely restricted to the amygdala and medial prefrontal cortex, with stress producing few changes in the mRNA or protein levels of inflammatory mediators within the hippocampus or hypothalamus. Consistent with previous research, stress resulted in a general elevation in multiple inflammatory mediators within the circulation. These data indicate that neuroinflammatory responses to stress do not appear to be generalized across brain structures and exhibit a high degree of spatiotemporal specificity. Given the impact of inflammatory signaling on neural excitability and emotional behavior, these data may provide a platform with which to explore the importance of inflammatory signaling within the prefrontocortical-amygdala circuit in the regulation of the neurobehavioral responses to stress.

  4. Acute pelvic inflammatory disease: pictorial essay focused on computed tomography and magnetic resonance imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Febronio, Eduardo Miguel; Rosas, George de Queiroz; D' Ippolito, Giuseppe, E-mail: giuseppe_dr@uol.com.br [Department of Imaging Diagnosis, Escola Paulista de Medicina - Universidade Federal de Sao Paulo (EPMUnifesp), Sao Paulo, SP (Brazil)

    2012-11-15

    The present study was aimed at describing key computed tomography and magnetic resonance imaging findings in patients with acute abdominal pain derived from pelvic inflammatory disease. Two radiologists consensually selected and analyzed computed tomography and magnetic resonance imaging studies performed between January 2010 and December 2011 in patients with proven pelvic inflammatory disease leading to presentation of acute abdomen. Main findings included presence of intracavitary fluid collections, anomalous enhancement of the pelvic excavation and densification of adnexal fat planes. Pelvic inflammatory disease is one of the leading causes of abdominal pain in women of childbearing age and it has been increasingly been diagnosed by means of computed tomography and magnetic resonance imaging supplementing the role of ultrasonography. It is crucial that radiologists become familiar with the main sectional imaging findings in the diagnosis of this common cause of acute abdomen (author)

  5. Transduction of PEP-1-heme oxygenase-1 into insulin-producing INS-1 cells protects them against cytokine-induced cell death

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Su Jin; Kang, Hyung Kyung [Department of Physiology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of); Song, Dong Keun [Department of Pharmacology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of); Eum, Won Sik; Park, Jinseu [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Choi, Soo Young, E-mail: sychoi@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Kwon, Hyeok Yil, E-mail: hykwon@hallym.ac.kr [Department of Physiology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of)

    2015-06-05

    Pro-inflammatory cytokines play a crucial role in the destruction of pancreatic β-cells, thereby triggering the development of autoimmune diabetes mellitus. We recently developed a cell-permeable fusion protein, PEP-1-heme oxygenase-1 (PEP-1-HO-1) and investigated the anti-inflammatory effects in macrophage cells. In this study, we transduced PEP-1-HO-1 into INS-1 insulinoma cells and examined its protective effect against cytokine-induced cell death. PEP-1-HO-1 was successfully delivered into INS-1 cells in time- and dose-dependent manner and was maintained within the cells for at least 48 h. Pre-treatment with PEP-1-HO-1 increased the survival of INS-1 cells exposed to cytokine mixture (IL-1β, IFN-γ, and TNF-α) in a dose-dependent manner. PEP-1-HO-1 markedly decreased cytokine-induced production of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA). These protective effects of PEP-1-HO-1 against cytokines were correlated with the changes in the levels of signaling mediators of inflammation (iNOS and COX-2) and cell apoptosis/survival (Bcl-2, Bax, caspase-3, PARP, JNK, and Akt). These results showed that the transduced PEP-1-HO-1 efficiently prevented cytokine-induced cell death of INS-1 cells by alleviating oxidative/nitrosative stresses and inflammation. Further, these results suggested that PEP-1-mediated HO-1 transduction may be a potential therapeutic strategy to prevent β-cell destruction in patients with autoimmune diabetes mellitus. - Highlights: • We showed that PEP-1-HO-1 was efficiently delivered into INS-1 cells. • Transduced PEP-1-HO-1 exerted a protective effect against cytokine-induced cell death. • Transduced PEP-1-HO-1 inhibited cytokine-induced ROS and NO accumulation. • PEP-1-HO-1 suppressed cytokine-induced expression of iNOS, COX-2, and Bax. • PEP-1-HO-1 transduction may be an efficient tool to prevent β-cell destruction.

  6. Corticosteroids reverse cytokine-induced block of survival and differentiation of oligodendrocyte progenitor cells from rats

    Directory of Open Access Journals (Sweden)

    Marx Romy

    2008-09-01

    protein. The most potent corticosteroid tested, dexamethasone, was shown to counteract cytokine effects on membrane surface extension and capacitance. Furthermore, coapplication of dexamethasone blocked the cytokine-induced downregulation of the inwardly rectifying potassium current in 80% of the precursor cells and restored the cytokine-blocked down-regulation of the voltage activated Na+- and K+ currents during subsequent differentiation. Conclusion Our results show that treatment of oligodendrocyte precursors with the inflammatory cytokines TNF-α and IFN-γ block the differentiation of oligodendrocyte precursors at the level of the differentiation of the voltage-gated ion currents. Co-treatment with corticosteroids at the time of cytokine application restores to a considerable extent survival and differentiation of oligodendrocytes at the level of morphological, myelin protein as well as ion current maturation suggesting the option for a functional restoration of cytokine-damaged immature oligodendrocytes.

  7. Characterization and antagonism of cytokine-induced eosinophil priming

    NARCIS (Netherlands)

    Rosas Rosas, Ana Marcela

    2006-01-01

    Allergic asthma is an inflammatory disease characterized by bronchial hyper-responsiveness, airway inflammation, and reversible obstruction of the airways. In humans, cytokine activated eosinophils are thought to be important players in this process since they can release inflammatory mediators afte

  8. Can New Inflammatory Markers Improve the Diagnosis of Acute Appendicitis?

    DEFF Research Database (Denmark)

    Andersson, Manne; Rubér, Marie; Ekerfelt, Christina;

    2014-01-01

    , and myeloperoxidase [MPO]) were compared with traditional diagnostic variables included in the Appendicitis Inflammatory Response (AIR) score (right iliac fossa pain, vomiting, rebound tenderness, guarding, white blood cell [WBC] count, proportion neutrophils, C-reactive protein and body temperature) in 432 patients...

  9. Factors modulating the inflammatory response in acute gouty arthritis

    NARCIS (Netherlands)

    Cleophas, M.C.P.; Crisan, T.O.; Joosten, L.A.B.

    2017-01-01

    PURPOSE OF REVIEW: Gout is a common debilitating form of arthritis and despite our extensive knowledge on the pathogenesis its prevalence is still rising quickly. In the current review, we provide a concise overview of recent discoveries in factors tuning the inflammatory response to soluble uric

  10. Protective effects of St. John's wort extract and its component hyperforin against cytokine-induced cytotoxicity in a pancreatic beta-cell line.

    Science.gov (United States)

    Menegazzi, Marta; Novelli, Michela; Beffy, Pascale; D'Aleo, Valentina; Tedeschi, Elisa; Lupi, Roberto; Zoratti, Elisa; Marchetti, Piero; Suzuki, Hisanori; Masiello, Pellegrino

    2008-01-01

    In both type 1 and type 2 diabetes, increased production of cytokines on autoimmune or metabolic basis is supposed to trigger an inflammatory process leading to dysfunction and death of pancreatic beta-cells. Therefore, anti-inflammatory pharmacological approaches aimed at blocking cytokine signalling pathways and consequent cytotoxicity in beta-cells are highly advisable. Based on previous evidence of cytokine antagonistic effects in other cell types, we explored the protective action of Hypericum perforatum (St-John's-wort) extract and its component hyperforin against cytokine-induced functional impairment and apoptosis in the INS-1E beta-cell line, searching for the underlying mechanisms. The results showed that either St-John's-wort extract or hyperforin (at 1-3 microM) prevented cytokine-induced impairment in glucose-stimulated insulin secretion and protected cells against apoptosis in a dose-dependent fashion. Inducible-NO-synthase expression was also potently hindered by the vegetal compounds. Interestingly, cytokine-induced activations of the signal-transducer-and-activator-of-transcription-1 (STAT-1) and the nuclear-factor-kappaB (NF-kappaB) were both down-regulated by SJW extract or HPF (range 0.5-5 microM) when evaluated by electrophoretic-mobility-shift-assay. Other transcription factors (CBF-1, SP-1) were unaffected. Components of SJW extract other than HPF were much less effective in down-regulating cytokine signalling. Significantly, inhibition of cytokine-elicited STAT-1 and NF-kappaB activation was confirmed in isolated rat and human islets incubated in the presence of these vegetal compounds. In conclusion, St-John's-wort extract and hyperforin are non-peptidyl compounds which, at low concentrations, target key mechanisms of cytokine-induced beta-cell injury, thereby improving beta-cell function and survival. Thus, they are potentially valuable for the prevention or limitation of beta-cell loss in diabetes.

  11. Serum inflammatory cytokines combined with NIHSS to evaluate the condition of patients with acute ischemic stroke

    OpenAIRE

    Yu, Heng; LONG Chong-rong; Wang, Liang

    2013-01-01

    Objective To explore the changes of serum inflammatory cytokines and National Institute of Health Stroke Scale (NIHSS) score in acute ischemic stroke patients and their clinical significances on patients' condition assessment. Methods The serum levels of three cytokines, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (hs-CRP), were measured and compared between 90 acute ischemic stroke patients (ischemic stroke group) and 50 healthy ...

  12. Kaempferol, a dietary flavonoid, ameliorates acute inflammatory and nociceptive symptoms in gastritis, pancreatitis, and abdominal pain.

    Science.gov (United States)

    Kim, Shi Hyoung; Park, Jae Gwang; Sung, Gi-Ho; Yang, Sungjae; Yang, Woo Seok; Kim, Eunji; Kim, Jun Ho; Ha, Van Thai; Kim, Han Gyung; Yi, Young-Su; Kim, Ji Hye; Baek, Kwang-Soo; Sung, Nak Yoon; Lee, Mi-nam; Kim, Jong-Hoon; Cho, Jae Youl

    2015-07-01

    Kaempferol (KF) is the most abundant polyphenol in tea, fruits, vegetables, and beans. However, little is known about its in vivo anti-inflammatory efficacy and mechanisms of action. To study these, several acute mouse inflammatory and nociceptive models, including gastritis, pancreatitis, and abdominal pain were employed. Kaempferol was shown to attenuate the expansion of inflammatory lesions seen in ethanol (EtOH)/HCl- and aspirin-induced gastritis, LPS/caerulein (CA) triggered pancreatitis, and acetic acid-induced writhing. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Acute-onset chronic inflammatory demyelinating polyneuropathy with focal segmental glomerulosclerosis.

    Science.gov (United States)

    Quek, Amy May Lin; Soon, Derek; Chan, Yee Cheun; Thamboo, Thomas Paulraj; Yuki, Nobuhiro

    2014-06-15

    Inflammatory neuropathies have been reported to occur in association with nephrotic syndrome. Their underlying immuno-pathogenic mechanisms remain unknown. A 50-year-old woman concurrently presented with acute-onset chronic inflammatory demyelinating polyneuropathy and nephrotic syndrome secondary to focal segmental glomerulosclerosis. Both neuropathy and proteinuria improved after plasma exchange and steroids. Literature review of cases of concurrent inflammatory neuropathies and nephrotic syndrome revealed similar neuro-renal presentations. This neuro-renal condition may be mediated by autoantibodies targeting myelin and podocytes.

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

    Science.gov (United States)

    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.

  15. The inflammatory response in myocarditis and acute myocardial infarction

    NARCIS (Netherlands)

    Emmens, R.W.

    2016-01-01

    This thesis is about myocarditis and acute myocardial infarction (AMI). These are two cardiac diseases in which inflammation of the cardiac muscle occurs. In myocarditis, inflammation results in the elimination of a viral infection of the heart. During AMI, one of the coronary arteries is occluded,

  16. inflammatory drugs fail to enhance healing of acute hamstring ...

    African Journals Online (AJOL)

    Intern . r pylori e in. J 1993; n of. 96. ive as educing. 28-31. 85. cillin to ation of . MA ... site of the muscle tear) and isokinetic muscle performance ... sodium, influence the rate of healing of acute sports-related ... random code, held by the pharmaceutical company ..... conventional physiotherapy remains the treatment of choice.

  17. Human immunodeficiency virus seroconversion presenting with acute inflammatory demyelinating polyneuropathy: a case report

    Directory of Open Access Journals (Sweden)

    Sloan Derek J

    2008-12-01

    Full Text Available Abstract Introduction Acute Human Immunodeficiency Virus infection is associated with a range of neurological conditions. Guillain-Barré syndrome is a rare presentation; acute inflammatory demyelinating polyneuropathy is the commonest form of Guillain-Barré syndrome. Acute inflammatory demyelinating polyneuropathy has occasionally been reported in acute Immunodeficiency Virus infection but little data exists on frequency, management and outcome. Case presentation We describe an episode of Guillain-Barré syndrome presenting as acute inflammatory demyelinating polyneuropathy in a 30-year-old man testing positive for Immunodeficiency Virus, probably during acute seroconversion. Clinical suspicion was confirmed by cerebrospinal fluid analysis and nerve conduction studies. Rapid clinical deterioration prompted intravenous immunoglobulin therapy and early commencement of highly active anti-retroviral therapy. All symptoms resolved within nine weeks. Conclusion Unusual neurological presentations in previously fit patients are an appropriate indication for Immunodeficiency-Virus testing. Highly active anti-retroviral therapy with adequate penetration of the central nervous system should be considered as an early intervention, alongside conventional therapies such as intravenous immunoglobulin.

  18. Investigation of inflammatory markers in horses with acute abdominal pain

    DEFF Research Database (Denmark)

    Pihl, Tina Holberg; Kjelgaard-Hansen, Mads; Andersen, Pia Haubro

    Background The use of acute phase proteins as objective markers of underlying pathology may facilitate the decision-making regarding diagnosis, treatment and estimation of prognosis of colic horses in a referral hospital. Evaluation of acute phase proteins in both serum and peritoneal fluid...... of colic horses in a referral hospital have not been reported earlier. Objectives Evaluation of serum and peritoneal fluid (PF) levels of serum amyloid A (SAA) and haptoglobin in horses with colic. Methods Blood and PF samples were collected from 75 colic horses at admission to a referral hospital and from...... and haptoglobin can be measured in equine peritoneal fluid similar to measurements in serum. The peritoneal fluid concentrations are more indicative of diagnosis, treatment necessary and outcome than the serum concentrations. Potential relevance Evaluation of SAA and haptoglobin in serum and peritoneal fluid...

  19. Histone deacetylases 1 and 3 but not 2 mediate cytokine-induced beta cell apoptosis in INS-1 cells and dispersed primary islets from rats and are differentially regulated in the islets of type 1 diabetic children

    DEFF Research Database (Denmark)

    Lundh, M; Christensen, D P; Damgaard Nielsen, M

    2012-01-01

    of HDAC1, -2 and -3 rescued INS-1 cells from inflammatory damage. Small hairpin RNAs against HDAC1 and -3, but not HDAC2, reduced pro-inflammatory cytokine-induced beta cell apoptosis in INS-1 and primary rat islets. The protective properties of specific HDAC knock-down correlated with attenuated cytokine-induced......AIMS/HYPOTHESIS: Histone deacetylases (HDACs) are promising pharmacological targets in cancer and autoimmune diseases. All 11 classical HDACs (HDAC1-11) are found in the pancreatic beta cell, and HDAC inhibitors (HDACi) protect beta cells from inflammatory insults. We investigated which HDACs...... mediate inflammatory beta cell damage and how the islet content of these HDACs is regulated in recent-onset type 1 diabetes. METHODS: The rat beta cell line INS-1 and dispersed primary islets from rats, either wild type or HDAC1-3 deficient, were exposed to cytokines and HDACi. Molecular mechanisms were...

  20. How to differentiate acute pelvic inflammatory disease from acute appendicitis ? A decision tree based on CT findings.

    Science.gov (United States)

    El Hentour, Kim; Millet, Ingrid; Pages-Bouic, Emmanuelle; Curros-Doyon, Fernanda; Molinari, Nicolas; Taourel, Patrice

    2017-09-11

    To construct a decision tree based on CT findings to differentiate acute pelvic inflammatory disease (PID) from acute appendicitis (AA) in women with lower abdominal pain and inflammatory syndrome. This retrospective study was approved by our institutional review board and informed consent was waived. Contrast-enhanced CT studies of 109 women with acute PID and 218 age-matched women with AA were retrospectively and independently reviewed by two radiologists to identify CT findings predictive of PID or AA. Surgical and laboratory data were used for the PID and AA reference standard. Appropriate tests were performed to compare PID and AA and a CT decision tree using the classification and regression tree (CART) algorithm was generated. The median patient age was 28 years (interquartile range, 22-39 years). According to the decision tree, an appendiceal diameter ≥ 7 mm was the most discriminating criterion for differentiating acute PID and AA, followed by a left tubal diameter ≥ 10 mm, with a global accuracy of 98.2 % (95 % CI: 96-99.4). Appendiceal diameter and left tubal thickening are the most discriminating CT criteria for differentiating acute PID from AA. • Appendiceal diameter and marked left tubal thickening allow differentiating PID from AA. • PID should be considered if appendiceal diameter is < 7 mm. • Marked left tubal diameter indicates PID rather than AA when enlarged appendix. • No pathological CT findings were identified in 5 % of PID patients.

  1. Pathophysiological mechanisms of acute pancreatitis define inflammatory markers of clinical prognosis.

    Science.gov (United States)

    Minkov, Georgi A; Halacheva, Krasimira S; Yovtchev, Yovcho P; Gulubova, Maya V

    2015-07-01

    Development of acute pancreatitis illustrates the need to understand the basic mechanisms of disease progression to drive the exploration of therapeutic options. Cytokines play a major role in the pathogenesis of acute pancreatitis as underlying systemic inflammatory response, tissue damage, and organ dysfunction. However, little is known about circulating concentrations of these inflammatory markers and their real impact on clinical practice. Experimental studies have suggested that the prognosis for acute pancreatitis depends on the degree of pancreatic necrosis and the intensity of multisystem organ failure generated by the systemic inflammatory response. This suggests an intricate balance between localized tissue damage with proinflammatory cytokine production and a systemic anti-inflammatory response that restricts the inappropriate movement of proinflammatory agents into the circulation. Implication of such mediators suggests that interruption or blunting of an inappropriate immune response has the potential to improve outcome. A detailed understanding of pathophysiological processes and immunological aspects in patients with acute pancreatitis is the basis for the development of therapeutic strategies that will provide significant reductions in morbidity and mortality.

  2. Therapeutic effects of topical netrin-4 in a corneal acute inflammatory model

    Institute of Scientific and Technical Information of China (English)

    Yun; Han; Yi; Shao; Ting-Ting; Liu; Sang-Ming; Li; Wei; Li; Zu-Guo; Liu

    2015-01-01

    AIM: To evaluate the therapeutic effect of netrin-4 on the early acute phase of inflammation in the alkali-burned eye.METHODS: Eye drops containing netrin-4 or phosphate buffered saline(PBS) were administered to a alkali-burn-induced corneal acute inflammatory model four times daily. The clinical evaluations, including fluorescein staining and inflammatory index, were performed on day 1, 4 and 7 using slit lamp microscopy.Global specimens were collected on day 7 and processed for immunofluorescent staining. The levels of inflammatory mediators in the corneas were determined by real-time polymerase chain reaction(PCR).RESULTS: Exogenous netrin-4 administered on rat ocular surfaces showed more improvements in decreasing fluorescein staining on day 4 and 7, and resolved alkali burn-induced corneal inflammation index on day 7(P <0.01). The levels of IL-1β, IL-6, intercellular cell adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), monocyte chemotactic protein-1(MCP-1) and macrophage inflammatory protein-1(MIP-1) in corneas were decreased in netrin-4-treated groups(P <0.05). In addition, netrin-4 significantly reduced the expression of leukocyte common antigen 45(CD45) in the alkali-burn cornea(P <0.001).CONCLUSION: Topical netrin-4 accelerated wound healing and reduced the inflammation on alkali-burn rat model, suggesting a potential as an anti-inflammatory agent in the clinical to treat the acute inflammation.

  3. Inflammatory monocytes damage the hippocampus during acute picornavirus infection of the brain

    Directory of Open Access Journals (Sweden)

    Howe Charles L

    2012-03-01

    Full Text Available Abstract Background Neuropathology caused by acute viral infection of the brain is associated with the development of persistent neurological deficits. Identification of the immune effectors responsible for injuring the brain during acute infection is necessary for the development of therapeutic strategies that reduce neuropathology but maintain immune control of the virus. Methods The identity of brain-infiltrating leukocytes was determined using microscopy and flow cytometry at several acute time points following intracranial infection of mice with the Theiler's murine encephalomyelitis virus. Behavioral consequences of immune cell depletion were assessed by Morris water maze. Results Inflammatory monocytes, defined as CD45hiCD11b++F4/80+Gr1+1A8-, and neutrophils, defined as CD45hiCD11b+++F4/80-Gr1+1A8+, were found in the brain at 12 h after infection. Flow cytometry of brain-infiltrating leukocytes collected from LysM: GFP reporter mice confirmed the identification of neutrophils and inflammatory monocytes in the brain. Microscopy of sections from infected LysM:GFP mice showed that infiltrating cells were concentrated in the hippocampal formation. Immunostaining confirmed that neutrophils and inflammatory monocytes were localized to the hippocampal formation at 12 h after infection. Immunodepletion of inflammatory monocytes and neutrophils but not of neutrophils only resulted in preservation of hippocampal neurons. Immunodepletion of inflammatory monocytes also preserved cognitive function as assessed by the Morris water maze. Conclusions Neutrophils and inflammatory monocytes rapidly and robustly responded to Theiler's virus infection by infiltrating the brain. Inflammatory monocytes preceded neutrophils, but both cell types were present in the hippocampal formation at a timepoint that is consistent with a role in triggering hippocampal pathology. Depletion of inflammatory monocytes and neutrophils with the Gr1 antibody resulted in

  4. Cytokines induce tight junction disassembly in airway cells via an EGFR-dependent MAPK/ERK1/2-pathway.

    Science.gov (United States)

    Petecchia, Loredana; Sabatini, Federica; Usai, Cesare; Caci, Emanuela; Varesio, Luigi; Rossi, Giovanni A

    2012-08-01

    Epithelial barrier permeability is altered in inflammatory respiratory disorders by a variety of noxious agents through modifications of the epithelial cell structure that possibly involve tight junction (TJ) organization. To evaluate in vitro whether pro-inflammatory cytokines involved in the pathogenesis of respiratory disorders could alter TJ organization and epithelial barrier integrity, and to characterize the signal transduction pathway involved Calu-3 airway epithelial cells were exposed to TNF-a, IL-4 and IFN-g to assess changes in: (a) TJ assembly, that is, occludin and zonula occludens (ZO)-1 expression and localization, evaluated by confocal microscopy; (b) apoptotic activity, quantified using terminal transferase deoxyuridine triphosphate nick-end labeling staining; (c) epithelial barrier integrity, detected as transmembrane electrical resistance and expressed as G(T) values; (d) epidermal growth factor receptor (EGFR)-dependent mitogenactivated protein (MAP) kinase (MAPK)/extracellular signal-regulated kinases (ERK)1/2 phosphorylation, assessed by western blotting. Exposure to cytokines for 48 h induced a noticeable downregulation of the TJ transmembrane proteins. The degree ZO-1 and occludin colocalization was 62±2% in control cultures and significantly decreased in the presence of TNF-a (47±3%), IL-4 (43±1%) and INF-g (35±3%). Although no apoptosis induction was detected following exposure to cytokines, changes in the epithelial barrier integrity were observed, with a significant enhancement in paracellular conductance. G(T) values were, respectively, 1.030±0.0, 1.300±0.04, 1.260±0.020 and 2.220±0.015 (mS/cm²)1000 in control cultures and in those exposed to TNF-a, IFN-g and IL-4. The involvement of EGFR-dependent MAPK/ERK1/2 signaling pathway in cytokine-induced damage was demonstrated by a significant increase in threonine/tyrosine phosphorylation of ERK1/2, already detectable after 5 min incubation. All these cytokine-induced changes were

  5. Administration of reconstituted polyphenol oil bodies efficiently suppresses dendritic cell inflammatory pathways and acute intestinal inflammation.

    Directory of Open Access Journals (Sweden)

    Elisabetta Cavalcanti

    Full Text Available Polyphenols are natural compounds capable of interfering with the inflammatory pathways of several in vitro model systems. In this study, we developed a stable and effective strategy to administer polyphenols to treat in vivo models of acute intestinal inflammation. The in vitro suppressive properties of several polyphenols were first tested and compared for dendritic cells (DCs production of inflammatory cytokines. A combination of the polyphenols, quercetin and piperine, were then encapsulated into reconstituted oil bodies (OBs in order to increase their stability. Our results showed that administration of low dose reconstituted polyphenol OBs inhibited LPS-mediated inflammatory cytokine secretion, including IL-6, IL-23, and IL-12, while increasing IL-10 and IL-1Rα production. Mice treated with the polyphenol-containing reconstituted OBs (ROBs were partially protected from dextran sodium sulfate (DSS-induced colitis and associated weight loss, while mortality and inflammatory scores revealed an overall anti-inflammatory effect that was likely mediated by impaired DC immune responses. Our study indicates that the administration of reconstituted quercetin and piperine-containing OBs may represent an effective and potent anti-inflammatory strategy to treat acute intestinal inflammation.

  6. The effects of acute and chronic exercise on inflammatory markers in children and adults with a chronic inflammatory disease : a systematic review

    NARCIS (Netherlands)

    Ploeger, Hilde E.; Takken, Tim; de Greef, Mathieu H. G.; Timmons, Brian W.

    2009-01-01

    Background: Chronic inflammatory diseases strike millions of people all over the world, and exercise is often prescribed for these patients to improve overall fitness and quality of life. In healthy individuals, acute and chronic exercise is known to alter inflammatory markers; however, less is

  7. The effects of acute and chronic exercise on inflammatory markers in children and adults with a chronic inflammatory disease : a systematic review

    NARCIS (Netherlands)

    Ploeger, Hilde E.; Takken, Tim; de Greef, Mathieu H. G.; Timmons, Brian W.

    2009-01-01

    Background: Chronic inflammatory diseases strike millions of people all over the world, and exercise is often prescribed for these patients to improve overall fitness and quality of life. In healthy individuals, acute and chronic exercise is known to alter inflammatory markers; however, less is know

  8. Unique proliferation response in odontoblastic cells derived from human skeletal muscle stem cells by cytokine-induced matrix metalloproteinase-3

    Energy Technology Data Exchange (ETDEWEB)

    Ozeki, Nobuaki; Hase, Naoko; Kawai, Rie; Yamaguchi, Hideyuki; Hiyama, Taiki [Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Aichi (Japan); Kondo, Ayami [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650 (Japan); Nakata, Kazuhiko [Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Aichi (Japan); Mogi, Makio, E-mail: makio@dpc.agu.ac.jp [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650 (Japan)

    2015-02-01

    A pro-inflammatory cytokine mixture (CM: interleukin (IL)-1β, tumor necrosis factor-α and interferon-γ) and IL-1β-induced matrix metalloproteinase (MMP)-3 activity have been shown to increase the proliferation of rat dental pulp cells and murine stem cell-derived odontoblast-like cells. This suggests that MMP-3 may regulate wound healing and regeneration in the odontoblast-rich dental pulp. Here, we determined whether these results can be extrapolated to human dental pulp by investigating the effects of CM-induced MMP-3 up-regulation on the proliferation and apoptosis of purified odontoblast-like cells derived from human skeletal muscle stem cells. We used siRNA to specifically reduce MMP-3 expression. We found that CM treatment increased MMP-3 mRNA and protein levels as well as MMP-3 activity. Cell proliferation was also markedly increased, with no changes in apoptosis, upon treatment with CM and following the application of exogenous MMP-3. Endogenous tissue inhibitors of metalloproteinases were constitutively expressed during all experiments and unaffected by MMP-3. Although treatment with MMP-3 siRNA suppressed cell proliferation, it also unexpectedly increased apoptosis. This siRNA-mediated increase in apoptosis could be reversed by exogenous MMP-3. These results demonstrate that cytokine-induced MMP-3 activity regulates cell proliferation and suppresses apoptosis in human odontoblast-like cells. - Highlights: • Pro-inflammatory cytokines induce MMP-3 activity in human odontoblast-like cells. • Increased MMP-3 activity can promote cell proliferation in odontoblasts. • Specific loss of MMP-3 increases apoptosis in odontoblasts. • MMP-3 has potential as a promising new target for pupal repair and regeneration.

  9. Acute paretic syndrome in juvenile White Leghorn chickens resembles late stages of acute inflammatory demyelinating polyneuropathies in humans

    Directory of Open Access Journals (Sweden)

    Preisinger Rudolf

    2010-01-01

    Full Text Available Abstract Background Sudden limb paresis is a common problem in White Leghorn flocks, affecting about 1% of the chicken population before achievement of sexual maturity. Previously, a similar clinical syndrome has been reported as being caused by inflammatory demyelination of peripheral nerve fibres. Here, we investigated in detail the immunopathology of this paretic syndrome and its possible resemblance to human neuropathies. Methods Neurologically affected chickens and control animals from one single flock underwent clinical and neuropathological examination. Peripheral nervous system (PNS alterations were characterised using standard morphological techniques, including nerve fibre teasing and transmission electron microscopy. Infiltrating cells were phenotyped immunohistologically and quantified by flow cytometry. The cytokine expression pattern was assessed by quantitative real-time PCR (qRT-PCR. These investigations were accomplished by MHC genotyping and a PCR screen for Marek's disease virus (MDV. Results Spontaneous paresis of White Leghorns is caused by cell-mediated, inflammatory demyelination affecting multiple cranial and spinal nerves and nerve roots with a proximodistal tapering. Clinical manifestation coincides with the employment of humoral immune mechanisms, enrolling plasma cell recruitment, deposition of myelin-bound IgG and antibody-dependent macrophageal myelin-stripping. Disease development was significantly linked to a 539 bp microsatellite in MHC locus LEI0258. An aetiological role for MDV was excluded. Conclusions The paretic phase of avian inflammatory demyelinating polyradiculoneuritis immunobiologically resembles the late-acute disease stages of human acute inflammatory demyelinating polyneuropathy, and is characterised by a Th1-to-Th2 shift.

  10. Inflammatory Mechanisms of Organ Crosstalk during Ischemic Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Laura E. White

    2012-01-01

    Full Text Available Acute kidney injury (AKI is a common complication during inpatient hospitalization, and clinical outcomes remain poor despite advancements in renal replacement therapy. AKI in the setting of multiple organ failure (MOF remains a formidable challenge to clinicians and incurs an unacceptably high mortality rate. Kidney ischemia-reperfusion injury (IRI incites a proinflammatory cascade and releases cellular and soluble mediators with systemic implications for remote organ injury. Evidence from preclinical models cites mechanisms of organ crosstalk during ischemic AKI including the expression of cellular adhesion molecules, lymphocyte trafficking, release of proinflammatory cytokines and chemokines, and modification of the host innate and adaptive immune response systems. In this paper, the influence of kidney IRI on systemic inflammation and distant organ injury will be examined. Recent experimental data and evolving concepts of organ crosstalk during ischemic AKI will also be discussed in detail.

  11. CT appearance of acute inflammatory disease of the renal interstitium

    Energy Technology Data Exchange (ETDEWEB)

    Gold, R.P. (New York Medical Coll., Valhalla); McClennan, B.L.; Rottenberg, R.R.

    1983-08-01

    Today, infection remains the most common disease of the urinary tract and constitutes almost 75% of patient problems requiring urologic evaluation. There have been several major factors responsible for our better understanding of the nature and pathophysiology of urinary tract infection. One has been quantitated urine bacteriology and another, the discovery that a significant part of the apparently healthy adult female population has asymptomatic bacteriuria. Abnormal conditions such as neurogenic bladder, bladder malignancy, prolonged catheter drainage and reflux, altered host resistance, diabetes mellitus, and urinary tract obstruction, as well as pregnancy, may either predispose to or be implicated in the pathogenesis of urinary tract infection. There is a wide range of conditions that result in acute renal inflammation and those under discussion affect primarily the interstitium. This term refers to the connective tissue elements separating the tubules in the cortex and medulla. Hence, the interstitial nephritides are to be distinguished from the glomerulonephritides and fall into two general etiologic categories: infectious and noninfectious.

  12. Detection and significance of inflammatory factors and immunoglobulin in acute stage patients with infantile pneumonia

    Institute of Scientific and Technical Information of China (English)

    Xiao-Zheng Meng; Liang Qiao

    2016-01-01

    Objective:To investigate the detection and significance of inflammatory factors and immunoglobulin in acute stage patients with infantile pneumonia.Methods:A total of 80 cases of acute stage patients with infantile pneumonia were divided into mild group (n=33) and severe group (n=47) according to illness degrees, and 40 cases of healthy children were selected as control group. Serum CRP, Ig A, Ig G and Ig M levels were detected by nephelometry, IL-6 levels were detected by enzyme-linked immunosorbent assay. The levels of inflammatory factors (CRP, IL-6) and immunoglobulin indexes (Ig A, Ig G and Ig M) were compared among 3 groups.Results: The inflammatory factors (CRP, IL-6) in mild and severe group increased significantly compared with control group, CRP and IL-6 levels in severe group were were significantly higher than that in mild group (P<0.05). The levels of Ig A in mild and severe group decreased significantly compared with control group, Ig A level in severe group was significantly lower than that in mild group (P<0.05), the levels of Ig G and Ig M in mild and severe group increased significantly compared with control group, the levels of Ig G and Ig M in severe group were significantly higher than that in mild group (P<0.05). Conclusions:The levels of inflammatory factors are increased while immune function is decreased in acute stage patients with infantile pneumonia. Inflammation is stronger and immune function is worse with the severity of the disease. Detection of inflammatory factors and immunoglobulin levels is helpful to diagnose and treatment of acute stage patients with infantile pneumonia.

  13. Elevated white cell count in acute coronary syndromes: relationship to variants in inflammatory and thrombotic genes

    Directory of Open Access Journals (Sweden)

    Cannon Christopher P

    2004-06-01

    Full Text Available Abstract Background Elevated white blood cell counts (WBC in acute coronary syndromes (ACS increase the risk of recurrent events, but it is not known if this is exacerbated by pro-inflammatory factors. We sought to identify whether pro-inflammatory genetic variants contributed to alterations in WBC and C-reactive protein (CRP in an ACS population. Methods WBC and genotype of interleukin 6 (IL-6 G-174C and of interleukin-1 receptor antagonist (IL1RN intronic repeat polymorphism were investigated in 732 Caucasian patients with ACS in the OPUS-TIMI-16 trial. Samples for measurement of WBC and inflammatory factors were taken at baseline, i.e. Within 72 hours of an acute myocardial infarction or an unstable angina event. Results An increased white blood cell count (WBC was associated with an increased C-reactive protein (r = 0.23, p 3 (95% CI = -0.41, 0.77, and -0.03/mm3 (95% CI = -0.55, 0.86 for IL1RN. Moreover, the composite endpoint was not significantly affected by an interaction between WBC and the IL1 (p = 0.61 or IL6 (p = 0.48 genotype. Conclusions Cytokine pro-inflammatory genetic variants do not influence the increased inflammatory profile of ACS patients.

  14. The Impact of Acute Matriptase Inhibition in Hepatic Inflammatory Models

    Directory of Open Access Journals (Sweden)

    Judit Pomothy

    2016-01-01

    Full Text Available Purpose. Dysfunction of matriptase-2 can be involved in iron regulatory disorder via downregulation of hepcidin expression. In the present study, we investigated the effects of 3-amidinophenylalanine-derived matriptase inhibitors on porcine hepatic inflammatory cell models. Methods. Hepatocyte-Kupffer cell cocultures (ratio of 2 : 1 and 6 : 1 were treated with four structurally related matriptase inhibitors at 50 μM. Cell cytotoxicity and relative expressions of IL-6 and IL-8 and the levels of hepcidin were determined by MTS and porcine-specific ELISA. The extracellular H2O2 contents were analyzed by Amplex Red method. Results. Matriptase inhibitors at 50 µM for 24 h did not increase cell death rate. The elevated ROS production observed after short-term application of inhibitor MI-441 could be correlated with lowered hepcidin expression. MI-460 could significantly enhance hepcidin levels in the supernatants of cocultures (by 62.21±26.8% in hepatocyte-Kupffer cell, 2 : 1, and by 42.6±14.3% in hepatocyte-Kupffer cell, 6 : 1, cocultures, resp.. No significant changes were found in IL-6 and IL-8 levels in cocultures exposed to matriptase inhibitors. Conclusions. Based on in vitro findings, administration of MI-460 via modulation of hepcidin expression without cytotoxic and oxidative stress inducing properties might be a reliable alternative to treat iron overload in human and veterinary clinical practice.

  15. Cytokine-induced killer cells: NK-like T cells with cytotolytic specificity against leukemia.

    Science.gov (United States)

    Linn, Y C; Hui, Kam M

    2003-09-01

    Cytokine-induced killer (CIK) cells are a unique population of cytotoxic T lymphocytes (CTL) with the characteristic CD3+CD56+ phenotype. These cells have demonstrated higher proliferative and cytolytic activities in comparison to the reported CD3-CD56+ lymphokine activated killer (LAK) cells that are essentially activated natural killer (NK) cells. CIK cells are non-MHC-restricted in target cell recognition and killing. We have shown the feasibility of generating CIK cells from a series of marrow samples of patients with acute myeloid leukemia (AML) collected at diagnosis. At maturity, the CIK cells exhibit potent cytotoxicity against autologous AML targets as well as allogeneic myeloid leukemia cells, regardless of the HLA types of these targets. This observed cytotoxicity is not entirely due to NK cells as prior pre-absorption of the NK cells cytolytic activities does not abolish the subsequent cytotolytic activities against leukemic targets. It has also been reported by others that CIK cells are cytolytic against chronic myeloid leukemia (CML) cells, both in vitro and in the SCID mouse tumor model. In a mouse transplant model across MHC barrier, the CIK cells generated from the donor do not induce graft vs. host disease as observed for unfractionated donor splenocytes. In comparison to untreated control mice, the infusion of CIK cells results in the prolonged survival of murine leukemia-bearing mice. CIK cells also express CD94, part of the NK receptor comprising of CD94-NKG2 heterodimer. However, only low level of the killer immunoglobulin-like receptors are expressed by the CIK cells. In addition, as reported for the classical CTL, CIK cells could interact with dendritic cells (DC) to result in the enhancement of cytotolytic activities against tumor cells. The characteristic biological properties of the CIK cells would, therefore, enable them to be exploited for anti-leukemic therapy.

  16. Monocytes in systematic inflammatory response syndrome: Differences between sepsis and acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Vassilios Koussoulas; Michalis Tzivras; Vassiliki Karagianni; Ekaterini Spyridaki; Diamantis Plachouras; Helen Giamarellou; Evangelos J Giamarellos-Bourboulis

    2006-01-01

    AIM: To unravel the differences between systematic inflammatory response syndrome (SIRS) of acute pancreatitis compared to the same syndrome in sepsis.METHODS: Twenty-five patients were enrolled, 12 with sepsis and 13 acute pancreatitis. After diagnosis 20 mL blood was sampled. Half were assayed for isolation of monocytes and 10 mL was centrifuged for serum test of tumor necrosis factor alpha (TNFα) and interleukin-6(IL-6). Half of monocytes were incubated in the presence of patients' serum and supernatants were collected. The other half was treated for estimation of optical photometry under caspase-3 inhibition. TNFα and IL-6 were estimated by an enzyme immunoassay.RESULTS: median ± SE of serum IL-6 in septic patients and acute pancreatitis patients was 192.30 ± 35.40 ng/L and 21.00 ± 16.05 ng/L, respectively (P < 0.01). Respective values of caspase-3 were 0.94 ± 0.17 pmol/min 104 cells and 0.34 ± 0.09 pmol/min 104 cells (P < 0.05).IL-6 of monocyte supernatants of patients with sepsis was significantly increased after addition of patients' serum, while that of patients with acute pancreatitis did not show significant difference.CONCLUSION: The data have shown that monocyte activity is different between acute pancreatitis and sepsis. This phenomenon might be explained as a different pathway to the pro-inflammatory cytokines release or could be a novel anti-inflammatory response in acute pancreatitis.

  17. Allograft inflammatory factor-1 in the pathogenesis of bleomycin-induced acute lung injury.

    Science.gov (United States)

    Nagahara, Hidetake; Yamamoto, Aihiro; Seno, Takahiro; Obayashi, Hiroshi; Kida, Takashi; Nakabayashi, Amane; Kukida, Yuji; Fujioka, Kazuki; Fujii, Wataru; Murakami, Ken; Kohno, Masataka; Kawahito, Yutaka

    2016-02-01

    Allograft inflammatory factor-1 (AIF-1) is a protein expressed by macrophages infiltrating the area around the coronary arteries of rats with an ectopic cardiac allograft. Some studies have shown that expression of AIF-1 increased in a mouse model of trinitrobenzene sulfonic acid-induced acute colitis and in acute cellular rejection of human cardiac allografts. These results suggest that AIF-1 is related to acute inflammation. The current study used bleomycin-induced acute lung injury to analyze the expression of AIF-1 and to examine its function in acute lung injury. Results showed that AIF-1 was significantly expressed in lung macrophages and increased in bronchoalveolar lavage fluid from mice with bleomycin-induced acute lung injury in comparison to control mice. Recombinant AIF-1 increased the production of IL-6 and TNF-α from RAW264.7 (a mouse macrophage cell line) and primary lung fibroblasts, and it also increased the production of KC (CXCL1) from lung fibroblasts. These results suggest that AIF-1 plays an important role in the mechanism underlying acute lung injury.

  18. Flecainide Improve Sepsis Induced Acute Lung Injury by Controlling Inflammatory Response

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    Jia Song

    2016-08-01

    Full Text Available Background: Flecainide is an antiarrhythmic agent that is used primarily in the treatment of cardiac arrhythmias. Some evidences also suggest that flecainide can participate in alveolar fluid clearance and inflammatory responses. This experiment was aimed to evaluate the effects of flecainide on sepsis induced acute lung injury in a rat model. Methods: Rats were treated with subcutaneous infusion of saline or flecainide (0.1 or 0.2 mg/kg/hr by a mini-osmotic pump. Subcutaneous infusion was started 3 hours before and continued until 8 hours after intraperitoneal injection of saline or endotoxin. Animals were sacrificed for analyses of severity of acute lung injury with wet to dry (W/D ratio and lung injury score (LIS in lung and inflammatory responses with level of leukocyte, polymorphonuclear neutrophils (PMNs and inteleukin-8 (IL-8 in bronchoalveolar lavages fluid (BALF. Results: Flecainide markedly improved dose dependently sepsis induced acute lung injury as analysed by W/D ratio (from 2.24 ± 0.11 to 1.76 ± 0.09, p < 0.05 and LIS (from 3 to 1, p < 0.05, and inflammatory response as determined by leukocyte (from 443 ± 127 to 229 ± 95, p < 0.05, PMNs (from 41.43 ± 17.63 to 2.43 ± 2.61, p < 0.05 and IL-8 (from 95.00 ± 15.28 to 40.00 ± 10.21, p < 0.05 in BALF. Conclusions: Flecanide improve sepsis induced acute lung injury in rats by controlling inflammatory responses.

  19. Acute gouty arthritis as a manifestation of immune reconstitution inflammatory syndrome after initiation of antiretroviral therapy

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    Walter de Araujo Eyer-Silva

    2012-08-01

    Full Text Available Immune reconstitution inflammatory syndrome (IRIS in HIV-infected subjects initiating antiretroviral therapy most commonly involves new or worsening manifestations of previously subclinical or overt infectious diseases. Reports of non-infectious IRIS are much less common but represent important diagnostic and treatment challenges. We report on a 34-year-old HIV-infected male patient with no history of gout who developed acute gouty arthritis in a single joint one month after initiating highly active antiretroviral therapy.

  20. Prognostic Value of Circulating Inflammatory Cells in Patients with Stable and Acute Coronary Artery Disease

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    John A. L. Meeuwsen

    2017-07-01

    Full Text Available Atherosclerosis is a lipid driven chronic inflammatory disease underlying the majority of ischemic events such as myocardial infarction or stroke. Clinical management of ischemic events has improved considerably in the past decades. Accordingly, survival rates have increased. Nevertheless, 12% of patients die within 6 months after the initial event. To improve secondary prevention, appropriate risk prediction is key. However, up to date, there is no clinically available routine marker to identify patients at high risk for recurrent cardiovascular events. Due to the central role of inflammation in atherosclerotic lesion progression and destabilization, many studies have focused on the role of circulating inflammatory cells in these processes. This review summarizes the current evidence on the potential of circulating inflammatory cells as biomarkers for recurrent adverse manifestations in acute coronary syndrome and stable coronary artery disease patients.

  1. The changes and significance of serum inflammatory factors and hemodynamics in patients with acute cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    Xiao-Wei Lu

    2016-01-01

    Objective:To investigate the changes of serum inflammatory factors and hemodynamics in patients with acute cerebral infarction and its clinical significance.Methods: A total of 55 cases of acute cerebral infarction (ACI) patients as observation group, and cases of healthy physical examination were selected as the observation group, and 55 healthy persons as control group. ELISA method was used to detect inflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), C-reactive protein (CRP) and tumor necrosis factor (TNF-α) level, WA-880 heart and brain integrated digital hemodynamic monitor to detect bilateral carotid artery blood flow velocity, blood flow and peripheral resistance.Results:The serum levels of IL-8, CRP, IL-6 and TNF-α were higher in the observation group than in the control group, the difference was statistically significant (P<0.05). The blood flow velocity and blood flow velocity in the observation group were significantly lower than those in the control group. The difference was statistically significant (IL-8). With the increase of infarct size, serum IL-6, CRP,P<0.05 and TNF-α increased significantly (P<0.05).Conclusions:The changes of serum inflammatory factors and hemodynamic indexes can be used to judge the early cerebral infarction and the size of the infarct size of the index, the clinical dynamic monitoring of its changes in patients with acute cerebral infarction and the severity of the prognosis and the prognosis of the important significance of the judgment.

  2. Acute-phase inflammatory response in idiopathic sudden deafness: pathogenic implications.

    Science.gov (United States)

    López-González, Miguel A; Abrante, Antonio; López-Lorente, Carmen; Gómez, Antonio; Domínguez, Emilio; Esteban, Francisco

    2012-01-01

    The acute-phase inflammatory response in the peripheral bloodstream can be an expression of transient cerebral ischaemia in idiopathic sudden deafness. For this, a neurological and otorhinolaryngological examination of each patient, performing tests on audiometry, and tympanometry, haemogram, and cranial magnetic resonance were performed. The acute-phase inflammatory response manifests as an increased neutrophil/lymphocyte ratio that is detected 48-72 hours after the appearance of sudden deafness. This study shows that there is an acute-phase response in the peripheral bloodstream with an increased neutrophil/lymphocyte ratio as an expression of an inflammatory process that can be caused by transient cerebral ischaemia in sudden deafness. In addition, the increased neutrophil/lymphocyte ratio can rule out a viral origin of sudden deafness, since a viral infection lowers the neutrophil count and increases the lymphocyte count, thus reducing the neutrophil/lymphocyte ratio. These findings aid in understanding the pathogenic mechanisms involved in sudden deafness and offer better treatment to the patient.

  3. Acute-Phase Inflammatory Response in Idiopathic Sudden Deafness: Pathogenic Implications

    Directory of Open Access Journals (Sweden)

    Miguel A. López-González

    2012-01-01

    Full Text Available The acute-phase inflammatory response in the peripheral bloodstream can be an expression of transient cerebral ischaemia in idiopathic sudden deafness. For this, a neurological and otorhinolaryngological examination of each patient, performing tests on audiometry, and tympanometry, haemogram, and cranial magnetic resonance were performed. The acute-phase inflammatory response manifests as an increased neutrophil/lymphocyte ratio that is detected 48–72 hours after the appearance of sudden deafness. This study shows that there is an acute-phase response in the peripheral bloodstream with an increased neutrophil/lymphocyte ratio as an expression of an inflammatory process that can be caused by transient cerebral ischaemia in sudden deafness. In addition, the increased neutrophil/lymphocyte ratio can rule out a viral origin of sudden deafness, since a viral infection lowers the neutrophil count and increases the lymphocyte count, thus reducing the neutrophil/lymphocyte ratio. These findings aid in understanding the pathogenic mechanisms involved in sudden deafness and offer better treatment to the patient.

  4. Anti-inflammatory activity of Justicia prostrata gamble in acute and sub-acute models of inflammation.

    Science.gov (United States)

    Sanmugapriya, E; Shanmugasundaram, P; Venkataraman, S

    2005-01-01

    In this study, the aqueous (AQJP) and alcoholic (ALJP) extracts of the whole plant of Justicia prostrata Gamble (Acanthaceae) were screened for their acute and subacute anti-inflammatory activities using carrageenan-induced acute inflammation and cotton-pellet-induced granuloma (subacute inflammation), respectively, in rats. In the carrageenan-induced rat paw oedema model, both extracts were found to exhibit maximum reduction in paw volume at the first hour in a dose-dependent manner. At the dose of 500 mg/kg p.o., both extracts AQJP and ALJP showed maximum inhibition (51.39% and 62.5%, respectively) in rat paw oedema volume at the first hour of carrageenan-induced acute inflammation. In the cotton pellet granuloma assay, AQJP and ALJP at the dose of 500 mg/kg p.o. suppressed the transudative, exudative and proliferative phases of chronic inflammation. These extracts were able to (i) reduce the lipid peroxide content of exudates and liver and (ii) normalize the increased activity of acid and alkaline phosphatases in serum and liver of cotton pellet granulomatous rats. Preliminary phytochemical screening revealed the presence of lignans, triterpenes and phenolic compounds in ALJP, whereas phenolic compounds and glycosides in AQJP. The anti-inflammatory properties of these extracts may possibly be due to the presence of phenolic compounds. The anti-inflammatory effects produced by the extracts at the dose of 500 mg/kg, p.o. was comparable with the reference drug diclofenac sodium (5 mg/kg p.o.).

  5. Serial measurement of lipid profile and inflammatory markers in patients with acute myocardial infarction

    Science.gov (United States)

    Shrivastava, Amit Kumar; Singh, Harsh Vardhan; Raizada, Arun; Singh, Sanjeev Kumar

    2015-01-01

    Serum concentration of lipids and lipoproteins changes during the course of acute coronary syndrome as a consequence of the inflammatory response. The objective of this study was to evaluate the effect of acute myocardial infarction (AMI) on the levels of lipid profile and inflammatory markers. We investigated 400 patients with AMI who were admitted within 24 h of onset of symptoms. Serum levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL) were determined by standard enzymatic methods along with high sensitive C-reactive protein (hs-CRP) (latex enhanced immunoturbidimetric assay) and cytokines, interleukin (IL)-6 and IL-10 (quantitative ''sandwich'' enzyme-linked immunosorbent assay). The results indicate a trend of reduced TC, LDL, and HDL, and elevated TG levels, along with pro- and anti-inflammatory markers (p < 0.001), between day 1 and the day 2 serum samples of AMI patients. However, corrections in the serum levels have been observed at day 7. Our results demonstrate significant variations in the mean lipid levels and inflammatory markers between days 1, 2 and 7 after AMI. Therefore, it is recommended that the serum lipids should be assessed within 24 hours after infarction. Early treatment of hyperlipidemia provides potential benefits. Exact knowledge regarding baseline serum lipids and lipoprotein levels as well as their varying characteristics can provide a rational basis for clinical decisions about lipid lowering therapy. PMID:26535040

  6. Are acute exacerbations of chronic inflammatory appendicitis triggered by coprostasis and/or coproliths?

    Institute of Scientific and Technical Information of China (English)

    George Sgourakis; Georgios C Sotiropoulos; Ernesto P Molmenti; Charis Eibl; Stylianous Bonticous; Jurgen Moege; Christoph Berchtold

    2008-01-01

    AIM:To examine the role of coprostasis and coproliths in recurrent appendicitis.METHODS:We evaluated four hundred and twentyseven consecutive pathology reports of all appendectomy specimens from January 2003 to December 2004.Findings were categorised as showing acute append icitis,acute recurrent appendicitis,subacute recurrentappendicitis,chronic appendicitis,or appendices without inflammation.All patients had presented with acute right lower quadrant pain.In 94 instances,there was a history of recurrent similar episodes in the past.RESULTS:Of the 427 histology reports,294 were interpreted as showing acute appendicitis,56 acute recurrent appendicitis,34 subacute recurrent appen-dicitis,28chronic appendicitis,and 15 non-inflamed appendices.Coprostasis was observed in 58 patients (13.58%) and the presence of coprolith in 6 (1.4%).Coprostasis,and age,were among the predictors in the final model.CONCLUSION:Coprostasis but not coproliths seems to be a contributing factor to acute exacerbations of chronic inflammatory appendicitis.

  7. Acute-onset chronic inflammatory demyelinating polyneuropathy in hantavirus and hepatitis B virus coinfection

    Science.gov (United States)

    Lim, Jong Youb; Lim, Young-Ho; Choi, Eun-Hi

    2016-01-01

    Abstract Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired autoimmune disorder with progressive weakness. Acute-onset CIDP resembles Guillain-Barre syndrome (GBS), a rapidly progressive disorder, and follows a chronic course. To our knowledge, no case of acute-onset CIDP in hantavirus and hepatitis B virus (HBV) coinfection has been reported previously. Clinical findings: We report a case of acute-onset CIDP that was initially diagnosed as GBS. Diagnoses: A 44-year-old male logger complained of acute quadriplegia and dyspnea. Mechanical ventilation was initiated. He was an HBV carrier with mild elevation of hepatic enzyme, and positive for hantavirus antibody. He was diagnosed with GBS and immunoglobulin therapy was administered. Interventions: After 8 months, quadriplegia and hypesthesia recurred. Immunoglobulin therapy at this time had no effect, but steroid therapy had some effect. Outcomes: A diagnosis of CIDP was made. After 2 months, severe extremity pain and dyspnea developed again, and steroid pulse therapy was initiated. Conclusion: Besides GBS, acute-onset CIDP can occur with hantavirus and HBV coinfection. Patients with this coinfection in whom GBS has been initially diagnosed should be followed up for a long time, because of the possibility of relapse or deterioration, and acute-onset CIDP should always be considered. PMID:27930572

  8. Anti-inflammatory effects of Asparagus cochinchinensis extract in acute and chronic cutaneous inflammation.

    Science.gov (United States)

    Lee, Do Yeon; Choo, Byung Kil; Yoon, Taesook; Cheon, Myeong Sook; Lee, Hye Won; Lee, A Yeong; Kim, Ho Kyoung

    2009-01-12

    Although Asparagus cochinchinensis Merrill (Liliaceae) has long been used in traditional Korean and Chinese medicine to treat inflammatory diseases, the underlying mechanism(s) by which these effects are induced remains to be defined. We investigated the effects of 70% ethanolic extract from Asparagus cochinchinensis Merrill (ACE) on skin inflammation in mice. Production of pro-inflammatory cytokines (tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta), activation of myeloperoxidase, and histological assessment were examined in acute and chronic skin inflammation using 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear edema. We also performed acetic acid-induced vascular permeability test. ACE inhibited topical edema in the mouse ear, following administration at 200mg/kg (i.p.), leading to substantial reductions in skin thickness and tissue weight, inflammatory cytokine production, neutrophil-mediated myeloperoxidase (MPO) activity, and various histopathological indicators. Furthermore, ACE was effective at reducing inflammatory damage induced by chronic TPA exposure and evoked a significant inhibition of vascular permeability induced by acetic acid in mice. These results demonstrate that ACE is an effective anti-inflammatory agent in murine phorbol ester-induced dermatitis, and suggest that the compound may have therapeutic potential in a variety of immune-related cutaneous diseases.

  9. Cytokine effects on the basal ganglia and dopamine function: the subcortical source of inflammatory malaise.

    Science.gov (United States)

    Felger, Jennifer C; Miller, Andrew H

    2012-08-01

    Data suggest that cytokines released during the inflammatory response target subcortical structures including the basal ganglia as well as dopamine function to acutely induce behavioral changes that support fighting infection and wound healing. However, chronic inflammation and exposure to inflammatory cytokines appears to lead to persisting alterations in the basal ganglia and dopamine function reflected by anhedonia, fatigue, and psychomotor slowing. Moreover, reduced neural responses to hedonic reward, decreased dopamine metabolites in the cerebrospinal fluid and increased presynaptic dopamine uptake and decreased turnover have been described. This multiplicity of changes in the basal ganglia and dopamine function suggest fundamental effects of inflammatory cytokines on dopamine synthesis, packaging, release and/or reuptake, which may sabotage and circumvent the efficacy of current treatment approaches. Thus, examination of the mechanisms by which cytokines alter the basal ganglia and dopamine function will yield novel insights into the treatment of cytokine-induced behavioral changes and inflammatory malaise. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Retention of cytokine-inducing substances inside high-flux dialyzers.

    Science.gov (United States)

    Lufft, V; Mahiout, A; Shaldon, S; Koch, K M; Schindler, R

    1996-01-01

    Reprocessing of dialyzers is often performed with nonsterile solutions possibly contaminated with bacterial-derived cytokine-inducing substances. We investigated the retention of cytokine-inducing substances inside the dialyzer during reprocessing in a closed loop in vitro hemodialysis system using a polyamide high flux membrane. After the first in vitro circulation of human whole blood, rinse of the blood compartment (BC) and reverse ultrafiltration (RUF) was performed with either cytokine-inducing substance-free saline or saline contaminated with filtrates from Pseudomonas cultures (6 ng/ml LAL-reactive material); subsequently, dialyzers were stored in 2% formaldehyde. Dialyzers were rinsed with approximately 15 liters pyrogen-free saline before the second circulation using blood from the same donor; the effluates were free of cytokine-inducing substances and formaldehyde. Before and after the blood circulations, peripheral blood mononuclear cells (PBMC) were separated and total production of IL-1 alpha and IL-1 beta was determined after overnight incubation. In noncirculated PBMC as well as in PBMC separated after whole blood circulation with pyrogen-free processed dialyzers, production of IL-1 beta was not detectable. After contaminated rinse of the BC, production of IL-1 beta could be observed (1,600 +/- 1,100 pg/ml, mean +/- SEM). When pyrogen-free RUF was performed after contaminated BC rinse, IL-1 beta production averaged 163 +/- 92 pg/ml when using reused dialyzers, but 1,820 +/- 880 pg/ml when using new dialyzers. After reuse with pyrogen-free BC-rinse and contaminated RUF no IL-1 beta synthesis was observed; however, when pyrogen-free BC-rinse and contaminated RUF was applied to new dialyzers, IL-1 beta synthesis averaged 1,620 +/- 1,200 pg/ml. We conclude that cytokine-inducing substances are retained inside the dialyzer, probably by adsorption to the membrane as well as to the protein layer covering the membrane and are still biologically active after

  11. Detection of Hyperechoic Inflammatory Fatty Tissue during Transabdominal Ultrasonography: Diagnostic Role in Acute Abdomen

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    Park, Seong Jin; Lee, Hae Kyung; Yi, Bum Ha [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of); Kim, Hyun Cheol [Soonchunhyang University Cheonan Hospital, Cheonan (Korea, Republic of)

    2005-12-15

    To assess the incidence and diagnostic role of hyperechoic inflammatory fatty tissue (HIFT) in transabdominal ultrasonography (TAUS) for acute abdomen. With TAUS, we examined 98 consecutive patients (68 women, 30 men: mean age, 32 years: age range, 4-84 years) having acute abdominal pain. We examined the abdomen and pelvis by TAUS to determine the cause of acute abdomen, to check for the presence of HIFT, and to investigate whether it was easier and earlier to find the main cause and HIFT presence. We also prospectively evaluated the shape, distribution, and diagnostic role of HIFT. Final diagnoses consisted of 47 cases of acute appendicitis, 14 of enterocolitis, 13 of PID, 7 of gynecological hemoperitoneum, 5 of colonic diverticulitis, 3 of ovarian torsion, 2 of colon perforation, 2 of only presence of non-specific HIFT, 1 of mesenteric lymphadenitis, and 4 of normal. HIFT were seen in 67 patients (68.4%), including 44/47(93.6%) of acute appendicitis, 2/14(14.3%) of enterocolitis, 11/13(84.6%) of PID, 0/7 of hemoperitoneum, 5/5 of colonic diverticulitis, 0/3 of ovarian torsion, 2/2 of colon perforation, and 1/1 mesenteric lymphadenitis. HIFT were detected earlier than the main cause in 17/44 of acute appendicitis, 6/11 of PID, and 4/5 of colonic diverticulitis. In acute appendicitis, the shape of HIFT appeared as fat thickening along the mesoappendix in 12/44, fat thickening along the mesoappendix and the opposite side in 13/44, fat encircled appendix in 6/44, fatty mass wrapping abscess in 10/44, and diffuse intraperitoneal fat thickening in 3/44. In PID, HIFT appeared as a single fatty mass in the pelvis and lower abdomen in 6/11, wrapping pelvic abscess in 2/11, and multiple fatty masses scattered in abdomen and pelvis in 3/11. In colonic diverticulitis, all 5 cases appeared as hyperechoic hemispheric mass covering the inflamed diverticulum. HIFT are a usual US finding in patients with acute abdomen, particularly on abdominal and pelvic inflammatory conditions

  12. [Differential diagnostics of acute inflammatory diseases and tumors of the neck].

    Science.gov (United States)

    Vuĭtsik, N B; Butkevich, A Ts; Kuntsevich, G I; Zemlianoĭ, A B

    2008-01-01

    The purpose of the investigation was to assess the clinical significance of ultrasonography for differential diagnostics between acute inflammatory and tumorous lesions of the neck. One hundred and eighty-six patients with soft-tissue lesions of the neck aged 18 to 74 (mean age 31.45 +/- 8.39 years), 95 (51%) males and 91 (49%) females were examined. Basing on clinical and ultrasonographic examination, the patients were divided into two groups: 149 or 80% patients with acute inflammatory lesions (Group 1), and 37 or 20% patients with tumorous lesions (Group 2). Thirty-four of the 149 Group 1 patients (22.82%) had lymphadenitis, 30 (20.13%) had soft tissue infiltrates, 13 (8.72%) had abscesses, 19 (12.72%) had phlegmons, 32 (21.48%) had acute inflammatory changes in the major salivary glands, 3 (2.01%) had teratomas with signs of inflammation, and 17 (11.41%) patients had inflammatory changes in the tumors. Of 37 patients with tumorous lesions, 16 (43.2%) had salivary gland tumors, 12 (32.4%) had metastases in the lymphatic nodes, and 9 (24.3%) had neurofibromatosis. Soft tissue ultrasonography was performed using Sonos-5500 and Image-Point ultrasound scanners with 7.5 MHz sensors (Hewlett-Packard, USA), Logio-pro, Uoluson-730 Expert (General Electric, USA), and Premium Edition (ACUSON Antares, Siemens, Germany) with 5 to 13 MHz wide-frequency sensors. Visualization was performed in B-modes using tissue harmonics, color duplex scanning, Sie Scape panoramic visualization, contrast visualization and Sight 4D and 3D-Scape modes. The results of ultrasonography were analyzed taking into account additional methods such as computed and magnetic resonance tomography, intraoperative findings, the results of puncture biopsy, histological, morphological, and bacteriological studies. The study demonstrates that ultrasonography is the method of choice, which is in some cases enough to establish a diagnosis of an acute inflammatory disease or a tumorous formation of various

  13. Acute-Phase Inflammatory Response to Single-Bout HIIT and Endurance Training: A Comparative Study

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    Felix Kaspar

    2016-01-01

    Full Text Available Objective. This study compared acute and late effect of single-bout endurance training (ET and high-intensity interval training (HIIT on the plasma levels of four inflammatory cytokines and C-reactive protein and insulin-like growth factor 1. Design. Cohort study with repeated-measures design. Methods. Seven healthy untrained volunteers completed a single bout of ET and HIIT on a cycle ergometer. ET and HIIT sessions were held in random order and at least 7 days apart. Blood was drawn before the interventions and 30 min and 2 days after the training sessions. Plasma samples were analyzed with ELISA for the interleukins (IL, IL-1β, IL-6, and IL-10, monocyte chemoattractant protein-1 (MCP-1, insulin growth factor 1 (IGF-1, and C-reactive protein (CRP. Statistical analysis was with Wilcoxon signed-rank tests. Results. ET led to both a significant acute and long-term inflammatory response with a significant decrease at 30 minutes after exercise in the IL-6/IL-10 ratio (−20%; p=0.047 and a decrease of MCP-1 (−17.9%; p=0.03. Conclusion. This study demonstrates that ET affects the inflammatory response more adversely at 30 minutes after exercise compared to HIIT. However, this is compensated by a significant decrease in MCP-1 at two days associated with a reduced risk of atherosclerosis.

  14. A single administration of fish oil inhibits the acute inflammatory response in rats.

    Science.gov (United States)

    de Arruda, Laura Lícia Milani; Ames, Franciele Queiroz; de Morais, Damila Rodrigues; Grespan, Renata; Gil, Ana Paula Maziero; Silva, Maria Angélica Raffaini Covas Pereira; Visentainer, Jesuí Vergílio; Cuman, Roberto Kenji Nakamura; Bersani-Amado, Ciomar Aparecida

    2017-08-01

    To investigate the antiinflammatory effects of a single administration of fish oil (FO) on the acute inflammatory response. The paw edema and pleurisy models were used to evaluate the effects of FO dissolved in olive oil (FOP) orally administered in a single dose in rats. Nitric oxide (NO) concentrations in the pleural exudate were performed according to the Griess method and the cytokine concentrations were determined by Luminex bead-based multiplex assay. FOP treatment (30 and 300 mg/kg) significantly reduced paw edema. FOP treatment at 18.75, 37.5, 75.0, 150.0, and 300 mg/kg decreased both the volume of pleural exudate and cellular migration into the pleural cavity and each of these doses presented the same effectiveness. Treatment with FOP (300 mg/kg) reduced NO, TNF-α, IL-1β, and IL-6 concentrations in the pleural exudate. The present data provide evidence that FO has inhibitory effects on the acute inflammatory response when administered in a single dose in rats. This effect might be attributable to a direct inhibitory effect of FO on the production or release of inflammatory mediators that are involved in the pathological processes evaluated herein. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

  15. The Acute Inflammatory Response in Trauma / Hemorrhage and Traumatic Brain Injury: Current State and Emerging Prospects

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    Y Vodovotz

    2009-01-01

    Full Text Available Traumatic injury/hemorrhagic shock (T/HS elicits an acute inflammatory response that may result in death. Inflammation describes a coordinated series of molecular, cellular, tissue, organ, and systemic responses that drive the pathology of various diseases including T/HS and traumatic brain injury (TBI. Inflammation is a finely tuned, dynamic, highly-regulated process that is not inherentlydetrimental, but rather required for immune surveillance, optimal post-injury tissue repair, and regeneration. The inflammatory response is driven by cytokines and chemokines and is partiallypropagated by damaged tissue-derived products (Damage-associated Molecular Patterns; DAMP’s.DAMPs perpetuate inflammation through the release of pro-inflammatory cytokines, but may also inhibit anti-inflammatory cytokines. Various animal models of T/HS in mice, rats, pigs, dogs, and nonhumanprimates have been utilized in an attempt to move from bench to bedside. Novel approaches, including those from the field of systems biology, may yield therapeutic breakthroughs in T/HS andTBI in the near future.

  16. Immunopathology of rabies infection in mice selected for high or low acute inflammatory reaction

    Directory of Open Access Journals (Sweden)

    S. M. Achkar

    2007-01-01

    Full Text Available Rabies is a severe and lethal disease that produces a slight inflammatory response during the infection process. We analyzed the immunopathological mechanisms that occur in the central nervous system (CNS using mice genetically selected for maximal or minimal acute inflammatory reaction (AIRmax or AIRmin. As viral samples, we adopted the antigenic variant 3 (AgV3 of rabies virus from hematophagous bats and a fixed virus strain (PV1 43/3. Titration of specific antibodies was performed using enzyme-linked immunosorbent assay (ELISA. We observed a slight increase in IgG and IgG1 isotypes in infected AIRmax mice. Incubation period, determined by intracerebral inoculation with 100 LD50, was 6-7 days for PV1 43/4 strain and 9-10 days for AgV3. No difference in viral replication was noticed between AIRmax and AIRmin mice. Mortality was 100% with both viral strains. Histopathological analysis of brains and spinal cords showed inflammatory foci in all regions of the CNS. No differences were noticed in the number of neutrophils. Negri bodies were observed in practically all sites analyzed. Results suggested that inflammatory reaction is not a determining factor in the susceptibility to rabies infection.

  17. Genetics of acute inflammation: inflammatory reactions in inbred lines of mice and in their interline crosses.

    Science.gov (United States)

    Stiffel, C; Ibanez, O M; Ribeiro, O G; Decreusefond, C; Mouton, D; Siqueira, M; Biozzi, G

    1990-01-01

    Acute inflammation is induced by the subcutaneous injection of swollen polyacrylamide microbeads, its intensity measured by the cell and protein concentration of the local exudates. A large and continuous range of responses is obtained in different inbred strains of mice, which suggests a polygenic control of the inflammatory response. The variable levels of the global dominance observed in F1 hybrids issued from several parental combinations indicated that the pattern of alleles controlling high or low response was different in each parental strain. Balanced intercrossing of the 8 inbred strains studied has provided a genetically heterogeneous F3 population, presenting a high variability of responses. The value of the genetic part of F3 phenotypic variance, the spread of the interstrain differences, as well as the polygenic nature of the regulation of inflammatory responses pointed out the possibility to perform a bidirectional genetic selection by using the F3 mice as the foundation population, and response to microbeads as the selective phenotypic character.

  18. TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain.

    Science.gov (United States)

    Liu, Boyi; Fan, Lu; Balakrishna, Shrilatha; Sui, Aiwei; Morris, John B; Jordt, Sven-Eric

    2013-10-01

    Menthol, the cooling natural product of peppermint, is widely used in medicinal preparations for the relief of acute and inflammatory pain in sports injuries, arthritis, and other painful conditions. Menthol induces the sensation of cooling by activating TRPM8, an ion channel in cold-sensitive peripheral sensory neurons. Recent studies identified additional targets of menthol, including the irritant receptor, TRPA1, voltage-gated ion channels and neurotransmitter receptors. It remains unclear which of these targets contribute to menthol-induced analgesia, or to the irritating side effects associated with menthol therapy. Here, we use genetic and pharmacological approaches in mice to probe the role of TRPM8 in analgesia induced by L-menthol, the predominant analgesic menthol isomer in medicinal preparations. L-menthol effectively diminished pain behavior elicited by chemical stimuli (capsaicin, acrolein, acetic acid), noxious heat, and inflammation (complete Freund's adjuvant). Genetic deletion of TRPM8 completely abolished analgesia by L-menthol in all these models, although other analgesics (acetaminophen) remained effective. Loss of L-menthol-induced analgesia was recapitulated in mice treated with a selective TRPM8 inhibitor, AMG2850. Selective activation of TRPM8 with WS-12, a menthol derivative that we characterized as a specific TRPM8 agonist in cultured sensory neurons and in vivo, also induced TRPM8-dependent analgesia of acute and inflammatory pain. L-menthol- and WS-12-induced analgesia was blocked by naloxone, suggesting activation of endogenous opioid-dependent analgesic pathways. Our data show that TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. In contrast to menthol, selective TRPM8 agonists may produce analgesia more effectively, with diminished side effects.

  19. Spinal analgesic action of endomorphins in acute, inflammatory and neuropathic pain in rats.

    Science.gov (United States)

    Przewłocka, B; Mika, J; Labuz, D; Toth, G; Przewłocki, R

    1999-02-19

    We studied spinal analgesic and antiallodynic effects of endomorphin-1 and endomorphin-2 administered i.t. in comparison with Tyr-D-Ala-Gly-MePhe-Gly-ol (DAMGO) or morphine, during acute, inflammatory and neuropathic pain in rats chronically implanted with intrathecal cannulas. Endomorphin-1 and endomorphin-2 (2.5, 5, 10 microg i.t.) increased the tail-flick latency and, to the lesser extent, the paw pressure latency. The range of potencies in both those models of acute pain was as follows: DAMGO > morphine = endomorphin-1 > endomorphin-2. In a model of inflammatory pain, the number of formalin-induced flinching episodes was decreased by endomorphin-1. The effect of endomorphin-2 was much less pronounced. Both DAMGO and morphine significantly inhibited the pain-related behavior evoked by formalin. In a neuropathic pain model (sciatic nerve crushing in rats), endomorphin-1 and -2 (5 microg i.t.) had a statistically significant effect on the tail-flick latency and on the cold-water tail flick latency. Morphine, 5 microg, was found to be ineffective. Endomorphin-1 and -2 (2.5 and 5 microg i.t.) dose-dependently antagonized allodynia. Those effects of endomorphins were antagonized in acute (30 microg), inflammatory (30 microg) and neuropathic pain models (60 microg) by cyprodime, a selective mu-opioid receptor antagonist. In conclusion, our results show a strong analgesic action of endomorphins at the spinal cord level. The most interesting finding is a strong, stronger than in the case of morphine, antiallodynic effect of endomorphins in rats subjected to sciatic nerve crushing, which suggests a possible use of these compounds in a very difficult therapy of neuropathic pain.

  20. Melatonin Induces Anti-Inflammatory Effects to Play a Protective Role via Endoplasmic Reticulum Stress in Acute Pancreatitis.

    Science.gov (United States)

    Chen, Yina; Zhang, Jie; Zhao, Qian; Chen, Qinfen; Sun, Yangjie; Jin, Yin; Wu, Jiansheng

    2016-01-01

    Melatonin, which is mainly secreted by the pineal gland and released into blood, has anti-inflammatory properties in acute pancreatitis. Many studies show that melatonin can relieve inflammation in taurocholate-induced acute pancreatitis. However, the mechanisms of its anti-inflammatory effects are still undefined, especially the relationship between melatonin and endoplasmic reticulum stress. We explored the anti-inflammatory activity of melatonin in AR42J and rat models. The CCK-8 assay was used to assess effects of melatonin on AR42J cell viability. Inflammatory degree and the expressions of endoplasmic reticulum stress related molecules were examined by quantitative RT-PCR and western blotting. The degree of inflammation in the tissue was also accessed by pathological grading. Finally, we used the western blotting method to verify apoptosis and autophagy. Endoplasmic reticulum stress was obviously activated in early stage inflammation in AR42J and rat models. Melatonin could induce anti-inflammatory effects via endoplasmic reticulum stress. Melatonin significantly inhibited inflammatory cytokines and the expression of ERS-related molecules. Finally, it played a protective role by promoting apoptosis and autophagy of the cells, which were damaged in the process of inflammatory reaction. Melatonin induces anti-inflammatory effects via endoplasmic reticulum stress in acute pancreatitis to play a protective role. © 2016 The Author(s) Published by S. Karger AG, Basel.

  1. Melatonin Induces Anti-Inflammatory Effects to Play a Protective Role via Endoplasmic Reticulum Stress in Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Yina Chen

    2016-12-01

    Full Text Available Background/Aims: Melatonin, which is mainly secreted by the pineal gland and released into blood, has anti-inflammatory properties in acute pancreatitis. Many studies show that melatonin can relieve inflammation in taurocholate-induced acute pancreatitis. However, the mechanisms of its anti-inflammatory effects are still undefined, especially the relationship between melatonin and endoplasmic reticulum stress. We explored the anti-inflammatory activity of melatonin in AR42J and rat models. Methods: The CCK-8 assay was used to assess effects of melatonin on AR42J cell viability. Inflammatory degree and the expressions of endoplasmic reticulum stress related molecules were examined by quantitative RT-PCR and western blotting. The degree of inflammation in the tissue was also accessed by pathological grading. Finally, we used the western blotting method to verify apoptosis and autophagy. Results: Endoplasmic reticulum stress was obviously activated in early stage inflammation in AR42J and rat models. Melatonin could induce anti-inflammatory effects via endoplasmic reticulum stress. Melatonin significantly inhibited inflammatory cytokines and the expression of ERS-related molecules. Finally, it played a protective role by promoting apoptosis and autophagy of the cells, which were damaged in the process of inflammatory reaction. Conclusion: Melatonin induces anti-inflammatory effects via endoplasmic reticulum stress in acute pancreatitis to play a protective role.

  2. Cytokine-induced killer cells/dendritic cells and cytokine-induced killer cells immunotherapy for the treatment of esophageal cancer in China: a meta-analysis

    Science.gov (United States)

    Liu, Yan; Mu, Ying; Zhang, Anqi; Ren, Shaoda; Wang, Weihua; Xie, Jiaping; Zhang, Yingxin; Zhou, Changhui

    2017-01-01

    Background Immunotherapy based on cytokine-induced killer cells or combination of dendritic cells and cytokine-induced killer cells (CIK/DC-CIK) showed promising clinical outcomes for treating esophageal cancer (EC). However, the clinical benefit varies among previous studies. Therefore, it is necessary to systematically evaluate the curative efficacy and safety of CIK/DC-CIK immunotherapy as an adjuvant therapy for conventional therapeutic strategies in the treatment of EC. Materials and methods Clinical trials published before October 2016 and reporting CIK/DC-CIK immunotherapy treatment responses or safety for EC were searched in Cochrane Library, EMBASE, PubMed, Wanfang and China National Knowledge Internet databases. Research quality and heterogeneity were evaluated before analysis, and pooled analyses were performed using random- or fixed-effect models. Results This research covered 11 trials including 994 EC patients. Results of this meta-analysis indicated that compared with conventional therapy, the combination of conventional therapy with CIK/DC-CIK immunotherapy significantly prolonged the 1-year overall survival (OS) rate, overall response rate (ORR) and disease control rate (DCR) (1-year OS: P=0.0005; ORR and DCR: Pimmunotherapy, lymphocyte percentages of CD3+ and CD3−CD56+ subsets (P0.05). Conclusion The combination of CIK/DC-CIK immunotherapy and conventional therapy is safe and markedly prolongs survival time, enhances immune function and improves the treatment efficacy for EC.

  3. Hyperalgesia in a human model of acute inflammatory pain: a methodological study

    DEFF Research Database (Denmark)

    Pedersen, J L; Kehlet, H

    1998-01-01

    thresholds, (ii) mechanical and heat pain thresholds, (iii) pain to heat (43 degrees C and 45 degrees C, 5 s), (iv) secondary hyperalgesia, and (v) skin erythema were made 1.75 and 0.5 h before, and 0, 1, 2, 4, and 6 h after a burn injury. Sensory thresholds and hyperalgesia to heat and mechanical stimuli...... was demonstrated by significantly higher pain thresholds and lower pain responses on the second and third day of the study. The burn model is a sensitive psychophysical model of acute inflammatory pain, when cross-over designs and within-day comparisons are used, and the model is suitable for double-blind, placebo...

  4. Relationship between peritoneal macrophages and inflammatory reaction in a rat model of severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To investigate the relationship between peritoneal macrophages(PMAs)and inflammatory reaction in a rat model of severe acute pancreatitis(SAP).Methods Sprague-Dawley rats were randomly divided into control group and SAP group.To induce SAP in rats,40 g/L sodium taurocholate(0.1 mL/100 g)was injected into the pancreatic duct through retrograde exposure of pancreatic bile duct in hepatic porta.One-third of rats were sacrificed at 3,6 or 12 h after modeling.PMAs were extracted,and incubated for 24 h ...

  5. C1q/TNF-related protein-9 inhibits cytokine-induced vascular inflammation and leukocyte adhesiveness via AMP-activated protein kinase activation in endothelial cells.

    Science.gov (United States)

    Jung, Chang Hee; Lee, Min Jung; Kang, Yu Mi; Lee, Yoo La; Seol, So Mi; Yoon, Hae Kyeong; Kang, Sang-Wook; Lee, Woo Je; Park, Joong-Yeol

    2016-01-05

    Although recent studies have reported cardioprotective effects of C1q/TNF-related protein 9 (CTRP9), the closet adiponectin paralog, its role on cytokine-induced endothelial inflammation is unknown. We investigated whether CTRP9 prevented inflammatory cytokine-induced nuclear factor-kappa B (NF-κB) activation and inhibited the expression of adhesion molecules and a chemokine in the vascular endothelial cell. We used human aortic endothelial cells (HAECs) to examine the effects of CTRP9 on NF-κB activation and the expression of NF-κB-mediated genes, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1). Tumor necrosis factor alpha (TNFα) was used as a representative proinflammatory cytokine. In an adhesion assay using THP-1 cells, CTRP9 reduced TNFα-induced adhesion of monocytes to HAECs. Treatment with CTRP9 significantly decreased TNFα-induced activation of NF-κB, as well as the expression of ICAM-1, VCAM-1, and MCP-1. In addition, treatment with CTRP9 significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), the downstream target of AMPK. The inhibitory effect of CTRP9 on the expression of ICAM-1, VCAM-1, and MCP-1 and monocyte adhesion to HAECs was abolished after transfection with an AMPKα1-specific siRNA. Our study is the first to demonstrate that CTRP9 attenuates cytokine-induced vascular inflammation in endothelial cells mediated by AMPK activation.

  6. Cytokine-induced killer (CIK cell therapy for patients with hepatocellular carcinoma: efficacy and safety

    Directory of Open Access Journals (Sweden)

    Ma Yue

    2012-04-01

    Full Text Available Abstract Purpose To evaluate the efficacy of cytokine-induced killer (CIK cell therapy in the treatment of hepatocellular carcinoma. Materials and methods Randomized phase II and III trials on CIK cell-based therapy were identified by electronic searches using a combination of "hepatocellular carcinoma" and "cytokine-induced killer cells". Results The analysis showed significant survival benefit (one-year survival, p p p p p p +, CD4+, CD4+CD8+ and CD3+CD4+ T cells significantly increased in the CIK group, compared with the non-CIK group (p Conclusions CIK cell therapy demonstrated a significant superiority in prolonging the median overall survival, PFS, DCR, ORR and QoL of HCC patients. These results support further larger scale randomized controlled trials for HCC patients with or without the combination of other therapeutic methods.

  7. Urinary 1-Hydroxypyrene is Associated with Oxidative Stress and Inflammatory Biomarkers in Acute Myocardial Infarction

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    Fernando Freitas

    2014-09-01

    Full Text Available Several studies have associated exposure to environmental pollutants, especially polycyclic aromatic hydrocarbons (PAHs, with the development of cardiovascular diseases. Considering that 1-hydroxypyrene (1-OHP is the major biomarker of exposure to pyrenes, the purpose of this study was to evaluate the potential association between 1-OHP and oxidative stress/inflammatory biomarkers in patients who had suffered an acute myocardial infarction (AMI. After adopting the exclusion criteria, 58 post-infarction patients and 41 controls were sub-divided into smokers and non-smokers. Urinary 1-OHP, hematological and biochemical parameters, oxidative stress biomarkers (MDA, SOD, CAT, GPx and exogenous antioxidants and the inflammatory biomarker (hs-CRP were analyzed. 1-OHP levels were increased in post-infarct patients compared to controls (p < 0.05 and were correlated to MDA (r = 0.426, p < 0.01, CAT (r = 0.474, p < 0.001 and β-carotene (r = −0.309; p < 0.05 in non-smokers. Furthermore, post-infarction patients had elevated hs-CRP, MDA, CAT and GPx levels compared to controls for both smokers and non-smokers. Besides, β-carotene levels and SOD activity were decreased in post-infarction patients. In summary, our findings indicate that the exposure to pyrenes was associated to lipid damage and alterations of endogenous and exogenous antioxidants, demonstrating that PAHs contribute to oxidative stress and are associated to acute myocardial infarction.

  8. Polysaccharide extract of Mimosa tenuiflora stem barks stimulates acute inflammatory response via nitric oxide

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    Kaira Emanuella Sales da Silva-Leite

    2016-12-01

    Full Text Available Mimosa tenuiflora (Mimosaceae or “jurema-preta” is well distributed in the northeast Brazil, being popularly used to treat skin lesions, burns and inflammation. The healing effect of the alcoholic extract prepared with its barks corroborates the popular use. This study aimed to evaluate the inflammatory response of polysaccharides extracted from M. tenuiflora barks (EP-Mt by methanol/NaOH and ethanol precipitation. Inflammatory activity was assessed in rat models of acute inflammation (paw edema and peritonitis, by the following parameters: edema, vascular permeability, leukocyte migration, myeloperoxidase activity and pharmacological modulation of nitric oxide and prostaglandins. EP-Mt presented 3.8% yield, 41% carbohydrate and 0.34% protein. EP-Mt (0.01, 0.1, 1.0 mg kg-1 injected by subcutaneous route elicited paw edema that lasted from 30-420 min, with maximal effect at 1 mg kg-1 (40x vs. saline, and was inhibited by L-NAME (52% and dexamethasone (26%. EP-Mt (1 mg kg-1, via intraperitoneal stimulated leukocytes migration (2.2x, mainly neutrophils (6.5x and MPO activity (96%. The leukocyte migration elicited by EP-Mt was inhibited by dexamethasone (39% and L-NAME (38%. EP-Mt containing high carbohydrate content induces acute inflammation via nitric oxide, which open perspectives of application in pathological conditions of immunosuppression.

  9. Apolipoprotein CIII Reduces Proinflammatory Cytokine-Induced Apoptosis in Rat Pancreatic Islets via the Akt Prosurvival Pathway

    DEFF Research Database (Denmark)

    Størling, Joachim; Juntti-Berggren, Lisa; Olivecrona, Gunilla;

    2011-01-01

    Apolipoprotein CIII (ApoCIII) is mainly synthesized in the liver and is important for triglyceride metabolism. The plasma concentration of ApoCIII is elevated in patients with type 1 diabetes (T1D), and in vitro ApoCIII causes apoptosis in pancreatic ß-cells in the absence of inflammatory stress...... µg/ml) did not cause apoptosis. In the presence of the islet-cytotoxic cytokines IL-1ß + interferon-¿, ApoCIII reduced cytokine-mediated islet cell death and impairment of ß-cell function. ApoCIII had no effects on mitogen-activated protein kinases (c-Jun N-terminal kinase, p38, and ERK) and had...... of the survival serine-threonine kinase Akt. Inhibition of the Akt signaling pathway by the phosphatidylinositol 3 kinase inhibitor LY294002 counteracted the antiapoptotic effect of ApoCIII on cytokine-induced apoptosis. We conclude that ApoCIII in the presence of T1D-relevant proinflammatory cytokines reduces...

  10. Pulmonary Inflammatory Responses to Acute Meteorite Dust Exposures - to Acute Meteorite Dust Exposures - Exploration

    Science.gov (United States)

    Harrington, A. D.; McCubbin, F. M.; Kaur, J.; Smirnov, A.; Galdanes, K.; Schoonen, M. A. A.; Chen, L. C.; Tsirka, S. E.; Gordon, T.

    2017-01-01

    New initiatives to begin lunar and martian colonization within the next few decades are illustrative of the resurgence of interest in space travel. One of NASA's major concerns with extended human space exploration is the inadvertent and repeated exposure to unknown dust. This highly interdisciplinary study evaluates both the geochemical reactivity (e.g. iron solubility and acellular reactive oxygen species (ROS) generation) and the relative toxicity (e.g. in vitro and in vivo pulmonary inflammation) of six meteorite samples representing either basalt or regolith breccia on the surface of the Moon, Mars, and Asteroid 4Vesta. Terrestrial mid-ocean ridge basalt (MORB) is also used for comparison. The MORB demonstrated higher geochemical reactivity than most of the meteorite samples but caused the lowest acute pulmonary inflammation (API). Notably, the two martian meteorites generated some of the highest API but only the basaltic sample is significantly reactive geochemically. Furthermore, while there is a correlation between a meteorite's soluble iron content and its ability to generate acellular ROS, there is no direct correlation between a particle's ability to generate ROS acellularly and its ability to generate API. However, assorted in vivo API markers did demonstrate strong positive correlations with increasing bulk Fenton metal content. In summary, this comprehensive dataset allows for not only the toxicological evaluation of astromaterials but also clarifies important correlations between geochemistry and health.

  11. No inflammatory gene-expression response to acute exercise in human Achilles tendinopathy

    DEFF Research Database (Denmark)

    Pingel, Jessica; Fredberg, Ulrich; Mikkelsen, Lone Ramer

    2013-01-01

    Although histology data favour the view of a degenerative nature of tendinopathy, indirect support for inflammatory reactions to loading in affected tendons exists. The purpose of the present study was to elucidate whether inflammatory signalling responses after acute mechanical loading were more...... pronounced in tendinopathic versus healthy regions of human tendon and if treatment with non-steroidal anti-inflammatory medications (NSAID's) reduces this response. Twenty-seven tendinopathy patients (>6 months) were randomly assigned to a placebo (n = 14) or NSAID (Ibumetin NYCOMED GmbH Plant Oranienburg...... Germany (600 mg) × 3/day/1 week) group (n = 13) in a double-blinded-fashion. Tendon biopsies were taken from the painful and a healthy region of the same tendon 2 h after 1 h running. Gene-expression of several targets was analysed in the sampled Achilles tendon biopsies. The mRNA for TGF-ß, collagen...

  12. Elevated Circulating Levels of Inflammatory Markers in Patients with Acute Coronary Syndrome

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    Hamad Al Shahi

    2015-01-01

    Full Text Available Objective. We evaluated inflammatory cytokines and chemokine in peripheral blood mononuclear cells (PBMCs in patients with either acute coronary syndrome (ACS or stable coronary artery disease (CAD. Methods. We enrolled 20 ACS patients and 50 stable CAD patients without previous history of ACS who underwent cardiac catheterization. Patients with an estimated glomerular filtration rate of ≤30 mL/min/1.73 m2 and C-reactive protein of ≥1.0 mg/dL were excluded. Blood samples were collected from the patients just before catheterization, and PBMCs were isolated from the whole blood. The levels of inflammatory cytokines and chemokine were measured by using real-time quantitative polymerase chain reaction and immunoassays. Results. The expression of tumor necrosis factor alpha (TNF-α, interleukin- (IL- 6, IL-10, IL-23A, IL-27, and IL-37 was significantly higher in the ACS group than in the CAD group (P<0.05. In contrast, the expression of IL-33 was significantly lower in the ACS group than in the CAD group (P<0.05. The ACS patients had higher plasma levels of TNF-α, IL-6, and IL-10 in the ACS group than in the CAD group. Conclusion. Circulating levels of pro-/anti-inflammatory cytokines, including IL-23A, IL-27, IL-33, and IL-37, may be associated with the pathogenesis of atherosclerosis in ACS patients.

  13. Cold stress aggravates inflammatory responses in an LPS-induced mouse model of acute lung injury

    Science.gov (United States)

    Joo, Su-Yeon; Park, Mi-Ju; Kim, Kyun-Ha; Choi, Hee-Jung; Chung, Tae-Wook; Kim, Yong Jin; Kim, Joung Hee; Kim, Keuk-Jun; Joo, Myungsoo; Ha, Ki-Tae

    2016-08-01

    Although the relationship between environmental cold temperature and susceptibility to respiratory infection is generally accepted, the effect of ambient cold temperature on host reactivity in lung inflammation has not been fully studied. To examine the function of ambient cold temperature on lung inflammation, mice were exposed to 4 °C for 8 h each day for 14 days. In the lungs of mice exposed to cold stress, inflammatory cells in bronchoalveolar lavage (BAL) fluid and lung tissues were slightly increased by about twofold. However, the structures of pulmonary epithelial cells were kept within normal limits. Next, we examined the effect of cold stress on the inflammatory responses in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. The infiltration of neutrophils and inflammation of lung tissue determined by histology were significantly increased by exposure to ambient cold temperature. In addition, the production of pro-inflammatory cytokines including interleukin (IL)-12, IL-17, and monokine induced by gamma interferon (MIG) was elevated by exposure to cold stress. Therefore, we suggest that cold stress is a factor that exacerbates lung inflammation including ALI. To our knowledge, this is the first report on the relationship between cold stress and severity of lung inflammation.

  14. Vitamin D3 pretreatment regulates renal inflammatory responses during lipopolysaccharide-induced acute kidney injury.

    Science.gov (United States)

    Xu, Shen; Chen, Yuan-Hua; Tan, Zhu-Xia; Xie, Dong-Dong; Zhang, Cheng; Zhang, Zhi-Hui; Wang, Hua; Zhao, Hui; Yu, De-Xin; Xu, De-Xiang

    2015-12-22

    Vitamin D receptor (VDR) is highly expressed in human and mouse kidneys. Nevertheless, its functions remain obscure. This study investigated the effects of vitamin D3 (VitD3) pretreatment on renal inflammation during lipopolysaccharide (LPS)-induced acute kidney injury. Mice were intraperitoneally injected with LPS. In VitD3 + LPS group, mice were pretreated with VitD3 (25 μg/kg) at 48, 24 and 1 h before LPS injection. As expected, an obvious reduction of renal function and pathological damage was observed in LPS-treated mice. VitD3 pretreatment significantly alleviated LPS-induced reduction of renal function and pathological damage. Moreover, VitD3 pretreatment attenuated LPS-induced renal inflammatory cytokines, chemokines and adhesion molecules. In addition, pretreatment with 1,25(OH)2D3, the active form of VitD3, alleviated LPS-induced up-regulation of inflammatory cytokines and chemokines in human HK-2 cells, a renal tubular epithelial cell line, in a VDR-dependent manner. Further analysis showed that VitD3, which activated renal VDR, specifically repressed LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 subunit in the renal tubules. LPS, which activated renal NF-κB, reciprocally suppressed renal VDR and its target gene. Moreover, VitD3 reinforced the physical interaction between renal VDR and NF-κB p65 subunit. These results provide a mechanistic explanation for VitD3-mediated anti-inflammatory activity during LPS-induced acute kidney injury.

  15. Chemical composition, acute toxicity, antioxidant and anti-inflammatory activities of Moroccan Tetraclinis articulata L.

    Science.gov (United States)

    El Jemli, Meryem; Kamal, Rabie; Marmouzi, Ilias; Doukkali, Zouhra; Bouidida, El Houcine; Touati, Driss; Nejjari, Rachid; El Guessabi, Lahcen; Cherrah, Yahia; Alaoui, Katim

    2017-07-01

    Hydro-distilled essential oil (EO) from the leaves of the western Mediterranean and Moroccan endemic plant Tetraclinis articulata was analyzed by GC/MS and examined for its acute toxicity on mice, in order to establish the safe doses. Furthermore, the anti-Inflammatory activity was evaluated based on carrageenan and trauma induced rats paw edema and the antioxidant potential has been investigated using different methods including DPPH radical-scavenging assay, Trolox equivalent antioxidant capacity (TEAC) and Ferric-reducing antioxidant power assay (FRAP). The major identified compounds in GC/MS analysis were bornyl acetate (26.81%), camphor (22.40%) and α-pinene (7.16%), with 25 other minor constituents. No mortalities in acute toxicity were observed, indicating that the LD50 of T. articulata essential oil is highest than 5 g/kg. In the anti-inflammatory test based on chemical and mechanical induced trauma, the EO demonstrated an effective reduce swelling by 64.71 ± 9.38% and 69.09 ± 6.02% respectively obtained 6 h after administration at the dose of 200 mg/kg when compared to the control groups. Moreover in the antioxidant testing battery, T. articulata essential oil showed a promising scavenging effect measured by DPPH, TEAC and ferric-reducing power assays with IC50 values of 12.05 ± 0.24 mg/mL, 8.90 ± 0.17 mg/mL and 0.15 ± 0.01 mg/mL respectively. These results suggest that, the EO from the leaves of T. articulata constitutes a valuable source of anti-inflammatory and antioxidant metabolites. These findings argue for the possible integration of this oil in pharmaceutical, cosmetic and food industries.

  16. Chemical composition, acute toxicity, antioxidant and anti-inflammatory activities of Moroccan Tetraclinis articulata L.

    Directory of Open Access Journals (Sweden)

    Meryem El Jemli

    2017-07-01

    Full Text Available Hydro-distilled essential oil (EO from the leaves of the western Mediterranean and Moroccan endemic plant Tetraclinis articulata was analyzed by GC/MS and examined for its acute toxicity on mice, in order to establish the safe doses. Furthermore, the anti-Inflammatory activity was evaluated based on carrageenan and trauma induced rats paw edema and the antioxidant potential has been investigated using different methods including DPPH radical-scavenging assay, Trolox equivalent antioxidant capacity (TEAC and Ferric-reducing antioxidant power assay (FRAP. The major identified compounds in GC/MS analysis were bornyl acetate (26.81%, camphor (22.40% and α-pinene (7.16%, with 25 other minor constituents. No mortalities in acute toxicity were observed, indicating that the LD50 of T. articulata essential oil is highest than 5 g/kg. In the anti-inflammatory test based on chemical and mechanical induced trauma, the EO demonstrated an effective reduce swelling by 64.71 ± 9.38% and 69.09 ± 6.02% respectively obtained 6 h after administration at the dose of 200 mg/kg when compared to the control groups. Moreover in the antioxidant testing battery, T. articulata essential oil showed a promising scavenging effect measured by DPPH, TEAC and ferric-reducing power assays with IC50 values of 12.05 ± 0.24 mg/mL, 8.90 ± 0.17 mg/mL and 0.15 ± 0.01 mg/mL respectively. These results suggest that, the EO from the leaves of T. articulata constitutes a valuable source of anti-inflammatory and antioxidant metabolites. These findings argue for the possible integration of this oil in pharmaceutical, cosmetic and food industries.

  17. Therapeutic effects of sesame oil on monosodium urate crystal-induced acute inflammatory response in rats.

    Science.gov (United States)

    Hsu, Dur-Zong; Chen, Si-Jin; Chu, Pei-Yi; Liu, Ming-Yie

    2013-01-01

    Sesame oil has been used in traditional Taiwanese medicine to relieve the inflammatory pain in people with joint inflammation, toothache, scrapes, and cuts. However, scientific evidence related to the effectiveness or action mechanism of sesame oil on relief of pain and inflammation has not been examined experimentally. Here, we investigated the therapeutic effect of sesame oil on monosodium urate monohydrate (MSU) crystal-induced acute inflammatory response in rats. Air pouch, a pseudosynovial cavity, was established by injecting 24 mL of filtered sterile air subcutaneously in the backs of the rats. At day 0, inflammation in air pouch was induced by injecting MSU crystal (5 mg/rat, suspended in sterilized phosphate buffered saline, pH 7.4), while sesame oil (0, 1, 2, or 4 mL/kg, orally) was given 6 h after MSU crystal injection. Parameters in lavage and skin tissue from the air pouches were assessed 6 h after sesame oil was given. Sesame oil decreased MSU crystal-induced total cell counts, tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 levels in lavage and pouch tissue. Sesame oil significantly decreased leukocyte and neutrophil counts in lavage compared with MSU crystal alone group. Sesame oil decreased activated mast cell counts in skin tissue in MSU crystal-treated rats. Sesame oil significantly decreased nuclear factor (NF)-κB activity and IL-4 level in isolated mast cells from rats treated with MSU crystal. Furthermore, sesame oil decreased lavage complement proteins C3a and C5a levels in MSU crystal-treated rats. In conclusion, sesame oil shows a potent therapeutic effect against MSU crystal-induced acute inflammatory response in rats.

  18. The fecal microbiome in dogs with acute diarrhea and idiopathic inflammatory bowel disease.

    Directory of Open Access Journals (Sweden)

    Jan S Suchodolski

    Full Text Available BACKGROUND: Recent molecular studies have revealed a highly complex bacterial assembly in the canine intestinal tract. There is mounting evidence that microbes play an important role in the pathogenesis of acute and chronic enteropathies of dogs, including idiopathic inflammatory bowel disease (IBD. The aim of this study was to characterize the bacterial microbiota in dogs with various gastrointestinal disorders. METHODOLOGY/PRINCIPAL FINDINGS: Fecal samples from healthy dogs (n = 32, dogs with acute non-hemorrhagic diarrhea (NHD; n = 12, dogs with acute hemorrhagic diarrhea (AHD; n = 13, and dogs with active (n = 9 and therapeutically controlled idiopathic IBD (n = 10 were analyzed by 454-pyrosequencing of the 16S rRNA gene and qPCR assays. Dogs with acute diarrhea, especially those with AHD, had the most profound alterations in their microbiome, as significant separations were observed on PCoA plots of unweighted Unifrac distances. Dogs with AHD had significant decreases in Blautia, Ruminococcaceae including Faecalibacterium, and Turicibacter spp., and significant increases in genus Sutterella and Clostridium perfringens when compared to healthy dogs. No significant separation on PCoA plots was observed for the dogs with IBD. Faecalibacterium spp. and Fusobacteria were, however, decreased in the dogs with clinically active IBD, but increased during time periods of clinically insignificant IBD, as defined by a clinical IBD activity index (CIBDAI. CONCLUSIONS: Results of this study revealed a bacterial dysbiosis in fecal samples of dogs with various GI disorders. The observed changes in the microbiome differed between acute and chronic disease states. The bacterial groups that were commonly decreased during diarrhea are considered to be important short-chain fatty acid producers and may be important for canine intestinal health. Future studies should correlate these observed phylogenetic differences with functional changes in the intestinal

  19. Limited inflammatory response in rats after acute exposure to a silicon carbide nanoaerosol

    Science.gov (United States)

    Laloy, J.; Lozano, O.; Alpan, L.; Masereel, B.; Toussaint, O.; Dogné, J. M.; Lucas, S.

    2015-08-01

    Inhalation represents the major route of human exposure to manufactured nanomaterials (NMs). Assessments are needed about the potential risks of NMs from inhalation on different tissues and organs, especially the respiratory tract. The aim of this limited study is to determine the potential acute pulmonary toxicity in rats exposed to a dry nanoaerosol of silicon carbide (SiC) nanoparticles (NPs) in a whole-body exposure (WBE) model. The SiC nanoaerosol is composed of a bimodal size distribution of 92.8 and 480 nm. The exposure concentration was 4.91 mg/L, close to the highest recommended concentration of 5 mg/L by the Organisation for Economic Co-operation and Development. Rats were exposed for 6 h to a stable and reproducible SiC nanoaerosol under real-time measurement conditions. A control group was exposed to the filtered air used to create the nanoaerosol. Animals were sacrificed immediately, 24 or 72 h after exposure. The bronchoalveolar lavage fluid from rat lungs was recovered. Macrophages filled with SiC NPs were observed in the rat lungs. The greatest load of SiC and macrophages filled with SiC were observed on the rat lungs sacrificed 24 h after acute exposure. A limited acute inflammatory response was found up to 24 h after exposure characterized by a lactate dehydrogenase and total protein increase or presence of inflammatory cells in pulmonary lavage. For this study a WBE model has been developed, it allows the simultaneous exposure of six rats to a nanoaerosol and six rats to clean-filtered air. The nanoaerosol was generated using a rotating brush system (RBG-1000) and analyzed with an electrical low pressure impactor in real time.

  20. Autonomic nervous system modulation affects the inflammatory immune response in mice with acute Chagas disease.

    Science.gov (United States)

    Machado, Marcus Paulo Ribeiro; Rocha, Aletheia Moraes; de Oliveira, Lucas Felipe; de Cuba, Marília Beatriz; de Oliveira Loss, Igor; Castellano, Lucio Roberto; Silva, Marcus Vinicius; Machado, Juliana Reis; Nascentes, Gabriel Antonio Nogueira; Paiva, Luciano Henrique; Savino, Wilson; Junior, Virmondes Rodrigues; Brum, Patricia Chakur; Prado, Vania Ferreira; Prado, Marco Antonio Maximo; Silva, Eliane Lages; Montano, Nicola; Ramirez, Luis Eduardo; Dias da Silva, Valdo Jose

    2012-11-01

    The aim of the present study was to evaluate the effects of changes to the autonomic nervous system in mice during the acute phase of Chagas disease, which is an infection caused by the parasite Trypanosoma cruzi. The following types of mice were inoculated with T. cruzi (CHG): wild-type (WT) and vesicular acetylcholine transporter knockdown (KDVAChT) C57BL/6j mice; wild-type non-treated (NT) FVB mice; FVB mice treated with pyridostigmine bromide (PYR) or salbutamol (SALB); and β(2)-adrenergic receptor knockout (KOβ2) FVB mice. During infection and at 18-21 days after infection (acute phase), the survival curves, parasitaemia, electrocardiograms, heart rate variability, autonomic tonus and histopathology of the animals were evaluated. Negative control groups were matched for age, genetic background and treatment. The KDVAChT-CHG mice exhibited a significant shift in the electrocardiographic, autonomic and histopathological profiles towards a greater inflammatory immune response that was associated with a reduction in blood and tissue parasitism. In contrast, the CHG-PYR mice manifested reduced myocardial inflammation and lower blood and tissue parasitism. Similar results were observed in CHG-SALB animals. Unexpectedly, the KOβ2-CHG mice exhibited less myocardial inflammation and higher blood and tissue parasitism, which were associated with reduced mortality. These findings could have been due to the increase in vagal tone observed in the KOβ2 mice, which rendered them more similar to the CHG-PYR animals. In conclusion, our results indicate a marked immunomodulatory role for the parasympathetic and sympathetic autonomic nervous systems, which inhibit both the inflammatory immune response and parasite clearance during the acute phase of experimental Chagas heart disease in mice.

  1. Functional role of monocytes and macrophages for the inflammatory response in acute liver injury

    Directory of Open Access Journals (Sweden)

    Henning W Zimmermann

    2012-10-01

    Full Text Available Different etiologies such as drug toxicity, acute viral hepatitis B or acetaminophen poisoning can cause acute liver injury (ALI or even acute liver failure (ALF. Excessive cell death of hepatocytes in the liver is known to result in a strong hepatic inflammation. Experimental murine models of liver injury highlighted the importance of hepatic macrophages, so-called Kupffer cells, for initiating and driving this inflammatory response by releasing proinflammatory cytokines and chemokines including tumor necrosis factor (TNF, interleukin-6 (IL-6, IL-1-beta or monocyte chemoattractant protein 1 (MCP-1, CCL2 as well as activating other non-parenchymal liver cells, e.g. endothelial or hepatic stellate cells (HSC. Many of these proinflammatory mediators can trigger hepatocytic cell death pathways, e.g. via caspase activation, but also activate protective signaling pathways, e.g. via nuclear factor kappa B (NF-kB. Recent studies in mice demonstrated that these macrophage actions largely depend on the recruitment of monocytes into the liver, namely of the inflammatory Ly6c+ (Gr1+ monocyte subset as precursors of tissue macrophages. The chemokine receptor CCR2 and its ligand MCP-1/CCL2 promote monocyte subset infiltration upon liver injury. In contrast, the chemokine receptor CX3CR1 and its ligand fractalkine (CX3CL1 are important negative regulators of monocyte infiltration by controlling their survival and differentiation into functionally diverse macrophage subsets upon injury. The recently identified cellular and molecular pathways for monocyte subset recruitment, macrophage differentiation and interactions with other hepatic cell types in the injured liver may therefore represent interesting novel targets for future therapeutic approaches in ALF.

  2. Limited inflammatory response in rats after acute exposure to a silicon carbide nanoaerosol

    Energy Technology Data Exchange (ETDEWEB)

    Laloy, J., E-mail: julie.laloy@unamur.be [University of Namur (UNamur), Department of Pharmacy, Namur Nanosafety Centre (NNC), Namur Research Institute for Life Sciences NARILIS (Belgium); Lozano, O. [University of Namur (UNamur), Research Centre in Physics of Matter and Radiation (PMR), Namur Nanosafety Centre NNC, Namur Research Institute for Life Sciences NARILIS (Belgium); Alpan, L.; Masereel, B. [University of Namur (UNamur), Department of Pharmacy, Namur Nanosafety Centre (NNC), Namur Research Institute for Life Sciences NARILIS (Belgium); Toussaint, O. [University of Namur (UNamur), Laboratory of Cellular Biochemistry and Biology (URBC), Namur Nanosafety Centre NNC, Namur Research Institute for Life Sciences NARILIS (Belgium); Dogné, J. M. [University of Namur (UNamur), Department of Pharmacy, Namur Nanosafety Centre (NNC), Namur Research Institute for Life Sciences NARILIS (Belgium); Lucas, S. [University of Namur (UNamur), Research Centre in Physics of Matter and Radiation (PMR), Namur Nanosafety Centre NNC, Namur Research Institute for Life Sciences NARILIS (Belgium)

    2015-08-15

    Inhalation represents the major route of human exposure to manufactured nanomaterials (NMs). Assessments are needed about the potential risks of NMs from inhalation on different tissues and organs, especially the respiratory tract. The aim of this limited study is to determine the potential acute pulmonary toxicity in rats exposed to a dry nanoaerosol of silicon carbide (SiC) nanoparticles (NPs) in a whole-body exposure (WBE) model. The SiC nanoaerosol is composed of a bimodal size distribution of 92.8 and 480 nm. The exposure concentration was 4.91 mg/L, close to the highest recommended concentration of 5 mg/L by the Organisation for Economic Co-operation and Development. Rats were exposed for 6 h to a stable and reproducible SiC nanoaerosol under real-time measurement conditions. A control group was exposed to the filtered air used to create the nanoaerosol. Animals were sacrificed immediately, 24 or 72 h after exposure. The bronchoalveolar lavage fluid from rat lungs was recovered. Macrophages filled with SiC NPs were observed in the rat lungs. The greatest load of SiC and macrophages filled with SiC were observed on the rat lungs sacrificed 24 h after acute exposure. A limited acute inflammatory response was found up to 24 h after exposure characterized by a lactate dehydrogenase and total protein increase or presence of inflammatory cells in pulmonary lavage. For this study a WBE model has been developed, it allows the simultaneous exposure of six rats to a nanoaerosol and six rats to clean-filtered air. The nanoaerosol was generated using a rotating brush system (RBG-1000) and analyzed with an electrical low pressure impactor in real time.

  3. Pannexin-2-deficiency sensitizes pancreatic beta-cells to cytokine-induced apoptosis in vitro and impairs glucose tolerance in vivo

    DEFF Research Database (Denmark)

    Berchtold, Lukas A.; Miani, Michela; Diep, Thi A.

    2017-01-01

    Pannexins (Panx's) are membrane proteins involved in a variety of biological processes, including cell death signaling and immune functions. The role and functions of Panx's in pancreatic β-cells remain to be clarified. Here, we show Panx1 and Panx2 expression in isolated islets, primary β-cells......, and β-cell lines. The expression of Panx2, but not Panx1, was downregulated by interleukin-1β (IL-1β) plus interferon-γ (IFNγ), two pro-inflammatory cytokines suggested to contribute to β-cell demise in type 1 diabetes (T1D). siRNA-mediated knockdown (KD) of Panx2 aggravated cytokine-induced apoptosis...... in rat INS-1E cells and primary rat β-cells, suggesting anti-apoptotic properties of Panx2. An anti-apoptotic function of Panx2 was confirmed in isolated islets from Panx2-/- mice and in human EndoC-βH1 cells. Panx2 KD was associated with increased cytokine-induced activation of STAT3 and higher...

  4. Acute Inflammatory Demyelinating Polyneuropathy and a Unilateral Babinski/Plantar Reflex

    Directory of Open Access Journals (Sweden)

    Davide Cattano

    2008-01-01

    Full Text Available Acquired acute demyelinating peripheral polyneuropathy (AADP is a general classification of pathologies that could affect secondary the peripheral nervous system. They are characterized by an autoimmune process directed towards myelin. Clinically they are characterized by progressive weakness and mild sensory changes. Acute inflammatory demyelinating polyneuropathy often is referred to as Guillain-Barré syndrome (GBS. GBS is the major cause of acute nontraumatic paralysis in healthy people and it is caused by autoimmune response to viral agents (influenza, coxsackie, Epstein-Barr virus, or cytomegalovirus or bacterial infective organisms (Campylobacter jejuni, Mycoplasma pneumoniae. A detailed history, with symptoms of progressive usually bilateral weakness, hyporeflexia, with a typical demyelinating EMG pattern supports the diagnosis. Progressive affection of respiratory muscles and autonomic instability coupled with a protracted and unpredictable recovery normally results in the need for ICU management. We present a case report of a patient with a typical GBS presentation but with a unilateral upgoing plantar reflex (Babinski sign. A unifying diagnosis was made and based on a literature search in Pubmed appears to be the first described case of its kind.

  5. Acute inflammatory demyelinating polyneuropathy and a unilateral babinski/plantar reflex.

    Science.gov (United States)

    Cattano, Davide; O'connor, Brian; Shakir, Ra'ad; Giunta, Francesco; Palazzo, Mark

    2008-01-01

    Acquired acute demyelinating peripheral polyneuropathy (AADP) is a general classification of pathologies that could affect secondary the peripheral nervous system. They are characterized by an autoimmune process directed towards myelin. Clinically they are characterized by progressive weakness and mild sensory changes. Acute inflammatory demyelinating polyneuropathy often is referred to as Guillain-Barré syndrome (GBS). GBS is the major cause of acute nontraumatic paralysis in healthy people and it is caused by autoimmune response to viral agents (influenza, coxsackie, Epstein-Barr virus, or cytomegalovirus) or bacterial infective organisms (Campylobacter jejuni, Mycoplasma pneumoniae). A detailed history, with symptoms of progressive usually bilateral weakness, hyporeflexia, with a typical demyelinating EMG pattern supports the diagnosis. Progressive affection of respiratory muscles and autonomic instability coupled with a protracted and unpredictable recovery normally results in the need for ICU management. We present a case report of a patient with a typical GBS presentation but with a unilateral upgoing plantar reflex (Babinski sign). A unifying diagnosis was made and based on a literature search in Pubmed appears to be the first described case of its kind.

  6. Association of calprotectin with leukocyte chemotactic and inflammatory mediators following acute aerobic exercise.

    Science.gov (United States)

    Maharaj, Arun; Slusher, Aaron L; Zourdos, Michael C; Whitehurst, Michael; Fico, Brandon G; Huang, Chun-Jung

    2016-01-01

    The objective of this study was to examine whether acute aerobic exercise-mediated calprotectin in plasma would be associated with monocyte chemotactic protein-1 (MCP-1), myeloperoxidase (MPO), and interleukin-6 (IL-6) in healthy individuals. Eleven healthy participants, aged 18 to 30 years, were recruited to perform a 30-min bout of aerobic exercise at 75% maximal oxygen uptake. Acute aerobic exercise elicited a significant elevation across time in plasma calprotectin, MCP-1, MPO, and IL-6. Body mass index (BMI) was positively correlated with calprotectin area-under-the-curve with "respect to increase" (AUCi) and IL-6 AUCi. Furthermore, calprotectin AUCi was positively correlated with IL-6 AUCi and MPO AUCi, even after controlling for BMI. Although MPO AUCi was positively correlated with IL-6 AUCi, this relationship no longer existed after controlling for BMI. These results suggest that acute aerobic exercise could mediate innate immune response associated with calprotectin and its related leukocyte chemotactic and inflammatory mediators, especially in individuals with elevated BMI.

  7. Reverse kinetics of angiopoietin-2 and endotoxins in acute pyelonephritis: Implications for anti-inflammatory treatment?

    Science.gov (United States)

    Safioleas, Konstantinos; Giamarellos-Bourboulis, Evangelos J; Carrer, Dionyssia-Pinelopi; Pistiki, Aikaterini; Sabracos, Lambros; Deliveliotis, Charalambos; Chrisofos, Michael

    2016-05-01

    Based on former studies showing an antagonism between angiopoietin-2 (Ang-2) and bacterial endotoxins (LPS), we investigated the role of Ang-2 as immunomodulatory treatment. At first, kinetics of circulating LPS in Gram-negative pyelonephritis developing after urinary obstruction was studied. Serum LPS, interleukin (IL)-6 and Ang-2 were measured in 25 patients with acute pyelonephritis and sepsis before and after removal of the obstruction performed either with insertion of a pigtail catheter (n=12) or percutaneous drainage (n=13). At a second stage, Ang-2 was given as anti-inflammatory treatment in 40 rabbits one hour after induction of acute pyelonephritis by ligation of the ureter at the level of pelvo-ureteral junction and upstream bacterial inoculation. Survival was recorded; blood mononuclear cells were isolated and stimulated for the production of tumour necrosis factor-alpha (TNFα). The decrease in circulating LPS was significantly greater among patients undergoing drainage than pigtail insertion. This was accompanied by reciprocal changes of Ang-2 and IL-6. Treatment with Ang-2 prolonged survival from Escherichia coli pyelonephritis despite high levels of circulating LPS. When Ang-2 was given as treatment of Pseudomonas aeruginosa pyelonephritis, sepsis-induced decrease of TNFα production by circulating mononuclear cells was reversed without an effect on tissue bacterial overgrowth. It is concluded that Ang-2 and LPS follow reverse kinetics in acute pyelonephritis. When given as experimental treatment, Ang-2 prolongs survival through an effect on mononuclear cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Protein phosphatases and chromatin modifying complexes in the inflammatory cascade in acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Javier; Escobar; Javier; Pereda; Alessandro; Arduini; Juan; Sastre; Juan; Sandoval; Luis; Aparisi; Gerardo; López-Rodas; Luis; Sabater

    2010-01-01

    Acute pancreatitis is an inflammation of the pancreas that may lead to systemic inflammatory response syndrome and death due to multiple organ failure. Acinar cells, together with leukocytes, trigger the inflammatory cascade in response to local damage of the pancreas. Amplification of the inflammatory cascade requires up-regulation of proinflammatory cytokines and this process is mediated not only by nuclear factor κB but also by chromatinmodifying complexes and chromatin remodeling. Among the different families of histone acetyltransferases, the p300/CBP family seems to be particularly associated with the inflammatory process. cAMP activates gene expression via the cAMP-responsive element (CRE) and the transcription factor CRE-binding protein (CREB). CREB can be phosphorylated and activated by different kinases, such as protein kinase A and MAPK, and then it recruits the histone acetyltransferase co-activator CREB-binding protein (CBP) and its homologue p300. The recruitment of CBP/p300 and changes in the level of histone acetylation are required for transcription activation. Transcriptional repression is also a dynamic and essential mechanism of down-regulation of genes for resolution of inflammation, which seems to be mediated mainly by protein phosphatases (PP1, PP2A and MKP1) and histone deacetylases(HDACs) .Class HDACs are key transcriptional regulators whose activities are controlled via phosphorylationdependent nucleo/cytoplasmic shuttling. PP2A is responsible for dephosphorylation of class HDACs, triggeringnuclear localization and repression of target genes, whereas phosphorylation triggers cytoplasmic localization leading to activation of target genes. The potential benefit from treatment with phosphodiesterase inhibitors and histone deacetylase inhibitors is discussed.

  9. Inhibition of extracellular HMGB1 attenuates hyperoxia-induced inflammatory acute lung injury

    Directory of Open Access Journals (Sweden)

    Maria Entezari

    2014-01-01

    Full Text Available Prolonged exposure to hyperoxia results in acute lung injury (ALI, accompanied by a significant elevation in the levels of proinflammatory cytokines and leukocyte infiltration in the lungs. However, the mechanisms underlying hyperoxia-induced proinflammatory ALI remain to be elucidated. In this study, we investigated the role of the proinflammatory cytokine high mobility group box protein 1 (HMGB1 in hyperoxic inflammatory lung injury, using an adult mouse model. The exposure of C57BL/6 mice to ≥99% O2 (hyperoxia significantly increased the accumulation of HMGB1 in the bronchoalveolar lavage fluids (BALF prior to the onset of severe inflammatory lung injury. In the airways of hyperoxic mice, HMGB1 was hyperacetylated and existed in various redox forms. Intratracheal administration of recombinant HMGB1 (rHMGB1 caused a significant increase in leukocyte infiltration into the lungs compared to animal treated with a non-specific peptide. Neutralizing anti-HMGB1 antibodies, administrated before hyperoxia significantly attenuated pulmonary edema and inflammatory responses, as indicated by decreased total protein content, wet/dry weight ratio, and numbers of leukocytes in the airways. This protection was also observed when HMGB1 inhibitors were administered after the onset of the hyperoxic exposure. The aliphatic antioxidant, ethyl pyruvate (EP, inhibited HMGB1 secretion from hyperoxic macrophages and attenuated hyperoxic lung injury. Overall, our data suggest that HMGB1 plays a critical role in mediating hyperoxic ALI through the recruitment of leukocytes into the lungs. If these results can be translated to humans, they suggest that HMGB1 inhibitors provide treatment regimens for oxidative inflammatory lung injury in patients receiving hyperoxia through mechanical ventilation.

  10. Orally Administered Enoxaparin Ameliorates Acute Colitis by Reducing Macrophage-Associated Inflammatory Responses

    Science.gov (United States)

    Lean, Qi Ying; Eri, Rajaraman D.; Randall-Demllo, Sarron; Sohal, Sukhwinder Singh; Stewart, Niall; Peterson, Gregory M.; Gueven, Nuri; Patel, Rahul P.

    2015-01-01

    Inflammatory bowel diseases, such as ulcerative colitis, cause significant morbidity and decreased quality of life. The currently available treatments are not effective in all patients, can be expensive and have potential to cause severe side effects. This prompts the need for new treatment modalities. Enoxaparin, a widely used antithrombotic agent, is reported to possess anti-inflammatory properties and therefore we evaluated its therapeutic potential in a mouse model of colitis. Acute colitis was induced in male C57BL/6 mice by administration of dextran sulfate sodium (DSS). Mice were treated once daily with enoxaparin via oral or intraperitoneal administration and monitored for colitis activities. On termination (day 8), colons were collected for macroscopic evaluation and cytokine measurement, and processed for histology and immunohistochemistry. Oral but not intraperitoneal administration of enoxaparin significantly ameliorated DSS-induced colitis. Oral enoxaparin-treated mice retained their body weight and displayed less diarrhea and fecal blood loss compared to the untreated colitis group. Colon weight in enoxaparin-treated mice was significantly lower, indicating reduced inflammation and edema. Histological examination of untreated colitis mice showed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and the presence of edema, while all aspects of this pathology were alleviated by oral enoxaparin. Reduced number of macrophages in the colon of oral enoxaparin-treated mice was accompanied by decreased levels of pro-inflammatory cytokines. Oral enoxaparin significantly reduces the inflammatory pathology associated with DSS-induced colitis in mice and could therefore represent a novel therapeutic option for the management of ulcerative colitis. PMID:26218284

  11. Allicin enhances host pro-inflammatory immune responses and protects against acute murine malaria infection

    Directory of Open Access Journals (Sweden)

    Feng Yonghui

    2012-08-01

    Full Text Available Abstract Background During malaria infection, multiple pro-inflammatory mediators including IFN-γ, TNF and nitric oxide (NO play a crucial role in the protection against the parasites. Modulation of host immunity is an important strategy to improve the outcome of malaria infection. Allicin is the major biologically active component of garlic and shows anti-microbial activity. Allicin is also active against protozoan parasites including Plasmodium, which is thought to be mediated by inhibiting cysteine proteases. In this study, the immunomodulatory activities of allicin were assessed during acute malaria infection using a rodent malaria model Plasmodium yoelii 17XL. Methods To determine whether allicin modulates host immune responses against malaria infection, mice were treated with allicin after infection with P. yoelii 17XL. Mortality was checked daily and parasitaemia was determined every other day. Pro-inflammatory mediators and IL-4 were quantified by ELISA, while NO level was determined by the Griess method. The populations of dendritic cells (DCs, macrophages, CD4+ T and regulatory T cells (Treg were assessed by FACS. Results Allicin reduced parasitaemia and prolonged survival of the host in a dose-dependent manner. This effect is at least partially due to improved host immune responses. Results showed that allicin treatment enhanced the production of pro-inflammatory mediators such as IFN-γ, TNF, IL-12p70 and NO. The absolute numbers of CD4+ T cells, DCs and macrophages were significantly higher in allicin-treated mice. In addition, allicin promoted the maturation of CD11c+ DCs, whereas it did not cause major changes in IL-4 and the level of anti-inflammatory cytokine IL-10. Conclusions Allicin could partially protect host against P. yoelii 17XL through enhancement of the host innate and adaptive immune responses.

  12. Acute inflammatory bowel disease of the small intestine in adult: MDCT findings and criteria for differential diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Romano, Stefania [Department of Diagnostic Imaging, A.Cardarelli Hospital, Naples (Italy)], E-mail: stefromano@libero.it; Russo, Anna [Institute of Radiology, Second University of Naples, Naples (Italy); Daniele, Stefania; Tortora, Giovanni [Department of Diagnostic Imaging, A.Cardarelli Hospital, Naples (Italy); Maisto, Francesco [Institute of Radiology, Second University of Naples, Naples (Italy); Romano, Luigia

    2009-03-15

    Inflammatory changes of the intestine leading to acute abdomen could represent a frequent diagnostic challenge for radiologists actively involved in the emergency area. MDCT imaging findings needs to be evaluated considering the clinical history and symptoms and other abdominal findings that could be of help in differential diagnosis. Several protocols have been suggested and indicated in the imaging of patient with acute intestine. However, a CT protocol in which the precontrast scanning of the abdomen is followed by i.v. administration of contrast medium using the 45-55 s delay could be effective for an optimal visualization of the bowel wall. It is important to learn to recognize how the intestine reacts to the injury and how it 'talks', in order to become aware of the different patterns of disease manifestation related to an acute intestinal condition, for an effective diagnosis of active and acute inflammatory bowel disease.

  13. Role of CC chemokines (macrophage inflammatory protein-1 beta, monocyte chemoattractant protein-1, RANTES) in acute lung injury in rats

    DEFF Research Database (Denmark)

    Bless, N M; Huber-Lang, M; Guo, R F

    2000-01-01

    were cloned, the proteins were expressed, and neutralizing Abs were developed. mRNA and protein expression for MIP-1 beta and MCP-1 were up-regulated during the inflammatory response, while mRNA and protein expression for RANTES were constitutive and unchanged during the inflammatory response...... that in chemokine-dependent inflammatory responses in lung CC chemokines do not necessarily demonstrate redundant function.......The role of the CC chemokines, macrophage inflammatory protein-1 beta (MIP-1 beta), monocyte chemotactic peptide-1 (MCP-1), and RANTES, in acute lung inflammatory injury induced by intrapulmonary deposition of IgG immune complexes injury in rats was determined. Rat MIP-1 beta, MCP-1, and RANTES...

  14. Effect of insulin on the inflammatory and acute phase response after burn injury.

    Science.gov (United States)

    Jeschke, Marc G; Boehning, Darren F; Finnerty, Celeste C; Herndon, David N

    2007-09-01

    After a severe burn, the liver plays a pivotal role by modulating inflammatory processes, metabolic pathways, immune functions, and the acute phase response. Therefore, liver integrity and function are important for recovery. A thermal injury, however, causes hepatic damage by inducing hepatic edema, fatty infiltration, hepatocyte apoptosis, and metabolic derangements associated with insulin resistance and impaired insulin signaling. In preliminary studies, we found that these pathophysiological processes are related to hepatic inflammation, altered intracellular signaling, and mitochondrial dysfunction. We hypothesize that modulation of these processes with insulin could improve hepatic structure and function and, therefore, outcome of burned and critically ill patients. Insulin administration improves survival and decreases the rate of infections in severely burned and critically ill patients. Here, we show that insulin administration decreases the synthesis of proinflammatory cytokines and signal transcription factors and improves hepatic structure and function after a severe burn injury; insulin also restores hepatic homeostasis and improves hepatic dysfunction postburn via alterations in the signaling cascade.

  15. Role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in acute lung injury in rats

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Friedl, H P

    1995-01-01

    The role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the pathogenesis of acute lung injury in rats after intrapulmonary deposition of IgG immune complexes or intratracheal administration of LPS has been assessed. Critical to these studies was the cloning and functional expression...... of rat MIP-1 alpha. The resulting product shared 92% and 90% homology with the known murine sequence at the cDNA level and protein level, respectively. Recombinant rat MIP-1 alpha exhibited dose-dependent chemotactic activity for both rat and human monocytes and neutrophils, which could be blocked...... by anti-murine MIP-1 alpha Ab. Rat MIP-1 alpha mRNA and protein expression were determined as a function of time in both injury models. A time-dependent increase in MIP-1 alpha mRNA in lung extracts was observed in both models. In the LPS model, MIP-1 alpha protein could also be detected...

  16. Anti-inflammatory effects of apigenin in lipopolysaccharide-induced inflammatory in acute lung injury by suppressing COX-2 and NF-kB pathway.

    Science.gov (United States)

    Wang, Jing; Liu, Yu-Tao; Xiao, Lu; Zhu, Lingpeng; Wang, Qiujuan; Yan, Tianhua

    2014-12-01

    This study aims to evaluate the possible mechanisms responsible for the anti-inflammatory effects of apigenin lipopolysaccharide (LPS)-induced inflammatory in acute lung injury. In this study, the anti-inflammatory effects of apigenin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and the possible mechanisms involved in this protection were investigated. Pretreatment with apigenin prior to the administration of intratracheal LPS significantly induced a decrease in lung wet weight/dry weight ratio in total leukocyte number and neutrophil percent in the bronchoalveolar lavage fluid (BALF) and in IL-6 and IL-1β, the tumor neurosis factor-α (TNF-α) in the BALF. These results showed that anti-inflammatory effects of apigenin against the LPS-induced ALI may be due to its ability of primary inhibition of cyclooxygenase-2 (COX-2) gene expression and nuclear factor kB (NF-kB) gene expression of lung. The results presented here suggest that the protective mechanism of apigenin may be attributed partly to decreased production of proinflammatory cytokines through the inhibition of COX-2 and NF-kB activation. The results support that use of apigenin is beneficial in the treatment of ALI.

  17. Acute Inflammatory Bowel Disease Complicating Chronic Alcoholism and Mimicking Carcinoid Syndrome

    Directory of Open Access Journals (Sweden)

    Piercarlo Ballo

    2012-08-01

    Full Text Available We report the case of a woman with a history of chronic alcohol abuse who was hospitalized with diarrhea, severe hypokalemia refractory to potassium infusion, nausea, vomiting, abdominal pain, alternations of high blood pressure with phases of hypotension, irritability and increased urinary 5-hydroxyindoleacetic acid and cortisol. Although carcinoid syndrome was hypothesized, abdominal computed tomography and colonoscopy showed non-specific inflammatory bowel disease with severe colic wall thickening, and multiple colic biopsies confirmed non-specific inflammation with no evidence of carcinoid cells. During the following days diarrhea slowly decreased and the patient’s condition progressively improved. One year after stopping alcohol consumption, the patient was asymptomatic and serum potassium was normal. Chronic alcohol exposure is known to have several deleterious effects on the intestinal mucosa and can favor and sustain local inflammation. Chronic alcohol intake may also be associated with high blood pressure, behavior disorders, abnormalities in blood pressure regulation with episodes of hypotension during hospitalization due to impaired baroreflex sensitivity in the context of an alcohol withdrawal syndrome, increased urinary 5-hydroxyindoleacetic acid as a result of malabsorption syndrome, and increased urinary cortisol as a result of hypothalamic-pituitary-adrenal axis dysregulation. These considerations, together with the regression of symptoms and normalization of potassium levels after stopping alcohol consumption, suggest the intriguing possibility of a alcohol-related acute inflammatory bowel disease mimicking carcinoid syndrome.

  18. Acute inflammatory bowel disease complicating chronic alcoholism and mimicking carcinoid syndrome.

    Science.gov (United States)

    Ballo, Piercarlo; Dattolo, Pietro; Mangialavori, Giuseppe; Ferro, Giuseppe; Fusco, Francesca; Consalvo, Matteo; Chiodi, Leandro; Pizzarelli, Francesco; Zuppiroli, Alfredo

    2012-05-01

    We report the case of a woman with a history of chronic alcohol abuse who was hospitalized with diarrhea, severe hypokalemia refractory to potassium infusion, nausea, vomiting, abdominal pain, alternations of high blood pressure with phases of hypotension, irritability and increased urinary 5-hydroxyindoleacetic acid and cortisol. Although carcinoid syndrome was hypothesized, abdominal computed tomography and colonoscopy showed non-specific inflammatory bowel disease with severe colic wall thickening, and multiple colic biopsies confirmed non-specific inflammation with no evidence of carcinoid cells. During the following days diarrhea slowly decreased and the patient's condition progressively improved. One year after stopping alcohol consumption, the patient was asymptomatic and serum potassium was normal. Chronic alcohol exposure is known to have several deleterious effects on the intestinal mucosa and can favor and sustain local inflammation. Chronic alcohol intake may also be associated with high blood pressure, behavior disorders, abnormalities in blood pressure regulation with episodes of hypotension during hospitalization due to impaired baroreflex sensitivity in the context of an alcohol withdrawal syndrome, increased urinary 5-hydroxyindoleacetic acid as a result of malabsorption syndrome, and increased urinary cortisol as a result of hypothalamic-pituitary-adrenal axis dysregulation. These considerations, together with the regression of symptoms and normalization of potassium levels after stopping alcohol consumption, suggest the intriguing possibility of a alcohol-related acute inflammatory bowel disease mimicking carcinoid syndrome.

  19. Indium 111-labeled granulocyte scan in the diagnosis and management of acute inflammatory bowel disease

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    Nelson, R.L.; Subramanian, K.; Gasparaitis, A.; Abcarian, H.; Pavel, D.G. (Univ. of Illinois College of Medicine, Chicago (USA))

    1990-06-01

    The indium 111 granulocyte scan was used to evaluate 39 individuals known to have or suspected of having inflammatory bowel disease. Twenty-three of these individuals had positive scans and 16 had negative scans. Eighty-seven confirmatory studies, which consisted of barium radiography, endoscopy, operative findings, and histopathology, were performed in 37 of these individuals. The remaining two negative scans corroborated only by clinical course, CBC, and erythrocyte sedimentation rate. In addition, 10 follow-up scans were performed in six of the 39 patients to monitor therapy or investigate a change in symptoms. As an anatomic indicator of acute granulocytic infiltration of the intestinal lamina propria and crypts, the authors found that this scan had a 97 percent rate of sensitivity and 100 percent specificity. Specific indications for the use of the indium 111-labeled granulocyte scan are described. For the authors, in general, this test has become a vital adjunct to endoscopy and radiography in the diagnosis and management of patients with symptoms of inflammatory bowel disease.

  20. The Systemic Inflammatory Response Syndrome (SIRS in acutely hospitalised medical patients: a cohort study

    Directory of Open Access Journals (Sweden)

    Storgaard Merete

    2009-12-01

    Full Text Available Abstract Background Sepsis is an infection which has evoked a systemic inflammatory response. Clinically, the Systemic Inflammatory Response Syndrome (SIRS is identified by two or more symptoms including fever or hypothermia, tachycardia, tachypnoea and change in blood leucocyte count. The relationship between SIRS symptoms and morbidity and mortality in medical emergency ward patients is unknown. Methods We conducted a prospective cohort study of the frequency of SIRS and its relationship to sepsis and death among acutely hospitalised medical patients. In 437 consecutive patients, SIRS status, blood pressure, infection and comorbidity on admission was registered together with 28-day mortality. Results A hundred and fifty-four patients (35% had SIRS on admission, 211 patients (48% had no SIRS, and 72 patients (16% had insufficient data to evaluate their SIRS status. SIRS patients were 2.2 times more frequently infected, with 66/154 SIRS patients versus 41/211 non-SIRS patients: p Conclusion We found SIRS status on admission to be moderately associated with infection and strongly related to 28-day mortality.

  1. Autologous cytokine-induced killer (CIK) immunotherapy in a case of disseminated tuberculosis.

    Science.gov (United States)

    Ping, Xu; Junchi, Xu; Xinnian, Chen; Zhijian, Ye; Meiying, Wu

    2015-06-22

    A 23-year-old woman had dry cough, fever and chest tightness for 1 months. Through thoracic CT scan and serological examination, the patient was clinically diagnosed as disseminated tuberculosis. she was given anti-tuberculosis therapy combined with autologous cytokine-induced killer (CIK) immunotherapy. Through the close follow-ups we found that after immunotherapy Her condition would have a swift improvement and she do not appear liver damage after a large doses of antibiotic therapy. In conclusion, adjuvant autologous CIK immunotherapy is an effective approach for disseminated tuberculosis.

  2. Immune reconstitution inflammatory syndrome Kaposi sarcoma in the liver manifesting as acute obstructive hepatitis: another potential role for montelukast?

    Science.gov (United States)

    Read, P J; Lucas, S; Morris, S; Kulasegaram, R

    2013-02-01

    Immune reconstitution inflammatory syndrome has been described in Kaposi sarcoma, but does not usually manifest as acute hepatitis. We describe a case of rapid obstructive jaundice after initiation of antiretroviral therapy, in which the liver biopsy confirmed hepatic Kaposi sarcoma, and the clinical course was altered by the addition of montelukast.

  3. Comparing the effects of rapid and gradual cooling on body temperature and inflammatory response following acute hyperthermia

    Science.gov (United States)

    Hyperthermia negatively impacts human and animal health, and extreme cases can result in mortality if recovery is not appropriately managed. The study objective was to determine the effects of rapid versus gradual cooling on body temperature and the inflammatory response following exposure to acute ...

  4. Effect of surgical castration with or without oral meloxicam on the acute inflammatory response in yearling beef bulls

    Science.gov (United States)

    Pain management and welfare are increasingly prevalent concerns within animal agriculture. Analgesics may alleviate pain and inflammation associated with castration of beef cattle. This study was conducted to elucidate the effects of surgical castration on the acute inflammatory response and immunom...

  5. Effect of surgical castration with or without meloxicam on the acute inflammatory response in yearling beef bulls

    Science.gov (United States)

    Pain management and welfare are increasingly prevalent concerns within animal agriculture and oral analgesics may alleviate the pain associated with castration. This study was conducted to elucidate the effects of surgical castration on the acute inflammatory response and immunomodulation and whethe...

  6. The Acute Inflammatory Response in Trauma/Hemorrhage and Traumatic Brain Injury : Current State and Emerging Prospects

    NARCIS (Netherlands)

    Namas, R.; Ghuma, A.; Hermus, L.; Zamora, R.; Okonkwo, D. O.; Billiar, T. R.; Vodovotz, Y.

    2009-01-01

    Traumatic injury/hemorrhagic shock (T/HS) elicits an acute inflammatory response that may result in death. Inflammation describes a coordinated series of molecular, cellular, tissue, organ, and systemic responses that drive the pathology of various diseases including T/HS and traumatic brain injury

  7. Effects of kadsurenone on the systemic inflammatory response in rat model of acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Jun Yao; Qingyong; Lin Wang

    2006-01-01

    Objective: To study the effects of kadsurenone on inflammatory mediators Platelet-activating factor (PAF),tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in rat model of acute pancreatitis(AP). Methods: SD male rats (104)were randomly divided into sham group (n = 24), AP group (n = 40) and kadsurenone group (n = 40). The rats were killed 3,6, 12 and 24 hours after operation. The serum level of PAF, TNF-α and IL-6 was measured. Results: The serum level of PAF,TNF-α and IL-6 of AP group was significantly increased(P < 0.01)compared with control group. The serum level of TNF-α got to a peak 6 hours after operation, and the serum IL-6 getting to a peak 12 hours after operation in AP group. After kadsurenone was administered to AP rats, pancreas and lung myeloperoxidase (MPO), serum amylase activity was reduced. Histology showed a trend toward improvement. The serum level of PAF, TNF-α and IL-6 was significantly decreased (P < 0.05). Conclusion:Kadsurenone can reduce the severity of systemic inflammation in rats with AP and relieve the damage of the pancreas and lung in AP rats. These results suggested that kadsurenone may be useful in the treatment of acute pancreatitis.

  8. Effect of rosuvastatin on inflammatory factors and carotid atherosclerotic plaque in patients with acute ischemic stroke

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    YAN Jun

    2013-10-01

    Full Text Available Carotid atherosclerosis is closely related with ischemic stroke occurrence, development and recurrence. This study aims to make an evaluation of the effects of rosuvastatin on inflammatory factors, serum lipid and carotid atherosclerotic plaque in patients with acute ischemic stroke. In this study, 98 patients with acute ischemic stroke and carotid atherosclerosis were given oral administration of rosuvastatin calcium (10 mg once every night, and the course of treatment was 6 months. After treatment, the changes of serum high-sensitivity C-reactive protein (hs-CRP, tumor necrosis factor-alpha (TNF-α and blood lipid were measured, as well as carotid atherosclerotic intima-media thickness (IMT and the calculation of carotid atherosclerotic plaque score. According to the examination results, after 6 months' treatment with rosuvastatin, serum hs-CRP, TNF-α, total cholesterol (TC, triglyceride (TG and low-density lipoprotein cholestrol (LDL-C decreased significantly (P < 0.01, for all, while high-density lipoprotein cholestrol (HDL-C increased significantly (P < 0.01; the total number of plaque reduced, while the number of stable plaque increased (P < 0.05; carotid artery IMT and carotid artery plaque score decreased significantly (P < 0.05. There were significant differences between before and after treatment. The results of this study show that rosuvastatin plays a role in anti-inflammation and alleviates the degree of carotid atherosclerotic plaque.

  9. Evaluation of inflammatory cytokines as prognostic markers in experimental acute pancreatitis in rats

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    Paran Haim

    2000-01-01

    Full Text Available Background: Early evaluation of the severity of acute pancreatitis requires measurements of many variables. Clinical parameters as well as CT scan have traditionally been used as predictors of severity, and complications. None of them however can predict the outcome early and reliably. Inflammatory cytokines were shown to play an important role in the inflammatory cascade, which occurs early in the course of the disease. The aim of the present study is to evaluate the predictive value of plasma interleukin-6 (IL-6 and interleukin-1 (IL-1 levels in experimental pancreatitis in rats. Methods: Male wistar rats were anesthetized and pancreatitis was induced by intraparenchymal injection of 5% (group 2 and 10% (group 3 sodium taurocholate (TC, resulting in 2 distinct groups of severity. In sham controls (group 1, saline was injected into the pancreas in the same fashion. Blood samples were obtained before and 2, 4, 24, and 96 hours after the induction of pancreatitis and plasma amylase, lipase, LDH, IL-1 and IL-6 levels were measured. Mortality was recorded every 8 hours. Pancreatitis severity was also assessed by histopathology. Results: Four hours after pancreatitis induction, plasma amylase, lipase and LDH levels were markedly increased in the pancreatitis groups. In the sham control group, moderate increases were also observed. No consistent significant difference in amylase, lipase or LDH levels was observed between the groups. At 2 hours from pancreatitis induction, IL-6 levels increased mildly in-groups 1 and 2, and decreased to the baseline levels at 24 hours. In-group 3, the increase in IL-6 levels was significantly higher then in-groups 1 and 2 (p=0.029 and 0.036 respectively, and correlated well with pancreatitis severity as defined by pathology (p=0.01 and mortality rates (p=0.037. No difference in IL-1 levels was observed at 2,4 and 24 hours from induction. At 96 hours IL-1 levels were higher in group 3 then in groups 1 and 2 (p=0

  10. Acute estrogen surge enhances inflammatory nociception without altering spinal Fos expression.

    Science.gov (United States)

    Ralya, Andrew; McCarson, Kenneth E

    2014-07-11

    Chronic pain is a major neurological disorder that can manifest differently between genders or sexes. The complex actions of sex hormones may underlie these differences; previous studies have suggested that elevated estrogen levels can enhance pain perception. The purpose of this study was to investigate the hypothesis that acute, activational effects of estradiol (E2) increase persistent inflammatory nociception, and anatomically where this modulation occurs. Spinal expression of Fos is widely used as a marker of nociceptive activation. This study used formalin-evoked nociception in ovariectomized (OVX) adult female rats and measured late-phase hindlimb flinching and Fos expression in the spinal cord, and their modification by acute estrogen supplementation similar to a proestrus surge. Six days after ovariectomy, female rats were injected subcutaneously (s.c.) with 10μg/kg E2 or vehicle. Twenty-four hours later, 50μL of 1.25% or 100μL of 5% formalin was injected into the right hindpaw; hindlimb flinches were counted, and spinal cords removed 2h after formalin injection. The numbers of Fos-expressing neurons in sections of the lumbar spinal cord were analyzed using immunohistochemistry. Formalin-induced inflammation produced a dose-dependent increase in late-phase hindlimb flinching, and E2 pretreatment increased flinching following 5%, but not 1.25% formalin injection. Despite the modification of behavior by E2, the number of spinal Fos-positive neurons was not altered by E2 pretreatment. These findings demonstrate that an acute proestrus-like surge in serum estrogen can produce a stimulus-intensity-dependent increase in inflammation-evoked nociceptive behavior. However, the lack of effect on spinal Fos expression suggests that this enhancement of nociceptive signaling by estrogen is independent of changes in peripheral activation of, expression of the immediate early gene Fos by, or signal throughput of spinal nociceptive neurons.

  11. Inflammatory neuropathies.

    Science.gov (United States)

    Whitesell, Jackie

    2010-09-01

    Inflammatory neuropathies are acquired disorders of peripheral nerves and occasionally of the central nervous system that can affect individuals at any age. The course can be monophasic, relapsing, or progressive. Inflammatory neuropathies are classified as acute or chronic. The acute form reaches a nadir by 4 weeks and the chronic form over 8 weeks or greater. The most common example of an acute inflammatory neuropathy is acute inflammatory demyelinating polyradiculoneuropathy (AIDP), which is part of the Guillain-Barré syndrome (GBS). The most common chronic inflammatory neuropathy is chronic inflammatory demyelinating polyradiculopathy (CIDP). Other chronic inflammatory neuropathies are multifocal motor neuropathy (MMN) and the Lewis-Sumner syndrome. The Fisher syndrome and Bickerstaff brainstem encephalitis occur acutely and have clinical overlap with AIDP.

  12. Genetic and metabolic signals during acute enteric bacterial infection alter the microbiota and drive progression to chronic inflammatory disease

    Energy Technology Data Exchange (ETDEWEB)

    Kamdar, Karishma; Khakpour, Samira; Chen, Jingyu; Leone, Vanessa; Brulc, Jennifer; Mangatu, Thomas; Antonopoulos, Dionysios A.; Chang, Eugene B; Kahn, Stacy A.; Kirschner, Barbara S; Young, Glenn; DePaolo, R. William

    2016-01-13

    Chronic inflammatory disorders are thought to arise due to an interplay between predisposing host genetics and environmental factors. For example, the onset of inflammatory bowel disease is associated with enteric proteobacterial infection, yet the mechanistic basis for this association is unclear. We have shown previously that genetic defiency in TLR1 promotes acute enteric infection by the proteobacteria Yersinia enterocolitica. Examining that model further, we uncovered an altered cellular immune response that promotes the recruitment of neutrophils which in turn increases metabolism of the respiratory electron acceptor tetrathionate by Yersinia. These events drive permanent alterations in anti-commensal immunity, microbiota composition, and chronic inflammation, which persist long after Yersinia clearence. Deletion of the bacterial genes involved in tetrathionate respiration or treatment using targeted probiotics could prevent microbiota alterations and inflammation. Thus, acute infection can drive long term immune and microbiota alterations leading to chronic inflammatory disease in genetically predisposed individuals.

  13. Immune and inflammatory response in pigs during acute influenza caused by H1N1 swine influenza virus.

    Science.gov (United States)

    Pomorska-Mól, Małgorzata; Markowska-Daniel, Iwona; Kwit, Krzysztof; Czyżewska, Ewelina; Dors, Arkadiusz; Rachubik, Jarosław; Pejsak, Zygmunt

    2014-10-01

    Swine influenza (SI) is an acute respiratory disease of pigs, caused by swine influenza virus (SIV). Little is known about the inflammatory response in the lung during acute SI and its correlation with clinical signs or lung pathology. Moreover, until now there has been a limited amount of data available on the relationship between the concentrations of pro- and anti-inflammatory cytokines in the lungs and the serum concentration of acute-phase proteins (APPs) in SIV-infected pigs. In the present study, the porcine inflammatory and immune responses during acute influenza caused by H1N1 SIV (SwH1N1) were studied. Nine pigs were infected intratracheally, and five served as controls. Antibodies against SIV were measured by haemagglutination inhibition assay, and the influenza-virus-specific T-cell response was measured using a proliferation assay. C-reactive protein (CRP), haptoglobin (Hp), serum amyloid A (SAA), and pig major acute-phase protein (Pig-MAP) the concentrations in serum and concentration of IL-1β, IL-6, IL-8, IL-10, TNF-α and IFN-γ in lung tissues were measured using commercial ELISAs.

  14. TRAIL administration down-modulated the acute systemic inflammatory response induced in a mouse model by muramyldipeptide or lipopolysaccharide.

    Science.gov (United States)

    Marcuzzi, Annalisa; Secchiero, Paola; Crovella, Sergio; Zauli, Giorgio

    2012-10-01

    The potent inducer of apoptosis TRAIL/Apo2 ligand is now under considerations in clinical trials for the treatment of different types of cancer. Since the natural history of cancer is often characterized by microbial infections, we have investigated the effect of recombinant human TRAIL in a mouse model of systemic acute inflammation of microbial origin represented by BALB/c mice treated with either bacterial muramyldipeptide (MDP) or lipopolysaccharide (LPS). When administered intraperitoneally (i.p.), these inflammatory bacterial compounds triggered a severe systemic inflammatory response within 2h, represented by body temperature elevation, increase of circulating serum amyloid-A (SAA) and of the number of leukocytes in the peritoneal cavity. Moreover, both MDP and LPS induced a significant elevation of the circulating levels of several inflammatory cytokines and chemokines. Noteworthy, pre-treatment with recombinant human TRAIL 48 and 72 h before administration of either MDP or LPS, significantly counteracted all acute inflammatory responses, including the elevation of key pro-inflammatory cytokines/chemokines such as IL-1α, IL-6, G-CSF, MCP-1. These data demonstrate for the first time that TRAIL has a potent anti-inflammatory activity, which might be beneficial for the anti-tumoral activity of TRAIL.

  15. Activation of endogenous anti-inflammatory mediator cyclic AMP attenuates acute pyelonephritis in mice induced by uropathogenic Escherichia coli.

    Science.gov (United States)

    Wei, Yang; Li, Ke; Wang, Na; Cai, Gui-Dong; Zhang, Ting; Lin, Yan; Gui, Bao-Song; Liu, En-Qi; Li, Zong-Fang; Zhou, Wuding

    2015-02-01

    The pathogenesis of pyelonephritis caused by uropathogenic Escherichia coli (UPEC) is not well understood. Here, we show that besides UPEC virulence, the severity of the host innate immune response and invasion of renal epithelial cells are important pathogenic factors. Activation of endogenous anti-inflammatory mediator cAMP significantly attenuated acute pyelonephritis in mice induced by UPEC. Administration of forskolin (a potent elevator of intracellular cAMP) reduced kidney infection (ie, bacterial load, tissue destruction); this was associated with attenuated local inflammation, as evidenced by the reduction of renal production of proinflammatory mediators, renal infiltration of inflammatory cells, and renal myeloperoxidase activity. In primary cell culture systems, forskolin not only down-regulated UPEC-stimulated production of proinflammatory mediators by renal tubular epithelial cells and inflammatory cells (eg, monocyte/macrophages) but also reduced bacterial internalization by renal tubular epithelial cells. Our findings clearly indicate that activation of endogenous anti-inflammatory mediator cAMP is beneficial for controlling UPEC-mediated acute pyelonephritis in mice. The beneficial effect can be explained at least in part by limiting excessive inflammatory responses through acting on both renal tubular epithelial cells and inflammatory cells and by inhibiting bacteria invasion of renal tubular epithelial cells. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  16. Pharmacological characterisation of anti-inflammatory compounds in acute and chronic mouse models of cigarette smoke-induced inflammation

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    Mok Joanie

    2010-09-01

    Full Text Available Abstract Background Candidate compounds being developed to treat chronic obstructive pulmonary disease are typically assessed using either acute or chronic mouse smoking models; however, in both systems compounds have almost always been administered prophylactically. Our aim was to determine whether the prophylactic effects of reference anti-inflammatory compounds in acute mouse smoking models reflected their therapeutic effects in (more clinically relevant chronic systems. Methods To do this, we started by examining the type of inflammatory cell infiltrate which occurred after acute (3 days or chronic (12 weeks cigarette smoke exposure (CSE using female, C57BL/6 mice (n = 7-10. To compare the effects of anti-inflammatory compounds in these models, mice were exposed to either 3 days of CSE concomitant with compound dosing or 14 weeks of CSE with dosing beginning after week 12. Budesonide (1 mg kg-1; i.n., q.d., roflumilast (3 mg kg-1; p.o., q.d. and fluvastatin (2 mg kg-1; p.o., b.i.d. were dosed 1 h before (and 5 h after for fluvastatin CSE. These dose levels were selected because they have previously been shown to be efficacious in mouse models of lung inflammation. Bronchoalveolar lavage fluid (BALF leukocyte number was the primary endpoint in both models as this is also a primary endpoint in early clinical studies. Results To start, we confirmed that the inflammatory phenotypes were different after acute (3 days versus chronic (12 weeks CSE. The inflammation in the acute systems was predominantly neutrophilic, while in the more chronic CSE systems BALF neutrophils (PMNs, macrophage and lymphocyte numbers were all increased (p Conclusions These results demonstrate that the acute, prophylactic systems can be used to identify compounds with therapeutic potential, but may not predict a compound's efficacy in chronic smoke exposure models.

  17. Infusions of recipient-derived cytokine-induced killer cells of donor origin eradicated residual disease in a relapsed leukemia patient after allo-hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    ZHONG Zhao-dong; LUO Yi; ZOU Ping; ZHENG Jin-e; YAO Jun-xia; HUANG Shi-ang; ZHOU Dong-feng; YOU Yong

    2012-01-01

    A female patient diagnosed with acute myelocytic leukemia M5a (AML-M5a) relapsed 986 days after her allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from an unrelated male donor with matched human leukocyte antigen (HLA).Three re-induction chemotherapies were administered,and partial remission was achieved.The patient was given repetitive infusion of cytokine-induced killer (CIK) cells expanded from recipient peripheral mononuclear cells of full donor chimerism due to loss of contact of quondam donor for donor lymphocyte infusion (DLI) and rejection of second transplantation.The patient achieved complete cytogenetical remission.This strategy might overcome the obstacle of donor unavailability and present an appealing new therapeutic alternative to donor-recruited adoptive immunotherapy for relapsed disease at post-transplantation.

  18. Transduced Tat-DJ-1 protein inhibits cytokines-induced pancreatic RINm5F cell death

    Science.gov (United States)

    Jo, Hyo Sang; Yeo, Hyeon Ji; Cha, Hyun Ju; Kim, Sang Jin; Cho, Su Bin; Park, Jung Hwan; Lee, Chi Hern; Yeo, Eun Ji; Choi, Yeon Joo; Eum, Won Sik; Choi, Soo Young

    2016-01-01

    Loss of pancreatic β-cells by oxidative stress or cytokines is associated with diabetes mellitus (DM). DJ-1 is known to as a multifunctional protein, which plays an important role in cell survival. We prepared cell permeable wild type (WT) and mutant type (M26I) Tat-DJ-1 proteins to investigate the effects of DJ-1 against combined cytokines (IL-1β, IFN-γ and TNF-α)-induced RINm5F cell death. Both Tat-DJ-1 proteins were transduced into RINm5F cells. WT Tat-DJ-1 proteins significantly protected against cell death from cytokines by reducing intracellular toxicities. Also, WT Tat-DJ-1 proteins markedly regulated cytokines-induced pro- and anti-apoptosis proteins. However, M26I Tat-DJ-1 protein showed relatively low protective effects, as compared to WT Tat-DJ-1 protein. Our experiments demonstrated that WT Tat-DJ-1 protein protects against cytokine-induced RINm5F cell death by suppressing intracellular toxicities and regulating apoptosisrelated protein expression. Thus, WT Tat-DJ-1 protein could potentially serve as a therapeutic agent for DM and cytokine related diseases. [BMB Reports 2016; 49(5): 297-302] PMID:26996344

  19. An Investigation of the Ability of the Glutaraldehyde Test to Distinguish between Acute and Chronic Inflammatory Disease in Horses

    Directory of Open Access Journals (Sweden)

    Schumacher J

    2005-06-01

    Full Text Available The Glutaraldehyde test (GT, a rapid and inexpensive test, has been utilized empirically for many years in bovine practice for diagnosing inflammatory diseases. GT is used primarily to demonstrate increased serum concentrations of fibrinogen and globulin. Glutaraldehyde binds with free amino groups in fibrinogen and immunoglobulin to create a clot in a first degree chemical reaction. The clotting time of the GT estimates the content of proteins produced in response to inflammation. The applicability of GT for diagnosing inflammation in the horse has never been investigated. The objective of this study was to determine the ability of GT to distinguish between acute and chronic inflammatory disease in horses. Thirty-seven horses with suspected inflammatory diseases were evaluated using the GT, history, complete clinical examination and routine blood analysis. GT-times, laboratory results and clinical outcome were compared statistically. Horses that were determined to be acutely affected (based on history, clinical examination and routine blood analysis tended to have a negative GT (75%. Results of the GT did not correlate with blood fibrinogen concentration. Positive GT also predicted a fatal outcome in 69% of the clinical cases. The results of this trial indicate that GT can be a useful screening test to distinguish between acute and chronic inflammatory disease in horses.

  20. Acute endotoxin-induced thymic atrophy is characterized by intrathymic inflammatory and wound healing responses.

    Directory of Open Access Journals (Sweden)

    Matthew J Billard

    Full Text Available BACKGROUND: Productive thymopoiesis is essential for a robust and healthy immune system. Thymus unfortunately is acutely sensitive to stress resulting in involution and decreased T cell production. Thymic involution is a complication of many clinical settings, including infection, malnutrition, starvation, and irradiation or immunosuppressive therapies. Systemic rises in glucocorticoids and inflammatory cytokines are known to contribute to thymic atrophy. Little is known, however, about intrathymic mechanisms that may actively contribute to thymus atrophy or initiate thymic recovery following stress events. METHODOLOGY/PRINCIPAL FINDINGS: Phenotypic, histologic and transcriptome/pathway analysis of murine thymic tissue during the early stages of endotoxemia-induced thymic involution was performed to identify putative mechanisms that drive thymic involution during stress. Thymus atrophy in this murine model was confirmed by down-regulation of genes involved in T cell development, cell activation, and cell cycle progression, correlating with observed phenotypic and histologic thymus involution. Significant gene changes support the hypothesis that multiple key intrathymic pathways are differentially activated during stress-induced thymic involution. These included direct activation of thymus tissue by LPS through TLR signaling, local expression of inflammatory cytokines, inhibition of T cell signaling, and induction of wound healing/tissue remodeling. CONCLUSIONS/SIGNIFICANCE: Taken together, these observations demonstrated that in addition to the classic systemic response, a direct intrathymic response to endotoxin challenge concurrently contributes to thymic involution during endotoxemia. These findings are a substantial advancement over current understanding of thymus response to stress and may lead to the development of novel therapeutic approaches to ameliorate immune deficiency associated with stress events.

  1. The Systemic Inflammatory Response Syndrome (SIRS) in acutely hospitalised medical patients: a cohort study.

    Science.gov (United States)

    Comstedt, Pål; Storgaard, Merete; Lassen, Annmarie T

    2009-12-27

    Sepsis is an infection which has evoked a systemic inflammatory response. Clinically, the Systemic Inflammatory Response Syndrome (SIRS) is identified by two or more symptoms including fever or hypothermia, tachycardia, tachypnoea and change in blood leucocyte count. The relationship between SIRS symptoms and morbidity and mortality in medical emergency ward patients is unknown. We conducted a prospective cohort study of the frequency of SIRS and its relationship to sepsis and death among acutely hospitalised medical patients. In 437 consecutive patients, SIRS status, blood pressure, infection and comorbidity on admission was registered together with 28-day mortality. A hundred and fifty-four patients (35%) had SIRS on admission, 211 patients (48%) had no SIRS, and 72 patients (16%) had insufficient data to evaluate their SIRS status. SIRS patients were 2.2 times more frequently infected, with 66/154 SIRS patients versus 41/211 non-SIRS patients: p SIRS patients with 15/154 SIRS patients versus 3/211 non-SIRS patients: p = 0.001, RR 6.9 (95% CI 2.0-23.3). Most of the deaths among patients with SIRS occurred among patients with malignant conditions. Septic shock developed in 4/154 (3%) of the patients with SIRS, whereas this occurred in only one of the 211 patients (0.5%) without SIRS on arrival: p = 0.08, RR 5.5 (95% CI 0.6-48.6). We found SIRS status on admission to be moderately associated with infection and strongly related to 28-day mortality.

  2. Anti-Inflammatory Effect of Emblica officinalis in Rodent Models of Acute and Chronic Inflammation: Involvement of Possible Mechanisms

    Directory of Open Access Journals (Sweden)

    Mahaveer Golechha

    2014-01-01

    Full Text Available Emblica officinalis, commonly known as amla in Ayurveda, is unarguably the most important medicinal plant for prevention and treatment of various ailments. The present study investigated the anti-inflammatory activity of hydroalcoholic extract of Emblica officinalis (HAEEO. Acute inflammation in rats was induced by the subplantar injection of carrageenan, histamine, serotonin, and prostaglandin E2 and chronic inflammation was induced by the cotton pellet granuloma. Intraperitoneal (i.p. administration of HAEEO at all the tested doses (300, 500, and 700 mg/kg significantly (P<0.001 inhibited rat paw edema against all phlogistic agents and also reduced granuloma formation. However, at the dose of 700 mg/kg, HAEEO exhibited maximum anti-inflammatory activity in all experimental models, and the effects were comparable to that of the standard anti-inflammatory drugs. Additionally, in paw tissue the antioxidant activity of HAEEO was also measured and it was found that HAEEO significantly (P<0.001 increased glutathione, superoxide dismutase, and catalase activity and subsequently reduced lipid peroxidation evidenced by reduced malondialdehyde. Taken all together, the results indicated that HAEEO possessed potent anti-inflammatory activity and it may hold therapeutic promise in the management of acute and chronic inflammatory conditions.

  3. Anti-inflammatory effects of eugenol on lipopolysaccharide-induced inflammatory reaction in acute lung injury via regulating inflammation and redox status.

    Science.gov (United States)

    Huang, Xianfeng; Liu, Yuanyuan; Lu, Yingxun; Ma, Chunhua

    2015-05-01

    Acute lung injury (ALI) represents a clinical syndrome that results from complex responses of the lung to a multitude of direct and indirect insults. This study aims to evaluate the possible mechanisms responsible for the anti-inflammatory effects of eugenol (EUL) on lipopolysaccharide (LPS)-induced inflammatory reaction in ALI. ALI was induced in mice by intratracheal instillation of LPS (0.5 mg/kg), and EUL (5, and 10 mg/kg) was injected intraperitoneally 1h prior to LPS administration. After 6h, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The findings suggest that the protective mechanism of EUL may be attributed partly to decreased production of proinflammatory cytokines through the regulating inflammation and redox status. The results support that use of EUL is beneficial in the treatment of ALI.

  4. Melatonin Does Not Affect Oxidative/Inflammatory Biomarkers in a Closed-Chest Porcine Model of Acute Myocardial Infarction

    DEFF Research Database (Denmark)

    Halladin, Natalie L.; Ekelof, Sarah; Jensen, Svend Eggert

    2014-01-01

    Aim: To test whether melatonin reduces oxidative and inflammatory biomarkers in a closed-chest porcine model of acute myocardial infarction. Materials and Methods: Twenty pigs were randomized to receive a total dosage of 200 mg (0.4 mg/ml) of melatonin, or placebo immediately prior to reperfusion....... There was an increase in hs-TnT, but no significant difference between the melatonin-treated and placebo-treated groups. There were no significant differences in development of any of the circulating plasma markers between the two groups. Conclusion: Melatonin treatment did not result in reduction of inflammatory...

  5. Maintenance of a positive outlook during acute stress protects against pro-inflammatory reactivity and future depressive symptoms

    Science.gov (United States)

    Aschbacher, K.; Epel, E.; Wolkowitz, O.M.; Prather, A.A.; Puterman, E.; Dhabhar, F.S.

    2014-01-01

    Cognitive and affective responses to acute stress influence pro-inflammatory cytokine reactivity, and peripheral cytokines (particularly lnterleukin-1 beta (IL-1β)), can act on the brain to promote depressive symptoms. It is unknown whether acute stress-induced changes in positive affect and cognitions (POS) and pro-inflammatory reactivity predict future depressive symptoms. We examined acute stress responses among women, to determine prospective predictors of depressive symptoms. Hypotheses: 1) Stress-induced decreases in POS will be associated with stress-related increases in circulating IL-1β. 2) Acute stress-induced decreases in POS and increases in IL-1β reactivity will predict increases in depressive symptoms one year later. Thirty-five post-menopausal women were exposed to acute stress with the Trier Social Stress Task (TSST) and provided blood samples under resting conditions and 30 minutes after the conclusion of the TSST, which were assayed for IL-1β. IL-1β reactivity was quantified as post minus pre-TSST. Failure to maintain POS was quantified as the decrease in POS during the TSST. Change in depressive symptoms from the study baseline to the following year was determined. Greater acute stress-induced declines in POS were significantly associated with increased IL-1β reactivity (p≤.02), which significantly predicted increases in depressive symptoms over the following year (p<.01), controlling for age, body mass index, chronic stress, antidepressant use and baseline depressive symptoms. IL-1β reactivity was a significant mediator of the relationship between POS decline and future increases in depressive symptoms (p=.04). Difficulty maintaining positivity under stress and heightened pro-inflammatory reactivity may be markers and/or mechanisms of risk for future increases in depressive symptoms. PMID:22119400

  6. Effects of Acute Lithium Treatment on Brain Levels of Inflammatory Mediators in Poststroke Rats

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    Matthew Boyko

    2015-01-01

    Full Text Available Stroke is a leading cause of mortality and morbidity worldwide. Few therapeutic options with proven efficacy are available for the treatment of this disabling disease. Lithium is the gold standard treatment for bipolar disorder. Moreover, lithium has been shown to exhibit neuroprotective effects and therapeutic efficacy as a treatment of other neurological disorders. This study was undertaken to examine the effects of lithium on brain inflammatory mediators levels, fever, and mortality in postischemic stroke rats. Ischemic stroke was induced by occlusion of the mid cerebral artery (MCAO. Pretreatment with a single dose of lithium at 2 hours before MCAO induction significantly reduced the elevation in interleukin- (IL- 6 and prostaglandin E2 levels in brain of post-MCAO rats, as compared to vehicle-treated animals. On the other hand, lithium did not affect the elevation in IL-1α, IL-10, IL-12, and tumor necrosis factor-α levels in brain of post-MCAO rats. Moreover, pretreatment with lithium did not alter post-MCAO fever and mortality. These results suggest that acute pretreatment with a single dose of lithium did not markedly affect post-MCAO morbidity and mortality in rats.

  7. Inflammatory myofibroblastic tumor presenting as acute abdomen: report of one case.

    Science.gov (United States)

    Wen, Hsiu-Huei; Cheng, Kui-Lin; Hung, Yau-Kan; Chang, Pei-Yeh

    2007-01-01

    Inflammatory myofibroblastic tumor (IMT) is a very rare benign tumor composed of myofibroblastic spindle cells of uncertain etiology, which can occur at any age and affect any organ system. More and more cases of IMT in children have been described in pediatric literature in recent years. However, this tumor occurring intraabdominally in children has rarely been reported in Taiwan. Here we present a 1-year-9-month-old boy who had fever and abdominal pain only for 2 days, symptoms mimicking acute abdomen. After imaging study, a huge tumor nearly 10 cm in diameter was incidentally found over the right abdomen with unknown origin and nature. After surgical removal of the tumor, IMT was confirmed by the pathological findings. It is very difficult to make an accurate preoperative diagnosis on this tumor according to past experience, so the role of pathological diagnosis with immunohistochemical study becomes important. This case illustrates that IMT should be considered as a possible cause of intra-abdominal mass in children who have fever of unknown origin.

  8. The impact of obesity on pentraxin 3 and inflammatory milieu to acute aerobic exercise.

    Science.gov (United States)

    Slusher, Aaron L; Mock, J Thomas; Whitehurst, Michael; Maharaj, Arun; Huang, Chun-Jung

    2015-02-01

    Pentraxin 3 (PTX3) has recently been linked to obesity-associated inflammation, serving as a cardioprotective modulator against cardiovascular disease (CVD). Aerobic exercise has been shown to enhance plasma PTX3 levels; however, the impact of obesity on PTX3 response to exercise remains unknown. Therefore, this study sought to examine whether obese subjects would have an attenuated plasma PTX3 response compared to normal-weight subjects following acute aerobic exercise. The relationship of plasma PTX3 with pro-inflammatory cytokines (IL-6 and TNF-α) was also examined. Twenty healthy subjects (10 obese [4 males and 6 females] and 10 normal-weight [4 males, 6 females]) performed 30min of continuous submaximal aerobic exercise. At baseline, obese subjects exhibited approximately 40% lower plasma PTX3 and a 7-fold greater IL-6 concentration compared to normal-weight subjects. In response to exercise, no difference was observed in PTX3 or IL-6 as indicated by area-under-the-curve "with respect to increase" (AUCi) analyses. Furthermore, PTX3 AUCi was positively correlated with cardiorespiratory fitness levels (VO(2max)) (r=0.594, p=0.006), even after controlling for body mass index. These findings suggest that in addition to obesity-associated complications, low cardiorespiratory fitness levels could impact exercise-induced PTX3 elevations, thereby potentially diminishing PTX3's effects of anti-inflammation and/or cardioprotection. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Acute effects of walking on inflammatory and cardiovascular risk in sedentary post-menopausal women.

    Science.gov (United States)

    Davis, Jillian; Murphy, Marie; Trinick, Tom; Duly, Ellie; Nevill, Alan; Davison, Gareth

    2008-02-01

    Biochemical markers of inflammation are emerging as new predictors of risk of cardiovascular disease (CVD) and may alter acutely with exercise. Few studies have been conducted on the effects of walking on these markers or whether different walking intensities elicit varied effects. As there is growing interest in modifiable lifestyle factors such as walking to reduce CVD risk, these inflammatory responses warrant investigation. The aim of this study was to compare the effects of walking at 50% versus 70% of predicted maximal heart rate on C-reactive protein (CRP), plasma fibrinogen, and triglycerides in sedentary post-menopausal women. Twelve post-menopausal women (mean age 58 years, s +/-6; stature 1.62 m, s+/-0.06; body mass 66.8 kg, s +/-6.2) completed two 30-min treadmill walks in a randomized cross-over design. Fasted blood samples were taken (for the determination of plasma fibrinogen, CRP, and lipids) before, immediately after, and 1 and 24 h after exercise. Triglyceride concentrations decreased from pre-exercise to 24 h post exercise at both walking intensities (time x group interaction, P 0.05). The results of this study suggest that fasting plasma triglycerides are decreased on the morning after 30 min of brisk walking at either 50% or 70% of maximal heart rate (moderate and vigorous intensity).

  10. Prolonged pretreatment of mice with cholera toxin, but not isoproterenol, alleviates acute lethal systemic inflammatory response.

    Science.gov (United States)

    Wang, Jingyang; Guo, Xiangrui; Cao, Junxia; Zhang, Xueying; Zhang, Jiyan; Sun, Dejun; Wang, Qingyang

    2014-11-01

    Isoproterenol, a synthetic non-selective β-adrenergic agonist, is often used during the immediate postoperative period after open heart surgery for its chronotropic and vasodilatory effects. It has been demonstrated that isoproterenol pretreatment followed by immediate LPS administration leads to reduced tumor necrosis factor-α (TNF-α) response in vivo. However, sepsis never happens immediately after the surgery, but rather severe immune dysfunction occurs at least 24h later. It remains elusive what effects isoproterenol might exert to innate immunity during the period. In this scenario, we investigated the effects of 24-h isoproterenol pretreatment on septic shock induced by experimental endotoxemia and bacterial peritonitis, with cholera toxin as another cAMP elevator. Unexpectedly, we found that isoproterenol and cholera toxin exhibited distinct effects in acute lethal systemic inflammatory response. Isoproterenol worsened liver injury without enhancing NK/NKT activity. Meanwhile, cholera toxin but not isoproterenol showed dramatically reduced TNF-α response in LPS induced septic shock. Our data provide a caution for the clinical use of isoproterenol and suggest that isoproterenol has cAMP-independent functions.

  11. Autologous cytokine-induced killer cells in equal to liver protectant in a patient with metastatic rectal cancer

    Institute of Scientific and Technical Information of China (English)

    Yanyi Ren; Zhaozhe Liu; Zhenyu Ding; Xiaodong Xie

    2013-01-01

    The cytokine-induced killer (CIK) therapy was an effective treatment for many cancers. We report a patient with postoperative rectal cancer received autologous CIK therapy combined with raltitrexed chemotherapy. After the adjuvant therapy, the serum transaminase was persistently elevated, and lung metastases was observed. Due to hepatic injury, only cytokine-induced killer therapy was administered, and it rectified transaminase. The following regimens of CIK therapy and low-dose raltitrexed could diminish the metastatic lesion, improve the quality of life and prolong the survival time. It reveals that the CIK cells may repair the hepatic injury.

  12. Cytokine-Induced NK-Like T Cells: From Bench to Bedside

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    Yeh Ching Linn

    2010-01-01

    Full Text Available Cytokine-induced killer (CIK cells are polyclonal T effector cells generated when cultured under cytokine stimulation. CIK cells exhibit potent, non-MHC-restricted cytolytic activities against susceptible tumor cells of both autologous and allogeneic origins. Over the past 20 years, CIK cells have evolved from experimental observations into early clinical studies with encouraging preliminary efficacy towards susceptible autologous and allogeneic tumor cells in both therapeutic and adjuvant settings. This paper is our attempt to summarize the available published literature related to CIK cells. Looking into the future, we anticipate that the continuous therapeutic application of CIK cells will likely be developed along two major directions: overcoming the challenge to organize large prospective randomized clinical trials to define the roles of CIK cells in cancer immunotherapy and expanding its spectrum of cytotoxicity towards resistant tumor cells through experimental manipulations.

  13. Inhaled aerosolized insulin ameliorates hyperglycemia-induced inflammatory responses in the lungs in an experimental model of acute lung injury

    OpenAIRE

    Fan, Wei; Nakazawa, Koichi; Abe, Shinya; Inoue, Miori; Kitagawa, Masanobu; Nagahara, Noriyuki; Makita, Koshi

    2013-01-01

    Introduction Previous studies have shown that patients with diabetes mellitus appear to have a lower prevalence of acute lung injury. We assumed that insulin prescribed to patients with diabetes has an anti-inflammatory property and pulmonary administration of insulin might exert beneficial effects much more than intravenous administration. Methods Twenty-eight mechanically ventilated rabbits underwent lung injury by saline lavage, and then the animals were allocated into a normoglycemia grou...

  14. Effect of emergency operation combined with somatostatin therapy on inflammatory state and liver function levels in patients with acute cholecystitis

    Institute of Scientific and Technical Information of China (English)

    Shi-Zhong Li

    2016-01-01

    Objective:To study the effect of emergency operation combined with somatostatin therapy on inflammatory state and liver function levels in patients with acute cholecystitis.Methods:A total of 146 acute cholecystitis patients who accepted laparoscopic cholecystectomy in our hospital from May 2012 to October 2015 were selected as the research subjects and divided into somatostatin group and normal control group. Then the operation, perioperative energy metabolism as well as postoperative inflammatory state and liver function levels of the two groups were analyzed.Results:Operative field exposure of somatostatin group was clearer, local tissue edema and exudation were lighter and conversion rate to laparotomy was lower; perioperative REE of somatostatin group were significantly lower than those of normal control group; the very day after operation, numeration of leukocyte, neutrophil ratio as well as serum resistin, hypersensitive C-reactive protein and tumor necrosis factor-α, interleukin-6, total bilirubin, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase levels of somatostatin group were significantly lower than those of normal control group while prealbumin level was significantly higher than that of normal control group.Conclusions:Perioperative application of somatostatin can reduce the body's inflammatory response, local tissue edema and liver function injury. It is an ideal treatment for perioperative acute cholecystitis.

  15. An Immunohistochemical Study of Inflammatory Cell Changes and Matrix Remodeling With and Without Acute Hydrops in Keratoconus.

    Science.gov (United States)

    Fan Gaskin, Jennifer C; Loh, I-Ping; McGhee, Charles N J; Sherwin, Trevor

    2015-09-01

    To determine the inflammatory cell and matrix changes in advanced keratoconus, including acute hydrops, using immunohistochemical analysis. The corneal tissue from eight subjects with keratoconus undergoing corneal transplantation (three keratoconic buttons, five buttons post acute hydrops—one of them with extensive neovascularization following hydrops) was compared with tissue from two normal corneoscleral rims (n = 10). The corneas were sectioned and analyzed with specific markers for macrophages, lymphocytes, dendritic cells, and scar associated matrix molecules laminin, fibronectin, tenascin-C, and type III collagen. Populations of cells using markers for macrophages, leucocytes and antigen presenting cells were found to be associated with the epithelium and stroma of keratoconic tissue. Populations of these cells appeared decreased in hydrops-associated keratoconus except for a large increase in leucocytes in the stroma and endothelium associated with neovascularization. Extracellular matrix deposition was found to be uniquely demonstrated in localized areas of the stroma, corresponding to the site of hydrops involvement. Immunohistochemical analysis revealed a chronic, inflammatory process with recruitment of immunoinflammatory cells and deposition of scar tissue in keratoconus. The inflammatory markers were somewhat attenuated in hydrops-associated keratoconus corneas and thus inflammation was not considered to be a major factor in the development of acute corneal hydrops.

  16. Influence of Vitamin C Supplementation on Oxidative Stress and Neutrophil Inflammatory Response in Acute and Regular Exercise

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    Ljiljana M. Popovic

    2015-01-01

    Full Text Available Exercise induces a multitude of physiological and biochemical changes in blood affecting its redox status. Tissue damage resulting from exercise induces activation of inflammatory cells followed by the increased activity of myeloperoxidase (MPO in circulation. Vitamin C readily scavenges free radicals and may thereby prevent oxidative damage of important biological macromolecules. The aim of this study was to examine the effect of vitamin C supplementation on oxidative stress and neutrophil inflammatory response induced by acute and regular exercise. Experiment was conducted on acute exercise group (performing Bruce Treadmill Protocol (BTP and regular training group. Markers of lipid peroxidation, malondialdehyde (MDA, MPO activity, and vitamin C status were estimated at rest and after BTP (acute exercise group and before and after vitamin C supplementation in both groups. Our results showed increased postexercise Asc in serum independently of vitamin supplementation. They also showed that vitamin C can significantly decrease postexercise MDA level in both experimental groups. Increased postexercise MPO activity has been found in both groups and was not affected by vitamin C supplementation. We concluded that vitamin C supplementation can suppress lipid peroxidation process during exercise but cannot affect neutrophil inflammatory response in either exercise group.

  17. Effect of alprostadil combined with butylphthalide on the serum inflammatory factors and coagulable function in patients with acute ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Wen-Zhuo Dai; Yue-Nan Kong

    2016-01-01

    Objective:To observe the effect of alprostadil combined with butylphthalide on the serum inflammatory factors, coagulable function in patients of acute ischemic stroke.Methods: A total of 84 cases of patients with acute ischemic stroke were randomly divided into observation group (44 cases) and control group (40 cases). The observation group was given alprostadil combined and butylphthalide based on conventional treatment, and the control group was given alprostadil based on conventional treatment. Treatment was developed for 14 d to observe the changes of serum inflammatory factors (IL-6, IL-8, CRP, TNF-α) and coagulation correlated parameters (PT, FIB, DDI, TXB2, PAI-1) between the two groups.Results: After treatment, IL-6, IL-8, CRP, TNF-α of the two groups decreased obviously compared with before, PT increased and FIB, DDI, TXB2, PAI-1 decreased obviously compared with before. All indexes of the observation group were improved more significantly than that of the control group, with statistical difference.Conclusion:Alprostadil combined with butylphthalide can help to inhibit inflammatory reaction and improve high coagulation state in treatment of acute ischemic stroke.

  18. Pertussis toxin, an inhibitor of G(αi PCR, inhibits bile acid- and cytokine-induced apoptosis in primary rat hepatocytes.

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    Golnar Karimian

    Full Text Available Excessive hepatocyte apoptosis is a common event in acute and chronic liver diseases leading to loss of functional liver tissue. Approaches to prevent apoptosis have therefore high potential for the treatment of liver disease. G-protein coupled receptors (GPCR play crucial roles in cell fate (proliferation, cell death and act through heterotrimeric G-proteins. G(αiPCRs have been shown to regulate lipoapoptosis in hepatocytes, but their role in inflammation- or bile acid-induced apoptosis is unknown. Here, we analyzed the effect of inhibiting G(αiPCR function, using pertussis toxin (PT, on bile acid- and cytokine-induced apoptosis in hepatocytes. Primary rat hepatocytes, HepG2-rNtcp cells (human hepatocellular carcinoma cells or H-4-II-E cells (rat hepatoma cells were exposed to glycochenodeoxycholic acid (GCDCA or tumor necrosis factor-α (TNFα/actinomycin D (ActD. PT (50-200 nmol/L was added 30 minutes prior to the apoptotic stimulus. Apoptosis (caspase-3 activity, acridine orange staining and necrosis (sytox green staining were assessed. PT significantly reduced GCDCA- and TNFα/ActD-induced apoptosis in rat hepatocytes (-60%, p<0.05 in a dose-dependent manner (with no shift to necrosis, but not in HepG2-rNtcp cells or rat H-4-II-E cells. The protective effect of pertussis toxin was independent of the activation of selected cell survival signal transduction pathways, including ERK, p38 MAPK, PI3K and PKC pathways, as specific protein kinase inhibitors did not reverse the protective effects of pertussis toxin in GCDCA-exposed hepatocytes.Pertussis toxin, an inhibitor of G(αiPCRs, protects hepatocytes, but not hepatocellular carcinoma cells, against bile acid- and cytokine-induced apoptosis and has therapeutic potential as primary hepatoprotective drug, as well as adjuvant in anti-cancer therapy.

  19. The effect of aqueous Elaeagnus angustifolia extract on acute non-inflammatory diarrhea in 1-5 year old children

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    Khoshdel Abofazl

    2014-01-01

    Full Text Available Introduction: Acute diarrhea is one of the most important causes of global childhood mortality and morbidity. The most common complication of acute diarrhea is dehydration. The aim of this study was to evaluate the use of aqueous Elaeagnus angustifolia extract in controlling non-inflammatory diarrhea in a hospital setting. Methods: In this case–controlled randomized double blind clinical trial 80 children in age range of 1-5 years were admitted in pediatric ward with diagnosis of non-inflammatory diarrhea. The patients were randomly divided into two equal groups of 40 cases. The subject in the first group received aqueous Elaeagnus angustifolia extract, 1.2 ml/Kg single dose for 4 days duration and the second group (control group 1.2 cm/Kg distilled water single dose for 4 days duration. Data analysis were performed by Chi-square and t-tests, using SPSS software. Results: The groups were similar regarding gender, mean age, and frequency, and consistency of defecation (p> 0.05. Although the children seemed better in regard to frequency and consistency of defecation, however the results showed that aqueous extract of Elaeagnus angustifolia was not significantly effective in the treatment of non-inflammatory diarrhea. Conclusion: The results of this study demonstrated that the use of aqueous extract of Elaeagnus angustifolia was not effective in the treatment of non-inflammatory diarrhea in children.

  20. Pro-inflammatory genetic profile and familiarity of acute myocardial infarction

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    Ianni Manuela

    2012-06-01

    Full Text Available Abstract Background Acute myocardial infarction (AMI is a multifactorial disease with a complex pathogenesis where lifestyle, individual genetic background and environmental risk factors are involved. Altered inflammatory responses are implicated in the pathogenesis of atherosclerosis and a premature AMI of parents is associated with an increased risk of the disease in their offspring (Offs. However, the genetic background of familiarity for AMI is still largely unknown. To understand which genes may predispose to increased risk of cardiovascular disease gene polymorphism of immune regulatory genes, and clinical events from the Offs of parents with an early AMI were investigated. Genetics data from Offs were compared with those obtained from healthy subjects and an independent cohort of patients with clinical sporadic AMI. Rates of clinical events during a 24 years follow up from Offs and from an independent Italian population survey were also evaluated. Results This study showed that a genetic signature consisting of the concomitant presence of the CC genotype of VEGF, the A allele of IL-10 and the A allele of IFN-γ was indeed present in the Offs population. In fact, the above genetic markers were more frequent in unaffected Offs (46.4% and patients with sporadic AMI (31.8% than in the CTR (17.3% and the differences were highly statistically significant (Offs vs CTR: p = 0.0001, OR = 4.129; AMI vs CTR: p = 0.0001, OR = 2.224. During the 24-year follow-up, Offs with a positive familiarity in spite of a relatively young age showed an increased prevalence of diabetes, ischemic heart disease and stroke. These findings reinforce the notion that subjects with a familial history of AMI are at risk of an accelerated aging of cardiovascular system resulting in cardiovascular events. Conclusion Our data suggest that selected genes with immune regulatory functions are part of the complex genetic background contributing to familiarity

  1. Effect of Tanshinone IIA on cardiac function and inflammatory cytokines in patients with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Yan Li

    2016-01-01

    Objective:To explore the effect of Tanshinone IIA on the cardiac function and inflammatory cytokines in patients with acute myocardial infarction (AMI).Methods:A total of 70 patients with AMI who were admitted in our hospital from March, 2015 to March, 2016 were included in the study and randomized into the observation group and the control group. On the basis of routine treatments, the patients in the control group were given urokinase 1-1.5 million U + 0.5% NaCl 100 mL, iv drip, 30-45min, aspirin from the initial dosage of 300 mg/d to 100 mg/d on the second day, and low molecular weight heparin sodium, 7 500-1 000 IU/time, twice/d, subcutaneous injection. Seven-day treatment was regarded as one course. On the above basis, the patients in the observation group were given Tanshinone IIA 60 mg + 5% glucose 250 mL, iv drip, 1 time/d. Seven-day treatment was regarded as one course. The efficacy was evaluated after seven-day treatment. ELISA was used to detect hs-CRP, TNF-α, and IL-6 levels before and after treatment. The color Doppler ultrasound diagnostic apparatus was used to monitor LVEF, LVESD, LVEDD, and IVST. The occurrence of adverse cardiac events was observed. Results:After treatment, LVEF in the two groups was significantly elevated, LVESD, LVEDD, and IVST were significantly reduced when compared with before treatment (P<0.05), and those in the observation group were significantly superior to those in the control group (P<0.05). After treatment, the serum hs-CRP, TNF-α, and IL-6 levels in the two groups were significantly reduced when compared with before treatment (P<0.05), and the reduced degree in the observation group was significantly superior to that in the control group (P<0.05). The occurrence rate of arrhythmia, cardiogenic shock, and heart rate in the observation group was significantly lower than that in the control group (P<0.05).Conclusions:Tanshinone IIA in the treatment of AMI can effectively improve the cardiac function after thrombolysis

  2. A unique protein profile of peripheral neutrophils from COPD patients does not reflect cytokine-induced protein profiles of neutrophils in vitro

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    Koenderman Leo

    2011-09-01

    Full Text Available Abstract Background Inflammation, both local and systemic, is a hallmark of chronic obstructive pulmonary disease (COPD. Inflammatory mediators such as TNFα and GM-CSF are secreted by lung epithelium, alveolar macrophages and other inflammatory cells and are thought to be important contributors in the pathogenesis of COPD. Indeed, neutrophils are activated by these cytokines and these cells are one of the major inflammatory cell types recruited to the pulmonary compartment of COPD patients. Furthermore, these inflammatory mediators are found in the peripheral blood of COPD patients and, therefore, we hypothesized that TNFα/GM-CSF-induced protein profiles can be found in peripheral neutrophils of COPD patients. Methods Using fluorescence 2-dimensional difference gel electrophoresis we investigated differentially regulated proteins in peripheral neutrophils from COPD patients and healthy age-matched control subjects. Furthermore, protein profiles from COPD patients were compared with those of neutrophils of healthy age-matched controls that were stimulated with TNFα and/or GM-CSF in vitro. Protein gels were compared using DeCyder 7.0 software. Results We identified 7 significantly regulated protein spots between peripheral neutrophils from COPD patients and age-matched healthy control subjects. Stimulation of peripheral neutrophils with TNFα, GM-CSF or TNFα + GM-CSF in vitro resulted in 13, 20 and 22 regulated protein spots, respectively. However, these cytokine-induced protein differences did not correspond with the protein differences found in neutrophils from COPD patients. Conclusion These results show that neutrophils from COPD patients have a unique protein profile compared to neutrophils from healthy age-matched controls. Furthermore, the neutrophil profiles of COPD patients do not reflect putative dominant signals induced by TNFα, GM-CSF or their combination. Our results indicate that systemic neutrophil responses in COPD patients

  3. Changing patterns of acute phase proteins and inflammatory mediators in experimental caprine coccidiosis.

    Science.gov (United States)

    Hashemnia, Mohammad; Khodakaram-Tafti, Azizollah; Razavi, Seyed Mostafa; Nazifi, Saeed

    2011-09-01

    This experiment was conducted to assess the changing patterns and relative values of acute phase proteins and inflammatory cytokines in experimental caprine coccidiosis. Eighteen newborn kids were allocated to 3 equal groups. Two groups, A and B, were inoculated with a single dose of 1×10(3) and1×10(5) sporulated oocysts of Eimeria arloingi, respectively. The third group, C, received distilled water as the control. Blood samples were collected from the jugular vein of each kid in both groups before inoculation and at days 7, 14, 21, 28, 35, and 42 post-inoculation (PI), and the levels of haptoglobin (Hp), serum amyloid A (SAA), TNF-α, and IFN-γ were measured. For histopathological examinations, 2 kids were selected from each group, euthanized, and necropsied on day 42 PI. Mean Hp concentrations in groups A and B (0.34 and 0.68 g/L) at day 7 PI were 3.2 and 6.3 times higher than the levels before inoculation. The mean SAA concentrations in groups A and B (25.6 and 83.5 µg/ml) at day 7 PI were 4.2 and 13.7 times higher than the levels before inoculation. The magnitude and duration of the Hp and SAA responses correlated well with the inoculation doses and the severity of the clinical signs and diarrhea in kids. These results were consistent with the histopathological features, which showed advanced widespread lesions in group B. In both groups, significant correlations were observed for TNF-α and IFN-γ with SAA and Hp, respectively. In conclusion, Hp and SAA can be useful non-specific diagnostic indicators in caprine coccidiosis.

  4. Inflammatory responses are not sufficient to cause delayed neuronal death in ATP-induced acute brain injury.

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    Hey-Kyeong Jeong

    Full Text Available BACKGROUND: Brain inflammation is accompanied by brain injury. However, it is controversial whether inflammatory responses are harmful or beneficial to neurons. Because many studies have been performed using cultured microglia and neurons, it has not been possible to assess the influence of multiple cell types and diverse factors that dynamically and continuously change in vivo. Furthermore, behavior of microglia and other inflammatory cells could have been overlooked since most studies have focused on neuronal death. Therefore, it is essential to analyze the precise roles of microglia and brain inflammation in the injured brain, and determine their contribution to neuronal damage in vivo from the onset of injury. METHODS AND FINDINGS: Acute neuronal damage was induced by stereotaxic injection of ATP into the substantia nigra pars compacta (SNpc and the cortex of the rat brain. Inflammatory responses and their effects on neuronal damage were investigated by immunohistochemistry, electron microscopy, quantitative RT-PCR, and stereological counting, etc. ATP acutely caused death of microglia as well as neurons in a similar area within 3 h. We defined as the core region the area where both TH(+ and Iba-1(+ cells acutely died, and as the penumbra the area surrounding the core where Iba-1(+ cells showed activated morphology. In the penumbra region, morphologically activated microglia arranged around the injury sites. Monocytes filled the damaged core after neurons and microglia died. Interestingly, neither activated microglia nor monocytes expressed iNOS, a major neurotoxic inflammatory mediator. Monocytes rather expressed CD68, a marker of phagocytic activity. Importantly, the total number of dopaminergic neurons in the SNpc at 3 h (∼80% of that in the contralateral side did not decrease further at 7 d. Similarly, in the cortex, ATP-induced neuron-damage area detected at 3 h did not increase for up to 7 d. CONCLUSIONS: Different cellular

  5. Serum albumin protects from cytokine-induced pancreatic beta cell death by a phosphoinositide 3-kinase-dependent mechanism

    DEFF Research Database (Denmark)

    Kiaer, Caroline; Thams, Peter

    2009-01-01

    ) inhibitors LY294002 (25 micromol/l) and wortmannin (1 micromol/l), suggesting that albumin may rescue beta cells from cytokine-induced cell death by activation of PI3K. In accordance, albumin stimulated phosphorylation of Akt, a down-stream target for PI3K. In conclusion, it is suggested that albumin may...

  6. Correlative mRNA and protein expression of middle and inner ear inflammatory cytokines during mouse acute otitis media.

    Science.gov (United States)

    Trune, Dennis R; Kempton, Beth; Hausman, Frances A; Larrain, Barbara E; MacArthur, Carol J

    2015-08-01

    Although the inner ear has long been reported to be susceptible to middle ear disease, little is known of the inflammatory mechanisms that might cause permanent sensorineural hearing loss. Recent studies have shown inner ear tissues are capable of expressing inflammatory cytokines during otitis media. However, little quantitative information is available concerning cytokine gene expression in the inner ear and the protein products that result. Therefore, this study was conducted of mouse middle and inner ear during acute otitis media to measure the relationship between inflammatory cytokine genes and their protein products with quantitative RT-PCR and ELISA, respectively. Balb/c mice were inoculated transtympanically with heat-killed Haemophilus influenzae and middle and inner ear tissues collected for either quantitative RT-PCR microarrays or ELISA multiplex arrays. mRNA for several cytokine genes was significantly increased in both the middle and inner ear at 6 h. In the inner ear, these included MIP-2 (448 fold), IL-6 (126 fold), IL-1β (7.8 fold), IL-10 (10.7 fold), TNFα (1.8 fold), and IL-1α (1.5 fold). The 24 h samples showed a similar pattern of gene expression, although generally at lower levels. In parallel, the ELISA showed the related cytokines were present in the inner ear at concentrations higher by 2-122 fold higher at 18 h, declining slightly from there at 24 h. Immunohistochemistry with antibodies to a number of these cytokines demonstrated they occurred in greater amounts in the inner ear tissues. These findings demonstrate considerable inflammatory gene expression and gene products in the inner ear following acute otitis media. These higher cytokine levels suggest one potential mechanism for the permanent hearing loss seen in some cases of acute and chronic otitis media.

  7. Inflammatory pre-conditioning of mesenchymal multipotent stromal cells improves their immunomodulatory potency in acute pyelonephritis in rats.

    Science.gov (United States)

    Plotnikov, Egor Y; Pulkova, Natalya V; Pevzner, Irina B; Zorova, Ljubava D; Silachev, Denis N; Morosanova, Maria A; Sukhikh, Gennady T; Zorov, Dmitry B

    2013-06-01

    Acute pyelonephritis is one of the most frequent infectious diseases of the urinary tract and a leading cause of kidney failure worldwide. One strategy for modulating excessive inflammatory responses in pyelonephritis is administration of mesenchymal multipotent stromal cells (MMSCs). The putative protective effect of injection of MMSCs against experimental acute pyelonephritis was examined. We used in vivo experimental model of APN where bacteria are introduced in the bladder of rat. Three days after, intravenous injection of MMSCs was done. On the 7th day blood samples and kidneys were taken for further analysis. We found obvious signs of oxidative stress and inflammation in the kidney in acute pyelonephritis in rats. Particularly, pro-inflammatory cytokine tumor necrosis factor-α levels, malondialdehyde, nitrite and myeloperoxidase activity were significantly increased. Histologic evaluation revealed numerous attributes of inflammation and tissue damage in the kidney. Treatment with MMSCs caused a remarkable decrease of all of these pathologic signs in renal tissue. Also, activated leukocytes induced pre-conditioning-like signaling in MMSCs. We showed alterations of expression or activity of inducible nitric oxide synthase, transforming growth factor-β, matrix metalloproteinase-2 and glycogen synthase kinase-3β, which could mediate immunomodulation and protective effects of MMSCs. This signaling could be characterized as inflammatory pre-conditioning. The beneficial capacity of MMSCs to alleviate renal inflammation was more pronounced when pre-conditioned MMSCs were used. This approach could be used to prime MMSCs with different inflammatory modulators to enhance their engraftment and function in an immunoprotected fashion. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  8. Pro-inflammatory action of MIF in acute myocardial infarction via activation of peripheral blood mononuclear cells.

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    David A White

    Full Text Available OBJECTIVES: Macrophage migration inhibitory factor (MIF, a pro-inflammatory cytokine, has been implicated in the pathogenesis of multiple inflammatory disorders. We determined changes in circulating MIF levels, explored the cellular source of MIF, and studied the role of MIF in mediating inflammatory responses following acute myocardial infarction (MI. METHODS AND RESULTS: We recruited 15 patients with MI, 10 patients with stable angina and 10 healthy volunteers and measured temporal changes of MIF in plasma. Expression of MIF, matrix metalloproteinase-9 (MMP-9 and interleukin-6 (IL-6 in cultured peripheral blood mononuclear cells (PBMCs and the media were measured by ELISA or real-time PCR. Compared to controls, plasma levels of MIF and IL-6 were significantly elevated at admission and 72 h post-MI. In contrast, expression of MIF, MMP-9 and IL-6 by PBMCs from MI patients was unchanged at admission, but significantly increased at 72 h. Addition of MIF activated cultured PBMCs by upregulating expression of inflammatory molecules and also synergistically enhanced stimulatory action of IL-1β which were inhibited by anti-MIF interventions. In a mouse MI model we observed similar changes in circulating MIF as seen in patients, with reciprocal significant increases in plasma MIF and reduction of MIF content in the infarct myocardium at 3 h after MI. MIF content in the infarct myocardium was restored at 72 h post-MI and was associated with robust macrophage infiltration. Further, anti-MIF intervention significantly reduced inflammatory cell infiltration and expression of monocyte chemoattractant protein-1 at 24 h and incidence of cardiac rupture in mice post-MI. CONCLUSION: MI leads to a rapid release of MIF from the myocardium into circulation. Subsequently MIF facilitates PBMC production of pro-inflammatory mediators and myocardial inflammatory infiltration. Attenuation of these events, and post-MI cardiac rupture, by anti-MIF interventions suggests

  9. LPS-induced lung inflammation in marmoset monkeys - an acute model for anti-inflammatory drug testing.

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    Sophie Seehase

    Full Text Available Increasing incidence and substantial morbidity and mortality of respiratory diseases requires the development of new human-specific anti-inflammatory and disease-modifying therapeutics. Therefore, new predictive animal models that closely reflect human lung pathology are needed. In the current study, a tiered acute lipopolysaccharide (LPS-induced inflammation model was established in marmoset monkeys (Callithrix jacchus to reflect crucial features of inflammatory lung diseases. Firstly, in an ex vivo approach marmoset and, for the purposes of comparison, human precision-cut lung slices (PCLS were stimulated with LPS in the presence or absence of the phosphodiesterase-4 (PDE4 inhibitor roflumilast. Pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α and macrophage inflammatory protein-1 beta (MIP-1β were measured. The corticosteroid dexamethasone was used as treatment control. Secondly, in an in vivo approach marmosets were pre-treated with roflumilast or dexamethasone and unilaterally challenged with LPS. Ipsilateral bronchoalveolar lavage (BAL was conducted 18 hours after LPS challenge. BAL fluid was processed and analyzed for neutrophils, TNF-α, and MIP-1β. TNF-α release in marmoset PCLS correlated significantly with human PCLS. Roflumilast treatment significantly reduced TNF-α secretion ex vivo in both species, with comparable half maximal inhibitory concentration (IC(50. LPS instillation into marmoset lungs caused a profound inflammation as shown by neutrophilic influx and increased TNF-α and MIP-1β levels in BAL fluid. This inflammatory response was significantly suppressed by roflumilast and dexamethasone. The close similarity of marmoset and human lungs regarding LPS-induced inflammation and the significant anti-inflammatory effect of approved pharmaceuticals assess the suitability of marmoset monkeys to serve as a promising model for studying anti-inflammatory drugs.

  10. Effect of parenteral infusion of fish oil-based lipid emulsion on systemic inflammatory cytokines and lung eicosanoid levels in experimental acute pancreatitis.

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    Garla, Priscila; Garib, Ricardo; Torrinhas, Raquel S; Machado, Marcel C C; Calder, Philip C; Waitzberg, Dan L

    2017-02-01

    Parenteral fish oil lipid emulsion (FOLE) might mitigate inflammation after injury. Acute pancreatitis (AP) can occur following major surgery and is characterized by tissue and systemic release of inflammatory mediators that contributes to the systemic inflammatory response syndrome and multiple organ failure.

  11. Dark chocolate attenuates intracellular pro-inflammatory reactivity to acute psychosocial stress in men: A randomized controlled trial.

    Science.gov (United States)

    Kuebler, Ulrike; Arpagaus, Angela; Meister, Rebecca E; von Känel, Roland; Huber, Susanne; Ehlert, Ulrike; Wirtz, Petra H

    2016-10-01

    Flavanol-rich dark chocolate consumption relates to lower risk of cardiovascular mortality, but underlying mechanisms are elusive. We investigated the effect of acute dark chocolate consumption on inflammatory measures before and after stress. Healthy men, aged 20-50years, were randomly assigned to a single intake of either 50g of flavanol-rich dark chocolate (n=31) or 50g of optically identical flavanol-free placebo-chocolate (n=34). Two hours after chocolate intake, both groups underwent the 15-min Trier Social Stress Test. We measured DNA-binding-activity of the pro-inflammatory transcription factor NF-κB (NF-κB-BA) in peripheral blood mononuclear cells, as well as plasma and whole blood mRNA levels of the pro-inflammatory cytokines IL-1β and IL-6, and the anti-inflammatory cytokine IL-10, prior to chocolate intake as well as before and several times after stress. We also repeatedly measured the flavanol epicatechin and the stress hormones epinephrine and cortisol in plasma and saliva, respectively. Compared to the placebo-chocolate-group, the dark-chocolate-group revealed a marginal increase in IL-10 mRNA prior to stress (p=0.065), and a significantly blunted stress reactivity of NF-κB-BA, IL-1β mRNA, and IL-6 mRNA (p's⩽0.036) with higher epicatechin levels relating to lower pro-inflammatory stress reactivity (p's⩽0.033). Stress hormone changes to stress were controlled. None of the other measures showed a significant chocolate effect (p's⩾0.19). Our findings indicate that acute flavanol-rich dark chocolate exerts anti-inflammatory effects both by increasing mRNA expression of the anti-inflammatory cytokine IL-10 and by attenuating the intracellular pro-inflammatory stress response. This mechanism may add to beneficial effects of dark chocolate on cardiovascular health. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Acute phase protein concentrations in serum and milk from healthy cows, cows with clinical mastitis and cows with extramammary inflammatory conditions

    NARCIS (Netherlands)

    Nielsen, B.H.; Jacobsen, S.; Andersen, P.H.; Niewold, T.A.; Heegaard, P.M.H.

    2004-01-01

    The concentrations of the two acute phase proteins, serum amyloid A and haptoglobin, in serum and milk were compared in 10 cows with clinical mastitis, 11 cows with extramammary inflammatory conditions and 10 clinically healthy control cows. The concentrations of both acute phase proteins were highe

  13. Acute and chronic local inflammatory reaction after implantation of different extracellular porcine dermis collagen matrices in rats.

    Science.gov (United States)

    Lucke, Silke; Hoene, Andreas; Walschus, Uwe; Kob, Anette; Pissarek, Jens-Wolfgang; Schlosser, Michael

    2015-01-01

    Two cross-linked acellular porcine dermal collagen matrices (Permacol and NRX) were implanted into rats and the acute and chronic local inflammatory tissue reactions were investigated after 7, 14, 28, and 112 days. Both membranes were stable in vivo for up to 112 days. All investigated immune cell populations (CD68+ macrophages, CD163+ macrophages, T lymphocytes, MHC class II positive cells, mast cells, and NK cells) were present. Their amount decreased significantly over time compared to day 7 after implantation. A change from an acute to a chronic inflammation and an associated shift from proinflammatory M1-like to anti-inflammatory M2-like macrophages were observed. In the early phase there was a significant correlation of T cells to CD68+ (M1-like) macrophages, whereas in the chronic phase T lymphocytes were positively correlated with CD163+ (M2-like) macrophages. The material NRX showed an enhanced inflammatory reaction in comparison to Permacol possibly caused by material characteristics such as a twofold higher thickness of the membrane, roughness, and water absorption capacity. Nevertheless, a more pronounced regenerative process as, for example, indicated by nestin expression demonstrated its possible suitability for applications as wound repair material.

  14. Acute and Chronic Local Inflammatory Reaction after Implantation of Different Extracellular Porcine Dermis Collagen Matrices in Rats

    Directory of Open Access Journals (Sweden)

    Silke Lucke

    2015-01-01

    Full Text Available Two cross-linked acellular porcine dermal collagen matrices (Permacol and NRX were implanted into rats and the acute and chronic local inflammatory tissue reactions were investigated after 7, 14, 28, and 112 days. Both membranes were stable in vivo for up to 112 days. All investigated immune cell populations (CD68+ macrophages, CD163+ macrophages, T lymphocytes, MHC class II positive cells, mast cells, and NK cells were present. Their amount decreased significantly over time compared to day 7 after implantation. A change from an acute to a chronic inflammation and an associated shift from proinflammatory M1-like to anti-inflammatory M2-like macrophages were observed. In the early phase there was a significant correlation of T cells to CD68+ (M1-like macrophages, whereas in the chronic phase T lymphocytes were positively correlated with CD163+ (M2-like macrophages. The material NRX showed an enhanced inflammatory reaction in comparison to Permacol possibly caused by material characteristics such as a twofold higher thickness of the membrane, roughness, and water absorption capacity. Nevertheless, a more pronounced regenerative process as, for example, indicated by nestin expression demonstrated its possible suitability for applications as wound repair material.

  15. Association between inflammatory mediators and angiographic morphologic features indicating thrombus formation in patients with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    LI Dong-bao; HUA Qi; LIU Zhi; LI Jing; XU Li-qing; WANG Shan; JIN Wei-ying

    2009-01-01

    Background Inflammatory mechanisms had played an important role in the occurrence and prognosis of acute myocardial infarction,inflammatory mediators was associated with adverse outcomes of acute myocardial infarction.This study tested the hypothesis that in the acute phase of myocardial infarction with ST-segment elevation,neutrophil count and high-sensitivity C-reactive protein are predictive of angiographic morphologic features that indicate thrombus formation in the infarct-related artery.Methods This retrospective study included 182 consecutive patients with acute myocardial infarction and ST-segment elevation.Patients were assigned to a thrombus-formation group(n=77)and a non-thrombus-formation group(n=106).All patients had a Killip's classification≤3 and onset<12 hours prior to presentation.All the cases were going to undergo coronary angiography,including primary percutaneous coronary intervention,simple coronary angiography,or thrombolysis in a coronary artery(or arteries)or coronary artery bypass graft(s).Blood samples for measurement of high-sensitivity C-reactive protein and for routine blood laboratory studies were collected prior to coronary angiography.Results The levels of high-sensitivity C-reactive protein,total leukocyte counts,neutrophil counts,and neutrophil/lymphocyte ratios were substantially higher in the thrombus-formation group than in the non-thrombus-formation group patients(for each,P<0.05).Stepwise Logistic regression analyses identified high-sensitivity C-reactive protein,neutrophil count,and neutrophil/lymphocyte ratio as independent predictors of thrombus formation in the infarct-related artery(for each,P<0.05).Conclusions In patients with acute myocardial infarction,higher neutrophil counts,neutrophil/lymphocyte ratio,and levels of high-sensitivity C-reactive protein are predictors to indicate thrombus formation.

  16. Effects of Xuebijing injection combined with ulinastatin on endotoxin and inflammatory factors in treatment of severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Hua-Xin Xiao; Ke-Jiang Tang

    2016-01-01

    Objective: To investigate the effects of Xuebijing injection combined with ulinastatin on endotoxin and inflammatory factors in treatment of severe acute pancreatitis. Methods:A total of 52 patients with severe acute pancreatitis in our hospital from July 2014 to July 2015 were selected and divided into two groups:Group A (n=26) and Group B (n=26). All of the patients received conventional treatment and necessary nutrition support. Patients of Group A were treated with ulinastatin on the basis of conventional treatment and nutrition support. Patients of Group B were treated with Xuebijing injection on the basis of Group A. Before and after treatment, the levels of serum endotoxin, hs-CRP, IL-6, IL-8, IL-10 and TNF-αwere detected. Results:After treatment, the levels of hs-CRP and endotoxin in two groups were lower than before treatment, and the Group B decreased more significantly than the Group A. The levels of IL-6, IL-8 and TNF-αin two groups were lower than before treatment, and the Group B decreased more than the Group A, while levels of IL-10 increased more than before treatment, and the Group B increased more than the Group A. Conclusion:Xuebijing injection combined with ulinastatin can significantly improve the clinical treatment effect through reducing serum endotoxin levels and inhibiting the release of inflammatory factors of patients with severe acute pancreatitis.

  17. The Impact of Sleep Restriction and Simulated Physical Firefighting Work on Acute Inflammatory Stress Responses.

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    Alexander Wolkow

    Full Text Available This study investigated the effect restricted sleep has on wildland firefighters' acute cytokine levels during 3 days and 2 nights of simulated physical wildfire suppression work.Firefighters completed multiple days of physical firefighting work separated by either an 8-h (Control condition; n = 18 or 4-h (Sleep restriction condition; n = 17 sleep opportunity each night. Blood samples were collected 4 times a day (i.e., 06:15, 11:30, 18:15, 21:30 from which plasma cytokine levels (IL-6, IL-8, IL-1β, TNF-α, IL-4, IL-10 were measured.The primary findings for cytokine levels revealed a fixed effect for condition that showed higher IL-8 levels among firefighters who received an 8-h sleep each night. An interaction effect demonstrated differing increases in IL-6 over successive days of work for the SR and CON conditions. Fixed effects for time indicated that IL-6 and IL-4 levels increased, while IL-1β, TNF-α and IL-8 levels decreased. There were no significant effects for IL-10 observed.Findings demonstrate increased IL-8 levels among firefighters who received an 8-h sleep when compared to those who had a restricted 4-h sleep. Firefighters' IL-6 levels increased in both conditions which may indicate that a 4-h sleep restriction duration and/or period (i.e., 2 nights was not a significant enough stressor to affect this cytokine. Considering the immunomodulatory properties of IL-6 and IL-4 that inhibit pro-inflammatory cytokines, the rise in IL-6 and IL-4, independent of increases in IL-1β and TNF-α, could indicate a non-damaging response to the stress of simulated physical firefighting work. However, given the link between chronically elevated cytokine levels and several diseases, further research is needed to determine if firefighters' IL-8 and IL-6 levels are elevated following repeated firefighting deployments across a fire season and over multiple fire seasons.

  18. Suppression of the acute inflammatory response of porcine alveolar- and liver macrophages

    NARCIS (Netherlands)

    Izeboud, C.A.; Monshouwer, M.; Witkamp, R.F.; Miert, A.S.J. van

    2000-01-01

    During infection and inflammation drug disposition and hepatic metabolism are markedly affected in mammals. Pro-inflammatory mediators play an important role in the suppression of (cytochrome-P450-mediated) drug metabolism. Inflammatory mediators like cytokines, nitric oxide (NO), reactive oxygen sp

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

    Science.gov (United States)

    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.

  20. Cytokine-induced killer (CIK) cells:from basic research to clinical translation

    Institute of Scientific and Technical Information of China (English)

    Yelei Guo; Weidong Han

    2015-01-01

    The accumulation of basic researches and clinical studies related to cytokine-induced killer (CIK) cells has confirmed their safety and feasibility in treating malignant diseases. This review summarizes the available published literature related to the biological characteristics and clinical applications of CIK cells in recent years. A number of clinical trials with CIK cells have been implemented during the progressive phases of cancer, presenting potential widespread applications of CIK cells for the future. Furthermore, this review briefly compares clinical applications of CIK cells with those of other adoptive immunotherapeutic cells. However, at present, there are no uniform criteria or large-scale preparations of CIK cells. The overall clinical response is difficult to evaluate because of the use of autologous CIK cells. Based on these observations, several suggestions regarding uniform criteria and universal sources for CIK cell preparations and the use of CIK cells either combined with chemotherapy or alone as a primary strategy are briefly proposed in this review. Large-scale, controlled, grouped, and multi-center clinical trials on CIK cell-based immunotherapy should be conducted under strict supervision. These interventions might help to improve future clinical applications and increase the clinical curative effects of CIK cells for a broad range of malignancies in the future.

  1. Mitochondrial oxidative stress significantly influences atherogenic risk and cytokine-induced oxidant production.

    Science.gov (United States)

    Harrison, Corey M; Pompilius, Melissa; Pinkerton, Kent E; Ballinger, Scott W

    2011-05-01

    Oxidative stress associated with cardiovascular disease (CVD) risk factors contributes to disease development. However, less is known whether specific subcellular components play a role in disease susceptibility. In this regard, it has been previously reported that vascular mitochondrial damage and dysfunction are associated with atherosclerosis. However, no studies have determined whether altered mitochondrial oxidant production directly influences atherogenic susceptibility and response in primary cells to atherogenic factors such as tumor necrosis factor-α (TNF-α). We undertook this study to determine whether increased mitochondrial oxidant production affects atherosclerotic lesion development associated with CVD risk factor exposure and endothelial cell response to TNF-α. We assessed atherosclerotic lesion formation, oxidant stress, and mitochondrial DNA damage in male apolipoprotein E (apoE)-null mice with normal and decreased levels of mitochondrial superoxide dismutase-2 (SOD2; apoE(-/-) and apoE(-/-), SOD2(+/-), respectively) exposed to environmental tobacco smoke or filtered air. Atherogenesis, oxidative stress, and mitochondrial damage were significantly higher in apoE(-/-), SOD2(+/-) mice than in apoE(-/-) controls. Furthermore, experiments with small interfering RNA in endothelial cells revealed that decreased SOD2 activity increased TNF-α-mediated cellular oxidant levels compared with controls. Endogenous mitochondrial oxidative stress is an important CVD risk factor that can modulate atherogenesis and cytokine-induced endothelial cell oxidant generation. Consequently, CVD risk factors that induce mitochondrial damage alter cellular response to endogenous atherogenic factors, increasing disease susceptibility.

  2. Clinical Studies Applying Cytokine-Induced Killer Cells for the Treatment of Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Clara E. Jäkel

    2012-01-01

    Full Text Available Metastatic renal cell carcinoma (RCC seems to be resistant to conventional chemo- and radiotherapy and the general treatment regimen of cytokine therapy produces only modest responses while inducing severe side effects. Nowadays standard of care is the treatment with VEGF-inhibiting agents or mTOR inhibition; nevertheless, immunotherapy can induce complete remissions and long-term survival in selected patients. Among different adoptive lymphocyte therapies, cytokine-induced killer (CIK cells have a particularly advantageous profile as these cells are easily available, have a high proliferative rate, and exhibit a high antitumor activity. Here, we reviewed clinical studies applying CIK cells, either alone or with standard therapies, for the treatment of RCC. The adverse events in all studies were mild, transient, and easily controllable. In vitro studies revealed an increased antitumor activity of peripheral lymphocytes of participants after CIK cell treatment and CIK cell therapy was able to induce complete clinical responses in RCC patients. The combination of CIK cell therapy and standard therapy was superior to standard therapy alone. These studies suggest that CIK cell immunotherapy is a safe and competent treatment strategy for RCC patients and further studies should investigate different treatment combinations and schedules for optimal application of CIK cells.

  3. Effect of chaetocin on renal cell carcinoma cells and cytokine-induced killer cells

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    Rombo, Roman

    2016-04-01

    Full Text Available We examined the cytotoxic effects of chaetocin on clear cell renal cell carcinoma (ccRCC cells and the possibility to combine the effects of chaetocin with the effects of cytokine-induced killer cells (CIK assayed by MTT assay and FACS analysis. Chaetocin is a thiodioxopiperazine produced by fungi belonging to the chaetomiaceae family. In 2007, it was first reported that chaetocin shows potent and selectiveanti-cancer activity by inducing reactive oxygen species. CIK cells are generated from CD3+/CD56- T lymphocytes with double negative phenotype that are isolated from human blood. The addition of distinct interleukins and antibodies results in the generation of CIK cells that are able to specifically target and destroy renal carcinoma cells. The results of this research state that the anti-ccRCC activity of chaetocin is weak and does not show a high grade of selectivity on clear cell renal cell carcinoma cells. Although the CIK cells show a high grade of selective anti-ccRCC activity, this effect could not be improved by the addition of chaetocin. So chaetocin seems to be no suitable agent for specific targeting ccRCC cells or for the combination therapy with CIK cells in renal cancer.

  4. Cytokine-induced killer cells eradicate bone and soft-tissue sarcomas.

    Science.gov (United States)

    Sangiolo, Dario; Mesiano, Giulia; Gammaitoni, Loretta; Leuci, Valeria; Todorovic, Maja; Giraudo, Lidia; Cammarata, Cristina; Dell'Aglio, Carmine; D'Ambrosio, Lorenzo; Pisacane, Alberto; Sarotto, Ivana; Miano, Sara; Ferrero, Ivana; Carnevale-Schianca, Fabrizio; Pignochino, Ymera; Sassi, Francesco; Bertotti, Andrea; Piacibello, Wanda; Fagioli, Franca; Aglietta, Massimo; Grignani, Giovanni

    2014-01-01

    Unresectable metastatic bone sarcoma and soft-tissue sarcomas (STS) are incurable due to the inability to eradicate chemoresistant cancer stem-like cells (sCSC) that are likely responsible for relapses and drug resistance. In this study, we investigated the preclinical activity of patient-derived cytokine-induced killer (CIK) cells against autologous bone sarcoma and STS, including against putative sCSCs. Tumor killing was evaluated both in vitro and within an immunodeficient mouse model of autologous sarcoma. To identify putative sCSCs, autologous bone sarcoma and STS cells were engineered with a CSC detector vector encoding eGFP under the control of the human promoter for OCT4, a stem cell gene activated in putative sCSCs. Using CIK cells expanded from 21 patients, we found that CIK cells efficiently killed allogeneic and autologous sarcoma cells in vitro. Intravenous infusion of CIK cells delayed autologous tumor growth in immunodeficient mice. Further in vivo analyses established that CIK cells could infiltrate tumors and that tumor growth inhibition occurred without an enrichment of sCSCs relative to control-treated animals. These results provide preclinical proof-of-concept for an effective strategy to attack autologous sarcomas, including putative sCSCs, supporting the clinical development of CIK cells as a novel class of immunotherapy for use in settings of untreatable metastatic disease.

  5. Acute phase protein haptoglobin as inflammatory marker in serum and synovial fluid in an equine model of arthritis.

    Science.gov (United States)

    Barrachina, Laura; Remacha, Ana Rosa; Soler, Lourdes; García, Natalia; Romero, Antonio; Vázquez, Francisco José; Vitoria, Arantza; Álava, María Ángeles; Lamprave, Fermín; Rodellar, Clementina

    2016-12-01

    Acute phase proteins are useful inflammatory markers in horses. Haptoglobin (Hp) serum level is increased in horses undergoing different inflammatory processes, including arthritis. However, Hp concentration has not been assessed in inflammatory synovial fluid (SF). The aim of the present study was to investigate the Hp response in serum and SF in horses undergoing experimentally induced arthritis. For this purpose, serum and SF samples were collected from 12 animals before amphotericin B-induced arthritis was created (T0, healthy) and 15days after the lesion induction (T1, joint inflammation) and Hp was determined by single radial immunodiffusion. The Hp increase between T0 and T1 was significant in both serum and SF, and serum Hp concentration at T0 was significantly higher than in SF, but significant differences were not found at T1, indicating a higher Hp increase in SF. A significant positive correlation for Hp concentration between serum and SF samples was found. These results highlight the potential usefulness of Hp as inflammatory marker in horses, showing for the first time the increase of Hp in SF from joint inflammation in the horse. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Functional role of gap junctions in cytokine-induced leukocyte adhesion to endothelium in vivo

    Science.gov (United States)

    Véliz, Loreto P.; González, Francisco G.; Duling, Brian R.; Sáez, Juan C.; Boric, Mauricio P.

    2008-01-01

    To assess the hypothesis that gap junctions (GJs) participate on leukocyte-endothelium interactions in the inflammatory response, we compared leukocyte adhesion and transmigration elicited by cytokine stimulation in the presence or absence of GJ blockers in the hamster cheek pouch and also in the cremaster muscle of wild-type (WT) and endothelium-specific connexin 43 (Cx43) null mice (Cx43e−/−). In the cheek pouch, topical tumor necrosis factor-α (TNF-α; 150 ng/ml, 15 min) caused a sustained increment in the number of leukocytes adhered to venular endothelium (LAV) and located at perivenular regions (LPV). Superfusion with the GJ blockers 18-α-glycyrrhetinic acid (AGA; 75 μM) or 18-β-glycyrrhetinic acid (50 μM) abolished the TNF-α-induced increase in LAV and LPV; carbenoxolone (75 μM) or oleamide (100 μM) reduced LAV by 50 and 75%, respectively, and LPV to a lesser extent. None of these GJ blockers modified venular diameter, blood flow, or leukocyte rolling. In contrast, glycyrrhizin (75 μM), a non-GJ blocker analog of AGA, was devoid of effect. Interestingly, when AGA was removed 90 min after TNF-α stimulation, LAV started to rise at a similar rate as in control. Conversely, application of AGA 90 min after TNF-α reduced the number of previously adhered cells. In WT mice, intrascrotal injection of TNF-α (0.5 μg/0.3 ml) increased LAV (fourfold) and LPV (threefold) compared with saline-injected controls. In contrast to the observations in WT animals, TNF-α stimulation did not increase LAV or LPV in Cx43e−/− mice. These results demonstrate an important role for GJ communication in leukocyte adhesion and transmigration during acute inflammation in vivo and further suggest that endothelial Cx43 is key in these processes. PMID:18599597

  7. Acute pelvic inflammatory disease in a sub-Saharan country: a cross sectional descriptive study

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    Elie Nkwabong

    2015-06-01

    Conclusions: Acute PID is common among young, single women with multiple sexual partners, who should be regularly screened for the various sexually transmissible infections. The micro-organisms frequently responsible for acute PID were genital tract mycoplasmas, whose identification should be included among the routine tests done to women with acute PID. Cases of acute PID due to intra-uterine procedures reminds us that adequate asepsis should be observed during these procedures. [Int J Reprod Contracept Obstet Gynecol 2015; 4(3.000: 809-813

  8. Acute restraint stress induces specific changes in nitric oxide production and inflammatory markers in the rat hippocampus and striatum.

    Science.gov (United States)

    Chen, Hsiao-Jou Cortina; Spiers, Jereme G; Sernia, Conrad; Lavidis, Nickolas A

    2016-01-01

    Chronic mild stress has been shown to cause hippocampal neuronal nitric oxide synthase (NOS) overexpression and the resultant nitric oxide (NO) production has been implicated in the etiology of depression. However, the extent of nitrosative changes including NOS enzymatic activity and the overall output of NO production in regions of the brain like the hippocampus and striatum following acute stress has not been characterized. In this study, outbred male Wistar rats aged 6-7 weeks were randomly allocated into 0 (control), 60, 120, or 240 min stress groups and neural regions were cryodissected for measurement of constitutive and inducible NOS enzymatic activity, nitrosative status, and relative gene expression of neuronal and inducible NOS. Hippocampal constitutive NOS activity increased initially but was superseded by the inducible isoform as stress duration was prolonged. Interestingly, hippocampal neuronal NOS and interleukin-1β mRNA expression was downregulated, while the inducible NOS isoform was upregulated in conjunction with other inflammatory markers. This pro-inflammatory phenotype within the hippocampus was further confirmed with an increase in the glucocorticoid-antagonizing macrophage migration inhibitory factor, Mif, and the glial surveillance marker, Ciita. This indicates that despite high levels of glucocorticoids, acute stress sensitizes a neuroinflammatory response within the hippocampus involving both pro-inflammatory cytokines and inducible NOS while concurrently modulating the immunophenotype of glia. Furthermore, there was a delayed increase in striatal inducible NOS expression while no change was found in other pro-inflammatory mediators. This suggests that short term stress induces a generalized increase in inducible NOS signaling that coincides with regionally specific increased markers of adaptive immunity and inflammation within the brain.

  9. Effects of Baicalin on inflammatory mediators and pancreatic acinar cell apoptosis in rats with sever acute pancreatitis

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    zhang xiping

    2009-02-01

    Full Text Available

    • BACKGROUND: To investigate the effects of Baicalin and Octreotide on inflammatory mediators and pancreatic acinar cells apoptosis of rats with severe acute pancreatitis (SAP.
    • METHODS: SD rats were randomly divided into sham operated group (I group, model control group (II group, Baicalin treated group (III group and Octreotide treated group (IV group. Each group was also divided into subgroup of 3, 6 and 12 h (n = 15. The mortality rate, ascites/body weight ratio as well as the level of endotoxin, NO and ET-1 in blood were measured. The pathological severity score of pancreas, apoptotic indexes, and expression levels of Bax and Bcl-2 proteins in each group were investigated.
    • RESULTS: The survival rate of III and IV group has a significant difference compared with II group (P12 h < 0.05. The ascites volume, contents of inflammatory mediators in blood and pathological severity score of pancreas of III and IV group declined at different degrees compared to II group (P < 0.05, P < 0.01 or P < 0.001. Apoptotic index in III group was significantly higher than that in II group at 3 and 6 h (P3, 6 h < 0.05. Apoptotic index in IV group was significantly higher than that in II group at pancreatic tail at 6 h (P6 h < 0.05. Expression level of Bax in III group was significantly higher than that in II group (pancreatic head P3 h,6 h < 0.01, pancreatic tail P3 h < 0.001.
    • CONCLUSIONS: Compared with Octreotide in the treatment of SAP, the protective mechanisms of Baicalin include reducing the excessive inflammatory mediators’ release, inducing the pancreatic acinar cells apoptosis.
    • KEY WORDS: Severe acute pancreatitis, baicalin, octreotide, inflammatory mediators, apoptosis, tissue microarrays.

  10. The role of Vitamin D in immuno-inflammatory responses in Ankylosing Spondylitis patients with and without Acute Anterior Uveitis

    OpenAIRE

    Mitulescu, TC; Stavaru, C; Voinea, LM; Banica, LM; Matache, C; Predeteanu, D

    2016-01-01

    Hypothesis:Abnormal Vitamin D (Vit D) level could have consequences on the immuno-inflammatory processes in Ankylosing Spondylitis (AS). Aim:The purpose of this study was to analyze the role of Vitamin D in the interplay between immune and inflammation effectors in AS associated-Acute Anterior Uveitis (AAU). Methods and Results:25-hydroxyvitamin D (Vit D), LL-37 peptide, IL-8 and Serum Amyloid A (SAA) were identified and quantified in the serum/ plasma of thirty-four AS patients [eleven AS pa...

  11. Effects of resolvin D1 on inflammatory responses and oxidative stress of lipopolysaccharide-induced acute lung injury in mice

    Institute of Scientific and Technical Information of China (English)

    Wang Lei; Yuan Ruixia; Yao Chengyue; Wu Qingping; Marie Christelle; Xie Wanli; Zhang Xingcai

    2014-01-01

    Background A variety of inflammatory mediators and effector cells participate together in acute lung injury,and lead to secondary injury that is due to an inflammatory cascade and secondary diffuse lung parenchyma injury.Inflammation is associated with an oxidative stress reaction,which is produced in the development of airway inflammation,and which has positive feedback on inflammation itself.Resolvin D1 can reduce the infiltration of neutrophils,regulate cytokine levels and reduce the inflammation reaction,and thereby promote the resolution of inflammation.The purpose of this study is to investigate the effects of resolvin D1 on an inflammatory response and oxidative stress during lipopolysaccharide (LPS)-induced acute lung injury.Methods LPS (3 mg/kg) was used to induce the acute lung injury model.Pretreatment resolvin D1 (100 ng/mouse) was given to mice 30 minutes before inducing acute lung injury.Mice were observed at 6 hours,12 hours,1 day,2 days,3 days,4 days and 7 days after LPS was administrated,then they were humanely sacrificed.We collected bronchoalveolar lavage fluid (BALF) and the lung tissues for further analysis.Paraffin section and HE staining of the lung tissues were made for histopathology observations.Parts of the lung tissues were evaluated for wet-to-dry (W/D) weight ratio.tumor necrosis factor (TNF)-α,inter leukin (IL)-1β,IL-10 and myeloperoxidase (MPO) were detected by enzyme-linked immunosorbent assay (ELISA).A lipid peroxidation malondialdehyde (MDA) assay kit was used to detect MDA.A total superoxide dismutase assay kit with WST-1 was used to analyze superoxide dismutase (SOD).We determined the apoptosis of neutrophils by Flow Cytometry.A real-time quantitative PCR Detecting System detected the expression of mRNA for heme oxygenase (HO)-1.Results Pretreatment with resolvin D1 reduced the pathological damage in the lung,decreased the recruitment of neutrophils and stimulated their apoptosis.It markedly decreased the expressions of TNF

  12. Antioxidant system of oral cavity in children with inflammatory diseases oral mucosa and acute forms of leukemia under the treatment

    OpenAIRE

    Kovach, I. V.; Khotimskаy, J. V.

    2017-01-01

    Kovach I. V., Khotimskаy J. V. Antioxidant system of oral cavity in children with inflammatory diseases oral mucosa and acute forms of leukemia under the treatment. Journal of Education, Health and Sport. 2017;7(1):387-395. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.276515 http://ojs.ukw.edu.pl/index.php/johs/article/view/4246         The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part B item 754 (09.12.2016)....

  13. Lest we forget Hansen's disease (leprosy): an unusual presentation with an acute onset of inflammatory polyarthritis and the rheumatology experience.

    Science.gov (United States)

    Sheetal, Salvi; Arvind, Chopra

    2009-04-01

    Several forms of arthritis and rheumatism can sometimes complicate leprosy. However, its presentation as an acute onset arthritis is unusual. We report two adult male naïve patients who presented to our rheumatology outpatient clinic with acute onset inflammatory polyarthritis, skin rash and mild sensory neurodeficit. Borderline lepromatous leprosy (in type I lepra reaction) was diagnosed. We also refer to 19 case records of Hansen arthritis in the clinic database (1998-2007) from approximately 35,000 patients and a community study to highlight the missed diagnosis of Hansen's disease and its unusual association with rheumatoid arthritis. In countries like India where leprosy is endemic, this disease also merits attention in rheumatology clinics.

  14. Effect of sympathetic nerve block on acute inflammatory pain and hyperalgesia

    DEFF Research Database (Denmark)

    Pedersen, J L; Rung, G W; Kehlet, H

    1997-01-01

    BACKGROUND: Sympathetic nerve blocks relieve pain in certain chronic pain states, but the role of the sympathetic pathways in acute pain is unclear. Thus the authors wanted to determine whether a sympathetic block could reduce acute pain and hyperalgesia after a heat injury in healthy volunteers....

  15. Risk of acute pancreatitis in patients with cronic inflammatory bowel disease

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Højgaard; Fonager, Kirsten; Sørensen, Henrik Toft;

    1999-01-01

    of patients with acute pancreatitis was compared with expected numbers on the basis of age, sex, and calendar-specific incidence rates in the general population. RESULTS: Overall, 15,526 patients were discharged and followed up for 112,824 person-years. The standardized incidence ratio (SIR) for acute...

  16. The role and importance of glycosylation of acute phase proteins with focus on alpha-1 antitrypsin in acute and chronic inflammatory conditions.

    Science.gov (United States)

    McCarthy, Cormac; Saldova, Radka; Wormald, Mark R; Rudd, Pauline M; McElvaney, Noel G; Reeves, Emer P

    2014-07-03

    Acute phase proteins (APPs) are a group of circulating plasma proteins which undergo changes quantitatively or qualitatively at the time of inflammation. Many of these APPs are glycosylated, and it has been shown that alterations in glycosylation may occur in inflammatory and malignant conditions. Changes in glycosylation have been studied as potential biomarkers in cancer and also in chronic inflammatory conditions and have been shown to correlate with disease severity in certain conditions. Serine protease inhibitors (serpins), many of which are also APPs, are proteins involved in the control of proteases in numerous pathways. Alpha-1 Antitrypsin (AAT) is the most abundant serpin within the circulation and is an APP which has been shown to increase in response to inflammation. The primary role of AAT is maintaining the protease/antiprotease balance in the lung, but it also possesses important anti-inflammatory and immune-modulating properties. Several glycoforms of AAT exist, and they possess differing properties in regard to plasma half-life and stability. Glycosylation may also be important in determining the immune modulatory properties of AAT. The review will focus on the role and importance of glycosylation in acute phase proteins with particular attention to AAT and its use as a biomarker of disease. The review describes the processes involved in glycosylation, how glycosylation changes in differing disease states, and the alterations that occur to glycans of APPs with disease and inflammation. Finally, the review explores the importance of changes in glycosylation of AAT at times of inflammation and in malignant conditions and how this may impact upon the functions of AAT.

  17. The role of plasma coating on the permeation of cytokine-inducing substances through dialyser membranes.

    Science.gov (United States)

    Lonnemann, G; Schindler, R; Lufft, V; Mahiout, A; Shaldon, S; Koch, K M

    1995-01-01

    We studied the effects of coating of dialyser membranes with plasma proteins on the permeation of bacteria-derived cytokine-inducing substances (CIS). An in vitro dialysis circuit using polysulphone (PS) or modified cellulose triacetate (mCT) dialysers was used. Precoating of the dialysers was performed by recirculation of 10% normal human plasma for 30 min in the blood compartment and subsequent rinse with pyrogen-free saline. Samples from the blood compartment were tested for induction of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and tumour necrosis factor (TNF alpha) at various time points after challenging the dialysate with sterile culture supernatants from Pseudomonas aeruginosa. Contamination of the dialysate resulted in the appearance of CIS in the blood compartment of both polysuphone modified cellulose triacetate (IL-1 alpha: PS, time 0: 81 +/- 11 pg/ml, time 60 min: 4747 +/- 1822 pg/ml, P < 0.05; mCT, time 0: 235 +/- 141 pg/ml, time 60 min: 1632 +/- 531 pg/ml, P < 0.05). The plasma protein layer reduced the penetration of CIS significantly only for polysulphone (IL-1 alpha: PS, time 60: 4747 +/- 1822 versus 880 +/- 525 pg/ml, P < 0.05; modified cellulose triacetate, time 60 min: 1632 +/- 531 pg/ml versus 930 +/- 326 pg/ml). Samples from the blood compartment contained < 6 pg/ml LAL-reactive material at all time points. We conclude that plasma coating of polysulphone dialysers reduces the permeability for CIS derived from Pseudomonas, either by reducing the effective pore size or by adsorption of proteins that bind CIS.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Plasma leptin, insulin and free tryptophan contribute to cytokine-induced anorexia.

    Science.gov (United States)

    Sato, Tomoi; Laviano, Alessandro; Meguid, Michael M; Rossi-Fanelli, Filippo

    2003-01-01

    Cytokines contribute to anorexia of diseases. Tumor Necrosis Factor (TNF) and/or interleukin-1 (IL-1) stimulate leptin release, but not insulin. Both affect hypothalamus to decrease food intake (FI). Hypothalamic serotonin (5HT) decreases FI. Its synthesis depends on brain availability of precursor, tryptophan (TRP), which depends on plasma free TRP. Purpose is to test involvement of plasma leptin, insulin, TRP, and thus hypothalamic 5HT in cytokine-induced anorexia in rats. In male rats, IL-1alpha (10 mg/kg/d; n=9), TNFalpha (30 mg/kg/d; n=9), Il-1alpha+TNFalpha (10:30 mg/kg/d; n=9), TRP (100 mg/kg/d, n=8) and saline (n=8; Control) were injected sc for 2 days. FI, BW, plasma free and total TRP, leptin and insulin, and body fat were measured. Data analyzed via ANOVA. IL-1alpha and IL-1alpha+TNFalpha vs others decreased FI and BW. TNFalpha and TRP did not change FI and BW. Plasma total TRP was higher in TRP vs IL-1alpha, TNFalpha, and IL-1alpha+TNFalpha. Plasma free TRP was higher in IL-1alpha and IL-1alpha+TNFalpha vs Control. IL-1alpha and IL-1alpha+TNFalpha decreased leptin and body fat. Insulin in Control was lower than others. Data suggest: i) IL-1alpha increases plasma free TRP, but not total TRP, thus increases hypothalamic 5HT synthesis, resulting in anorexia; ii) leptin does not mediate anorexia, but; iii) insulin may contribute to anorexia induced by cytokines.

  19. Establishment of Adoptive Immunotherapy Transfusion Time of Cytokine-induced Killer Cells

    Institute of Scientific and Technical Information of China (English)

    Wu Changping; Deng Haifeng; Jiang Jingting

    2013-01-01

    Objective:To investigate the variation of immunophenotype and cytotoxic activity of autologous cytokine-induced killer (CIK) cells in patients with malignant tumors, and explore the best time of adoptive immunotherapy infusion of CIK cells. Methods:Peripheral blood mononuclear cells (PBMC) in 40 patients with malignant tumors were collected and cultivated into CIK cells in vitro by biotechnology under induction of several kinds of cytokines including interferon γ (IFN-γ), recombinant human interleukin 1α (rhIL-1α), CD3 monoclonal antibody (CD3McAb) and recombinant human interleukin 2 (rhIL-2). Immunophenotypes were dynamically monitored by lfow cytometry (FCM), and cytotoxic activity was analyzed by methyl thiazolyl tetrazolium (MTT) method. Results:After induction and expansion at different time, CD3+, CD3+CD8+and CD3+CD56+in mononuclear cells (MNC) had an up-regulated tendency. CD3+CD4+reached the peak on day 7, and then decreased slowly;CD25 reached the peak in earlier period of cultivation (3-7 days), and decreased slowly in 7-14 days, and then decreased rapidly in 14-21 days. Human leukocyte antigen DR (HLA-DR) was on the rise in 0-14 days, and decreased rapidly after reaching the peak on day 14. The cytotoxic activity of mature CIK cells was signiifcantly higher than that of non-activated PBMC, and the difference was statistically signiifcant (P Conclusion:PBMC can be induced into typical CIK cells for about 14 days when CD3+CD56+cells are at the logarithmic phase. The best time of CIK cell adoptive immunotherapy transfusion for the patients with malignant tumors is on day 14.

  20. Use of Synthetic Derivatives To Determine the Minimal Active Structure of Cytokine-Inducing Lipoteichoic Acid▿

    Science.gov (United States)

    Deininger, Susanne; Figueroa-Perez, Ignacio; Sigel, Stefanie; Stadelmaier, Andreas; Schmidt, Richard R.; Hartung, Thomas; von Aulock, Sonja

    2007-01-01

    Lipoteichoic acid (LTA) from gram-positive bacteria is the counterpart to lipopolysaccharide from gram-negative bacteria. LTA, which activates Toll-like receptor 2 (TLR2), induces a unique cytokine and chemokine pattern. The chemical synthesis of LTA proved its immunostimulatory properties. To determine the minimal active structure of LTA, we reduced synthetic LTA in a number of steps down to the synthetic anchor and employed these molecules to stimulate interleukin-8 (IL-8) release in human whole blood. Ten times more of the synthetic structures with four to six d-alanine-substituted polyglycerophosphate units (50 nM) than of the native LTA preparation was required to induce IL-8 release. A further reduction to three backbone units with two or no d-alanine residues resulted in cytokine induction only from 500 nM. The synthetic anchor was not able to induce IL-8 release even at 5 μM. When the LTA derivatives were used at 500 nM, they induced increasing levels of IL-8 and tumor necrosis factor alpha with increasing elongation of the backbone. Peritoneal macrophages were less responsive than human blood to the synthetic structures. Therefore, TLR2 dependency could be shown only with cells from TLR2-deficient mice for the two largest synthetic structures. This was confirmed by using TLR2-transfected HEK 293 cells. Taken together, these data indicate that although the synthetic anchor (which, unlike the native anchor, contains only myristic acid) cannot induce cytokine release, the addition of three backbone units, even without d-alanine substituents, confers this ability. Lengthening of the chain with d-alanine-substituted backbone units results in increased cytokine-inducing potency and a more sensitive response. PMID:17928431

  1. Revving up Natural Killer Cells and Cytokine-Induced Killer Cells Against Hematological Malignancies

    Science.gov (United States)

    Pittari, Gianfranco; Filippini, Perla; Gentilcore, Giusy; Grivel, Jean-Charles; Rutella, Sergio

    2015-01-01

    Natural killer (NK) cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors, NK Group 2 member D (NKG2D), NKG2A/CD94, NKp46, and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells. In this respect, interleukin (IL)-15 and IL-21 are instrumental in driving NK-cell differentiation and maturation, and hold great promise for the design of optimal NK-cell culture protocols. Cytokine-induced killer (CIK) cells possess phenotypic and functional hallmarks of both T cells and NK cells. Similar to T cells, they express CD3 and are expandable in culture, while not requiring functional priming for in vivo activity, like NK cells. CIK cells may offer some advantages over other cell therapy products, including ease of in vitro propagation and no need for exogenous administration of IL-2 for in vivo priming. NK cells and CIK cells can be expanded using a variety of clinical-grade approaches, before their infusion into patients with cancer. Herein, we discuss GMP-compliant strategies to isolate and expand human NK and CIK cells for immunotherapy purposes, focusing on clinical trials of adoptive transfer to patients with hematological malignancies. PMID:26029215

  2. Revving up natural killer cells and cytokine-induced killer cells against hematological malignancies

    Directory of Open Access Journals (Sweden)

    Gianfranco ePittari

    2015-05-01

    Full Text Available Natural killer (NK cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors (KIR, NK Group 2 member D (NKG2D, NKG2A/CD94, NKp46 and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells. In this respect, interleukin (IL-15 and IL-21 are instrumental in driving NK-cell differentiation and maturation, and hold great promise for the design of optimal NK-cell culture protocols.Cytokine-induced killer (CIK cells possess phenotypic and functional hallmarks of both T cells and NK cells. Similar to T cells, they express CD3 and are expandable in culture, while not requiring functional priming for in vivo activity, like NK cells. CIK cells may offer some advantages over other cell therapy products, including ease of in vitro propagation and no need for exogenous administration of IL-2 for in vivo priming.NK cells and CIK cells can be expanded using a variety of clinical-grade approaches, before their infusion into patients with cancer. Herein, we discuss GMP-compliant strategies to isolate and expand human NK and CIK cells for immunotherapy purposes, focusing on clinical trials of adoptive transfer to patients with hematological malignancies.

  3. Combining robust state estimation with nonlinear model predictive control to regulate the acute inflammatory response to pathogen.

    Science.gov (United States)

    Zitelli, Gregory; Djouadi, Seddik M; Day, Judy D

    2015-10-01

    The inflammatory response aims to restore homeostasis by means of removing a biological stress, such as an invading bacterial pathogen. In cases of acute systemic inflammation, the possibility of collateral tissue damage arises, which leads to a necessary down-regulation of the response. A reduced ordinary differential equations (ODE) model of acute inflammation was presented and investigated in [10]. That system contains multiple positive and negative feedback loops and is a highly coupled and nonlinear ODE. The implementation of nonlinear model predictive control (NMPC) as a methodology for determining proper therapeutic intervention for in silico patients displaying complex inflammatory states was initially explored in [5]. Since direct measurements of the bacterial population and the magnitude of tissue damage/dysfunction are not readily available or biologically feasible, the need for robust state estimation was evident. In this present work, we present results on the nonlinear reachability of the underlying model, and then focus our attention on improving the predictability of the underlying model by coupling the NMPC with a particle filter. The results, though comparable to the initial exploratory study, show that robust state estimation of this highly nonlinear model can provide an alternative to prior updating strategies used when only partial access to the unmeasurable states of the system are available.

  4. Effects of recombinant sCR1 on the immune inflammatory reaction in acute spinal cord injury tissue of rats

    Institute of Scientific and Technical Information of China (English)

    李良满; 朱悦; 范广宇

    2005-01-01

    Objective: To determine the effects of recombinant soluble complement receptor type I (sCR1) on the immune inflammatory reaction in acute spinal cord injury tissue of rats and its protective effects. Results: The motor function of rat in sCR1 group at 3 d, 7 d, and 14 d was obviously better than that in NS group (P<0.01, P<0.01, P<0.01). C3c positive expression in sCR1 group at each time point after injury was obviously less than that in NS group (P<0.01). The myeloperoxidase activity in sCR1 group at each time point after injury was obviously less than that in NS group (P<0.01). Conclusions: Recombinant soluble complement receptor type I (sCR1) can lessen the immune inflammatory reaction in acute spinal cord injury tissue and relieve secondary spinal cord injury by inhibiting the activation of the complement system.

  5. Anti-inflammatory and anti-oxidative effects of alpha-lipoic acid in experimentally induced acute otitis media.

    Science.gov (United States)

    Tatar, A; Korkmaz, M; Yayla, M; Gozeler, M S; Mutlu, V; Halici, Z; Uslu, H; Korkmaz, H; Selli, J

    2016-07-01

    To investigate the anti-inflammatory, anti-oxidative and tissue protective effects, as well as the potential therapeutic role, of alpha-lipoic acid in experimentally induced acute otitis media. Twenty-five guinea pigs were assigned to one of five groups: a control (non-otitis) group, and otitis-induced groups treated with saline, penicillin G, alpha-lipoic acid, or alpha-lipoic acid plus penicillin G. Tissue samples were histologically analysed, and oxidative parameters in tissue samples were measured and compared between groups. The epithelial integrity was better preserved, and histological signs of inflammation and secretory metaplasia were decreased, in all groups compared to the saline treated otitis group. In the alpha-lipoic acid plus penicillin G treated otitis group, epithelial integrity was well preserved and histological findings of inflammation were significantly decreased compared to the saline, penicillin G and alpha-lipoic acid treated otitis groups. The most favourable oxidative parameters were observed in the control group, followed by the alpha-lipoic acid plus penicillin G treated otitis group. Alpha-lipoic acid, with its antioxidant, anti-inflammatory and tissue protective properties, may decrease the clinical sequelae and morbidity associated with acute otitis media.

  6. Anti-Inflammatory and Antinociceptive Effects of Salbutamol on Acute and Chronic Models of Inflammation in Rats: Involvement of an Antioxidant Mechanism

    Directory of Open Access Journals (Sweden)

    Hulya Uzkeser

    2012-01-01

    Full Text Available The possible role of β-2 adrenergic receptors in modulation of inflammatory and nociceptive conditions suggests that the β-2 adrenergic receptor agonist, salbutamol, may have beneficial anti-inflammatory and analgesic effects. Therefore, in this study, we induced inflammatory and nociceptive responses with carrageenan-induced paw edema or cotton-pellet-induced granuloma models, both of which result in oxidative stress. We hypothesized that salbutamol would prevent inflammatory and nociceptive responses by stimulating β-2 adrenergic receptors and the prevention of generation of ROS during the acute inflammation process in rats. Both doses of salbutamol used in the study (1 and 2 mg/kg effectively blocked the acute inflammation and inflammatory nociception induced by carrageenan. In the cotton-pellet-induced granuloma test, both doses of salbutamol also significantly decreased the weight of granuloma tissue on the cotton pellets when compared to the control. Anti-inflammatory and analgesic effects of salbutamol were found to be comparable with those of indomethacin. Salbutamol decreased myeloperoxidase (MPO activity and lipid peroxidation (LPO level and increased the activity of superoxide dismutase (SOD and level of glutathione (GSH during the acute phase of inflammation. In conclusion, salbutamol can decrease acute and chronic inflammation, possibly through the stimulation of β-2 adrenergic receptors. This anti-inflammatory effect may be of significance in asthma treatment, where inflammation also takes part in the etiopathology. This study reveals that salbutamol has significant antioxidative effects, which at least partially explain its anti-inflammatory capabilities. These findings presented here may also shed light on the roles of β-2 adrenergic receptors in inflammatory and hyperalgesic conditions.

  7. Anti-inflammatory and antinociceptive effects of salbutamol on acute and chronic models of inflammation in rats: involvement of an antioxidant mechanism.

    Science.gov (United States)

    Uzkeser, Hulya; Cadirci, Elif; Halici, Zekai; Odabasoglu, Fehmi; Polat, Beyzagul; Yuksel, Tugba Nurcan; Ozaltin, Seda; Atalay, Fadime

    2012-01-01

    The possible role of β-2 adrenergic receptors in modulation of inflammatory and nociceptive conditions suggests that the β-2 adrenergic receptor agonist, salbutamol, may have beneficial anti-inflammatory and analgesic effects. Therefore, in this study, we induced inflammatory and nociceptive responses with carrageenan-induced paw edema or cotton-pellet-induced granuloma models, both of which result in oxidative stress. We hypothesized that salbutamol would prevent inflammatory and nociceptive responses by stimulating β-2 adrenergic receptors and the prevention of generation of ROS during the acute inflammation process in rats. Both doses of salbutamol used in the study (1 and 2 mg/kg) effectively blocked the acute inflammation and inflammatory nociception induced by carrageenan. In the cotton-pellet-induced granuloma test, both doses of salbutamol also significantly decreased the weight of granuloma tissue on the cotton pellets when compared to the control. Anti-inflammatory and analgesic effects of salbutamol were found to be comparable with those of indomethacin. Salbutamol decreased myeloperoxidase (MPO) activity and lipid peroxidation (LPO) level and increased the activity of superoxide dismutase (SOD) and level of glutathione (GSH) during the acute phase of inflammation. In conclusion, salbutamol can decrease acute and chronic inflammation, possibly through the stimulation of β-2 adrenergic receptors. This anti-inflammatory effect may be of significance in asthma treatment, where inflammation also takes part in the etiopathology. This study reveals that salbutamol has significant antioxidative effects, which at least partially explain its anti-inflammatory capabilities. These findings presented here may also shed light on the roles of β-2 adrenergic receptors in inflammatory and hyperalgesic conditions.

  8. Perfluorocarbon attenuates inflammatory cytokines, oxidative stress and histopathologic changes in paraquat-induced acute lung injury in rats.

    Science.gov (United States)

    Khalighi, Zahra; Rahmani, Asghar; Cheraghi, Javad; Ahmadi, Mohammad Reza Hafezi; Soleimannejad, Koroush; Asadollahi, Ruhangiz; Asadollahi, Khairollah

    2016-03-01

    The effects of perfluorocarbon (PFC) on paraquat (PQ) induced acute lung injury (ALI) was evaluated among rats. Twenty four Wistar rats were divided into 4 groups: control group injected by saline physiologic 0.9%, PFC group injected by Perfluorocarbon, PQ group injected by PQ and PQ+PFC group injected by PFC one hour after receiving paraquat. Bronchoalveular fluid content, inflammatory cytokines, oxidative and histopathologic changes were measured after 72 h. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and transforming growth factor-β1(TGF-β1) in the PQ group were increased compared to either control or PFC groups, but their levels decreased in PQ+PFC group significantly (p<0.05). Also, histopathologic evaluation revealed an increase in malondialdehyde (MDA) and hydroxyproline (HP) in the PQ group but a decrease in PQ+PFC group significantly (p<0.01). PFC emulsion by its anti-inflammatory, anti-oxidative and anti-fibrotic properties can reduce the inflammatory and fibrotic alterations, pulmonary oedema, and pulmonary histopathologic changes created by PQ.

  9. Anti-inflammatory and antioxidant functions of high-density lipoprotein subclasses in patients with acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Ying TAN

    2013-02-01

    Full Text Available Objective  To assess the anti-inflammatory and antioxidant functions of high-density lipoprotein (HDL subclasses (HDL2 and HDL3 in patients with acute coronary syndrome (ACS, and to elucidate whether incapacitation of HDL subclasses occurred in ACS patients. Methods  Forty ACS patients hospitalized in Nanfang Hospital from Jan. 2011 to Jan. 2012 (ACS group, and 40 subjects simultaneously receiving health examination (control group were enrolled in present study. Plasma lipid and hypersensitive C reactive protein (hs-CRP levels, HDL subclasses inflammatory index (HII, paraoxonase-1 (PON1 activity and lipid hydroperoxide (LOOH levels in both groups were measured. Results  The low-density lipoprotein cholesterol (LDL-C and hs-CRP levels were higher in ACS group than in control group (P0.05. Conclusions  The incapacitation of HDL subclasses may occur in ACS patients, with an attenuated antioxidant ability and accentuated proinflammatory function. Mature HDL2 possesses better anti-inflammatory and antioxidant function than HDL3, thus playing a better cardioprotective effect.

  10. Effect of tirofiban combined with clopidogrel on serum inflammatory factors and coagulation functions in patients with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Jing Hu; Chao-Ying Jin; Yun-Fang Zhou

    2016-01-01

    Objective:To observe the effect of tirofiban combined with clopidogrel on serum inflammatory factors and coagulation functions in patients with acute myocardial infarction (AMI).Methods:A total of 106 patients with AMI were selected and randomly divided into observation group (55 cases) and control group (51 cases). The control group was given clopidogrel based on conventional therapy, and the observation was given tirofiban based on the control group. For 2 weeks, the changes of serum inflammatory factors (TNF-α, hs-CRP, IL-6, P-selection) and coagulation functions (PT, TT, APTT) between the two groups were observed.Results:After treatment, TNF-α, hs-CRP, L-6 and P-selection levels in the two group both decreased compared with that before treatment (P<0.05), TNF-α, hs-CRP, L-6 and P-selection levels in the observation group were decreased more significantly than that in the control group (P<0.05). After treatment, PT, TT and APTT levels in the two group both extended compared with that before treatment (P<0.05), PT, TT and APTT levels in the observation group were improved more significantly than that in the control group (P<0.05). There was no significant difference in adverse reactions between the two groups (P<0.05).Conclusions:Tirofiban combined with clopidogrel could restrain inflammatory response and regulate coagulation functions more significant in patients with AMI, and better than that of using clopidogrel alone.

  11. Pro- versus anti-inflammatory cytokine profile in African children with acute oro-facial noma (cancrum oris, noma).

    Science.gov (United States)

    Phillips, Reshma S; Enwonwu, Cyril O; Falkler, William A

    2005-01-01

    Fresh noma is a severe orofacial necrosis with an astonishingly rapid development. It is seen mainly in malnourished children less than 4 years old from developing countries. Cytokines play a central role in oral mucosal inflammation. We therefore studied the relevance of circulating cytokines to noma, and the key microorganisms associated with the lesion. Nigerian village children with acute noma (n=68) and their neighborhood village (n=63) as well as urban (n=45) counterparts of comparable age and free of overt infections were evaluated for serum cytokine levels by ELISA. Oral bacteria were studied by polymerase chain reaction. Evaluation of random cases of the village and noma children showed marked depletion (pnoma children than in the healthy urban children, but less so when compared to their neighborhood village counterparts. The increase in levels of the anti-inflammatory/regulatory cytokines (IL-4, IL-10 and TGF-beta) was less marked relative to the pro-inflammatory cytokines. Bacteria observed at the highest frequencies in noma lesions were P. intermedia (83%), T. forsythensis (83%), P. gingivalis (50%), C. rectus (50%) and T. denticola (50%). We conclude that noma is an immunopathological response to potent bacterial factors resulting in uncontrolled production of cytokines and possibly other, still unknown, inflammatory mediators.

  12. Aspirin-triggered resolvin D1 down-regulates inflammatory responses and protects against endotoxin-induced acute kidney injury

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jiao [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Shetty, Sreerama [Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, TX 75708 (United States); Zhang, Ping [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China); Gao, Rong; Hu, Yuxin [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Wang, Shuxia [Graduate Center for Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Li, Zhenyu [Division of Cardiovascular Medicine, University of Kentucky, Lexington, KY 40536 (United States); Fu, Jian, E-mail: jian.fu@uky.edu [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States)

    2014-06-01

    The presence of endotoxin in blood can lead to acute kidney injury (AKI) and septic shock. Resolvins, the endogenous lipid mediators derived from docosahexaenoic acid, have been reported to exhibit potent anti-inflammatory action. Using a mouse model of lipopolysaccharide (LPS)-induced AKI, we investigated the effects of aspirin-triggered resolvin D1 (AT-RvD1) on inflammatory kidney injury. Administration of AT-RvD1 1 h after LPS challenge protected the mice from kidney injury as indicated by the measurements of blood urea nitrogen, serum creatinine, and morphological alterations associated with tubular damage. The protective effects were evidenced by decreased neutrophil infiltration in the kidney indicating reduction in inflammation. AT-RvD1 treatment restored kidney cell junction protein claudin-4 expression, which was otherwise reduced after LPS challenge. AT-RvD1 treatment inhibited endotoxin-induced NF-κB activation and suppressed LPS-induced ICAM-1 and VCAM-1 expression in the kidney. Moreover, AT-RvD1 treatment markedly decreased LPS-induced IL-6 level in the kidney and blocked IL-6-mediated signaling including STAT3 and ERK phosphorylation. Our findings demonstrate that AT-RvD1 is a potent anti-inflammatory mediator in LPS-induced kidney injury, and AT-RvD1 has therapeutic potential against AKI during endotoxemia.

  13. Proteins of the Hageman Factor System in an Inflammatory Reaction in the Acute Period of Severe Brain Injury

    Directory of Open Access Journals (Sweden)

    T. I. Borshchikova

    2010-01-01

    Full Text Available Objective: to study the time course of changes and an association of contact factors and their inhibitors with the global values of hemocoagulation, fibrinolysis, and inflammatory reactants in acute severe brain injury (SBI in order to deepen notions of Hageman factor system functioning. Subjects and methods. One hundred and thirteen patients with SBI were examined on 1 to 21 days of injury. The level of unconsciousness averaged a Glasgow coma score of 6.8±0.25. A control group included 23 healthy individuals. The investigators determined the activity of contact factors (prekallikrein, high-molecular-weight kininogen, factors XII, XI and their inhibitors (total activity of the protein C system, the activity and quantity of antithrombin III, C1 esterase inhibitor, a^antitrypsin, fl^-antiplasmin, fl^-macroglobulin, hemostatic parameters (blood fibrinolytic activity by an euglobulin test; factor XII-kallikrein-dependent fibrinolysis, treptokinase induced fibrinolysis by calculating the plasminogen reserve index, activated partial thromboplastin time, fibrinogen, D-dimer, and soluble fibrin monomer complexes, and inflammatory reactants (C-reactive protein, IL10, IL2, IL4, IL5, IL6, IL8, IL10, IL12p70, TNF-a, and IFN-y. Results. The acute period of SBI was marked by significant deficiency and imbalance of contact factors and their physiological inhibitors. In SBI, prekallikrein rather than factor XII plays a central role in the function of the contact factor system due to inflammatory inhibition of Hageman factor synthesis, which disturbs its key role in the reactions of contact activation of homeostatic proteolytic systems. Out of the considered systems, the activation of which is associated with contact factors, the function of the internal mechanism of fibrinolysis is largely changed; at the same time the internal hemocoagulation activation pathway remains virtually intact. When an inflammatory reaction develops after SBI, normal Hageman factor

  14. Attenuation of Acute Phase Injury in Rat Intracranial Hemorrhage by Cerebrolysin that Inhibits Brain Edema and Inflammatory Response.

    Science.gov (United States)

    Yang, Yang; Zhang, Yan; Wang, Zhaotao; Wang, Shanshan; Gao, Mou; Xu, Ruxiang; Liang, Chunyang; Zhang, Hongtian

    2016-04-01

    The outcome of intracerebral hemorrhage (ICH) is mainly determined by the volume of the hemorrhage core and the secondary brain damage to penumbral tissues due to brain swelling, microcirculation disturbance and inflammation. The present study aims to investigate the protective effects of cerebrolysin on brain edema and inhibition of the inflammation response surrounding the hematoma core in the acute stage after ICH. The ICH model was induced by administration of type VII bacterial collagenase into the stratum of adult rats, which were then randomly divided into three groups: ICH + saline; ICH + Cerebrolysin (5 ml/kg) and sham. Cerebrolysin or saline was administered intraperitoneally 1 h post surgery. Neurological scores, extent of brain edema content and Evans blue dye extravasation were recorded. The levels of pro-inflammatory factors (IL-1β, TNF-α and IL-6) were assayed by Real-time PCR and Elisa kits. Aquaporin-4 (AQP4) and tight junction proteins (TJPs; claudin-5, occludin and zonula occluden-1) expression were measured at multiple time points. The morphological and intercellular changes were characterized by Electron microscopy. It is found that cerebrolysin (5 ml/kg) improved the neurological behavior and reduced the ipsilateral brain water content and Evans blue dye extravasation. After cerebrolysin treated, the levels of pro-inflammatory factors and AQP4 in the peri-hematomal areas were markedly reduced and were accompanied with higher expression of TJPs. Electron microscopy showed the astrocytic swelling and concentrated chromatin in the ICH group and confirmed the cell junction changes. Thus, early cerebrolysin treatment ameliorates secondary injury after ICH and promotes behavioral performance during the acute phase by reducing brain edema, inflammatory response, and blood-brain barrier permeability.

  15. Effects of phonophoresis with Arnica montana onto acute inflammatory process in rat skeletal muscles: an experimental study.

    Science.gov (United States)

    Alfredo, Patrícia P; Anaruma, Carlos A; Pião, Antônio C S; João, Silvia M A; Casarotto, Raquel A

    2009-05-01

    This study aimed at verifying the effects of phonophoresis associated with Arnica montana on the acute phase of an inflammatory muscle lesion. Forty Wistar male rats (300+/-50 g), of which the Tibialis Anterior muscle was surgically lesioned, were divided into four groups (n=10 each): control group received no treatment; the ultrasound group (US) was treated in pulsed mode with 1-MHz frequency, 0.5 W/cm(2) intensity (spatial and temporal average - SATA), duty cycle of 1:2 (2 ms on, 4 ms off, 50%), time of application 3 min per session, one session per day, for 3 days; the phonophoresis or ultrasound plus arnica (US+A) group was treated with arnica with the same US parameters plus arnica gel; and the arnica group (A) was submitted to massage with arnica gel, also for 3 min, once a day, for 3 days. Treatment started 24h after the surgical lesion. On the 4th day after lesion creation, animals were sacrificed and sections of the lesioned, inflamed muscle were removed for quantitative (mononuclear and polymorphonuclear cell count) and qualitative histological analysis. Collected data from the 4 groups were statistically analyzed and the significance level set at p<0.05. Results show higher mononuclear cell density in all three treated groups with no significant difference between them, but values were significantly different (p<0.0001) when compared to control group's. As to polymorphonuclear cell density, significant differences were found between control group (p=0.0134) and US, US+A and A groups; the arnica group presented lesser density of polymorphonuclear cells when compared (p=0.0134) to the other groups. No significant difference was found between US and US+A groups. While the massage with arnica gel proved to be an effective anti-inflammatory on acute muscle lesion in topic use, these results point to ineffectiveness of Arnica montana phonophoresis, US having seemingly checked or minimized its anti-inflammatory effect.

  16. Telmisartan treatment targets inflammatory cytokines to suppress the pathogenesis of acute colitis induced by dextran sulphate sodium.

    Science.gov (United States)

    Arumugam, Somasundaram; Sreedhar, Remya; Thandavarayan, Rajarajan A; Giridharan, Vijayasree V; Karuppagounder, Vengadeshprabhu; Pitchaimani, Vigneshwaran; Afrin, Mst Rejina; Miyashita, Shizuka; Nomoto, Mayumi; Harima, Meilei; Suzuki, Hiroshi; Nakamura, Takashi; Nakamura, Masahiko; Suzuki, Kenji; Watanabe, Kenichi

    2015-08-01

    The renin angiotensin system (RAS) is essential for the regulation of cardiovascular and renal functions to maintain the fluid and electrolyte homeostasis. Recent studies have demonstrated a locally expressed RAS in various tissues of mammals, which is having pathophysiological roles in those organ system. Interestingly, local RAS has important role during the inflammatory bowel disease pathogenesis. Further to delineate its role and also to identify the potential effects of telmisartan, an angiotensin receptor blocker, we have used a mouse model of acute colitis induced by dextran sulphate sodium. We have used 0.01 and 5mg/kg body weight doses of telmisartan and administered as enema to facilitate the on-site action and to reduce the systemic adverse effects. Telmisartan high dose treatment significantly reduced the disease activity index score when compared with the colitis control mice. In addition, oxidative stress and endoplasmic reticulum stress markers expression were also significantly reduced when compared with the colitis control mice. Subsequent experiments were carried out to investigate some of the mechanisms underlying its anti-inflammatory effects and identified that the mRNA levels of pro-inflammatory cytokines such as tumour necrosis factor α, interleukin 1β, interleukin 6 and monocyte chemoattractant protein 1 as well as cellular DNA damage were significantly suppressed when compared with the colitis control mice. Similarly the apoptosis marker proteins such as cleaved caspase 3 and 7 levels were down-regulated and anti-apoptotic protein Bcl2 level was significantly upregulated by telmisartan treatment. These results indicate that blockade of RAS by telmisartan can be an effective therapeutic option against acute colitis.

  17. Pro-inflammatory responses of human bronchial epithelial cells to acute nitrogen dioxide exposure.

    Science.gov (United States)

    Ayyagari, Vijayalakshmi N; Januszkiewicz, Adolph; Nath, Jayasree

    2004-04-15

    Nitrogen dioxide (NO2) is an environmental oxidant, known to be associated with lung epithelial injury. In the present study, cellular pro-inflammatory responses following exposure to a brief high concentration of NO2 (45 ppm) were assessed, using normal human bronchial epithelial (NHBE) cells as an in vitro model of inhalation injury. Generation and release of pro-inflammatory mediators such as nitric oxide (NO), IL-8, TNF-alpha, IFN-gamma and IL-1beta were assessed at different time intervals following NO2 exposure. Effects of a pre-existing inflammatory condition was tested by treating the NHBE cells with different inflammatory cytokines such as IFN-gamma, IL-8, TNF-alpha, IL-1beta, either alone or in combination, before exposing them to NO2. Immunofluorescence studies confirmed oxidant-induced formation of 3-nitrotyrosine in the NO2-exposed cells. A marked increase in the levels of nitrite (as an index of NO) and IL-8 were observed in the NO2-exposed cells, which were further enhanced in the presence of the cytokines. Effects of various NO inhibitors combined, with immunofluorescence and Western blotting data, indicated partial contribution of the nitric oxide synthases (NOSs) toward the observed increase in nitrite levels. Furthermore, a significant increase in IL-1beta and TNF-alpha generation was observed in the NO2-exposed cells. Although NO2 exposure alone did induce slight cytotoxicity (<12%), but presence of inflammatory cytokines such as TNF-alpha and IFN-gamma resulted in an increased cell death (28-36%). These results suggest a synergistic role of inflammatory mediators, particularly of NO and IL-8, in NO2-mediated early cellular changes. Our results also demonstrate an increased sensitivity of the cytokine-treated NHBE cells toward NO2, which may have significant functional implications in vivo.

  18. Azathioprine-induced Acute Pancreatitis in Patients with Inflammatory Bowel Diseases—A Prospective Study on Incidence and Severity

    Science.gov (United States)

    Mohl, Wolfgang; Bokemeyer, Bernd; Bündgens, Burkhard; Büning, Jürgen; Miehlke, Stephan; Hüppe, Dietrich; Maaser, Christian; Klugmann, Tobias; Kruis, Wolfgang; Siegmund, Britta; Helwig, Ulf; Weismüller, Joseph; Drabik, Attyla; Stallmach, Andreas

    2016-01-01

    Background and Aims: Azathioprine [AZA] is recommended for maintenance of steroid-free remission in inflammatory bowel disease IBD. The aim of this study has been to establish the incidence and severity of AZA-induced pancreatitis, an idiosyncratic and major side effect, and to identify specific risk factors. Methods: We studied 510 IBD patients [338 Crohn’s disease, 157 ulcerative colitis, 15 indeterminate colitis] with initiation of AZA treatment in a prospective multicentre registry study. Acute pancreatitis was diagnosed in accordance with international guidelines. Results: AZA was continued by 324 [63.5%] and stopped by 186 [36.5%] patients. The most common cause of discontinuation was nausea [12.2%]. AZA-induced pancreatitis occurred in 37 patients [7.3%]. Of these: 43% were hospitalised with a median inpatient time period of 5 days; 10% had peripancreatic fluid collections; 24% had vomiting; and 14% had fever. No patient had to undergo nonsurgical or surgical interventions. Smoking was the strongest risk factor for AZA-induced acute pancreatitis [p < 0.0002] in univariate and multivariate analyses. Conclusions: AZA-induced acute pancreatitis is a common adverse event in IBD patients, but in this study had a mild course in all patients. Smoking is the most important risk factor. PMID:26468141

  19. Mesenchymal Stem Cell Derived Secretome and Extracellular Vesicles for Acute Lung Injury and Other Inflammatory Lung Diseases

    Science.gov (United States)

    Monsel, Antoine; Zhu, Ying-gang; Gudapati, Varun; Lim, Hyungsun; Lee, Jae W.

    2017-01-01

    Introduction Acute respiratory distress syndrome is a major cause of respiratory failure in critically ill patients. Despite extensive research into its pathophysiology, mortality remains high. No effective pharmacotherapy exists. Based largely on numerous preclinical studies, administration of mesenchymal stem or stromal cell (MSC) as a therapeutic for acute lung injury holds great promise, and clinical trials are currently underway. However, concern for the use of stem cells, specifically the risk of iatrogenic tumor formation, remains unresolved. Accumulating evidence now suggest that novel cell-free therapies including MSC-derived conditioned medium and extracellular vesicles released from MSCs might constitute compelling alternatives. Areas covered The current review summarizes the preclinical studies testing MSC conditioned medium and/or MSC extracellular vesicles as treatment for acute lung injury and other inflammatory lung diseases. Expert opinion While certain logistical obstacles limit the clinical applications of MSC conditioned medium such as the volume required for treatment, the therapeutic application of MSC extracellular vesicles remains promising, primarily due to ability of extracellular vesicles to maintain the functional phenotype of the parent cell. However, utilization of MSC extracellular vesicles will require large-scale production and standardization concerning identification, characterization and quantification. PMID:27011289

  20. Rapid response of advanced squamous non-small cell lung cancer with thrombocytopenia after first-line treatment with pembrolizumab plus autologous cytokine-induced killer cells

    Directory of Open Access Journals (Sweden)

    Zhenzhen eHui

    2015-12-01

    Full Text Available We present the first clinical evidence of advanced squamous non-small cell lung cancer with severe thrombocytopenia showing dramatic improvement after first-line treatment with pembrolizumab plus cytokine-induced killer cells.

  1. Expression of ICAM-1 and acute inflammatory cell infiltration in the early phase of radiation colitis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Ikeda, Yuji; Ito, Masahiro; Matsuu, Mutsumi; Shichijo, Kazuko; Fukuda, Eiichiro; Nakayama, Toshiyuki; Nakashima, Masahiro; Naito, Shinji; Sekine, Ichiro [Nagasaki Univ. (Japan). Atomic Bomb Disease Inst.

    2000-09-01

    Inflammatory cell infiltration of the colon is observed at an early stage of radiation-induced colitis. The emigration of inflammatory cells from the circulation requires interactions between cell adhesion molecules on the vascular endothelium and molecules on the surface of leukocytes. To elucidate this process, the present work analyzes the kinetics of the expression of intercellular adhesion molecule-1 (ICAM-1) and the accumulation of inflammatory myeloperoxidase (MPO)-positive cells in relation to the appearance of acute radiation colitis prior to an overt radiation-induced ulcer. Colon tissues were obtained from Wistar Kyoto rats at various times after 22.5 Gy irradiation to the rectum. Histologically, crypt depletion and numerous inflammatory cells were observed 4 days after irradiation, and mucosal ulcer 6 days after irradiation. ICAM-1 immunopositivity was present in the endothelial cells of small vessels in the mucosa of both control and irradiated rats. ICAM-1 mRNA expression was detected in normal colon and irradiated colon by reverse transcription-PCR. In Northern blotting, ICAM-1 mRNA levels were found to increase markedly in the irradiated colon compared to the normal colon. In Western blotting, ICAM-1 protein expression also increased with a peak one day after irradiation, and remained elevated up to 6 days thereafter. The number of MPO-positive cells in lamina propria mucosa increased in a time-dependent fashion from 6 h to 6 days after irradiation. These data suggest that up-regulation of ICAM-1 in endothelial cells and accumulation of MPO positive cells play important roles in the development of radiation-induced colonic ulcer. (author)

  2. Uric acid promotes an acute inflammatory response to sterile cell death in mice

    Science.gov (United States)

    Kono, Hajime; Chen, Chun-Jen; Ontiveros, Fernando; Rock, Kenneth L.

    2010-01-01

    Necrosis stimulates inflammation, and this response is medically relevant because it contributes to the pathogenesis of a number of diseases. It is thought that necrosis stimulates inflammation because dying cells release proinflammatory molecules that are recognized by the immune system. However, relatively little is known about the molecular identity of these molecules and their contribution to responses in vivo. Here, we investigated the role of uric acid in the inflammatory response to necrotic cells in mice. We found that dead cells not only released intracellular stores of uric acid but also produced it in large amounts postmortem as nucleic acids were degraded. Using newly developed Tg mice that have reduced levels of uric acid either intracellularly and/or extracellularly, we found that uric acid depletion substantially reduces the cell death–induced inflammatory response. Similar results were obtained with pharmacological treatments that reduced uric acid levels either by blocking its synthesis or hydrolyzing it in the extracellular fluids. Importantly, uric acid depletion selectively inhibited the inflammatory response to dying cells but not to microbial molecules or sterile irritant particles. Collectively, our data identify uric acid as a proinflammatory molecule released from dying cells that contributes significantly to the cell death–induced inflammatory responses in vivo. PMID:20501947

  3. Enhanced acute anti-inflammatory effects of CORM-2-loaded nanoparticles via sustained carbon monoxide delivery.

    Science.gov (United States)

    Qureshi, Omer Salman; Zeb, Alam; Akram, Muhammad; Kim, Myung-Sic; Kang, Jong-Ho; Kim, Hoo-Seong; Majid, Arshad; Han, Inbo; Chang, Sun-Young; Bae, Ok-Nam; Kim, Jin-Ki

    2016-11-01

    The aim of this study was to enhance the anti-inflammatory effects of carbon monoxide (CO) via sustained release of CO from carbon monoxide-releasing molecule-2-loaded lipid nanoparticles (CORM-2-NPs). CORM-2-NPs were prepared by hot high pressure homogenization method using trilaurin as a solid lipid core and Tween 20/Span 20/Myrj S40 as surfactant mixture. The physicochemical properties of CORM-2-NPs were characterized and CO release from CORM-2-NPs was assessed by myoglobin assay. In vitro anti-inflammatory effects were evaluated by nitric oxide assay in lipopolysaccharide-stimulated RAW 264.7 macrophages. In vivo anti-inflammatory activity was investigated by measuring paw volumes and histological examination in carrageenan-induced rat paw edema. Spherical CORM-2-NPs were around 100nm with narrow particle size distribution. The sustained CO release from CORM-2-NPs was observed and the half-life of CO release increased up to 10 times compared with CORM-2 solution. CORM-2-NPs showed enhanced in vitro anti-inflammatory effects by inhibition of nitric oxide production. Edema volume in rat paw was significantly reduced after treatment with CORM-2-NPs. Taken together, CORM-2-NPs have a great potential for CO therapeutics against inflammation via sustained release of CO. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Cytokine-Induced Killer Cells Kill Chemo-surviving Melanoma Cancer Stem Cells.

    Science.gov (United States)

    Gammaitoni, Loretta; Giraudo, Lidia; Macagno, Marco; Leuci, Valeria; Mesiano, Giulia; Rotolo, Ramona; Sassi, Francesco; Sanlorenzo, Martina; Zaccagna, Alessandro; Pisacane, Alberto; Senetta, Rebecca; Cangemi, Michela; Cattaneo, Giulia; Martin, Valentina; Coha, Valentina; Gallo, Susanna; Pignochino, Ymera; Sapino, Anna; Grignani, Giovanni; Carnevale-Schianca, Fabrizio; Aglietta, Massimo; Sangiolo, Dario

    2017-05-01

    Purpose: The MHC-unrestricted activity of cytokine-induced killer (CIK) cells against chemo-surviving melanoma cancer stem cells (mCSC) was explored, as CSCs are considered responsible for chemoresistance and relapses.Experimental Design: Putative mCSCs were visualized by engineering patient-derived melanoma cells (MC) with a lentiviral vector encoding eGFP under expression control by stemness gene promoter oct4 Their stemness potential was confirmed in vivo by limiting dilution assays. We explored the sensitivity of eGFP(+) mCSCs to chemotherapy (CHT), BRAF inhibitor (BRAFi) or CIK cells, as single agents or in sequence, in vitro First, we treated MCs in vitro with fotemustine or dabrafenib (BRAF-mutated cases); then, surviving MCs, enriched in mCSCs, were challenged with autologous CIK cells. CIK cell activity against chemoresistant mCSCs was confirmed in vivo in two distinct immunodeficient murine models.Results: We visualized eGFP(+) mCSCs (14% ± 2.1%) in 11 MCs. The tumorigenic precursor rate in vivo was higher within eGFP(+) MCs (1/42) compared with the eGFP(-) counterpart (1/4,870). In vitro mCSCs were relatively resistant to CHT and BRAFi, but killed by CIK cells (n = 11, 8/11 autologous), with specific lysis ranging from 95% [effector:tumor ratio (E:T), 40:1] to 20% (E:T 1:3). In vivo infusion of autologous CIK cells into mice bearing xenografts from three distinct melanomas demonstrated significant tumor responses involving CHT-spared eGFP(+) mCSCs (P = 0.001). Sequential CHT-immunotherapy treatment retained antitumor activity (n = 12, P = 0.001) reducing mCSC rates (P = 0.01).Conclusions: These findings are the first demonstration that immunotherapy with CIK cells is active against autologous mCSCs surviving CHT or BRAFi. An experimental platform for mCSC study and rationale for CIK cells in melanoma clinical study is provided. Clin Cancer Res; 23(9); 2277-88. ©2016 AACR. ©2016 American Association for Cancer Research.

  5. Preliminary Study of Local Immunotherapy with Autologous Cytokine-Induced Killer Cells for Glioma Patients

    Institute of Scientific and Technical Information of China (English)

    Li Lin; Yonggao Mu; Zhongping Chen

    2008-01-01

    OBJECTIVE Cytokine-induced killer (CIK) cells are T-cells that display effective anti-tumor activity. In this study, we investigated the anti-tumor activity of CIK cells in vitro, and conducted a preliminary investigation using autologous CIK cells to treat glioma patients through local administration.METHODS The CIK cells were derived from peripheral blood monocytes (PBMCs) of the glioma patients. The anti-tumor activity of the CIK cells against human T98-G glioma cell was tested In vitro. In addition, the autologous CIK cells were locally administrated into the tumor cavity in the malignant glioma patients through an Ommaya reservoir which was pre-inserted during tumor resection. The 4×108 CIK cells in a 5 ml suspension were injected once a week 2 times per cycle. Five hundreds KU of IL-2 was injected every other day.RESULTS (I) With incubation, the CIK cells showed dual staining of CD3+CD56+ with a positive rate of 3.45% on day 10 and 55.2% on day 30. In vitro anti-tumor activity (againstT98-G cells) of the CIK cells reached the highest level after 18 days of incubation with different effector/target (E:T) ratios. (ii)Six patients received autologous CIK cell treatment (10 cycles).Two patients showed no recurrence and are still alive (24 and 10 months), while 4 cases had a recurrence 3 of which have died. The mean survival time from the first CIK cell treatment to the end of follow-up was 12.5 months. The main side-effects of the local CIK cell treatment was brain edema, which was controlled by mannitol in most of the cases. However for one patient injection of CIK cells and IL-2 had to be discontinued.CONCLUSION In vitro CIK cells are effective anti-glioma T-cells. Local therapy with CIK cells has potential anti-glioma efficacy and tolerable side-effects.

  6. Luteolin protects mice from severe acute pancreatitis by exerting HO-1-mediated anti-inflammatory and antioxidant effects

    Science.gov (United States)

    Xiong, Jie; Wang, Kezhou; Yuan, Chunxiao; Xing, Rong; Ni, Jianbo; Hu, Guoyong; Chen, Fengling; Wang, Xingpeng

    2017-01-01

    Reseda odorata L. has long been used in traditional Asian medicine for the treatment of diseases associated with oxidative injury and acute inflammation, such as endotoxemia, acute lung injury, acute myocardial infarction and hepatitis. Luteolin, the main component of Reseda odorata L., which is also widely found in many natural herbs and vege tables, has been shown to induce heme oxygenase-1 (HO-1) expression to exert anti-inflammatory and antioxidant effects. In this study, we aimed to examine the effects of luteolin on mice with severe acute pancreatitis (SAP), and to explore the underlying mechanisms. Cerulein and lipopolysaccharide were used to induce SAP in male Institute of Cancer Research (ICR) mice in the SAP group. The SAP group was divided into 4 subgroups, as follows: the vehicle, luteolin, zinc protoporphyrin (ZnPP) only, and luteolin (Lut) + ZnPP (luteolin plus zinc protoporphyrin treatment) groups. The wet/dry weight ratios, hematoxylin and eosin staining and pathological scores of pancreatic tissues were assessed and compared to those of the control mice. Amylase, lipase, nuclear factor-κB (NF-κB) and myeloperoxidase activities, and malondialdehyde, tumor necrosis factor α (TNFα), interleukin (IL)-6, IL-10 and HO-1 levels, as well as the expression of HO-1 were determined in serum and/or pancreatic tissue samples. SAP was successfully induced in male mice compared to normal control mice. The wet/dry weight ratios, pathological scores, and amylase and lipase activity, as well as the levels of TNFα and IL-6 were significantly reduced in the pancreatic tissues of the mice in the Lut group compared with those of the mice in the vehicle group. The Lut group exhibited a significant increase in HO-1 expression in the pancreas and enhanced serum HO-1 and IL-10 levels compared with the vehicle group. The suppression of HO-1 activity in the ZnPP group significantly abolished the protective effects of luteolin. NF-κB expression in the pancreatic tissues

  7. The pro- and anti-inflammatory markers in patients with acute myocardial infarction and chronic stable angina.

    Science.gov (United States)

    Wojakowski, Wojciech; Maslankiewicz, Katarzyna; Ochala, Andrzej; Wyderka, Rafal; Zuk-Popiolek, Izabela; Flak, Zbigniew; Mroz, Iwona; Tendera, Michal

    2004-08-01

    The aim of this study was to assess the plasma levels of VEGF and interleukin-10 in patients with acute myocardial infarction (AMI) and stable chronic angina (SA) and correlate the values with traditional CHD risk factors, left ventricular ejection fraction (LVEF) and established inflammatory marker hsCRP. Fifty patients with AMI and 30 with SA were enrolled. IL-10 levels in AMI patients were lower than in SA patients (9.81 +/- 5.0 versus 22.63 +/- 8.38 pg/ml, p 40% and Killip class I-II (338.8 +/- 51.59 versus 271.8 +/- 50.51 pg/ml; p 6 h versus inflamatory markers and CHD risk factors and the function of the left ventricle on admission.

  8. Impact of systemic inflammatory response syndrome and surgical Apgar score on post-operative acute kidney injury.

    Science.gov (United States)

    Toyonaga, Y; Asayama, K; Maehara, Y

    2017-08-28

    Surgical Apgar Score (SAS) is relatively weakly associated with post-operative outcomes in emergency surgery, compared with elective surgery. A combination of systemic inflammatory response syndrome (SIRS) and SAS may be useful for prediction of poor outcomes after emergency surgery. A retrospective study was conducted in patients who underwent emergency abdominal or cerebral surgery from January 2005 to December 2010. AKI was diagnosed using Acute Kidney Injury Network criteria for 2 days after surgery. Pre-operative SIRS was defined as SIRS score ≥ 2. Patients were divided into those with SAS ≥ 5 and SIRS (OR 1.9, 95% CI: 1.2-2.9, P SIRS and SAS SIRS and SAS SIRS and SAS SIRS and SAS are independently associated with post-operative AKI. Simultaneous use of pre-operative SIRS and SAS may improve prediction of poor post-operative outcomes. © 2017 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  9. Toll-Like Receptor-9 (TLR9) is Requisite for Acute Inflammatory Response and Injury Following Lung Contusion.

    Science.gov (United States)

    Suresh, Madathilparambil V; Thomas, Bivin; Dolgachev, Vladislav A; Sherman, Matthew A; Goldberg, Rebecca; Johnson, Mark; Chowdhury, Aulina; Machado-Aranda, David; Raghavendran, Krishnan

    2016-10-01

    Lung contusion (LC) is a significant risk factor for the development of acute respiratory distress syndrome. Toll-like receptor 9 (TLR9) recognizes specific unmethylated CpG motifs, which are prevalent in microbial but not vertebrate genomic DNA, leading to innate and acquired immune responses. TLR9 signaling has recently been implicated as a critical component of the inflammatory response following lung injury. The aim of the present study was to evaluate the contribution of TLR9 signaling to the acute physiologic changes following LC. Nonlethal unilateral closed-chest LC was induced in TLR9 (-/-) and wild-type (WT) mice. The mice were sacrificed at 5, 24, 48, and 72-h time points. The extent of injury was assessed by measuring bronchoalveolar lavage, cells (cytospin), albumin (permeability injury), and cytokines (inflammation). Following LC, only the TLR9 (-/-) mice showed significant reductions in the levels of albumin; release of pro-inflammatory cytokines IL-1β, IL-6, and Keratinocyte chemoattractant; production of macrophage chemoattractant protein 5; and recruitment of alveolar macrophages and neutrophil infiltration. Histological evaluation demonstrated significantly worse injury at all-time points for WT mice. Macrophages, isolated from TLR9 (-/-) mice, exhibited increased phagocytic activity at 24 h after LC compared with those isolated from WT mice. TLR9, therefore, appears to be functionally important in the development of progressive lung injury and inflammation following LC. Our findings provide a new framework for understanding the pathogenesis of lung injury and suggest blockade of TLR9 as a new therapeutic strategy for the treatment of LC-induced lung injury.

  10. Clinical aspects of acute inflammatory diseases of the brain; Klinisch-neurologische Aspekte akut-entzuendlicher Hirnerkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Block, F.; Nolden-Koch, M. [RWTH Aachen (Germany). Neurologische Klinik

    2000-11-01

    Despite the progress, which has been made in diagnosis and therapy of encephalitis and bacterial meningitis, these acute inflammatory diseases of the brain still display a certain amount of morbidity and mortality. History, physical examination, analysis of serum and cerebrospinal fluid and radiological examination are the mainstay for the diagnosis of these diseases. With respect to the acute inflammatory diseases of the brain computed tomography and magnetic resonance imaging fulfil three purposes: 1. They can be used to clarify the diagnosis and to rule out other diseases. 2. They can identify the focus from which a bacterial meningitis can evolve. 3. Complications like edema, cerebral vasculitis, septic sinus thrombosis, hydrocephalus or abscess can be visualized. If the diagnosis is made early, the possible complications are recognized in good time and the appropriate therapy is started immediately, then morbidity and mortality can be kept at a minimum. (orig.) [German] Die bakterielle Meningitis und die Enzephalitis sind akut-entzuendliche Hirnerkrankungen, die trotz aller Fortschritte in der Diagnostik und Therapie mit einer nicht unerheblichen Morbiditaet und Mortalitaet behaftet sind. Die Anamnese, die koerperliche Untersuchung, die laborchemische Diagnostik von Blut und Liquor und die Bildgebung sind die wesentlichen Saeulen in der Diagnostik akut-entzuendlicher Hirnerkrankungen. Die Bildgebung, die mittels Computertomographie bzw. Kernspintomographie erfolgt, hat in diesem Zusammenhang 3 Aufgaben: 1. Sie kann dazu beitragen, die Diagnose zu sichern bzw. differentialdiagnostisch in Erwaegung zu ziehende Erkrankungen auszuschliessen oder nachzuweisen. 2. Sie kann bei der bakteriellen Meningitis entzuendliche Foci im Bereich der Nasennebenhoehlen, des Mastoids oder des Mittelohrs erkennen, die sofort operativ saniert werden muessen. 3. Komplikationen akut-entzuendlicher Hirnerkrankungen koennen bei entsprechendem klinischem Verdacht mittels Bildgebung

  11. Effect of alanyl glutamine on the acute inflammatory reaction and immunological function in elderly patients with intestinal obstruction

    Institute of Scientific and Technical Information of China (English)

    Fei-Guo Ma

    2016-01-01

    Objective:To explore the application value of alanyl glutamine in improving the acute inflammatory reaction and immunological function in elderly patients with intestinal obstruction.Methods:A total of 97 elderly patients with intestinal obstruction who were admitted in our hospital were included in the study and randomized into the treatment group (n=49) and the control group (n=48). The patients in the control group were given total parenteral nutrition (TPN) treatment. On this basis, the patients in the treatment group were given intravenous injection of alanyl glutamine for 1 week. The plasma prealbumin, albumin, serum related cytokines, L/M, and DAO before and after treatment in the two groups were detected. The serum immunoglobulin and T lymphocyte subsets before and after treatment in the two groups were compared.Results:The plasma prealbumin and albumin levels after treatment in the observation group were significantly higher than those in the control group, while the serum CRP, IL-6, and TNF-α levels in the two groups were significantly reduced when compared with before treatment, and those in the observation group were significantly lower than those in the control group. When compared with before treatment, L/M and plasma DAO level after treatment in the control group were significantly elevated, while those in the observation group were significantly reduced, and the comparison between the two groups was statistically significant. The serum IgG and IgA levels after treatment in the observation group were significantly higher than those in the control group. The serum CD4+, CD8+, and CD4+/CD8+ after treatment in the two groups were significantly elevated when compared with before treatment, and those in the observation group were significantly higher than those in the control group.Conclusions:Alanyl glutamine in the treatment of elderly intestinal obstruction can significantly improve the acute inflammatory reaction and immunological function, with a

  12. Crypt abscess-associated microbiota in inflammatory bowel disease and acute self-limited colitis

    Institute of Scientific and Technical Information of China (English)

    Harry; Sokol; Nadia; Vasquez; Nadia; Hoyeau-Idrissi; Philippe; Seksik; Laurent; Beaugerie; Anne; Lavergne-Slove; Philippe; Pochart; Philippe; Marteau

    2010-01-01

    AIM:To evaluate whether crypt abscesses frominflammatory bowel disease(IBD)patients containbacteria and to establish their nature.METHODS:We studied 17 ulcerative colitis patients,11 Crohn's disease patients,7 patients with acute selflimited colitis(ASLC)and normal colonic biopsies from5 subjects who underwent colonoscopy for colon cancer screening.A fluorescent in situ hybridization techniquewas applied to colonic biopsies to assess the microbiotacomposition of the crypts and crypt abscesses.RESULTS:Crypts...

  13. Co-culture of neural crest stem cells (NCSC and insulin producing beta-TC6 cells results in cadherin junctions and protection against cytokine-induced beta-cell death.

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    Anongnad Ngamjariyawat

    Full Text Available PURPOSE: Transplantation of pancreatic islets to Type 1 diabetes patients is hampered by inflammatory reactions at the transplantation site leading to dysfunction and death of insulin producing beta-cells. Recently we have shown that co-transplantation of neural crest stem cells (NCSCs together with the islet cells improves transplantation outcome. The aim of the present investigation was to describe in vitro interactions between NCSCs and insulin producing beta-TC6 cells that may mediate protection against cytokine-induced beta-cell death. PROCEDURES: Beta-TC6 and NCSC cells were cultured either alone or together, and either with or without cell culture inserts. The cultures were then exposed to the pro-inflammatory cytokines IL-1β and IFN-γ for 48 hours followed by analysis of cell death rates (flow cytometry, nitrite production (Griess reagent, protein localization (immunofluorescence and protein phosphorylation (flow cytometry. RESULTS: We observed that beta-TC6 cells co-cultured with NCSCs were protected against cytokine-induced cell death, but not when separated by cell culture inserts. This occurred in parallel with (i augmented production of nitrite from beta-TC6 cells, indicating that increased cell survival allows a sustained production of nitric oxide; (ii NCSC-derived laminin production; (iii decreased phospho-FAK staining in beta-TC6 cell focal adhesions, and (iv decreased beta-TC6 cell phosphorylation of ERK(T202/Y204, FAK(Y397 and FAK(Y576. Furthermore, co-culture also resulted in cadherin and beta-catenin accumulations at the NCSC/beta-TC6 cell junctions. Finally, the gap junction inhibitor carbenoxolone did not affect cytokine-induced beta-cell death during co-culture with NCSCs. CONCLUSION: In summary, direct contacts, but not soluble factors, promote improved beta-TC6 viability when co-cultured with NCSCs. We hypothesize that cadherin junctions between NCSC and beta-TC6 cells promote powerful signals that maintain beta

  14. The changes of inflammatory cytokines and their clinical significance in patients of inferior ST-segment elevation acute myocardial infarction with anterior ST-segment depression

    Institute of Scientific and Technical Information of China (English)

    叶明

    2014-01-01

    Objective To investigate the level of Hs-CRP,Fib,IL-6,TNF-α,MDA,SOD,and analyze the correlation between the level of plasma inflammatory cytokines and clinical significance in patients with anterior ST-segment depression.Methods We chose 360 patients with inferior ST Segment elavation acute myocardial infarction from May 2007 to Sep 2012 in emergency department of

  15. Mass-spectrometric identification of T-kininogen I/thiostatin as an acute-phase inflammatory protein suppressed by curcumin and capsaicin.

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    Bina Joe

    Full Text Available Curcumin and capsaicin are dietary xenobiotics with well-documented anti-inflammatory properties. Previously, the beneficial effect of these spice principles in lowering chronic inflammation was demonstrated using a rat experimental model for arthritis. The extent of lowering of arthritic index by the spice principles was associated with a significant shift in macrophage function favoring the reduction of pro-inflammatory molecules such as reactive oxygen species and production and release of anti-inflammatory metabolites of arachidonic acid. Beyond the cellular effects on macrophage function, oral administration of curcumin and capsaicin caused alterations in serum protein profiles of rats injected with adjuvant to develop arthritis. Specifically, a 72 kDa acidic glycoprotein, GpA72, which was elevated in pre-arthritic rats, was significantly lowered by feeding either curcumin or capsaicin to the rats. Employing the tandem mass spectrometric approach for direct sequencing of peptides, here we report the identification of GpA72 as T-kininogen I also known as Thiostatin. Since T-kininogen I is an early acute-phase protein, we additionally tested the efficiency of curcumin and capsaicin to mediate the inflammatory response in an acute phase model. The results demonstrate that curcumin and capsaicin lower the acute-phase inflammatory response, the molecular mechanism for which is, in part, mediated by pathways associated with the lowering of T-kininogen I.

  16. Effects of glutamine supplementation on gut barrier,glutathione content and acute phase response in malnourished rats during inflammatory shock

    Institute of Scientific and Technical Information of China (English)

    Liliana Belmonte; Philippe Ducrotté; Pierre Déchelotte; Mo(i)se Co(e)ffier; Florence Le Pessot; Olga Miralles-Barrachina; Martine Hiron; Antony Leplingard; Jean-Fran(c)ois Lemeland; Bernadette Hecketsweiler; Maryvonne Daveau

    2007-01-01

    AIM:To evaluate the effect of glutamine on intestinal mucosa integrity, glutathione stores and acute phase response in protein-depleted rats during an inflammatory shock.METHODS: Plasma acute phase proteins (APP),jejunal APP mRNA levels, liver and jejunal glutathione concentrations were measured before and one, three and seven days after turpentine injection in 4 groups of control, protein-restricted, protein-restricted rats supplemented with glutamine or protein powder.Bacterial translocation in mesenteric lymph nodes and intestinal morphology were also assessed.RESULTS: Protein deprivation and turpentine injection significantly reduced jejunal villus height, and crypt depths. Mucosal glutathione concentration significantly decreased in protein-restricted rats. Before turpentine oil, glutamine supplementation restored villus heights and glutathione concentration (3.24 ± 1.05 vs 1.72 ±0.46 μmol/g tissue, P < 0.05) in the jejunum, whereas in the liver glutathione remained low. Glutamine markedly increased jejunal α1-acid glycoprotein mRNA level after turpentine oil but did not affect its plasma concentration. Bacterial translocation in protein-restricted rats was not prevented by glutamine or protein powder supplementation.CONCLUSION: Glutamine restored gut glutathione stores and villus heights in malnourished rats but had no preventive effect on bacterial translocation in our model.

  17. Acute inflammatory demyelinating polyneuropathy associated with pegylated interferon 2a therapy for chronic hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    Vijay Khiani; Thomas Kelly; Adeel Shibli; Donald Jensen; Smruti R Mohanty

    2008-01-01

    The combination of pogylated interferon (Peg-IFN) and ribavirin is the standard of care for chronic hepatitis C virus (HCV) infection treatment. In general, common side effects related to this combination therapy are mild and are very well tolerated. However, peripheral neuropathy including demyelinating polyneuropathy related to Peg-IFN is extremely rare. We present the first case of an acute inflammatory demyelinating polyneuropathy (AIDP)associated with Peg-IFN-α 2a (Pegasys) after 16 wk of a combination therapy with Pegasys and ribavirin in a 65-year-old woman with chronic HCV infection.She developed tingling, numbness, and weakness of her upper and lower extremities and was hospitalized for acute neurological deficits. Her clinical course,neurological findings, an electromyogram (EHG), nerve conductions studies (NCS), muscle biopsy, and a sural nerve biopsy were all consistent with AIDP likely related to Pegasys use. The patient recovered completely with the use of intravenous immunoglobulin (IVIG) including physical therapy and neurological rehabilitation. It is very important that gastroenterologists and/or hepatologists recognize this rare neurological complication related to Peg-IFN treatment very early, since it requires a prompt discontinuation of therapy including an immediate referral to a neurologist for the confirmation of diagnosis, management, and the prevention of long-term neurological deficits.

  18. Sabiporide improves cardiovascular function, decreases the inflammatory response and reduces mortality in acute metabolic acidosis in pigs.

    Directory of Open Access Journals (Sweden)

    Dongmei Wu

    Full Text Available INTRODUCTION: Acute metabolic acidosis impairs cardiovascular function and increases the mortality of critically ill patients. However, the precise mechanism(s underlying these effects remain unclear. We hypothesized that targeting pH-regulatory protein, Na(+/H(+ exchanger (NHE1 could be a novel approach for the treatment of acute metabolic acidosis. The aim of the present study was to examine the impact of a novel NHE1 inhibitor, sabiporide, on cardiovascular function, blood oxygen transportation, and inflammatory response in an experimental model of metabolic acidosis produced by hemorrhage-induced hypovolemia followed by an infusion of lactic acid. METHODS AND RESULTS: Anesthetized pigs were subjected to hypovolemia for 30 minutes. The animals then received a bolus infusion of sabiporide (3 mg/kg or vehicle, followed by an infusion of lactic acid for 2 hours. The animals were continuously monitored for additional 3 hours. Hypovolemia followed by a lactic acid infusion resulted in a severe metabolic acidosis with blood pH falling to 6.8. In association with production of the acidemia, there was an excessive increase in pulmonary artery pressure (PAP and pulmonary vascular resistance (PVR. Treatment with sabiporide significantly attenuated the increase in PAP by 38% and PVR by 67%, as well as significantly improved cardiac output by 51%. Sabiporide treatment also improved mixed venous blood oxygen saturation (55% in sabiporide group vs. 28% in control group, and improved systemic blood oxygen delivery by 36%. In addition, sabiporide treatment reduced plasma levels of TNF-α (by 33%, IL-6 (by 63%, troponin-I (by 54%, ALT (by 34%, AST (by 35%, and urea (by 40%. CONCLUSION: These findings support the possible beneficial effects of sabiporide in the treatment of acute metabolic acidosis and could have implications for the treatment of metabolic acidosis in man.

  19. Acute Inflammatory Response to Low-, Moderate-, and High-Load Resistance Exercise in Women With Breast Cancer-Related Lymphedema.

    Science.gov (United States)

    Cormie, Prue; Singh, Benjamin; Hayes, Sandi; Peake, Jonathan M; Galvão, Daniel A; Taaffe, Dennis R; Spry, Nigel; Nosaka, Kazunori; Cornish, Bruce; Schmitz, Kathryn H; Newton, Robert U

    2016-09-01

    Background Resistance exercise is emerging as a potential adjunct therapy to aid in the management of breast cancer-related lymphedema (BCRL). However, the mechanisms underlying the relationships between the acute and long-term benefits of resistance exercise on BCRL are not well understood. Purpose To examine the acute inflammatory response to upper-body resistance exercise in women with BCRL and to compare these effects between resistance exercises involving low, moderate, and high loads. The impact on lymphedema status and associated symptoms was also compared. Methods A total of 21 women, 62 ± 10 years old, with BCRL participated in the study. Participants completed low-load (15-20 repetition maximum [RM]), moderate-load (10-12 RM), and high-load (6-8 RM) exercise sessions consisting of 3 sets of 6 upper-body resistance exercises. Sessions were completed in a randomized order separated by a 7- to 10-day wash-out period. Venous blood samples were obtained to assess markers of exercise-induced muscle damage and inflammation. Lymphedema status was assessed using bioimpedance spectroscopy and arm circumferences, and associated symptoms were assessed using Visual Analogue Scales for pain, heaviness, and tightness. Measurements were conducted before and 24 hours after the exercise sessions. Results No significant changes in creatine kinase, C-reactive protein, interleukin-6, and tumor necrosis factor-α were observed following the 3 resistance exercise sessions. There were no significant changes in arm swelling or symptom severity scores across the 3 resistance exercise conditions. Conclusions The magnitude of acute exercise-induced inflammation following upper-body resistance exercise in women with BCRL does not vary between resistance exercise loads. © The Author(s) 2015.

  20. A recurrence of Guillain-Barr and eacute; syndrome or a case of acute-onset chronic inflammatory demyelinating polyneuropathy in the course of chronic hepatitis B?

    Directory of Open Access Journals (Sweden)

    Guner Celik Koyuncu

    2016-12-01

    Full Text Available Chronic inflammatory demyelinating polyneuropathy is a demyelinating polyneuropathy characterized by distal/proximal weakness, which shows gradual progression over a period of 8 weeks or longer. Guillan-Barre Syndrome is a condition characterized by acute monophasic paralysis typically following an infectious assault, and it usually peaks in severity over 3-4 weeks at most. Although rare, there are acute-onset chronic inflammatory demyelinating polyneuropathy cases that show progression over a period shorter than 4 weeks, as is the case in Guillan-Barre Syndrome .This report discusses a case of chronic inflammatory demyelinating polyneuropathy in a HBsAg-positive patient, which started as Guillan-Barre Syndrome but showed 3 recurrences within 6 months, each with rapidly progressing quadriplegia, respiratory arrest, and elevated liver enzymes and HBV DNA. [Cukurova Med J 2016; 41(4.000: 782-786

  1. Shift towards pro-inflammatory intestinal bacteria aggravates acute murine colitis via Toll-like receptors 2 and 4.

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    Markus M Heimesaat

    Full Text Available BACKGROUND: Gut bacteria trigger colitis in animal models and are suspected to aggravate inflammatory bowel diseases. We have recently reported that Escherichia coli accumulates in murine ileitis and exacerbates small intestinal inflammation via Toll-like receptor (TLR signaling. METHODOLOGY AND PRINCIPAL FINDINGS: Because knowledge on shifts in the intestinal microflora during colitis is limited, we performed a global survey of the colon flora of C57BL/10 wild-type (wt, TLR2(-/-, TLR4(-/-, and TLR2/4(-/- mice treated for seven days with 3.5% dextrane-sulfate-sodium (DSS. As compared to wt animals, TLR2(-/-, TLR4(-/-, and TLR2/4(-/- mice displayed reduced macroscopic signs of acute colitis and the amelioration of inflammation was associated with reduced IFN-gamma levels in mesenteric lymph nodes, lower amounts of neutrophils, and less FOXP3-positive T-cells in the colon in situ. During acute colitis E. coli increased in wt and TLR-deficient mice (P<0.05, but the final numbers reached were significantly lower in TLR2(-/-, TLR4(-/- and TLR2/4(-/- animals, as compared to wt controls (P<0.01. Concentrations of Bacteroides/ Prevotella spp., and enterococci did not increase during colitis, but their numbers were significantly reduced in the colon of DSS-treated TLR2/4(-/- animals (P<0.01. Numbers of lactobacilli and clostridia remained unaffected by colitis, irrespective of the TLR-genotype of mice. Culture-independent molecular analyses confirmed the microflora shifts towards enterobacteria during colitis and showed that the gut flora composition was similar in both, healthy wt and TLR-deficient animals. CONCLUSIONS AND SIGNIFICANCE: DSS-induced colitis is characterized by a shift in the intestinal microflora towards pro-inflammatory Gram-negative bacteria. Bacterial products exacerbate acute inflammation via TLR2- and TLR4-signaling and direct the recruitment of neutrophils and regulatory T-cells to intestinal sites. E. coli may serve as a biomarker

  2. Neospora caninum: Cloning and expression of a gene coding for cytokine-inducing Neospora caninum profilin

    Science.gov (United States)

    Profilins are actin-binding proteins that in T. gondii stimulate innate immunity in mice by binding Toll-like receptors (TLR) on dendritic cells (DC) leading to release of inflammatory cytokines, primarily IL-12 and IFN-'. The purpose of the present study was to characterize Neospora caninum profil...

  3. Plasticity of the systemic inflammatory response to acute infection during critical illness: development of the riboleukogram.

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    Jonathan E McDunn

    Full Text Available BACKGROUND: Diagnosis of acute infection in the critically ill remains a challenge. We hypothesized that circulating leukocyte transcriptional profiles can be used to monitor the host response to and recovery from infection complicating critical illness. METHODOLOGY/PRINCIPAL FINDINGS: A translational research approach was employed. Fifteen mice underwent intratracheal injections of live P. aeruginosa, P. aeruginosa endotoxin, live S. pneumoniae, or normal saline. At 24 hours after injury, GeneChip microarray analysis of circulating buffy coat RNA identified 219 genes that distinguished between the pulmonary insults and differences in 7-day mortality. Similarly, buffy coat microarray expression profiles were generated from 27 mechanically ventilated patients every two days for up to three weeks. Significant heterogeneity of VAP microarray profiles was observed secondary to patient ethnicity, age, and gender, yet 85 genes were identified with consistent changes in abundance during the seven days bracketing the diagnosis of VAP. Principal components analysis of these 85 genes appeared to differentiate between the responses of subjects who did versus those who did not develop VAP, as defined by a general trajectory (riboleukogram for the onset and resolution of VAP. As patients recovered from critical illness complicated by acute infection, the riboleukograms converged, consistent with an immune attractor. CONCLUSIONS/SIGNIFICANCE: Here we present the culmination of a mouse pneumonia study, demonstrating for the first time that disease trajectories derived from microarray expression profiles can be used to quantitatively track the clinical course of acute disease and identify a state of immune recovery. These data suggest that the onset of an infection-specific transcriptional program may precede the clinical diagnosis of pneumonia in patients. Moreover, riboleukograms may help explain variance in the host response due to differences in ethnic

  4. Effect of resveratrol on activation of nuclear factor kappa-B and inflammatory factors in rat model of acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Yong Meng; Qing-Yong Ma; Xiao-Ping Kou; Jun Xu

    2005-01-01

    AIM: To observe the effect of resveratrol on nuclear factor Kappa-B (NF-κB) activation and the inflammatory response in sodium taurocholate-induced pancreatitis in rats.METHODS: Seventy-two male SD rats were randomly divided into three groups: sham operation group (control),severe acute pancreatitis (SAP) group, and severe acute pancreatitis group treated with resveratrol (RES). A SAP model was established by injecting 4% sodium taurocholate 1 mL/kg through puncturing the pancreatic duct. In Res group, Res was given at 30 mg/kg b.m. intraperitoneally after the SAP model was successfully established. Eight animals from each group were sacrificed at 3, 6 and 12 h after modeling. The expression of NF-κB activation of pancreas was detected by immunohistochemical staining, whereas the levels of TNF-α and IL-8 in pancreatic tissues were estimated by radioimmunoassay. The pathological changes of pancreas and lungs were examined microscopically.RESULTS: Much less hyperemia, edema, dust-colored necrotic focus and soaps were noticed in pancreas in RES group than in SAP group. In RES group, hemorrhage,exudates and infiltration of inflammatory cells in pancreas and interstitial edema, destruction of alveolar wall in lung were significantly less than in SAP group. In the SAP group,the activation of NF-κB in pancreatic tissues was enhanced significantly at any measure point compared with control group (64.23±10.72% vs2.56±0.65%, 55.86±11.34% vs 2.32±0.42%, 36.23±2.30% vs 2.40±0.36% ,P <0.01), TNF-α,IL-8 were also increased and reached their peak at 6 h and then declined. The activation of NF-κB and the levels of TNF-α and IL-8 in RES group were significantly lower than those in SAP group (P<0.01): activation (52.63±9.45% vs 64.23±10.72%, 40.52±8.40% vs 55.86±11.34%, 29.83±5.37% vs36.23±2.30%), TN-α (132.76±15.68 pg/mL vs 158.36±12.58 pg/mL, 220.32±23.57 pg/mL vs 247.67± 11.62 pg/mL, 175.68±18.43 pg/mL vs 197.35±12.57 pg/mL) and IL-8 (0.62±0.21

  5. Acute phase protein concentrations in serum and milk from healthy cows, cows with clinical mastitis and cows with extramammary inflammatory conditions

    DEFF Research Database (Denmark)

    Nielsen, B.H.; Jacobsen, S.; Andersen, P.H.

    2004-01-01

    The concentrations of the two acute phase proteins, serum amyloid A and haptoglobin, in serum and milk were compared in 10 cows with clinical mastitis, 11 cows with extramammary inflammatory conditions and 10 clinically healthy control cows. The concentrations of both acute phase proteins were...... higher in the serum and milk of the cows with mastitis than in the cows in the other two groups. Four of the cows with extramammary inflammatory conditions had serum amyloid A concentrations in serum above 100 mug/ml, but negligible concentrations in milk, indicating that a pathogen must be present...... in the mammary gland for serum amyloid A to accumulate in milk. The acute phase protein concentrations in milk increased significantly with increasing somatic cell count, suggesting that they may be indicators of the severity of an infection....

  6. Effect of obesity on the acute inflammatory response in pregnant and cycling female rats.

    Science.gov (United States)

    Pohl, J; Luheshi, G N; Woodside, B

    2013-05-01

    Nonpregnant female rats have a lower inflammatory response to lipopolysaccharide (LPS) than males and, at late stages of gestation, the fever response to this immunogen is almost completely suppressed. We have shown in males that obesity exacerbates sickness responses to pathogenic stimuli. In the present study, we investigated whether obesity would have a similar effect in females and reverse some of the suppressive effects of pregnancy on the innate immune response. Lean and diet-induced obese adult Wistar rats were randomly separated into either cycling or mated groups. On day 18 of pregnancy or in the metestrous/dioestrous phase in cycling rats, a single injection of LPS (100 μg/kg) was administered and rats were sacrificed 8h or 24 h later. In pregnant females, LPS induced a higher increase in body temperature in obese rats only at the 24-h time point and lower hypothalamic interleukin (IL)-1β expression and higher circulating levels of IL-1 receptor antagonist (ra) than their cycling counterparts. Conversely, there was no suppression of inflammatory signals in the white adipose tissue of pregnant rats. At 24 h post LPS, the cell surface marker CD11c and IL-6 mRNA expression were increased in white adipose tissue from obese rats regardless of reproductive state, whereas IL-1ra was highest in the LPS-treated obese pregnant group. In cycling females, LPS induced a higher fever response in obese rats accompanied by higher circulating levels of IL-6 and IL-1ra, as well as an increase in circulating leptin only in the obese cycling group. In the hypothalamus, obese rats showed significantly higher expression of nuclear factor-IL-6 in at the 8-h time point. Collectively, these results show that diet-induced obesity in females is associated with a similar pattern of response to that previously observed in males. On the other hand, obesity had limited effects in pregnant rats, with the exception of white adipose tissue.

  7. Olprinone Attenuates the Acute Inflammatory Response and Apoptosis after Spinal Cord Trauma in Mice

    Science.gov (United States)

    Esposito, Emanuela; Mazzon, Emanuela; Paterniti, Irene; Impellizzeri, Daniela; Bramanti, Placido; Cuzzocrea, Salvatore

    2010-01-01

    Background Olprinone hydrochloride is a newly developed compound that selectively inhibits PDE type III and is characterized by several properties, including positive inotropic effects, peripheral vasodilatory effects, and a bronchodilator effect. In clinical settings, olprinone is commonly used to treat congestive cardiac failure, due to its inotropic and vasodilating effects. The mechanism of these cardiac effects is attributed to increased cellular concentrations of cAMP. The aim of the present study was to evaluate the pharmacological action of olprinone on the secondary damage in experimental spinal cord injury (SCI) in mice. Methodology/Principal Findings Traumatic SCI is characterized by an immediate, irreversible loss of tissue at the lesion site, as well as a secondary expansion of tissue damage over time. Although secondary injury should be preventable, no effective treatment options currently exist for patients with SCI. Spinal cord trauma was induced in mice by the application of vascular clips (force of 24 g) to the dura via a four-level T5–T8 laminectomy. SCI in mice resulted in severe trauma characterized by edema, neutrophil infiltration, and production of inflammatory mediators, tissue damage, apoptosis, and locomotor disturbance. Olprinone treatment (0.2 mg/kg, i.p.) 1 and 6 h after the SCI significantly reduced: (1) the degree of spinal cord inflammation and tissue injury (histological score), (2) neutrophil infiltration (myeloperoxidase activity), (3) nitrotyrosine formation, (4) pro-inflammatory cytokines, (5) NF-κB expression, (6) p-ERK1/2 and p38 expression and (7) apoptosis (TUNEL staining, FAS ligand, Bax and Bcl-2 expression). Moreover, olprinone significantly ameliorated the recovery of hind-limb function (evaluated by motor recovery score). Conclusions/Significance Taken together, our results clearly demonstrate that olprinone treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma. PMID

  8. Olprinone attenuates the acute inflammatory response and apoptosis after spinal cord trauma in mice.

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    Emanuela Esposito

    Full Text Available BACKGROUND: Olprinone hydrochloride is a newly developed compound that selectively inhibits PDE type III and is characterized by several properties, including positive inotropic effects, peripheral vasodilatory effects, and a bronchodilator effect. In clinical settings, olprinone is commonly used to treat congestive cardiac failure, due to its inotropic and vasodilating effects. The mechanism of these cardiac effects is attributed to increased cellular concentrations of cAMP. The aim of the present study was to evaluate the pharmacological action of olprinone on the secondary damage in experimental spinal cord injury (SCI in mice. METHODOLOGY/PRINCIPAL FINDINGS: Traumatic SCI is characterized by an immediate, irreversible loss of tissue at the lesion site, as well as a secondary expansion of tissue damage over time. Although secondary injury should be preventable, no effective treatment options currently exist for patients with SCI. Spinal cord trauma was induced in mice by the application of vascular clips (force of 24 g to the dura via a four-level T5-T8 laminectomy. SCI in mice resulted in severe trauma characterized by edema, neutrophil infiltration, and production of inflammatory mediators, tissue damage, apoptosis, and locomotor disturbance. Olprinone treatment (0.2 mg/kg, i.p. 1 and 6 h after the SCI significantly reduced: (1 the degree of spinal cord inflammation and tissue injury (histological score, (2 neutrophil infiltration (myeloperoxidase activity, (3 nitrotyrosine formation, (4 pro-inflammatory cytokines, (5 NF-kappaB expression, (6 p-ERK1/2 and p38 expression and (7 apoptosis (TUNEL staining, FAS ligand, Bax and Bcl-2 expression. Moreover, olprinone significantly ameliorated the recovery of hind-limb function (evaluated by motor recovery score. CONCLUSIONS/SIGNIFICANCE: Taken together, our results clearly demonstrate that olprinone treatment reduces the development of inflammation and tissue injury associated with spinal cord

  9. Intestinal ellagitannin metabolites ameliorate cytokine-induced inflammation and associated molecular markers in human colon fibroblasts.

    Science.gov (United States)

    Giménez-Bastida, Juan A; Larrosa, Mar; González-Sarrías, Antonio; Tomás-Barberán, Francisco; Espín, Juan C; García-Conesa, María-Teresa

    2012-09-12

    Pomegranate ellagitannins (ETs) are transformed in the gut to ellagic acid (EA) and its microbiota metabolites, urolithin A (Uro-A) and urolithin B (Uro-B). These compounds exert anti-inflammatory effects in vitro and in vivo. The aim of this study was to investigate the effects of Uro-A, Uro-B, and EA on colon fibroblasts, cells that play a key role in intestinal inflammation. CCD18-Co colon fibroblasts were exposed to a mixture of Uro-A, Uro-B, and EA, at concentrations comparable to those found in the colon (40 μM Uro-A, 5 μM Uro-B, 1 μM EA), both in the presence or in the absence of IL-1β (1 ng/mL) or TNF-α (50 ng/mL), and the effects on fibroblast migration and monocyte adhesion were determined. The levels of several growth factors and adhesion cytokines were also measured. The mixture of metabolites significantly inhibited colon fibroblast migration (∼70%) and monocyte adhesion to fibroblasts (∼50%). These effects were concomitant with a significant down-regulation of the levels of PGE(2), PAI-1, and IL-8, as well as other key regulators of cell migration and adhesion. Of the three metabolites tested, Uro-A exhibited the most significant anti-inflammatory effects. The results show that a combination of the ET metabolites found in colon, urolithins and EA, at concentrations achievable in the intestine after the consumption of pomegranate, was able to moderately improve the inflammatory response of colon fibroblasts and suggest that consumption of ET-containing foods has potential beneficial effects on gut inflammatory diseases.

  10. The Systemic Inflammatory Response Syndrome (SIRS) in acutely hospitalised medical patients: a cohort study

    DEFF Research Database (Denmark)

    Comstedt, Pal; Storgaard, Merete; Lassen, Annmarie T

    2009-01-01

    . The relationship between SIRS symptoms and morbidity and mortality in medical emergency ward patients is unknown. METHODS: We conducted a prospective cohort study of the frequency of SIRS and its relationship to sepsis and death among acutely hospitalised medical patients. In 437 consecutive patients, SIRS status......, blood pressure, infection and comorbidity on admission was registered together with 28-day mortality. RESULTS: A hundred and fifty-four patients (35%) had SIRS on admission, 211 patients (48%) had no SIRS, and 72 patients (16%) had insufficient data to evaluate their SIRS status. SIRS patients were 2.......2 times more frequently infected, with 66/154 SIRS patients versus 41/211 non-SIRS patients: ppatients with 15/154 SIRS patients versus 3/211 non-SIRS patients: p=0.001, RR...

  11. Yoghurt consumption regulates the immune cells implicated in acute intestinal inflammation and prevents the recurrence of the inflammatory process in a mouse model.

    Science.gov (United States)

    Chaves, Silvina; Perdigon, Gabriela; de Moreno de LeBlanc, Alejandra

    2011-05-01

    Crohn's disease and ulcerative colitis, two forms of inflammatory bowel disease, are important problems in industrialized countries. The complete etiology of these two diseases is still unknown but likely involves genetic, environmental, and immunological factors. The aim of the present work was to determine whether the anti-inflammatory effects reported for yoghurt in acute trinitrobenzene sulfonic acid-induced intestinal inflammation in mice also could prevent or attenuate the recurrent intestinal inflammation, thus maintaining remission. The innate response also was evaluated through participation of Toll-like receptors (TLRs) and the analysis of T-cell populations to determine the effects of yoghurt in an acute inflammatory bowel disease model. Yoghurt exerted a beneficial effect on acute intestinal inflammation by regulating T-cell expansion and modulating the expression of TLRs, with decrease of TLR4(+) and increase of TLR9(+) cells. The anti-inflammatory effect of yoghurt also was demonstrated in a recurrent inflammation model. Yoghurt administration during the remission phase prevented the recurrence of inflammation without producing undesirable side effects. The yoghurt effect may be mediated by increased interleukin 10 production and changes in intestinal microbiota.

  12. The inflammatory response in blood and in remote organs following acute kidney injury

    DEFF Research Database (Denmark)

    Brøchner, Anne Craveiro; Dagnaes-Hansen, Frederik; Højberg-Holm, Jimmy

    2014-01-01

    /R of both hind legs + LPS. In groups B and E, I/R times were identical. All mice were kept alive for 24 h and then sacrificed. Levels of interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α were measured in the blood. The activity of myeloperoxidase (MPO) in lungs, kidneys, and liver was evaluated...... infiltration of distant organs measured by the levels of MPO in the lung and liver also showed a significantly higher level in renal I/R compared to hind leg I/R. Renal I/R is associated with a more pronounced inflammatory response in blood and distant organs. The high cytokine levels measured following...... was that elevated levels of cytokines would be found in both blood and in organs distant to the kidneys. Forty mice were divided into five groups. The mice were subjected to the following operations: A: Sham only, no lipopolysaccharide (LPS); B: I/R of both kidneys + LPS; C: LPS only; D: Nephrectomy + LPS; E: I...

  13. Gut microbiome diversity in acute infective and chronic inflammatory gastrointestinal diseases in North India.

    Science.gov (United States)

    Kedia, Saurabh; Rampal, Ritika; Paul, Jaishree; Ahuja, Vineet

    2016-07-01

    The disease profile in the Indian population provides a unique opportunity for studying the host microbiome interaction in both infectious (amebiasis) and autoimmune diseases like inflammatory bowel disease (IBD) from a similar environment and genetic background. Analysis of fecal samples from untreated amebic liver abscess (ALA) patients, Entamoeba histolytica (Eh)-negative and -positive asymptomatic individuals, and pus samples from naive ALA patients revealed a significant reduction in Lactobacillus in asymptomatic individuals (Eh +ve) and ALA patients. Two anaerobic genera, namely Bacteroides and Peptostreptococcus, were detected in naive ALA pus samples. Analysis of fecal samples from amoebic colitis patients showed a significant decline in population of Bacteroides, Clostridium coccoides and leptum subgroup, Lactobacillus, Campylobacter, and Eubacterium, whereas a significant increase in Bifidobacterium was observed. Mucosa-associated bacterial flora analysis from IBD patients and healthy controls revealed a significant difference in concentration of bacteria among predominating and subdominating genera between ulcerative colitis (UC), Crohn's disease (CD) patients, and controls. In contrast to the mucosal studies, we found a significant increase in lactobacilli population in fecal samples of active UC patients. Another study revealed a significant decrease of Clostridium coccoides and leptum clusters in fecal samples of active UC patients along with decreased concentrations of fecal SCFAs, especially of n-butyrate, iso-butyrate, and acetate. We therefore found similar perturbations in gut microbiome in both infectious and autoimmune diseases, indicating inflammation to be the major driver for changes in gut microbiome.

  14. Aldehyde dehydrogenase-2 regulates nociception in rodent models of acute inflammatory pain.

    Science.gov (United States)

    Zambelli, Vanessa O; Gross, Eric R; Chen, Che-Hong; Gutierrez, Vanessa P; Cury, Yara; Mochly-Rosen, Daria

    2014-08-27

    Exogenous aldehydes can cause pain in animal models, suggesting that aldehyde dehydrogenase-2 (ALDH2), which metabolizes many aldehydes, may regulate nociception. To test this hypothesis, we generated a knock-in mouse with an inactivating point mutation in ALDH2 (ALDH2*2), which is also present in human ALDH2 of ~540 million East Asians. The ALDH2*1/*2 heterozygotic mice exhibited a larger response to painful stimuli than their wild-type littermates, and this heightened nociception was inhibited by an ALDH2-selective activator (Alda-1). No effect on inflammation per se was observed. Using a rat model, we then showed that nociception tightly correlated with ALDH activity (R(2) = 0.90) and that reduced nociception was associated with less early growth response protein 1 (EGR1) in the spinal cord and less reactive aldehyde accumulation at the insult site (including acetaldehyde and 4-hydroxynonenal). Further, acetaldehyde- and formalin-induced nociceptive behavior was greater in the ALDH2*1/*2 mice than in the wild-type mice. Finally, Alda-1 treatment was even beneficial when given after the inflammatory agent was administered. Our data in rodent models suggest that the mitochondrial enzyme ALDH2 regulates nociception and could serve as a molecular target for pain control, with ALDH2 activators, such as Alda-1, as potential non-narcotic, cardiac-safe analgesics. Furthermore, our results suggest a possible genetic basis for East Asians' apparent lower pain tolerance.

  15. Soluble factors from Lactobacillus reuteri CRL1098 have anti-inflammatory effects in acute lung injury induced by lipopolysaccharide in mice.

    Directory of Open Access Journals (Sweden)

    Milagros Griet

    Full Text Available We have previously demonstrated that Lactobacillus reuteri CRL1098 soluble factors were able to reduce TNF-α production by human peripheral blood mononuclear cells. The aims of this study were to determine whether L. reuteri CRL1098 soluble factors were able to modulate in vitro the inflammatory response triggered by LPS in murine macrophages, to gain insight into the molecular mechanisms involved in the immunoregulatory effect, and to evaluate in vivo its capacity to exert anti-inflammatory actions in acute lung injury induced by LPS in mice. In vitro assays demonstrated that L. reuteri CRL1098 soluble factors significantly reduced the production of pro-inflammatory mediators (NO, COX-2, and Hsp70 and pro-inflammatory cytokines (TNF-α, and IL-6 caused by the stimulation of macrophages with LPS. NF-kB and PI3K inhibition by L. reuteri CRL1098 soluble factors contributed to these inhibitory effects. Inhibition of PI3K/Akt pathway and the diminished expression of CD14 could be involved in the immunoregulatory effect. In addition, our in vivo data proved that the LPS-induced secretion of the pro-inflammatory cytokines, inflammatory cells recruitment to the airways and inflammatory lung tissue damage were reduced in L. reuteri CRL1098 soluble factors treated mice, providing a new way to reduce excessive pulmonary inflammation.

  16. Acute kidney injury and inflammatory response of sepsis following cecal ligation and puncture in d-galactose-induced aging rats.

    Science.gov (United States)

    Liu, Chao; Hu, Jie; Mao, Zhi; Kang, Hongjun; Liu, Hui; Fu, Wanlei; Lv, Yangfan; Zhou, Feihu

    2017-01-01

    Recently, the d-galactose (d-gal)-induced mimetic aging rat model has been widely used in studies of age-associated diseases, which have shown that chronic d-gal exposure induces premature aging similar to natural aging in rats. With the increasing rate of sepsis in the geriatric population, an easy-access animal model for preclinical studies of elderly sepsis is urgently needed. This study investigates whether a sepsis model that is established in d-gal-induced aging rats can serve as a suitable model for preclinical studies of elderly patients with sepsis. To investigate the acute kidney injury (AKI) and inflammatory response of sepsis following cecal ligation and puncture (CLP) in d-gal-induced aging rats. Twelve-week-old male Sprague Dawley rats were divided into low-dose d-gal (L d-gal, 125 mg/kg/d), high-dose d-gal (H d-gal, 500 mg/kg/d), and control groups. After daily subcutaneous injection of d-gal for 6 weeks, the CLP method was used to establish a sepsis model. The mortality was 73.3%, 40%, and 33.3% in the H d-gal, L d-gal, and control groups, respectively. Blood urea nitrogen, creatinine, plasma neutrophil gelatinase-associated lipocalin, interleukin-6, interleukin-10, and tumor necrosis factor-α were markedly increased in the H d-gal group after establishment of the sepsis model (H d-gal vs control, Paging rats are more likely to die from sepsis than are young rats, and probably this is associated with increased severity of septic AKI and an increased inflammatory response. Therefore, use of the high-dose- d-gal-induced aging rat model of sepsis for preclinical studies can provide more useful information for the treatment of sepsis in elderly patients.

  17. Effects of Acute Endurance Exercise Performed in the Morning and Evening on Inflammatory Cytokine and Metabolic Hormone Responses.

    Directory of Open Access Journals (Sweden)

    Hyeon-Ki Kim

    Full Text Available To compare the effects of endurance exercise performed in the morning and evening on inflammatory cytokine responses in young men.Fourteen healthy male participants aged 24.3 ± 0.8 years (mean ± standard error performed endurance exercise in the morning (0900-1000 h on one day and then in the evening (1700-1800 h on another day with an interval of at least 1 week between each trial. In both the morning and evening trials, the participants walked for 60 minutes at approximately 60% of the maximal oxygen uptake (VO2max on a treadmill. Blood samples were collected to determine hormones and inflammatory cytokines at pre-exercise, immediately post exercise, and 2 h post exercise.Plasma interleukin (IL-6 and adrenaline concentrations were significantly higher immediately after exercise in the evening trial than in the morning trial (P < 0.01, both. Serum free fatty acids concentrations were significantly higher in the evening trial than in the morning trial at 2 h after exercise (P < 0.05. Furthermore, a significant correlation was observed between the levels of IL-6 immediately post-exercise and free fatty acids 2 h post-exercise in the evening (r = 0.68, P < 0.01.These findings suggest that the effect of acute endurance exercise in the evening enhances the plasma IL-6 and adrenaline concentrations compared to that in the morning. In addition, IL-6 was involved in increasing free fatty acids, suggesting that the evening is more effective for exercise-induced lipolysis compared with the morning.

  18. Distending Pressure Did Not Activate Acute Phase or Inflammatory Responses in the Airways and Lungs of Fetal, Preterm Lambs.

    Directory of Open Access Journals (Sweden)

    Rebecca Y Petersen

    Full Text Available Mechanical ventilation at birth causes airway injury and lung inflammation in preterm sheep. Continuous positive airway pressure (CPAP is being increasingly used clinically to transition preterm infants at birth.To test if distending pressures will activate acute phase reactants and inflammatory changes in the airways of fetal, preterm lambs.The head and chest of fetal lambs at 128±1 day GA were surgically exteriorized. With placental circulation intact, fetal lambs were then randomized to one of five 15 minute interventions: PEEP of 0, 4, 8, 12, or 16 cmH2O. Recruitment volumes were recorded. Fetal lambs remained on placental support for 30 min after the intervention. The twins of each 0 cmH2O animal served as controls. Fetal lung fluid (FLF, bronchoalveolar lavage fluid (BAL, right mainstem bronchi and peripheral lung tissue were evaluated for inflammation.Recruitment volume increased from 0.4±0.04 mL/kg at 4 cmH2O to 2.4±0.3 mL/kg at 16 cmH2O. The lambs were surfactant deficient, and all pressures were below the opening inflection pressure on pressure-volume curve. mRNA expression of early response genes and pro-inflammatory cytokines did not increase in airway tissue or lung tissue at any pressure compared to controls. FLF and BAL also did not have increases in early response proteins. No histologic changes or Egr-1 activation was present at the pressures used.Distending pressures as high as 16 cmH2O did not recruit lung volume at birth and did not increase markers of injury in the lung or airways in non-breathing preterm fetal sheep.

  19. Correlation of serum inflammatory cytokine and immunoglobulin content with post-herpetic neuralgia in patients with acute herpes zoster

    Institute of Scientific and Technical Information of China (English)

    Hai-Jun Shi; Zhi-Qiang Cui

    2017-01-01

    Objective:To study the correlation of serum inflammatory cytokine and immunoglobulin content with post-herpetic neuralgia in patients with acute herpes zoster.Methods:Patients diagnosed with herpes zoster in our hospital between May 2012 and October 2015 were selected and divided into herpes zoster-post-herpetic neuralgia group (VZV-PHN group) and herpes zoster-control group (VZV-Con group) according to the incidence of post-herpetic neuralgia (PHN); healthy volunteers receiving physical examination in our hospital during the same period were selected as normal control group (Con group).Results: Serumβ-EP, NT, IFN-γ and IL-2 levels of VZV-PHN group and VZV-Con group were significantly lower than those of Con group (P<0.05), while SP, VGF, CGRP, IL-4, IL-6, IL-17, IL-21, TNF-α, IL-10, TGF-β1, IgG, IgM and IgA levels were significantly higher than those of Con group (P<0.05); serumβ-EP, NT, IFN-γ, IL-2, IgG, IgM and IgA levels of VZV-PHN group were significantly lower than those of VZV-Con group (P<0.05) while SP, VGF, CGRP, IL-4, IL-6, IL-17, IL-21, TNF-α, IL-10 and TGF-β1 levels were significantly higher than those of VZV-Con group (P<0.05);β-EP and NT were positively correlated with IFN-γ, IL-2, IgG, IgM and IgA, and negatively correlated with IL-4, IL-6, IL-17, IL-21, TNF-α, IL-10 and TGF-β1; SP, VGF and CGRP were negatively correlated with IFN-γ, IL-2, IgG, IgM and IgA, and positively correlated with IL-4, IL-6, IL-17, IL-21, TNF-α, IL-10 and TGF-β1.Conclusions:Abnormal secretion of inflammatory cytokines and immunoglobulin caused by humoral immune and cellular immune response disorder is associated with the occurrence of post-herpetic neuralgia in patients with acute herpes zoster.

  20. Preventive rather than therapeutic treatment with high fiber diet attenuates clinical and inflammatory markers of acute and chronic DSS-induced colitis in mice.

    Science.gov (United States)

    Silveira, Ana Letícia Malheiros; Ferreira, Adaliene Versiani Matos; de Oliveira, Marina Chaves; Rachid, Milene Alvarenga; da Cunha Sousa, Larissa Fonseca; Dos Santos Martins, Flaviano; Gomes-Santos, Ana Cristina; Vieira, Angelica Thomaz; Teixeira, Mauro Martins

    2017-02-01

    Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with important impact on global health. Prebiotic and probiotic strategies are thought to be useful in the context of experimental IBD. Here, we compared the effects of preventive versus therapeutic treatment with a high fiber diet (prebiotic) in combination or not with Bifidobacterium longum (probiotic) in a murine model of chronic colitis. Colitis was induced by adding dextran sulfate sodium (DSS) to drinking water for 6 days (acute colitis) or for 5 cycles of DSS (chronic colitis). Administration of the high fiber diet protected from acute colitis. Protection was optimal when diet was started 20 days prior to DSS. A 5-day pretreatment with acetate, a short-chain fatty acid, provided partial protection against acute colitis. In chronic colitis, pretreatment with the high fiber diet attenuated clinical and inflammatory parameters of disease. However, when the treatment with the high fiber diet started after disease had been established, overall protection was minimal. Similarly, delayed treatment with acetate or B. longum did not provide any protection even when the probiotic was associated with the high fiber diet. Preventive use of a high fiber diet or acetate clearly protects mice against acute and chronic damage induced by DSS in mice. However, protection is lost when therapies are initiated after disease has been established. These results suggest that any therapy aimed at modifying the gut environment (e.g., prebiotic or probiotic strategies) should be given early in the course of disease.

  1. Influence of acute hyperglycemia in human sepsis on inflammatory cytokine and counterregulatory hormone concentrations

    Institute of Scientific and Technical Information of China (English)

    Wen-Kui Yu; Wei-Qin Li; Ning Li; Jie-Shou Li

    2003-01-01

    AIM: In human sepsis, a prominent component of the hypermetabolite is impaired glucose tolerance (IGT) and hyperglycemia. Elevations in plasma glucose concentration impair immune function by altering cytokine production from macrophages. We assessed the role of glucose in the regulation of circulating levels of insulin, glucagon, cortisol,IL-6 and TNF-α in human sepsis with normal or impaired glucose tolerance.METHODS: According to the results of intravenous glucose tolerance test, forty patients were classified into two groups: control group (n=20) and IGT group (n=20).Plasma glucose levels were acutely raised in two groups and maintained at 15 mmol/L for 3 hours. Plasma insulin,glucagon and cortisol levels were measured by radioimmunoassay, the levels of TNF-α and IL-6 were detected by ELISA.RESULTS: In IGT group, the fasting concentrations of plasma glucose, insulin, glucagon, cortisol, IL-6 and TNFα levels were significantly higher than those in control group (P<0.05). During clamp, the control group had a higher average amount of dextrose infusion than the IGT group (P<0.01). In control group, plasma insulin levels rose from a basal value to a peak at an hour (P<0.05) and maintained at high levels. Plasma glucagon levels descended from a basal value to the lowest level within an hour (P<0.01)and low levels were maintained throughout the clamp. In IGT group, plasma insulin was more significantly elevated (P<0.01), and plasma glucagon levels were not significantly declined. Plasma cortisol levels were not significantly changed in two groups. In control group, plasma IL-6 and TNF-α levels rose (P<0.01) within 2 hours of the clamp and returned to basal values at 3 hours. In IGT group, increased levels of plasma cytokine lasted longer than in control group (3 hours vs. 2 hours, P<0.05), and the cytokine peaks of IGT group were higher (P<0.05) than those of control group.CONCLUSION: Acute hyperglycemia pricks up hyperinsulinemia and increases

  2. A comparative study of anti-inflammatory activity of lovastatin, simvastatin, atorvastatin and rosuvastatin on acute and chronic inflammation in animal models

    Institute of Scientific and Technical Information of China (English)

    Santoshkumar R Jeevangi; S Manjunath; Sachidananda G Shetti; Chetan Manjunath; Prashant Dass

    2012-01-01

    Objective: To study the anti-inflammatory activity of Lovastatin, Simvastatin, Atorvastatin, and Rosuvastatin on acute and chronic models of inflammation, to compare with the effect of Diclofenac sodium and amongst themselves in rats. Methods: Carrageenin induce rat paw edema method in which 5 animals of each group (6 groups) received orally 4% gum acacia, Diclofenac and 4 statins respectively 1 h before Carrageenin injection in paw. The paw edema volume measured with plethysmograph after 3 h and percentage inhibition of edema in various groups calculated. Rexin pellet granuloma method in which 4 rexin pellets were implanted into dorsum of skin of each rat of 6 groups (n=5) including control, Diclofenac and 4 statin groups respectively. Rats were orally fed with drugs daily for 7 days and on 8th day rexin pellets were removed after sacrificing the rat and dried in incubator 60oC overnight. Pellets were then weighed and percentage inhibition of granulation tissue was calculated and sent for histopathological examination.Results:All the 4 statins showed significant anti-inflammatory activity in the present study in both acute as well as chronic models of inflammation. The anti-inflammatory activity of the 4 statins was significant on comparison with Diclofenac. Lovastatin and Simvastatin demonstrated 10-20% more anti-inflammatory activity than Atorvastatin and Rosuvastatin. Conclusions: The present study revealed the anti-inflammatory effect of statins and thus suggests that the statins have a potential anti-atherosclerotic activity along with its lipid lowering property.

  3. Time course of systemic oxidative stress and inflammatory response induced by an acute exposure to Residual Oil Fly Ash

    Energy Technology Data Exchange (ETDEWEB)

    Marchini, T.; Magnani, N.D. [Cátedra de Química General e Inorgánica, Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAB Buenos Aires (Argentina); Paz, M.L. [Cátedra de Inmunología, Instituto de Estudios de la Inmunidad Humoral (IDEHU UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAB Buenos Aires (Argentina); Vanasco, V. [Cátedra de Química General e Inorgánica, Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAB Buenos Aires (Argentina); Tasat, D. [CESyMA, Facultad de Ciencia Tecnología, Universidad Nacional de General San Martín, Martín de Irigoyen 3100, 1650 San Martín, Buenos Aires (Argentina); González Maglio, D.H. [Cátedra de Inmunología, Instituto de Estudios de la Inmunidad Humoral (IDEHU UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, C1113AAB Buenos Aires (Argentina); and others

    2014-01-15

    It is suggested that systemic oxidative stress and inflammation play a central role in the onset and progression of cardiovascular diseases associated with the exposure to particulate matter (PM). The aim of this work was to evaluate the time changes of systemic markers of oxidative stress and inflammation, after an acute exposure to Residual Oil Fly Ash (ROFA). Female Swiss mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight) or saline solution, and plasma levels of oxidative damage markers [thiobarbituric acid reactive substances (TBARSs) and protein carbonyls], antioxidant status [reduced (GSH) and oxidized (GSSG) glutathione, ascorbic acid levels, and superoxide dismutase (SOD) activity], cytokines levels, and intravascular leukocyte activation were evaluated after 1, 3 or 5 h of exposure. Oxidative damage to lipids and decreased GSH/GSSG ratio were observed in ROFA-exposed mice as early as 1 h. Afterwards, increased protein oxidation, decreased ascorbic acid content and SOD activity were found in this group at 3 h. The onset of an adaptive response was observed at 5 h after the ROFA exposure, as indicated by decreased TBARS plasma content and increased SOD activity. The observed increase in oxidative damage to plasma macromolecules, together with systemic antioxidants depletion, may be a consequence of a systemic inflammatory response triggered by the ROFA exposure, since increased TNF-α and IL-6 plasma levels and polymorphonuclear leukocytes activation was found at every evaluated time point. These findings contribute to the understanding of the increase in cardiovascular morbidity and mortality, in association with environmental PM inhalation. - Highlights: • An acute exposure to ROFA triggers the occurrence of systemic oxidative stress. • Changes in plasmatic oxidative stress markers appear as early as 1 h after exposure. • ROFA induces proinflammatory cytokines release and intravascular leukocyte activation. • PMN

  4. New echocardiographic findings correlate with intramyocardial inflammation in endomyocardial biopsies of patients with acute myocarditis and inflammatory cardiomyopathy.

    Science.gov (United States)

    Escher, Felicitas; Kasner, Mario; Kühl, Uwe; Heymer, Johannes; Wilkenshoff, Ursula; Tschöpe, Carsten; Schultheiss, Heinz-Peter

    2013-01-01

    The diagnosis of acute myocarditis (AMC) and inflammatory cardiomyopathy (DCMi) can be difficult. Speckle tracking echocardiography with accurate assessments of regional contractility could have an outstanding importance for the diagnosis. N = 25 patients with clinically diagnosed AMC who underwent endomyocardial biopsies (EMBs) were studied prospectively. Speckle tracking imaging was examined at the beginning and during a mean follow-up period of 6.2 months. In the acute phase patients had markedly decreased left ventricular (LV) systolic function (mean LV ejection fraction (LVEF) 40.4 ± 10.3%). At follow-up in n = 8 patients, inflammation persists, correlating with a significantly reduced fractional shortening (FS, 21.5 ± 6.0%) in contrast to those without inflammation in EMB (FS 32.1 ± 7.1%, P < 0.05). All AMC patients showed a reduction in global systolic longitudinal strain (LS, -8.36 ± -3.47%) and strain rate (LSR, 0.53 ± 0.29 1/s). At follow-up, LS and LRS were significantly lower in patients with inflammation, in contrast to patients without inflammation (-9.4 ± 1.4 versus -16.8 ± 2.0%, P < 0.0001; 0.78 ± 0.4 versus 1.3 ± 0.3 1/s). LSR and LS correlate significantly with lymphocytic infiltrates (for CD3 r = 0.7, P < 0.0001, and LFA-1 r = 0.8, P < 0.0001). Speckle tracking echocardiography is a useful adjunctive assisting tool for evaluation over the course of intramyocardial inflammation in patients with AMC and DCMi.

  5. New Echocardiographic Findings Correlate with Intramyocardial Inflammation in Endomyocardial Biopsies of Patients with Acute Myocarditis and Inflammatory Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Felicitas Escher

    2013-01-01

    Full Text Available Background. The diagnosis of acute myocarditis (AMC and inflammatory cardiomyopathy (DCMi can be difficult. Speckle tracking echocardiography with accurate assessments of regional contractility could have an outstanding importance for the diagnosis. Methods and Results. N=25 patients with clinically diagnosed AMC who underwent endomyocardial biopsies (EMBs were studied prospectively. Speckle tracking imaging was examined at the beginning and during a mean follow-up period of 6.2 months. In the acute phase patients had markedly decreased left ventricular (LV systolic function (mean LV ejection fraction (LVEF 40.4±10.3%. At follow-up in n=8 patients, inflammation persists, correlating with a significantly reduced fractional shortening (FS, 21.5±6.0% in contrast to those without inflammation in EMB (FS 32.1±7.1%, P<0.05. All AMC patients showed a reduction in global systolic longitudinal strain (LS, −8.36±−3.47% and strain rate (LSR, 0.53±0.29 1/s. At follow-up, LS and LRS were significantly lower in patients with inflammation, in contrast to patients without inflammation (−9.4±1.4 versus −16.8±2.0%, P<0.0001; 0.78±0.4 versus 1.3±0.3 1/s. LSR and LS correlate significantly with lymphocytic infiltrates (for CD3 r=0.7, P<0.0001, and LFA-1 r=0.8, P<0.0001. Conclusion. Speckle tracking echocardiography is a useful adjunctive assisting tool for evaluation over the course of intramyocardial inflammation in patients with AMC and DCMi.

  6. Anti-nociceptive and anti-inflammatory effects of cyanocobalamin (vitamin B12) against acute and chronic pain and inflammation in mice.

    Science.gov (United States)

    Hosseinzadeh, H; Moallem, S A; Moshiri, M; Sarnavazi, M S; Etemad, L

    2012-07-01

    In this study, the anti-nociceptive and anti-inflammatory effects of cyanocobalamin (Vit B12) against acute and chronic pain and inflammation were evaluated in mice. Vit B12 (0.87, 1 and 1.77 mg/kg) were injected intraperitoneally. The anti-nociceptive effects against acute pain were examined using hot-plate and writhing tests. The chronic pain was examined 14 days after sciatic nerve ligation using the hot-plate test. Morphine (10 mg/kg) was used as a positive control. Anti-inflammatory effects of Vit B12 against acute and chronic inflammation were assessed using xylene-induced edema in ears and granuloma caused by compressed cotton implantation, respectively. In these tests, sodium diclofenac (15 mg/kg) was used as a positive control. Vit B12 showed a dose related effect in acute anti-nociceptive test and increased the anti-nociceptive effect of morphine in chronic treatment. Vit B12 demonstrated an anti-nociceptive effect in chronic studies as single or continues daily treatment and increased significantly the anti-nociceptive effect of morphine. All doses of Vit B12 significantly decreased xylene-induced ear edema. Maximum anti-inflammatory effect (37.5%) was obtained at dose of 1 mg/kg. In chronic inflammation, Vit B12 significantly decreased granuloma formation in mice. In conclusion our work presents some experimental evidence supporting the administration of cyanocobalamin in controlling acute and chronic neuropathic pain. Cyanocobalamin may have anti-inflammatory effect. It may reduce tolerance to anti-nociceptive effect of morphine as well. © Georg Thieme Verlag KG Stuttgart · New York.

  7. Acute inflammatory demyelinating polyneuropathy after treatment with pegylated interferon alfa-2a in a patient with chronic hepatitis C virus infection: a case report

    Directory of Open Access Journals (Sweden)

    Lahbabi Mounia

    2012-09-01

    Full Text Available Abstract Introduction The combination of polyethylene glycol (PEGylated interferon (pegylated interferon and ribavirin has been shown to be an effective treatment for chronic hepatitis C virus. In general, common side effects related to this combination therapy are mild and are well tolerated. However, peripheral neuropathy including demyelinating polyneuropathy related to PEG-interferon α2a (pegylated interferon alfa-2a is extremely rare. In the literature, only one case of acute inflammatory demyelinating polyneuropathy related to PEG-interferon α2a has been published previously. Case presentation To the best of our knowledge we present only the second case of acute inflammatory demyelinating polyneuropathy related to PEG-interferon α2a, occurring in a 63-year-old Caucasian man. He developed tingling, numbness, and weakness of his upper and lower extremities with acute neurological deficits after five weeks of a combination therapy with PEG-interferon α2a and ribavirin for chronic hepatitis C virus infection. His clinical course, neurological findings, and his electromyogram results were all consistent with acute inflammatory demyelinating polyneuropathy. Our patient recovered completely after interferon was stopped and symptomatic treatment and a further electromyogram showed a disappearance of neuropathy. Four weeks later, PEG-interferon α2a was reintroduced with a gradually increasing dose without any reappearance of neurological symptoms allowing hepatitis C seroconversion. Conclusions Recognition of this rare yet possible presentation is important for early and accurate diagnosis and treatment. This case report also suggests that the reintroduction of PEGylated interferon in patients who had presented with acute inflammatory demyelinating polyneuropathy related to interferon α may be safe, but this must be confirmed by further studies.

  8. Baclofen, a GABABR agonist, ameliorates immune-complex mediated acute lung injury by modulating pro-inflammatory mediators.

    Science.gov (United States)

    Jin, Shunying; Merchant, Michael L; Ritzenthaler, Jeffrey D; McLeish, Kenneth R; Lederer, Eleanor D; Torres-Gonzalez, Edilson; Fraig, Mostafa; Barati, Michelle T; Lentsch, Alex B; Roman, Jesse; Klein, Jon B; Rane, Madhavi J

    2015-01-01

    Immune-complexes play an important role in the inflammatory diseases of the lung. Neutrophil activation mediates immune-complex (IC) deposition-induced acute lung injury (ALI). Components of gamma amino butyric acid (GABA) signaling, including GABA B receptor 2 (GABABR2), GAD65/67 and the GABA transporter, are present in the lungs and in the neutrophils. However, the role of pulmonary GABABR activation in the context of neutrophil-mediated ALI has not been determined. Thus, the objective of the current study was to determine whether administration of a GABABR agonist, baclofen would ameliorate or exacerbate ALI. We hypothesized that baclofen would regulate IC-induced ALI by preserving pulmonary GABABR expression. Rats were subjected to sham injury or IC-induced ALI and two hours later rats were treated intratracheally with saline or 1 mg/kg baclofen for 2 additional hours and sacrificed. ALI was assessed by vascular leakage, histology, TUNEL, and lung caspase-3 cleavage. ALI increased total protein, tumor necrosis factor α (TNF-α and interleukin-1 receptor associated protein (IL-1R AcP), in the bronchoalveolar lavage fluid (BALF). Moreover, ALI decreased lung GABABR2 expression, increased phospho-p38 MAPK, promoted IκB degradation and increased neutrophil influx in the lung. Administration of baclofen, after initiation of ALI, restored GABABR expression, which was inhibited in the presence of a GABABR antagonist, CGP52432. Baclofen administration activated pulmonary phospho-ERK and inhibited p38 MAPK phosphorylation and IκB degradation. Additionally, baclofen significantly inhibited pro-inflammatory TNF-α and IL-1βAcP release and promoted BAL neutrophil apoptosis. Protective effects of baclofen treatment on ALI were possibly mediated by inhibition of TNF-α- and IL-1β-mediated inflammatory signaling. Interestingly, GABABR2 expression was regulated in the type II pneumocytes in lung tissue sections from lung injured patients, further suggesting a

  9. Baclofen, a GABABR agonist, ameliorates immune-complex mediated acute lung injury by modulating pro-inflammatory mediators.

    Directory of Open Access Journals (Sweden)

    Shunying Jin

    Full Text Available Immune-complexes play an important role in the inflammatory diseases of the lung. Neutrophil activation mediates immune-complex (IC deposition-induced acute lung injury (ALI. Components of gamma amino butyric acid (GABA signaling, including GABA B receptor 2 (GABABR2, GAD65/67 and the GABA transporter, are present in the lungs and in the neutrophils. However, the role of pulmonary GABABR activation in the context of neutrophil-mediated ALI has not been determined. Thus, the objective of the current study was to determine whether administration of a GABABR agonist, baclofen would ameliorate or exacerbate ALI. We hypothesized that baclofen would regulate IC-induced ALI by preserving pulmonary GABABR expression. Rats were subjected to sham injury or IC-induced ALI and two hours later rats were treated intratracheally with saline or 1 mg/kg baclofen for 2 additional hours and sacrificed. ALI was assessed by vascular leakage, histology, TUNEL, and lung caspase-3 cleavage. ALI increased total protein, tumor necrosis factor α (TNF-α and interleukin-1 receptor associated protein (IL-1R AcP, in the bronchoalveolar lavage fluid (BALF. Moreover, ALI decreased lung GABABR2 expression, increased phospho-p38 MAPK, promoted IκB degradation and increased neutrophil influx in the lung. Administration of baclofen, after initiation of ALI, restored GABABR expression, which was inhibited in the presence of a GABABR antagonist, CGP52432. Baclofen administration activated pulmonary phospho-ERK and inhibited p38 MAPK phosphorylation and IκB degradation. Additionally, baclofen significantly inhibited pro-inflammatory TNF-α and IL-1βAcP release and promoted BAL neutrophil apoptosis. Protective effects of baclofen treatment on ALI were possibly mediated by inhibition of TNF-α- and IL-1β-mediated inflammatory signaling. Interestingly, GABABR2 expression was regulated in the type II pneumocytes in lung tissue sections from lung injured patients, further suggesting

  10. Cytokine-induced activation of Mixed Lineage Kinase 3 requires TRAF2 and TRAF6

    OpenAIRE

    Korchnak, Amanda C.; Zhan, Yu; Aguilar, Michael T.; Chadee, Deborah N.

    2009-01-01

    Mixed Lineage Kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase (MAP3K) that activates multiple mitogen activated protein kinase (MAPK) pathways in response to growth factors, stresses and the pro-inflammatory cytokine, tumor necrosis factor (TNF). MLK3 is required for optimal activation of stress activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) signaling by TNF, however, the mechanism by which MLK3 is recruited and activated by the TNF receptor remains poorly und...

  11. Acutely exacerbated hypertension and increased inflammatory signs due to radiation treatment for metastatic pheochromocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Teno, Shinichi; Tanabe, Akiyo; Nomura, Kaoru; Demura, Hiroshi [Tokyo Women`s Medical Coll. (Japan)

    1996-10-01

    Hypertension and norepinephrine hypersecretion in a 59-year-old woman suffering from malignant pheochromocytoma with multiple metastases were appropriately controlled with {alpha}- and {beta}- blockers, and {alpha}-methyltyrosine ({alpha}-MT), a catecholamine-synthesis inhibitor. Metastasized vertebrae were treated with external radiation to relieve pain, but this treatment had to be interrupted at a total dose of 20 Gy because the patient suffered acutely exacerbated hypertension (200/110 mmHg), tachycardia (160 beats/min) and a low-grade fever. Simultaneously her serum levels of LDH, potassium, urea nitrogen, creatinine, white blood cell count, CRP and norepinephrine were significantly increased, suggesting that this episode was due to radiation-induced tissue destruction and the leakage of catecholamines and possibly interleukin-6, a cytokine mediating inflammation which is reportedly present in pheochromocytoma. The marked hypertension was controlled by continuous iv administration of phentolamine and propranolol. Although radiation therapy effectively relieves pain due to neoplasmic metastasis to the bone, physicians should be aware that life-threatening complications such as the above occur in malignant pheochromocytoma. Sufficient pretreatment with adrenergic blocking agents and/or {alpha}-MT and careful monitoring of the patient`s general condition during radiation therapy, even at a low dose, are highly recommended. (author)

  12. Clostridium difficile infection in acute flares of inflammatory bowel disease: A prospective study.

    Science.gov (United States)

    Sokol, Harry; Lalande, Valérie; Landman, Cecilia; Bourrier, Anne; Nion-Larmurier, Isabelle; Rajca, Sylvie; Kirchgesner, Julien; Seksik, Philippe; Cosnes, Jacques; Barbut, Frédéric; Beaugerie, Laurent

    2017-06-01

    Clostridium difficile infection (CDI) is a common complication in inflammatory bowel disease (IBD) and has been associated with poor IBD outcome. The aims of our study were to look for predictive factors of CDI in patients hospitalized for IBD flare and to evaluate a rapid testing strategy in this population. Consecutive patients hospitalized for IBD flare in Saint-Antoine Hospital (Paris, France) were prospectively tested for CDI with a defined strategy involving rapid testing and reference methods. Risk factors for CDI were investigated and performances of diagnostic tests were evaluated. C. difficile testing was performed at admission in 461 hospitalizations for IBD flare. CDI was diagnosed in 35 cases (7.6%) and non-toxigenic C. difficile was identified in 10 cases (2.2%). In multivariate analysis, UC phenotype was associated with CDI (OR 2.2, 95% CI 1.03-4.6, p=0.047). Glutamate dehydrogenase (GDH) test had a 97.1% sensitivity and a 100% negative predictive value for CDI diagnosis but a positive predictive value of 79.1%. Enzyme immunoassay (EIA)-based toxin detection (C. Diff Quik Chek complete(®), Alere) had a poor sensitivity and diagnosis was rescued by toxin PCR in 100% of cases. CDI is frequent in patients hospitalized for IBD flare. Clinical parameters do not help for the diagnosis and rapid testing should be performed in all patients. Currently, a negative result of an EIA-based toxin search associated with a positive GDH test cannot rule out a CDI and should not delay initiation of specific treatment in case of severe symptoms or high presumption. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  13. Could pyelonephritic scarring be prevented by anti-inflammatory treatment? An experimental model of acute pyelonephritis.

    Science.gov (United States)

    Bahat Özdoğan, Elif; Özdemir, Tuğba; Arslansoyu Çamlar, Seçil; Imamoğlu, Mustafa; Cobanoğlu, Ümit; Sönmez, Bircan; Tosun, İlknur; Doğan, Ismail

    2014-01-01

    This study aimed to demonstrate if the addition of anti-inflammatory treatment to antibiotic therapy shows any superiority to the treatment with antibiotic only. Forty-nine Wistar rats were divided into 7 groups. Pyelonephritis was performed by E. coli injection to upper pole of kidneys except control group. Group 2 was not treated. Ceftriaxone, ketoprofen, "ceftriaxone + ketoprofen," methylprednisolone, and "ceftriaxone + methylprednisolone" were given in the groups. The technetium-99m-dimercaptosuccinic acid scintigraphies were performed in 3rd day to detect pyelonephritis and 10th week to detect renal scarring. All kidneys were also histopathologically evaluated. When 3rd day and 10th week scintigraphies were compared, initial 2.00 ± 0.30 point pyelonephritis score resulted in 0.71 ± 0.36 renal scar score in "ceftriaxone + ketoprofen" group (P = 0.039). Initial 2.00 ± 0.43 point pyelonephritis score resulted in 0.86 ± 0.26 renal scar score in "ceftriaxone + methylprednisolone" group (P = 0.041). Renal scar score was declined in "ceftriaxone + ketoprofen" group and "ceftriaxone + methylprednisolone" group compared with no-treatment group on 10th week of the study (P = 0.026, P = 0.044). On histopathological evaluation, it was seen that renal scar prevalence and expansion declined significantly in "ceftriaxone + ketoprofen and ceftriaxone + methylprednisolone" (P = 0.011, P = 0.023). It was evidenced that ceftriaxone treatment in combination with ketoprofen or methylprednisolone declined scar formation in scintigraphic and histopathologic examinations of the kidneys.

  14. Silencing of microRNA-155 in mice during acute inflammatory response leads to derepression of c/ebp Beta and down-regulation of G-CSF

    DEFF Research Database (Denmark)

    Worm, Jesper; Stenvang, Jan; Petri, Andreas;

    2009-01-01

    microRNA-155 (miR-155) has been implicated as a central regulator of the immune system, but its function during acute inflammatory responses is still poorly understood. Here we show that exposure of cultured macrophages and mice to lipopolysaccharide (LPS) leads to up-regulation of miR-155......-stimulating factor (G-CSF), a central regulator of granulopoiesis during inflammatory responses. Consistent with these data, we show that silencing of miR-155 in LPS-treated mice by systemically administered LNA-antimiR results in derepression of the c/ebp Beta isoforms and down-regulation of G-CSF expression...

  15. Non-Steroid Anti-Inflammatory Drugs Are Better than Acetaminophen on Fever Control at Acute Stage of Fracture.

    Directory of Open Access Journals (Sweden)

    Kuang-Ting Yeh

    Full Text Available In addition to adequate surgical fixation and an aggressive rehabilitation program, pain relief is one of the most critical factors in the acute stage of fracture treatment. The most common analgesics are nonsteroid anti-inflammatory drugs and Acetaminophen, both of which relieve pain and reduce body temperature. In clinical experiences, they exhibit effective pain control; however, their influence on body temperature remains controversial. This study is aimed at determining the effects of analgesics at the acute stage of traumatic fracture by performing a clinical retrospective study of patients with fractures and a fracture animal model. The retrospective study revealed that, in the acetaminophen group, the mean value of postmedication body temperature (BT was significantly higher than that of the premedication BT. The change in BT was highly related with the medication rather than other risk factors. Forty eight 12-week-old male Wistar rats were divided into 6 groups: a control group, fracture group, fracture-Acetaminophen group, Acetaminophen group, fracture-Arcoxia group, and Arcoxia group. Fracture rats were prepared by breaking their unilateral tibia and fibula. Their inflammation conditions were evaluated by measuring their serum cytokine level and their physiological status was evaluated by estimating their central temperature, heart rate, and mean blood pressure. The hepatic adverse effects were assessed by measuring the serum levels of aspartate aminotransferase (sGOT and alanine aminotransferase (sGPT. The central temperature in the fracture-Acetaminophen group exceeded that in the groups fed normal saline water or Arcoxia. Accumulated hepatic injury was presented as steadily ascending curves of sGOT and sGPT. Inflammation-related cytokine levels were not higher in the Acetaminophen fracture group and were significantly lower in the fracture-Arcoxia group. Fever appeared to be aggravated by acetaminophen and more related to the

  16. Non-Steroid Anti-Inflammatory Drugs Are Better than Acetaminophen on Fever Control at Acute Stage of Fracture.

    Science.gov (United States)

    Yeh, Kuang-Ting; Wu, Wen-Tien; Subeq, Yi-Maun; Niu, Chi-Chien; Liao, Kuang-Wen; Chen, Ing-Ho; Wang, Jen-Hung; Lee, Ru-Ping

    2015-01-01

    In addition to adequate surgical fixation and an aggressive rehabilitation program, pain relief is one of the most critical factors in the acute stage of fracture treatment. The most common analgesics are nonsteroid anti-inflammatory drugs and Acetaminophen, both of which relieve pain and reduce body temperature. In clinical experiences, they exhibit effective pain control; however, their influence on body temperature remains controversial. This study is aimed at determining the effects of analgesics at the acute stage of traumatic fracture by performing a clinical retrospective study of patients with fractures and a fracture animal model. The retrospective study revealed that, in the acetaminophen group, the mean value of postmedication body temperature (BT) was significantly higher than that of the premedication BT. The change in BT was highly related with the medication rather than other risk factors. Forty eight 12-week-old male Wistar rats were divided into 6 groups: a control group, fracture group, fracture-Acetaminophen group, Acetaminophen group, fracture-Arcoxia group, and Arcoxia group. Fracture rats were prepared by breaking their unilateral tibia and fibula. Their inflammation conditions were evaluated by measuring their serum cytokine level and their physiological status was evaluated by estimating their central temperature, heart rate, and mean blood pressure. The hepatic adverse effects were assessed by measuring the serum levels of aspartate aminotransferase (sGOT) and alanine aminotransferase (sGPT). The central temperature in the fracture-Acetaminophen group exceeded that in the groups fed normal saline water or Arcoxia. Accumulated hepatic injury was presented as steadily ascending curves of sGOT and sGPT. Inflammation-related cytokine levels were not higher in the Acetaminophen fracture group and were significantly lower in the fracture-Arcoxia group. Fever appeared to be aggravated by acetaminophen and more related to the elevation of hepatic

  17. PICK1 confers anti-inflammatory effects in acute liver injury via suppressing M1 macrophage polarization.

    Science.gov (United States)

    Xie, Juan; Wu, Xiaoqin; Zhou, Qun; Yang, Yang; Tian, Yuanyao; Huang, Cheng; Meng, Xiaoming; Li, Jun

    2016-08-01

    Protein interacting with C kinase 1 (PICK1) is a scaffolding protein mainly implicated in neurological diseases, however, the function of PICK1 in acute liver injury (ALI) remains unknown. Our study found a dramatical decrease in mRNA and protein levels of PICK1 in liver tissues and isolated Kupffer cells (KCs) from the liver in mice with ALI. Furthermore, pretreatment the mice with ALI with FSC-231, a pharmacological inhibitor of PICK1, could significantly augment inflammatory response. Furthermore, in vitro studies showed that both lipopolysaccharide (LPS) and interferon gamma (IFN-γ) significantly reduced the expression of PICK1, while IL-4 elevated its expression in RAW 264.7 cells. Additionally, over-expression of PICK1 inhibited the expression of M1 biomarkers by suppressing NF-κB activity, and enhanced the expression of M2 biomarkers by promoting STAT6 activity. In contrast, knockdown of PICK1 or FSC-231 pretreatment promoted M1 polarization and suppressed M2 polarization. Besides, caveolin-1 was identified as a potential target gene controlled by PICK1 in RAW 264.7 cells. Mechanistic investigation revealed a dual role of PICK1 in regulating macrophage polarization and implied PICK1 as a potential therapeutic target in ALI.

  18. Modeling the pro-inflammatory tumor microenvironment in acute lymphoblastic leukemia predicts a breakdown of hematopoietic-mesenchymal communication networks

    Directory of Open Access Journals (Sweden)

    Jennifer Enciso

    2016-08-01

    Full Text Available Lineage fate decisions of hematopoietic cells depend on intrinsic factors and extrinsic signals provided by the bone marrow microenvironment, where they reside. Abnormalities in composition and function of hematopoietic niches have been proposed as key contributors of acute lymphoblastic leukemia (ALL progression. Our previous experimental findings strongly suggest that pro-inflammatory cues contribute to mesenchymal niche abnormalities that result in maintenance of ALL precursor cells at the expense of normal hematopoiesis. Here, we propose a molecular regulatory network interconnecting the major communication pathways between hematopoietic stem and progenitor cells (HSPCs and mesenchymal stromal cells (MSCs within the bone marrow. Dynamical analysis of the network as a Boolean model reveals two stationary states that can be interpreted as the intercellular contact status. Furthermore, simulations describe the molecular patterns observed during experimental proliferation and activation. Importantly, our model predicts instability in the CXCR4/CXCL12 and VLA4/VCAM1 interactions following microenvironmental perturbation due by temporal signaling from Toll like receptors (TLRs ligation. Therefore, aberrant expression of NF-κB induced by intrinsic or extrinsic factors may contribute to create a tumor microenvironment where a negative feedback loop inhibiting CXCR4/CXCL12 and VLA4/VCAM1 cellular communication axes allows for the maintenance of malignant cells.

  19. Pro-inflammatory-Related Loss of CXCL12 Niche Promotes Acute Lymphoblastic Leukemic Progression at the Expense of Normal Lymphopoiesis

    Science.gov (United States)

    Balandrán, Juan Carlos; Purizaca, Jessica; Enciso, Jennifer; Dozal, David; Sandoval, Antonio; Jiménez-Hernández, Elva; Alemán-Lazarini, Leticia; Perez-Koldenkova, Vadim; Quintela-Núñez del Prado, Henry; Rios de los Ríos, Jussara; Mayani, Héctor; Ortiz-Navarrete, Vianney; Guzman, Monica L.; Pelayo, Rosana

    2017-01-01

    Pediatric oncology, notably childhood acute lymphoblastic leukemia (ALL), is currently one of the health-leading concerns worldwide and a biomedical priority. Decreasing overall leukemia mortality in children requires a comprehensive understanding of its pathobiology. It is becoming clear that malignant cell-to-niche intercommunication and microenvironmental signals that control early cell fate decisions are critical for tumor progression. We show here that the mesenchymal stromal cell component of ALL bone marrow (BM) differ from its normal counterpart in a number of functional properties and may have a key role during leukemic development. A decreased proliferation potential, contrasting with the strong ability of producing pro-inflammatory cytokines and an aberrantly loss of CXCL12 and SCF, suggest that leukemic lymphoid niches in ALL BM are unique and may exclude normal hematopoiesis. Cell competence ex vivo assays within tridimensional coculture structures indicated a growth advantage of leukemic precursor cells and their niche remodeling ability by CXCL12 reduction, resulting in leukemic cell progression at the expense of normal niche-associated lymphopoiesis. PMID:28111575

  20. Modeling the Pro-inflammatory Tumor Microenvironment in Acute Lymphoblastic Leukemia Predicts a Breakdown of Hematopoietic-Mesenchymal Communication Networks.

    Science.gov (United States)

    Enciso, Jennifer; Mayani, Hector; Mendoza, Luis; Pelayo, Rosana

    2016-01-01

    Lineage fate decisions of hematopoietic cells depend on intrinsic factors and extrinsic signals provided by the bone marrow microenvironment, where they reside. Abnormalities in composition and function of hematopoietic niches have been proposed as key contributors of acute lymphoblastic leukemia (ALL) progression. Our previous experimental findings strongly suggest that pro-inflammatory cues contribute to mesenchymal niche abnormalities that result in maintenance of ALL precursor cells at the expense of normal hematopoiesis. Here, we propose a molecular regulatory network interconnecting the major communication pathways between hematopoietic stem and progenitor cells (HSPCs) and mesenchymal stromal cells (MSCs) within the BM. Dynamical analysis of the network as a Boolean model reveals two stationary states that can be interpreted as the intercellular contact status. Furthermore, simulations describe the molecular patterns observed during experimental proliferation and activation. Importantly, our model predicts instability in the CXCR4/CXCL12 and VLA4/VCAM1 interactions following microenvironmental perturbation due by temporal signaling from Toll like receptors (TLRs) ligation. Therefore, aberrant expression of NF-κB induced by intrinsic or extrinsic factors may contribute to create a tumor microenvironment where a negative feedback loop inhibiting CXCR4/CXCL12 and VLA4/VCAM1 cellular communication axes allows for the maintenance of malignant cells.

  1. The acute phase of inflammatory response involved in the wound-healing process after excimer laser treatment

    Directory of Open Access Journals (Sweden)

    Resan M

    2016-05-01

    hour after PRK treatment (P<0.001 for both groups, and IL-8 concentrations between control and experimental groups in samples collected 24 hours after LASIK and 24 hours after PRK treatment were greater after PRK treatment (P=0.0005. Comparison of average concentration values of proinflammatory cytokines in all the tested samples between LASIK and PRK groups showed significantly higher levels of IL-1β in the LASIK group 24 hours after treatment (P=0.0134, and of IL-6 in the PRK group 24 hours after treatment (P=0.0031. Conclusion: The acute phase of corneal wound healing after excimer laser treatment is defined by an intensive inflammatory response. After PRK treatment, there were increased concentrations of TNF-α and IL-1β in tear samples 1 hour after treatment, IL-6, 1 and 24 hours after treatment, and IL-8, 1 and 24 hours after treatment. After LASIK treatment, there were increased concentrations of IL-8 in tear samples 1 hour after treatment and IL-1β, 24 hours after treatment. Both PRK and LASIK methods are characterized with a significant inflammatory response. However, tear findings following PRK method showed more intensive inflammatory response than the findings after LASIK method. Keywords: LASIK, PRK, tears, proinflammatory cytokines, wound healing

  2. Acute kidney injury and inflammatory response of sepsis following cecal ligation and puncture in D-galactose-induced aging rats

    Directory of Open Access Journals (Sweden)

    Liu C

    2017-03-01

    Full Text Available Chao Liu,1,* Jie Hu,1,* Zhi Mao,1,* Hongjun Kang,1 Hui Liu,1 Wanlei Fu,2 Yangfan Lv,2 Feihu Zhou1 1Department of Critical Care Medicine, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China; 2Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of China *These authors contributed equally to this work Background: Recently, the D-galactose (D-gal-induced mimetic aging rat model has been widely used in studies of age-associated diseases, which have shown that chronic D-gal exposure induces premature aging similar to natural aging in rats. With the increasing rate of sepsis in the geriatric population, an easy-access animal model for preclinical studies of elderly sepsis is urgently needed. This study investigates whether a sepsis model that is established in D-gal-induced aging rats can serve as a suitable model for preclinical studies of elderly patients with sepsis.Objective: To investigate the acute kidney injury (AKI and inflammatory response of sepsis following cecal ligation and puncture (CLP in D-gal-induced aging rats.Methods: Twelve-week-old male Sprague Dawley rats were divided into low-dose D-gal (L D-gal, 125 mg/kg/d, high-dose D-gal (H D-gal, 500 mg/kg/d, and control groups. After daily subcutaneous injection of D-gal for 6 weeks, the CLP method was used to establish a sepsis model.Results: The mortality was 73.3%, 40%, and 33.3% in the H D-gal, L D-gal, and control groups, respectively. Blood urea nitrogen, creatinine, plasma neutrophil gelatinase-associated lipocalin, interleukin-6, interleukin-10, and tumor necrosis factor-α were markedly increased in the H D-gal group after establishment of the sepsis model (H D-gal vs control, P<0.05 at 12 h and 24 h post-CLP. The rate of severe AKI (RIFLE-F at 24 h post-CLP was 43% for both the control and L D-gal groups and 80% for the H D-gal group.Conclusion: High-dose-D-gal-induced aging rats are

  3. Anti-inflammatory and anti-apoptotic effects of (RS)-glucoraphanin bioactivated with myrosinase in murine sub-acute and acute MPTP-induced Parkinson's disease.

    Science.gov (United States)

    Galuppo, Maria; Iori, Renato; De Nicola, Gina Rosalinda; Bramanti, Placido; Mazzon, Emanuela

    2013-09-01

    This study was focused on the possible neuroprotective role of (RS)-glucoraphanin, bioactivated with myrosinase enzyme (bioactive RS-GRA), in an experimental mouse model of Parkinson's disease (PD). RS-GRA is one of the most important glucosinolates, a thiosaccharidic compound found in Brassicaceae, notably in Tuscan black kale seeds. RS-GRA was extracted by one-step anion exchange chromatography, further purified by gel-filtration and analyzed by HPLC. Following, pure RS-GRA was characterized by (1)H and (13)C NMR spectrometry and the purity was assayed by HPLC analysis of the desulfo-derivative according to the ISO 9167-1 method. The obtained purity has been of 99%. To evaluate the possible pharmacological efficacy of bioactive RS-GRA (administrated at the dose of 10mg/kg, ip +5μl/mouse myrosinase enzyme), C57BL/6 mice were used in two different sets of experiment (in order to evaluate the neuroprotective effects in different phases of the disease), according to an acute (2 injections·40mg/kg MPTP) and a sub-acute (5 injections·20mg/kg MPTP) model of PD. Behavioural test, body weight changes measures and immunohistochemical localization of the main PD markers were performed and post-hoc analysis has shown as bioactive RS-GRA is able to reduce dopamine transporter degradation, tyrosine hydroxylase expression, IL-1β release, as well as the triggering of neuronal apoptotic death pathway (data about Bax/Bcl-2 balance and dendrite spines loss) and the generation of radicalic species by oxidative stress (results focused on nitrotyrosine, Nrf2 and GFAP immunolocalization). These effects have been correlated with the release of neurotrophic factors, such as GAP-43, NGF and BDNF, that, probably, play a supporting role in the neuroprotective action of bioactive RS-GRA. Moreover, after PD-induction mice treated with bioactive RS-GRA are appeared more in health than animals that did not received the treatment both for phenotypic behaviour and for general condition

  4. Pseudoephedrine/ephedrine shows potent anti-inflammatory activity against TNF-α-mediated acute liver failure induced by lipopolysaccharide/D-galactosamine.

    Science.gov (United States)

    Wu, Zhongping; Kong, Xiangliang; Zhang, Tong; Ye, Jin; Fang, Zhaoqin; Yang, Xuejun

    2014-02-01

    The anti-inflammatory effects of pseudoephedrine/ephedrine were investigated using the experimental model of lipopolysaccharide (LPS)-induced acute liver failure in D-galactosamine (D-GalN)-sensitised male rats in order to elucidate effects other than sympathomimetic effects. Rats were intraperitoneally injected with D-GalN (400 mg/kg) and LPS (40 μg/kg) to induce acute liver failure. The treatment groups were then intraperitoneally administered pseudoephedrine/ephedrine at 0 h and 4 h after induction and the activation induced by treatment with pseudoephedrine and/or LPS on the primary Kupffer cells (KCs) was monitored. Compared with controls induced by GalN/LPS alone, pseudoephedrine dramatically reduced the infiltration of inflammatory cells and bile ductular hyperplasia and hepatic necrosis observed in liver sections. It inhibited both hepatocellular apoptosis and the expression of monocyte chemotactic protein-1. It lowered the production of tumour necrosis factor-α (TNF-α) in the beginning of acute liver failure induced by D-GalN/LPS. Correspondingly, levels of alanine aminotransferase (ALT), total bilirubin (TBIL) and malondialdehyde were attenuated. Ephedrine demonstrated all these identical protective effects as well. In addition, pseudoephedrine significantly suppressed the production of p-IκB-α, reducing the degradation of sequestered nuclear factor kappa B (NF-κB) in the cytoplasm, and inhibited the translocation of NF-κB/p65 to the nucleus, the transcription of TNF-α mRNA and the production of TNF-α in primary KCs. These results suggest that pseudoephedrine and ephedrine have a potent anti-inflammatory activity against D-GalN/LPS-induced acute liver failure in rats, and this comprehensive anti-inflammatory effect may result from the inhibition of TNF-α production.

  5. Effectiveness of anti-inflammatory treatment versus antibiotic therapy and placebo for patients with non-complicated acute bronchitis with purulent sputum. The BAAP Study protocol

    OpenAIRE

    Fernández Yvonne; Cots Josep M; Pera Helena; Morros Rosa; Bayona Carolina; Moragas Ana; Llor Carl; Miravitlles Marc; Boada Albert

    2011-01-01

    Abstract Background Acute bronchitis is one of the most prevalent respiratory infections in primary care, and in more than 90% of the cases antibiotics are prescribed, mainly when purulent expectoration is present. However, this process is usually viral in origin and the benefits of antibiotic treatment are marginal. On the other hand, in recent years bronchitis has been considered more as an inflammatory than an infectious process. Thus, the aim of this study is to evaluate the clinical effe...

  6. A double blind placebo controlled randomized trial of the effect of acute uric acid changes on inflammatory markers in humans: A pilot study.

    Science.gov (United States)

    Tanaka, Toshiko; Milaneschi, Yuri; Zhang, Yongqing; Becker, Kevin G; Zukley, Linda; Ferrucci, Luigi

    2017-01-01

    Uric acid has been linked with increased risk of chronic disease such as cardiovascular disease and this association has been attributed to a pro-inflammatory effect. Indeed, observational studies have shown that high uric acid is associated with high level of pro-inflammatory cytokines in the blood. However, whether high uric acid directly affects inflammation or rather represents a parallel defensive antioxidant mechanism in response to pathology that causes inflammation is unknown. To determine whether acute increase or decrease uric acid levels affects inflammation in healthy individuals, a randomized, placebo-controlled, double blind clinical study of uric acid or rasburicase with 20 healthy volunteers in each treatment-placebo group was conducted at the National Institute on Aging (NIA) Clinical Research Unit (CRU) at Harbor Hospital in Baltimore, MD. Change in inflammatory response was assessed by administering an oral lipid tolerance before and after the treatment of uric acid, rasburicase and placebo. Following uric acid administration, there was an accentuated increase in IL-6 during the oral lipid tolerance test (Puric acid with rasburicase. No side effects were reported throughout the trial. In health individuals, acute increase in uric acid results in an increased IL-6 response when challenged with lipid load. Such effect of amplification of inflammatory response may explain the higher risk of chronic diseases observed in subclinical hyperuricemia in observational studies. ClinicalTrials.gov NCT01323335.

  7. Atrial natriuretic peptide attenuates inflammatory responses on oleic acid-induced acute lung injury model in rats

    Institute of Scientific and Technical Information of China (English)

    ZHU Yao-bin; ZHANG Yan-bo; LIU Dong-hai; LI Xiao-feng; LIU Ai-jun; FAN Xiang-ming; QIAO Chen-hui

    2013-01-01

    Background An inflammatory response leading to organ dysfunction and failure continues to be a major problem after injury in many clinical conditions such as sepsis,severe burns,and trauma.It is increasingly recognized that atrial natriuretic peptide (ANP) possesses a broad range of biological activities,including effects on endothelial function and inflammation.A recent study has revealed that ANP exerts anti-inflammatory effects.In this study we tested the effects of human ANP (hANP) on lung injury in a model of oleic acid (OA)-induced acute lung injury (ALl) in rats.Methods Rats were randomly assigned to three groups (n=6 in each group).Rats in the control group received a 0.9% solution of NaCl (1 ml.kg1.h-1) by continuous intravenous infusion,after 30 minutes a 0.9% solution of NaCl (1 ml/kg) was injected intravenously,and then the 0.9% NaCl infusion was restarted.Rats in the ALl group received a 0.9% NaCl solution (1 ml·kg-1·h-1) intravenous infusion,after 30 minutes OA was injected intravenously (0.1 ml/kg),and then the 0.9% NaCl infusion was restarted.Rats in the hANP-treated ALI group received a hANP (0.1μg·kg-1·min-1) infusion,after 30 minutes OA was injected intravenously (0.1 ml/kg),and then the hANP infusion was restarted.The anti-inflammation effects of hANP were evaluated by histological examination and determination of serum cytokine levels.Results Serum intedeukin (IL)-1β,IL-6,IL-10 and tumor necrosis factor (TNF) α were increased in the ALI group at six hours.The levels of all factors were significantly lower in the hANP treated rats (P <0.005).Similarly,levels of IL-1β,IL-6,IL-10 and TNF-α were higher in the lung tissue in the ALI group at six hours.hANP treatment significantly reduced the levels of these factors in the lungs (P <0.005).Histological examination revealed marked reduction in interstitial congestion,edema,and inflammation.Conclusion hANP can attenuate inflammation in an OA-induced lung injury in rat model.

  8. Cytokine-Induced Cell Surface Expression of Adhesion Molecules in Vascular Endothelial Cells In vitro

    Institute of Scientific and Technical Information of China (English)

    陈红辉; 刘昌勤; 孙圣刚; 梅元武; 童萼塘

    2001-01-01

    Regulation of the adhesion molecules expression by cytokine in vascular endothelial cells was investigated. Human umbilical vein endothelial cells (HUVEC) were stimulated with cytokines, TNF-α (1-250 U/ml) or IL-1β (0.1-50 U/ml) for 24 h. HUVEC were also cultured with cytokines, TNF-α (100 U/ml) or IL-1β (10 U/ml), for 4-72 h, cell surface expression of adhesion molecules (ICAM-1 and VCAM-1) were detected and quantitated by immunocytochemical methods and computerized imaging analysis technique. Adhesion molecules expression were up-regulated by TNF-α, IL-1β in a concentration- and time-dependent manner. Some significant differences were observed between the effects of cytokines on the ICAM-1 and on VCAM-1 expression. Cytokines might directly induce the expression of ICAM-1 and VCAM-1 in vascular endothelial cells. Our observations indicate differential functions of the two adhesion molecules during the evolution of inflammatory responses in stroke.

  9. Cytokine-induced proapoptotic gene expression in insulin-producing cells is related to rapid, sustained, and nonoscillatory nuclear factor-kappaB activation

    DEFF Research Database (Denmark)

    Ortis, Fernanda; Cardozo, Alessandra K; Crispim, Daisy

    2006-01-01

    Cytokines, such as IL-1beta and TNF-alpha, contribute to pancreatic beta-cell death in type 1 diabetes mellitus. The transcription factor nuclear factor-kappaB (NF-kappaB) mediates cytokine-induced beta-cell apoptosis. Paradoxically, NF-kappaB has mostly antiapoptotic effects in other cell types....

  10. Clinical efficacy of immunotherapy of dendritic cell and cytokine-induced killer cell combined with chemotherapy for treatment of multiple myeloma

    Institute of Scientific and Technical Information of China (English)

    钟国成

    2013-01-01

    Objective This research was aimed to evaluate the immune mechanism and clinical effect of immunotherapy of dendritic cells(DC) and cytokine-induced killer cell(CIK) combined with chemotherapy on multiple myeloma(MM). Methods 60 patients with MM were randomly

  11. Effects of large dose of dexamethasone on inflammatory mediators and pancreatic cell apoptosis of rats with severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the influence of high dose of dexamethasone on inflammatory mediators and apoptosis of rats with severe acute pancreatitis (SAP).METHODS: SAP rats were randomly assigned to the model group and treatment group while the normal rats were assigned to the sham operation group. The mortality, ascite volumes, ascites/body weight ratio and pancreas pathological changes of all rats were observed at 3, 6 and 12 h after operation. Their contents of amylase and endotoxin in plasma and contents of tumor necrosis factor (TNF-α), phospholipase A2 (PLA2) and IL-6 in serum were also determined. The microarray sections of their pancreatic tissues were prepared, terminal transferase dUTP nick end labeling (TUNEL) staining was performed and apoptotic indexes were calculated. RESULTS: There was no marked difference between treatment group and model group in survival. The contents of amylase and endotoxin in plasma and contents of TNF-α, PLA2 and IL-6 in serum, ascite volumes, ascites/body weight ratio and pancreas pathological scores were all lower in treatment group than in model group to different extents at different time points [P < 0.05, 58.3 (26.4) ng/L vs 77.535 (42.157)ng/L in TNF-α content, 8.00 (2.00) points vs 9.00 (2.00)points in pathological score of pancreas respectively;P < 0.01, 0.042 (0.018) EU/mL vs 0.056 (0.0195) EU/mL in endotoxin content, 7791 (1863) U/L vs 9195 (1298)U/L in plasma amylase content, 1.53 (0.79) vs 2.38 (1.10) in ascites/body weight ratio, 8.00 (1.00) points vs 11.00 (1.50) points in pathological score of pancreas; P < 0.001, 3.36 (1.56) ng/L vs 5.65 (1.08) ng/L in IL-6 content, 4.50 (2.00) vs 7.20 (2.00), 4.20 (1.60) vs 6.40 (2.30), 3.40 (2.70) vs 7.90 (1.70) in ascite volumes,respectively]. The apoptotic indexes of pancreas head and pancreas tail were all higher in treatment group than in model group at 6 h[P < 0.01, 0.00 (2.00)% vs 0.00(0.00)%, 0.20 (1.80) vs 0.00 (0.00) in apoptosis indexes, respectively

  12. Effect of Early Hemofiltration on Pro- and Anti-inflammatory Responses and Multiple Organ Failure in Severe Acute Pancreatitis

    Institute of Scientific and Technical Information of China (English)

    杨智勇; 王春友; 陶京; 熊炯炘; 万赤丹; 周锋

    2004-01-01

    The effects of early hemofiltration on the serum levels of cytokines, pro- and anti-inflammatory balance and organ function in pigs with severe acute pancreatits (SAP) were studied. SAP pig model was induced by retrograde injection of artificial bile into the pancreatic duct. The pigs were randomly divided into SAP hemofiltration treatment group (HF group, n= 8) and SAP nonhemofiltration treatment group (NHF group, n=8). In the HF group, the animals were subjected to high-volume and zero-balance hemofiltration therapy. The results showed that as compared with NHF group, MAP, CVP and PaO2/FiO2 were significantly increased (P<0.01), while HR, urinary protein content, serum ALT level, pulmonary coefficient and lung wet/dry ratio obviously decreased (P<0.05) in HF group. Under a light microscope, the pulmonary histologic scoring was lower that in HF group (P<0.01) and the lesions of renal and liver tissues were milder. However,there was no significant difference in the pancreatic histologic scoring between the two groups. Six h after establishment of the model, the serum levels of TNF-α, IL-1β were lower, while the IL-10/TNF-α ratio was higher in HF group (all P<0.05). It was suggested that early hemofiltration could effectively remove the serum cytokines TNF-α and IL-1β in SAP pigs, elevate the ratio of IL-10/TNF-α, improve hemodynamics and alleviate the lesions of lung, kidney and liver tissues.

  13. Time course of systemic oxidative stress and inflammatory response induced by an acute exposure to Residual Oil Fly Ash.

    Science.gov (United States)

    Marchini, T; Magnani, N D; Paz, M L; Vanasco, V; Tasat, D; González Maglio, D H; Alvarez, S; Evelson, P A

    2014-01-15

    It is suggested that systemic oxidative stress and inflammation play a central role in the onset and progression of cardiovascular diseases associated with the exposure to particulate matter (PM). The aim of this work was to evaluate the time changes of systemic markers of oxidative stress and inflammation, after an acute exposure to Residual Oil Fly Ash (ROFA). Female Swiss mice were intranasally instilled with a ROFA suspension (1.0mg/kg body weight) or saline solution, and plasma levels of oxidative damage markers [thiobarbituric acid reactive substances (TBARSs) and protein carbonyls], antioxidant status [reduced (GSH) and oxidized (GSSG) glutathione, ascorbic acid levels, and superoxide dismutase (SOD) activity], cytokines levels, and intravascular leukocyte activation were evaluated after 1, 3 or 5h of exposure. Oxidative damage to lipids and decreased GSH/GSSG ratio were observed in ROFA-exposed mice as early as 1h. Afterwards, increased protein oxidation, decreased ascorbic acid content and SOD activity were found in this group at 3h. The onset of an adaptive response was observed at 5h after the ROFA exposure, as indicated by decreased TBARS plasma content and increased SOD activity. The observed increase in oxidative damage to plasma macromolecules, together with systemic antioxidants depletion, may be a consequence of a systemic inflammatory response triggered by the ROFA exposure, since increased TNF-α and IL-6 plasma levels and polymorphonuclear leukocytes activation was found at every evaluated time point. These findings contribute to the understanding of the increase in cardiovascular morbidity and mortality, in association with environmental PM inhalation.

  14. Inhibition of inflammatory responses by ambroxol, a mucolytic agent, in a murine model of acute lung injury induced by lipopolysaccharide.

    Science.gov (United States)

    Su, Xiao; Wang, Ling; Song, Yuanlin; Bai, Chunxue

    2004-01-01

    The aim of this study is to investigate whether ambroxol inhibits inflammatory responses in a murine model of lipopolysaccharide-induced acute lung injury (ALI). Mice (n=295) were first intratracheally instilled with lipopolysaccharide (LPS) to induce ALI and then received an intraperitoneal (i.p.) injection of either normal saline (NS), ambroxol (30 or 90 mg/kg per day) or dexamethasone (2.5 or 5 mg/kg per day) for 7 days. Metabolism (n=10, each), lung morphology (n=5, each) and wet-to-dry lung weight ratio (n=10, each) were studied. The levels of tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6) and transforming growth factor (TGF-beta1) and the protein concentration (n=5 or 7, each) in bronchoalveolar lavage (BAL) were measured. Mice with LPS-induced ALI that were treated with ambroxol at a dosage of 90 mg/kg per day significantly gained weight compared to the control and dexamethasone-treated groups. Ambroxol and dexamethasone significantly reduced the lung hemorrhage, edema, exudation, neutrophil infiltration and total lung injury histology score at 24 and 48 h. In addition, ambroxol and dexamethasone significantly attenuated the lung wet-to-dry weight ratio at 24 and 48 h (pambroxol- and dexamethasone-treated groups were significantly reduced at 24 and 48 h. The protein in BAL, an index of vascular permeability, was also significantly decreased in the ambroxol- and dexamethasone-treated groups (pAmbroxol inhibited proinflammatory cytokines, reduced lung inflammation and accelerated recovery from LPS-induced ALI.

  15. Acquired inflammatory demyelinating neuropathies.

    Science.gov (United States)

    Ensrud, E R; Krivickas, L S

    2001-05-01

    The acquired demyelinating neuropathies can be divided into those with an acute onset and course and those with a more chronic course. The acute neuropathies present as Guillain-Barré syndrome and include acute inflammatory demyelinating polyradiculoneuropathy (AIDP), Miller Fisher syndrome, acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and acute pandysautonomia. The chronic neuropathies are collectively known as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and include MADSAM (multifocal acquired demyelinating sensory and motor neuropathy, also know as Lewis-Sumner syndrome) and DADS (distal acquired demyelinating symmetric neuropathy) as variants. The clinical features, pathology, pathogenesis, diagnosis, treatment, rehabilitation, and prognosis of these neuropathies are discussed.

  16. Acute anti-inflammatory activity of ethanolic extract of leaves of Leucas indica by carrageenan induced paw oedema in wistar albino rats

    Directory of Open Access Journals (Sweden)

    Chandrashekar R.

    2013-06-01

    Full Text Available Background: Inflammation is basically a defense phenomenon but can lead to serious pathological conditions. It is treated by various agents with good to moderate success because of both considerable toxicity and side effects. There are various mediators to cause an inflammatory reaction that can contribute to the associated symptoms and tissue injury. Even though non steroidal anti-inflammatory drugs are the most commonly prescribed drugs in the world, their use as anti-inflammatory agents continues to be principally limited by their undesired side effects. Hence, the traditional medical practitioners and scientists are turning towards Indian System of Medicine (ISM. Methods: Dried powdered leaves of Leucas indica were subjected to solvent extraction by using 90 % ethanol. Based on acute oral toxicity study according to Organization for Economic Cooperation and Development (OECD guidelines No. 423, three doses of the test drug 75, 150 & 300mg/kg were selected and subjected to preclinical anti-inflammatory screening by carrageenin induced paw oedema in Wistar Albino rats. Results : Oral administration of Ethanolic Extract Of Leaves of Leucas Indica (EELLI at doses of 150 mg/kg and 300mg/kg showed significant anti-inflammatory activity 52.58% (p<0.01 and 36.87% (p<0.05 respectively compared to control. Conclusion: Even though oral administration of EELLI has shown significant anti-inflammatory activity, further studies are required to evaluate its comprehensive analysis including quantitative / semi quantitative analysis, characterize its chemical structure and assess its pharmacotherapeutic activities with exact mechanism of action as an anti-inflammatory agent. [Int J Basic Clin Pharmacol 2013; 2(3.000: 302-305

  17. Effect of two active compounds obtained from the essential oil of Cordia verbenacea on the acute inflammatory responses elicited by LPS in the rat paw

    Science.gov (United States)

    Medeiros, R; Passos, G F; Vitor, C E; Koepp, J; Mazzuco, T L; Pianowski, L F; Campos, M M; Calixto, J B

    2007-01-01

    Background and purpose: α-Humulene and trans-caryophyllene are sesquiterpene compounds identified in the essential oil of Cordia verbenacea which display topical and systemic anti-inflammatory effects in different experimental models. However, the molecular mechanisms through which they exert their anti-inflammatory activity still remain unclear. Here, we evaluate the effects of α-humulene and trans-caryophyllene on the acute inflammatory responses elicited by LPS. Experimental approach: The biological activities of α-humulene and trans-caryophyllene were investigated in a model of acute inflammation in rat paw, induced by LPS and characterized by paw oedema, neutrophil recruitment, cytokine production, activation of MAP kinases and NF-κB and up-regulated expression of kinin B1 receptors. Key results: Treatment with either α-humulene or trans-caryophyllene effectively reduced neutrophil migration and activation of NF-κB induced by LPS in the rat paw. However, only α-humulene significantly reduced the increase in TNF-α and IL-1β levels, paw oedema and the up-regulation of B1 receptors following treatment with LPS. Both compounds failed to interfere with the activation of the MAP kinases, ERK, p38 and JNK. Conclusions and Implications: Both α-humulene and trans-caryophyllene inhibit the LPS-induced NF-κB activation and neutrophil migration, although only α-humulene had the ability to prevent the production of pro-inflammatory cytokines TNF-α and IL-1β and the in vivo up-regulation of kinin B1 receptors. These data provide additional molecular and functional insights into the beneficial effects of the sesquiterpenes α-humulene and trans-caryophyllene isolated from the essential oil of Cordia verbenacea as agents for the management of inflammatory diseases. PMID:17471174

  18. High-frequency ultrasound evaluation of effects of early treatment with metoprolol on myocardial inflammatory cytokine expression in rats with acute myocardial infarction.

    Science.gov (United States)

    Wu, Wen; Huang, Linxiao; Zhang, Jiangxia; Gao, Yu; Yang, Yali

    2012-10-01

    This study evaluated the effects of early treatment with β-adrenergic blocker metoprolol on ventricular remodeling and function after acute myocardial infarction (AMI) by using high frequency ultrasound. The relationship between the efficacy and the expression level of cardiac myocardial inflammatory cytokine was examined in rats. The rat model of AMI was induced by ligating the left anterior descending artery. The surviving rats were randomly assigned to two experimental groups: MI control (MI) group and MI metoprolol (MI-B) group, with the rats undergoing sham operation serving as normal control (Sham). MI-B group was given metoprolol for 4 weeks (refer to the CCS-2 protocol) and the other two groups received equal volume of saline via intragastric (i.g.) administration. The ventricular remodeling and function were evaluated by high frequency ultrasound 4 weeks after the treatment. Then all rats were sacrificed for pathological examination and immunohistochemistrical detection of inflammatory cytokines, including IL-1β, IL-6, IL-10 and TNF-α. Compared with the MI group, the left ventricular end-systolic dimension, end-diastolic dimension, end-systolic volume and end-diastolic volume of the MI-B group were significantly decreased (Pmetoprolol treatment for AMI can regulate myocardial inflammatory cytokine expression to improve cardiac function and the underlying mechanism might be that it decreases the level of pro-inflammatory cytokines and increases the level of its anti-inflammatory counterparts in cardiac myocytes. Our study also showed that echocardiography is a useful technique for the structural and functional assessment of left ventricle after acute myocardial infarction.

  19. Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats

    Energy Technology Data Exchange (ETDEWEB)

    Marín-Prida, Javier [Centre for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, PO Box: 430, Havana (Cuba); Pavón-Fuentes, Nancy [International Centre for Neurological Restoration (CIREN), Ave. 25 e/ 158 y 160, Playa, PO Box: 11300, Havana (Cuba); Llópiz-Arzuaga, Alexey; Fernández-Massó, Julio R. [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba); Delgado-Roche, Liván [Centre for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, PO Box: 430, Havana (Cuba); Mendoza-Marí, Yssel; Santana, Seydi Pedroso; Cruz-Ramírez, Alieski; Valenzuela-Silva, Carmen; Nazábal-Gálvez, Marcelo; Cintado-Benítez, Alberto [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba); Pardo-Andreu, Gilberto L. [Centre for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, PO Box: 430, Havana (Cuba); Polentarutti, Nadia [Istituto Clinico Humanitas (IRCCS), Rozzano (Italy); Riva, Federica [Department of Veterinary Science and Public Health (DIVET), University of Milano (Italy); Pentón-Arias, Eduardo [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba); Pentón-Rol, Giselle [Centre for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Playa, PO Box: 6162, Havana (Cuba)

    2013-10-01

    Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24 h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD) were evaluated spectrophotometrically. The PCB treatment prevented the H{sub 2}O{sub 2} and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed. - Highlights: • Phycocyanobilin (PCB) prevents H{sub 2}O{sub 2} and glutamate induced PC12 cell viability loss. • Anterior cortex and striatum are highly vulnerable to cerebral hypoperfusion (CH). • PCB modulates 190 genes associated to inflammation in acute CH. • PCB regulates 19 genes mostly related to a detrimental pro-inflammatory environment. • PCB restores redox and immune balances showing promise as potential stroke therapy.

  20. Antinociceptive, anti-inflammatory effects and acute toxicity of aqueous and ethanolic extracts of Myrtus communis L. Aerial parts in mice.

    Science.gov (United States)

    Hosseinzadeh, Hossein; Khoshdel, Mohammad; Ghorbani, Maryam

    2011-12-01

    Myrtus communis L. aerial parts have been used in traditional medicine for the treatment of inflammatory disease. In this study 350 mice were divided into three main groups: negative (saline), positive (morphine or diclofenac) controls, and test groups. The acute toxicity was assessed for 2 days. Antinociceptive activity was performed using hot plate and writhing tests. The anti-inflammatory effect was investigated using xylene-induced ear edema and a cotton pellet test. According to phytochemical screening, the extracts contained tannins, alkaloids, and flavonoids. The LD50 values of the aqueous and ethanolic extracts were 0.473 and 0.79 g/kg, respectively. In hot plate test, the aqueous and ethanolic extracts showed significant antinociceptive activity that was inhibited by naloxone. The extracts exhibited antinociceptive activity against acetic acid-induced writhing and also showed significant activity against acute inflammation which was dose dependent for aqueous extract. The ethanolic (0.05 g/kg) and aqueous extracts (0.005, 0.015, and 0.03 g/kg) demonstrated anti-inflammatory effects against chronic inflammation. The aqueous and ethanolic extracts of the aerial parts of M communis L. showed antinociceptive effects and these may be mediated by opioid receptors.

  1. The role of germline promoters and I exons in cytokine-induced gene-specific class switch recombination.

    Science.gov (United States)

    Dunnick, Wesley A; Shi, Jian; Holden, Victoria; Fontaine, Clinton; Collins, John T

    2011-01-01

    Germline transcription precedes class switch recombination (CSR). The promoter regions and I exons of these germline transcripts include binding sites for activation- and cytokine-induced transcription factors, and the promoter regions/I exons are essential for CSR. Therefore, it is a strong hypothesis that the promoter/I exons regions are responsible for much of cytokine-regulated, gene-specific CSR. We tested this hypothesis by swapping the germline promoter and I exons for the murine γ1 and γ2a H chain genes in a transgene of the entire H chain C-region locus. We found that the promoter/I exon for γ1 germline transcripts can direct robust IL-4-induced recombination to the γ2a gene. In contrast, the promoter/I exon for the γ2a germline transcripts works poorly in the context of the γ1 H chain gene, resulting in expression of γ1 H chains that is type level. Nevertheless, the small amount of recombination to the chimeric γ1 gene is induced by IFN-γ. These results suggest that cytokine regulation of CSR, but not the magnitude of CSR, is regulated by the promoter/I exons.

  2. Cytokine-induced killer cells interact with tumor lysate-pulsed dendritic cells via CCR5 signaling.

    Science.gov (United States)

    Lee, Hong Kyung; Kim, Yong Guk; Kim, Ji Sung; Park, Eun Jae; Kim, Boyeong; Park, Ki Hwan; Kang, Jong Soon; Hong, Jin Tae; Kim, Youngsoo; Han, Sang-Bae

    2016-08-10

    The antitumor activity of cytokine-induced killer (CIK) cells can be increased by co-culturing them with tumor lysate-pulsed dendritic cells (tDCs); this phenomenon has been studied mainly at the population level. Using time-lapse imaging, we examined how CIK cells gather information from tDCs at the single-cell level. tDCs highly expressed CCL5, which bound CCR5 expressed on CIK cells. tDCs strongly induced migration of Ccr5(+/+) CIK cells, but not that of Ccr5(-/-) CIK cells or Ccr5(+/+) CIK cells treated with the CCR5 antagonist Maraviroc. Individual tDCs contacted Ccr5(+/+) CIK cells more frequently and lengthily than with Ccr5(-/-) CIK cells. Consequently, tDCs increased the antitumor activity of Ccr5(+/+) CIK cells in vitro and in vivo, but did not increase that of Ccr5(-/-) CIK cells. Taken together, our data provide insight into the mechanism of CIK cell activation by tDCs at the single-cell level.

  3. Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells

    Directory of Open Access Journals (Sweden)

    Claudia Schlimper

    2012-01-01

    Full Text Available Adoptive therapy of malignant diseases with cytokine-induced killer (CIK cells showed promise in a number of trials; the activation of CIK cells from cancer patients towards their autologous cancer cells still needs to be improved. Here, we generated CIK cells ex vivo from blood lymphocytes of colorectal cancer patients and engineered those cells with a chimeric antigen receptor (CAR with an antibody-defined specificity for carcinoembryonic antigen (CEA. CIK cells thereby gained a new specificity as defined by the CAR and showed increase in activation towards CEA+ colon carcinoma cells, but less in presence of CEA− cells, indicated by increased secretion of proinflammatory cytokines. Redirected CIK activation was superior by CAR-mediated CD28-CD3ζ than CD3ζ signaling only. CAR-engineered CIK cells from colon carcinoma patients showed improved activation against their autologous, primary carcinoma cells from biopsies resulting in more efficient tumour cell lysis. We assume that adoptive therapy with CAR-modified CIK cells shows improved selectivity in targeting autologous tumour lesions.

  4. Increased Efficacy of Brentuximab Vedotin (SGN-35) in Combination with Cytokine-Induced Killer Cells in Lymphoma

    Science.gov (United States)

    Esser, Laura; Weiher, Hans; Schmidt-Wolf, Ingo

    2016-01-01

    Brentuximab vedotin (SGN-35) is an antibody–drug conjugate with a high selectivity against CD30+ cell lines and more than 300-fold less activity against antigen-negative cells. In the last years, the results of many in vitro and in vivo studies have led to the fast approval of this drug to treat lymphoma patients. Another innovative method to treat tumor cells including lymphoma cells is the use cytokine-induced killer (CIK) cells, which have also been approved and proven to be a safe treatment with only minor adverse events. In this study, a possible additive effect when combining SGN-35 with CIK cells was investigated. The combinational treatment showed that it reduces the viability of CD30+ cell lines significantly in vitro. Additionally, the amount of lymphoma cells was significantly reduced when exposed to CIK cells as well as when exposed to SGN-35. A significant negative effect of SGN-35 on the function of CIK cells could be excluded. These results lead to the assumption that SGN-35 and CIK cells in combination might achieve better results in an in vitro setting compared to the single use of SGN-35 and CIK cells. Further investigations in in vivo models must be conducted to obtain a better understanding of the exact mechanisms of both treatments when applied in combination. PMID:27376285

  5. Increased effect of IMiDs by addition of cytokine-induced killer cells in multiple myeloma.

    Science.gov (United States)

    Bullok, Katharina F; Sippel, Christoph; Schmidt-Wolf, Ingo G H

    2016-12-01

    Immunomodulatory drugs (IMiDs), such as thalidomide, lenalidomide and pomalidomide, represent the basic principle of multiple myeloma treatment. However, the development of resistance is a limiting factor. Over the last years, the efficient application of cytokine-induced killer (CIK) cells has been reported as an alternative strategy to treat hematological neoplasms. In this study, we tested for a potential synergistic effect by combining the IMiDs thalidomide, lenalidomide and pomalidomide with CIK cells in different myeloma cell lines in vitro. Myeloma cells tested with CIK cells were significantly reduced. In the combination, myeloma cells were significantly reduced compared with cells only tested with IMiDs but not to the cells tested with CIK cells. Otherwise, the number of CIK cells was significantly reduced when treated with IMiDs. Because IMiDs are active in patients with myeloma, these results lead to the expectation that combination of IMiDs and CIK cells achieve better results in the treatment of multiple myeloma compared with the single use of IMiDs. Therefore, further examinations in an in vivo setting are necessary to have a closer look on the cellular interactions. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  6. p53 and nitric oxide are involved in cytokine-induced apoptosis in Kasumi-1 and Molt-4 Leukemics cells.

    Science.gov (United States)

    Maharath, Aishath; Fucharoen, Suthat; Tanyong, Dalina I

    2014-06-01

    Immunotherapy has been developed to treat cancers. There are many signaling pathways involved in cytokine induced apoptosis of many cancers but their role remains unclear in some cancers such as leukemia. To investigate the involvement of the nitric oxide (NO) and p53 tumor suppressor gene in apoptotic pathways induced by cytokines in leukemic cell lines. Leukemic cell lines, Kasumi-1 (AML-M2) and Molt- 4 (ALL) were treated with cytokines, interleukin-1β (IL-1β), tumor necrosis factor-α (TNFα), interferon-γ (IFN-γ). The effect of cytokines on the induction cell apoptosis was analysed by flow cytometry. In addition, nitric oxide production and p53 protein levels were measured by using the Griess method and Western blot, respectively. Upon cytokine treatment, there was a significant increase in the percentage of cell apoptosis in both leukemic cell lines. The highest apoptosis was shown in 40 U/ml IFN-γ treated cells. In addition, nitric oxide and p53 protein increased in IFN-γ treated cells. There was a reduction of apoptosis and p53 level after adding the inducible nitric oxide synthase inhibitor, SMT. p53 and nitric oxide are involved in the mediation of apoptosis induced by cytokines in Kasumi-1 and Molt-4 leukemic cell lines.

  7. Effect of aspirin plus clopidogrel on inflammatory markers in patients with non-ST-segment elevation acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background Aspirin can inhibit inflammatory reactions and platelet aggregation, but little is known about the effects of the combination of aspirin plus clopidogrel, a new antiplatelet agent, on inflammation. The purpose of this study was to determine whether aspirin plus clopidogrel can further suppress inflammation in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). Methods One hundred and fifteen patients with NSTEACS were randomized into two groups: group A (aspirin alone, n=58) and group B (aspirin plus clopidogrel, n=57). Patients in group A received a loading dose of 300 mg aspirin, then 100 mg per day. The patients in group B received a loading dose of 300 mg aspirin and 300 mg clopidogrel, then 100 mg aspirin and 75 mg clopidogrel per day. Serum high sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α(TNF-α) were measured in all patients at baseline prior to any drug treatment after admission, and at 7 and 30 days after beginning drug treatment. Thirty healthy volunteers on no medications were enrolled as controls (group C).Results Baseline levels of hs-CRP and TNF-αin group A and group B were significantly higher than those in group C. Seven days after administration, the levels of hs-CRP in both group A and group B decreased significantly [Group A: (6.15 ± 1.39) mg/L vs (9.18 ± 1.62) mg/L, P <0.01; Group B:(4.99 ± 1.62) mg/L vs (10.29 ± 1.47) mg/L, P<0.01]. Similarly, levels of TNF-αin both groups decreased at 7 days compared to baseline [Group A: (90.99 ± 28.91) pg/ml vs (117.20 ± 37.13) pg/ml, P <0.01; Group B: (74.32± 21.83) pg/ml vs (115.27 ± 32.11) pg/ml, P <0.01]. Thirty days after administration, the levels of hs-CRP in both group A and group B decreased further to (3.49 ± 1.53) mg/L, and (2.40 ± 1.17) mg/L respectively (P <0.01 for both comparisons). Levels of TNF-αin groups A and B also decreased significantly between 7 and 30 days, to 63.28 ± 29.01 pg/ml (group A) and (43.95 ± 17.10) pg

  8. Effect of rosuvastatin on serum cTNI, Cys-C, Hcy and myocardial enzyme, Inflammatory cytokines in acute myocardial infarction with PCI surgery

    Institute of Scientific and Technical Information of China (English)

    Na Shen; Zeng-Xin Yang

    2016-01-01

    Objective:To observe the effect of rosuvastatin on serum cTNI, Cys-C, Hcy and myocardial enzyme, inflammatory factors in acute myocardial infarction with percutaneous coronary intervention (PCI) surgery.Methods:A total of 80 patients with acute myocardial infarction were randomly divided into control group (40 cases) and experiment group (40 cases), the control group were given atorvastatin on the basis of basic therapy, and the experiment group were given rosuvastatin on the basis of basic therapy. The change of serum cTNI, Cys-C, Hcy, LDH, CK, CK-MB, IL-1β, IL-6, IL-17 in 24 hours and 8 weeks after PCI surgery of two groups were compared.Results:The serum cTNI, Cys-C, Hcy, LDH, CK, CK-MB, IL-1β, IL-6, IL-17 in 8 weeks after PCI surgery of two groups were significantly lower than that of 24 hours after PCI surgery (P<0.05). The serum cTNI, Cys-C, Hcy, LDH, CK, CK-MB, IL-1β, IL-6, IL-17 in 8 weeks after PCI surgery of experiment group were significantly lower than that of 8 weeks in control group (P<0.05).Conclusions: Rosuvastatin can significantly decrease the myocardial enzyme, inflammatory cytokines in acute myocardial infarction with PCI surgery. It plays an important role in protecting the heart function, reversing myocardial damage, and inhibiting cardiac remodeling.

  9. Assessment of inflammatory mediator, intestinal flora and Fas/FasL expression in patients with acute pancreatitis after lactulose combined with somatostatin therapy

    Institute of Scientific and Technical Information of China (English)

    Bing-Li Zheng; Jie Peng; Aihemaitibaikere

    2016-01-01

    Objective:To study the effect of lactulose combined with somatostatin therapy on inflammatory mediator, intestinal flora and Fas/FasL expression in patients with acute pancreatitis.Methods:A total of 56 patients with acute pancreatitis treated in our hospital between May 2013 and October 2015 were randomly divided into group A and group B, group A received lactulose, somatostatin combined with conventional therapy and group B received somatostatin combined with conventional therapy. Three days after treatment, the levels of inflammatory mediators, sFas and sFasL in serum, the expression of Fas and FasL in peripheral blood as well as the copy number of intestinal flora in feces tissue were determined. Results:Three days after treatment, IL-1β, IL-6, IL-8, IL-10, IL-18, sFas and sFasL content in serum of group A were significantly lower than those of group B,FasandFasL mRNA content and protein content in peripheral blood were significantly lower than those of group B, lactobacillus, bifidobacterium and bacteroides content in feces tissue were significantly higher than those of group B, and Escherichia coli, enterococcus and proteus content in feces tissue were significantly lower than those of group B.Conclusions:Lactulose combined with somatostatin treatment of acute pancreatitis can improve the intestinal mucosal barrier function, correct intestinal flora disturbance, relieve inflammation and inhibit the immunosuppression mediated by Fas/FasL.

  10. Anti-Inflammatory Effects of Licorice and Roasted Licorice Extracts on TPA-Induced Acute Inflammation and Collagen-Induced Arthritis in Mice

    Directory of Open Access Journals (Sweden)

    Ki Rim Kim

    2010-01-01

    Full Text Available The anti-inflammatory activity of licorice (LE and roated licorice (rLE extracts determined in the murine phorbol ester-induced acute inflammation model and collagen-induced arthritis (CIA model of human rheumatoid arthritis. rLE possessed greater activity than LE in inhibiting phorbol ester-induced ear edema. Oral administration of LE or rLE reduced clinical arthritis score, paw swelling, and histopathological changes in a murine CIA. LE and rLE decreased the levels of proinflammatory cytokines in serum and matrix metalloproteinase-3 expression in the joints. Cell proliferation and cytokine secretion in response to type II collagen or lipopolysaccharide stimulation were suppressed in spleen cells from LE or rLE-treated CIA mice. Furthermore, LE and rLE treatment prevented oxidative damages in liver and kidney tissues of CIA mice. Taken together, LE and rLE have benefits in protecting against both acute inflammation and chronic inflammatory conditions including rheumatoid arthritis. rLE may inhibit the acute inflammation more potently than LE.

  11. Acute-phase serum amyloid A: an inflammatory adipokine and potential link between obesity and its metabolic complications.

    Directory of Open Access Journals (Sweden)

    Rong-Ze Yang

    2006-06-01

    Full Text Available BACKGROUND: Obesity is associated with low-grade chronic inflammation, and serum markers of inflammation are independent risk factors for cardiovascular disease (CVD. However, the molecular and cellular mechanisms that link obesity to chronic inflammation and CVD are poorly understood. METHODS AND FINDINGS: Acute-phase serum amyloid A (A-SAA mRNA levels, and A-SAA adipose secretion and serum levels were measured in obese and nonobese individuals, obese participants who underwent weight-loss, and persons treated with the insulin sensitizer rosiglitazone. Inflammation-eliciting activity of A-SAA was investigated in human adipose stromal vascular cells, coronary vascular endothelial cells and a murine monocyte cell line. We demonstrate that A-SAA was highly and selectively expressed in human adipocytes. Moreover, A-SAA mRNA levels and A-SAA secretion from adipose tissue were significantly correlated with body mass index (r = 0.47; p = 0.028 and r = 0.80; p = 0.0002, respectively. Serum A-SAA levels decreased significantly after weight loss in obese participants (p = 0.006, as well as in those treated with rosiglitazone (p = 0.033. The magnitude of the improvement in insulin sensitivity after weight loss was significantly correlated with decreases in serum A-SAA (r = -0.74; p = 0.034. SAA treatment of vascular endothelial cells and monocytes markedly increased the production of inflammatory cytokines, e.g., interleukin (IL-6, IL-8, tumor necrosis factor alpha, and monocyte chemoattractant protein-1. In addition, SAA increased basal lipolysis in adipose tissue culture by 47%. CONCLUSIONS: A-SAA is a proinflammatory and lipolytic adipokine in humans. The increased expression of A-SAA by adipocytes in obesity suggests that it may play a critical role in local and systemic inflammation and free fatty acid production and could be a direct link between obesity and its comorbidities, such as insulin resistance and atherosclerosis. Accordingly, improvements

  12. A multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and HLA genotype.

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    Didier Payen

    Full Text Available BACKGROUND: To investigate the association between severity of acute kidney injury (AKI and outcome, systemic inflammatory phenotype and HLA genotype in severe sepsis. METHODOLOGY/PRINCIPAL FINDINGS: Prospective multicenter observational study done in 4 intensive care units in two university hospitals. Severe sepsis and septic shock patients with at least 2 organ failures based on the SOFA score were classified: 1 "no AKI", 2 "mild AKI" (grouping stage 1 and 2 of AKIN score and 3 "severe AKI" (stage 3 of AKIN score. Sequential measurements: The vasopressor dependency index (VDI; dose and types of drugs to evaluate the association between hemodynamic status and the development of early AKI; plasma levels of IL-10, macrophage migration inhibitory factor (MIF, IL-6 and HLA-DR monocyte expression. Genotyping of the 13 HLA-DRB1 alleles with deduction of presence of HLA-DRB3, -DRB4 and -DRB5 genes. We used multivariate analysis with competitive risk model to study associations. Overall, 176 study patients (146 with septic shock were classified from AKIN score as "no AKI" (n = 43, "mild AKI" (n = 74 or "severe AKI" (n = 59. The VDI did not differ between groups of AKI. After adjustment, "mild and severe AKI" were an independent risk factor for mortality (HR 2.42 95%CI[1.01-5.83], p = 0.048 and HR 1.99 95%CI[1.30-3.03], p = 0.001 respectively. "Severe AKI" had higher levels of plasma IL-10, MIF and IL-6 compared to "no AKI" and mild AKI (p<0.05 for each, with no difference in mHLA-DR at day 0. HLA-DRB genotyping showed a significantly lower proportion of 4 HLA-DRB alleles among patients requiring renal replacement therapy (RRT (58% than in patients with severe AKI who did not receive RRT (84% (p = 0.004. CONCLUSIONS: AKI severity is independently associated with mortality and plasma IL-10, MIF or IL-6 levels. Presence of 4 alleles of HLA-DRB in severe AKI patients seems associated with a lower need of RRT.

  13. The acute effects of strength training on inflammatory markers predicting atherosclerosis: a study on inactive middle-aged men

    Directory of Open Access Journals (Sweden)

    Bizheh N

    2011-06-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Cardiovascular diseases, especially atherosclerosis, are the main causes of morbidity and mortality worldwide. The disease has had an increasing prevalence in Iran in recent years. Homocysteine and C-reactive protein (CRP are two novel cardiovascular risk factors that independently predict risks of atherosclerosis. The purpose of this study was to investigate the effects of one session of circuit resistance training on the blood levels of the aforesaid inflammatory markers in inactive middle-aged men."n"nMethods: The participants of this study included twenty-three healthy but inactive middle-aged men who were overweight and were randomly divided into two experimental (n=14 and control (n=9 groups. The activity included doing exercises with the subjects' 35% one-repetition maximum (1-RM intensity at ten different stations. Blood levels of homocysteine and hs-CRP were measured before and after the exercise."n"nResults: Analysis of data using independent samples t-test showed a significant increment in the serum levels of homocysteine and hs-CRP after training in the experimental (P<0.05 versus the control group."n"nConclusion: Elevation of homocysteine levels is due to the increase in protein metabolism

  14. Acute-phase serum amyloid A: an inflammatory adipokine and potential link between obesity and its metabolic complications.

    Directory of Open Access Journals (Sweden)

    Rong-Ze Yang

    2006-06-01

    Full Text Available Obesity is associated with low-grade chronic inflammation, and serum markers of inflammation are independent risk factors for cardiovascular disease (CVD. However, the molecular and cellular mechanisms that link obesity to chronic inflammation and CVD are poorly understood.Acute-phase serum amyloid A (A-SAA mRNA levels, and A-SAA adipose secretion and serum levels were measured in obese and nonobese individuals, obese participants who underwent weight-loss, and persons treated with the insulin sensitizer rosiglitazone. Inflammation-eliciting activity of A-SAA was investigated in human adipose stromal vascular cells, coronary vascular endothelial cells and a murine monocyte cell line. We demonstrate that A-SAA was highly and selectively expressed in human adipocytes. Moreover, A-SAA mRNA levels and A-SAA secretion from adipose tissue were significantly correlated with body mass index (r = 0.47; p = 0.028 and r = 0.80; p = 0.0002, respectively. Serum A-SAA levels decreased significantly after weight loss in obese participants (p = 0.006, as well as in those treated with rosiglitazone (p = 0.033. The magnitude of the improvement in insulin sensitivity after weight loss was significantly correlated with decreases in serum A-SAA (r = -0.74; p = 0.034. SAA treatment of vascular endothelial cells and monocytes markedly increased the production of inflammatory cytokines, e.g., interleukin (IL-6, IL-8, tumor necrosis factor alpha, and monocyte chemoattractant protein-1. In addition, SAA increased basal lipolysis in adipose tissue culture by 47%.A-SAA is a proinflammatory and lipolytic adipokine in humans. The increased expression of A-SAA by adipocytes in obesity suggests that it may play a critical role in local and systemic inflammation and free fatty acid production and could be a direct link between obesity and its comorbidities, such as insulin resistance and atherosclerosis. Accordingly, improvements in systemic inflammation and insulin resistance

  15. Association of inflammatory cytokines/biomarkers with acute coronary syndrome and its correlation with severity and hospital outcome

    Directory of Open Access Journals (Sweden)

    Mohd Mahmudullah Razi

    2017-01-01

    Conclusions: The circulating levels of inflammatory markers such as IL-6 and TNF-α are significantly elevated in patients with ACS, supporting the view that inflammatory cytokines are associated with ACS. There is a direct correlation of the levels of IL-6 and TNF-α with the severity of ACS and in-hospital mortality in these cases.

  16. A novel anti-inflammatory and pro-resolving role for resolvin D1 in acute cigarette smoke-induced lung inflammation.

    Directory of Open Access Journals (Sweden)

    Hsi-Min Hsiao

    Full Text Available Cigarette smoke is a profound pro-inflammatory stimulus that contributes to acute lung injuries and to chronic lung disease including COPD (emphysema and chronic bronchitis. Until recently, it was assumed that resolution of inflammation was a passive process that occurred once the inflammatory stimulus was removed. It is now recognized that resolution of inflammation is a bioactive process, mediated by specialized lipid mediators, and that normal homeostasis is maintained by a balance between pro-inflammatory and pro-resolving pathways. These novel small lipid mediators, including the resolvins, protectins and maresins, are bioactive products mainly derived from dietary omega-3 and omega-6 polyunsaturated fatty acids (PUFA. We hypothesize that resolvin D1 (RvD1 has potent anti-inflammatory and pro-resolving effects in a model of cigarette smoke-induced lung inflammation.Primary human lung fibroblasts, small airway epithelial cells and blood monocytes were treated with IL-1β or cigarette smoke extract in combination with RvD1 in vitro, production of pro-inflammatory mediators was measured. Mice were exposed to dilute mainstream cigarette smoke and treated with RvD1 either concurrently with smoke or after smoking cessation. The effects on lung inflammation and lung macrophage populations were assessed.RvD1 suppressed production of pro-inflammatory mediators by primary human cells in a dose-dependent manner. Treatment of mice with RvD1 concurrently with cigarette smoke exposure significantly reduced neutrophilic lung inflammation and production of pro-inflammatory cytokines, while upregulating the anti-inflammatory cytokine IL-10. RvD1 promoted differentiation of alternatively activated (M2 macrophages and neutrophil efferocytosis. RvD1 also accelerated the resolution of lung inflammation when given after the final smoke exposure.RvD1 has potent anti-inflammatory and pro-resolving effects in cells and mice exposed to cigarette smoke. Resolvins

  17. Anti-inflammatory activity of four solvent fractions of ethanol extract of Mentha spicata L. investigated on acute and chronic inflammation induced rats.

    Science.gov (United States)

    Arumugam, P; Priya, N Gayatri; Subathra, M; Ramesh, A

    2008-07-01

    Anti-inflammatory effects of four solvent fractions of ethanol extract of Mentha spicata were evaluated in acute and chronic inflammation induced in Wistar albino rats. Lipid peroxidation (LPO) and some antioxidants produced during chronic inflammation were quantitated. Hexane (320mg/kg of body weight in 25% DMSO), chloroform (320mg/kg body weight in 25% DMSO), ethyl acetate (160mg/kg body weight in 25% DMSO), aqueous (320mg/kg of body weight in ddH(2)O) fractions, two negative control groups (25% DMSO and ddH(2)O) and two anti-inflammatory drugs (Diclofenac: 25mg/kg of body weight; Indomethacin: 10mg/kg of body weight both in ddH(2)O) were administered by oral intubations to the eight groups of rats consisting six animals, each. In acute study, 1% carrageenan was injected subcutaneously in the sub-plantar region of the right hind paw after 1h of administration of test doses. The increased paw edema was measured at 0.5, 1, 2, 4, 8, 16 and 24h intervals. In the chronic study, the oral administration was carried out for seven consecutive days. On eighth day, four sterile cotton pellets (50mg each) were implanted subcutaneously in the dorsal region of the rats. On the sixteenth day, the rats were sacrificed and the cotton pellets with granulomatous tissue were dissected out and weighed (fresh and dry). Both in chronic and acute inflammation, ethyl acetate (EAF) and aqueous fraction (AF) were effective. EAF is comparable with the positive standards in chronic inflammation. The results indicate that EAF's anti-inflammatory activity is largely due to its ability to modulate in vivo antioxidants.

  18. Curcumin modulates the inflammatory response and inhibits subsequent fibrosis in a mouse model of viral-induced acute respiratory distress syndrome.

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    Sreedevi Avasarala

    Full Text Available Acute Respiratory Distress Syndrome (ARDS is a clinical syndrome characterized by diffuse alveolar damage usually secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or non-infectious insult often leading to the development of intra-alveolar and interstitial fibrosis. Curcumin, the principal curcumoid of the popular Indian spice turmeric, has been demonstrated as an anti-oxidant and anti-inflammatory agent in a broad spectrum of diseases. Using our well-established model of reovirus 1/L-induced acute viral pneumonia, which displays many of the characteristics of the human ALI/ARDS, we evaluated the anti-inflammatory and anti-fibrotic effects of curcumin. Female CBA/J mice were treated with curcumin (50 mg/kg 5 days prior to intranasal inoculation with 10(7pfu reovirus 1/L and daily, thereafter. Mice were evaluated for key features associated with ALI/ARDS. Administration of curcumin significantly modulated inflammation and fibrosis, as revealed by histological and biochemical analysis. The expression of IL-6, IL-10, IFNγ, and MCP-1, key chemokines/cytokines implicated in the development of ALI/ARDS, from both the inflammatory infiltrate and whole lung tissue were modulated by curcumin potentially through a reduction in the phosphorylated form of NFκB p65. While the expression of TGFß1 was not modulated by curcumin, TGFß Receptor II, which is required for TGFß signaling, was significantly reduced. In addition, curcumin also significantly inhibited the expression of α-smooth muscle actin and Tenascin-C, key markers of myofibroblast activation. This data strongly supports a role for curcumin in modulating the pathogenesis of viral-induced ALI/ARDS in a pre-clinical model potentially manifested through the alteration of inflammation and myofibroblast differentiation.

  19. Effectiveness of anti-inflammatory treatment versus antibiotic therapy and placebo for patients with non-complicated acute bronchitis with purulent sputum. The BAAP Study protocol

    Directory of Open Access Journals (Sweden)

    Fernández Yvonne

    2011-06-01

    Full Text Available Abstract Background Acute bronchitis is one of the most prevalent respiratory infections in primary care, and in more than 90% of the cases antibiotics are prescribed, mainly when purulent expectoration is present. However, this process is usually viral in origin and the benefits of antibiotic treatment are marginal. On the other hand, in recent years bronchitis has been considered more as an inflammatory than an infectious process. Thus, the aim of this study is to evaluate the clinical effectiveness of a schedule of an oral anti-inflammatory compared with an antibiotic regimen and another group assigned to receive a placebo. Methods and design A total of 420 patients from 15 to 70 years of age with no associated comorbidity, presenting respiratory tract infection of at least one week of evolution, with cough as the predominant symptom, the presence of purulent expectoration and at least one other symptom of the respiratory tract (dyspnoea, wheezing, chest discomfort or pain, with no alternative explanation such as pneumonia, will be included in a prospective, randomised and controlled, clinical trial with placebo. The patients will be randomised to receive one of three treatments: ibuprofen, amoxycillin and clavulanic acid or placebo for 10 days. The main outcome measure is the number of days with frequent cough defined by the symptom diary with a score of 1 or more. Discussion This trial is designed to evaluate the number of days with frequent cough with anti-inflammatory treatment compared with antimicrobial treatment and placebo in previously healthy patients with a clinical picture of acute bronchitis and purulent expectoration. It is hypothesized that anti-inflammatory treatment is more effective than antibiotic treatment to reduce cough, which is the most disturbing symptom for patients with this infection. Trial registration ISRCTN07852892

  20. ANTI-INFLAMMATORY EFFECT OF ANTI-TNF-ALPHA siRNA CATIONIC PHOSPHOROUS DENDRIMERS NANOCOMPLEXES ADMINISTERED INTRANASALLY IN A MURINE ACUTE LUNG INJURY MODEL

    DEFF Research Database (Denmark)

    Bohr, Adam; Tsapis, Nicolas; Andreana, Ilaria

    2017-01-01

    was attributed to their higher pKa value leading to a stronger siRNA complexation and improved protection against enzymatic degradation resulting in a higher cellular uptake. The superior silencing effect of the pyrrolidinium dendriplexes, compared to non-complexed siRNA, was confirmed in vivo in an LPS......-induced murine model of short term acute lung injury upon lung delivery via nasal administration. These data suggest that phosphorous dendriplexes have a strong potential in lung delivery of siRNA for treating inflammatory lung diseases....

  1. Comparison of active constituents, acute toxicity, anti-nociceptive and anti-inflammatory activities of Porana sinensis Hemsl., Erycibe obtusifolia Benth. and Erycibe schmidtii Craib.

    Science.gov (United States)

    Chen, Zhiyong; Liao, Liping; Zhang, Zijia; Wu, Lihong; Wang, Zhengtao

    2013-11-25

    Erycibe obtusifolia and Erycibe schmidtii, which belong to the same genus as Erycibe, are widely used in traditional medicine for the treatment of joint pain and rheumatoid arthritis (RA). Porana sinensis has become a widely used substitute for Erycibe obtusifolia and Erycibe schmidtii as they have declined in the wild. In the present work, the content of the main active components, the acute toxicity, the anti-nociceptive and anti-inflammatory activities of Porana sinensis, Erycibe obtusifolia and Erycibe schmidtii were compared, and the mechanisms of anti-nociceptive and anti-inflammatory activities were discussed. A quantitative HPLC (high performance liquid chromatography) method was first developed to compare the content of the main active components (scopoletin, scopolin and chlorogenic acid). The anti-inflammatory and anti-nociceptive activities of 40% ethanolic extracts of the three plants were compared using the models of xylene-induced ear edema, formalin-induced inflammation, carrageenan-induced air pouch inflammation, acetic acid-induced writhing and formalin-induced nociception. The acute toxicity of the 40% ethanolic extracts of the three plants was studied. The assay suggested a large content of scopoletin, scopolin and chlorogenic acid in the three plants. The 40% ethanolic extracts of the three plants were almost non-toxic at the dose of 5g/kg and all of them showed significant anti-inflammatory effects in the tests of xylene-induced ear edema and formalin-induced inflammation. In the carrageenan-induced air pouch inflammation test, the synthesis of PGE2 was significantly inhibited by all the extracts. They significantly inhibited the number of contortions induced by acetic acid and the second phase of the formalin-induced licking response. Naloxone was not able to reverse the analgesic effect of these extracts. The study identifies the similarity of the three plants in their main active components as well as acute toxicity, anti-nociceptive and

  2. PEGylated interferon-beta modulates the acute inflammatory response and recovery when combined with forced exercise following cervical spinal contusion injury.

    Science.gov (United States)

    Sandrow-Feinberg, Harra R; Zhukareva, Victoria; Santi, Lauren; Miller, Kassi; Shumsky, Jed S; Baker, Darren P; Houle, John D

    2010-06-01

    Secondary degeneration leads to an expansion of the initial tissue damage sustained during a spinal cord injury (SCI). Dampening the cellular inflammatory response that contributes to this progressive tissue damage is one possible strategy for neuroprotection after acute SCI. We initially examined whether treatment with a PEGylated form of rat interferon-beta (IFN-beta) would modulate the expression of several markers of inflammation and neuroprotection at the site of a unilateral cervical level 5 contusion injury. Adult female Sprague-Dawley rats were injured using the Infinite Horizon Impactor at a force of 200 kdyn (equivalent to a severe injury) and a mean displacement of 1600-1800 mum. A single dose (5x10(6) units) of PEGylated IFN-beta or vehicle was administered 30 min following SCI. Here we demonstrate temporal changes in pro- and anti-inflammatory cytokine levels and the expression of heat shock proteins and iNOS (involved in neuroprotection) at the lesion epicenter and one segment caudally after SCI and PEG IFN-beta treatment. The results suggested a potential therapeutic treatment strategy for modulation of secondary damage after acute SCI. Therefore, we examined whether acute treatment with PEG IFN-beta would improve forelimb function alone or when combined with forced exercise (Ex). Animals began the Ex paradigm 5 days post SCI and continued for 5 days/week over 8 weeks. Locomotion (forelimb locomotor scale [FLS], hindlimb BBB, and TreadScan) and sensorimotor function (grid walking) was tested weekly. Additional outcome measures included lesion size and glial cell reactivity. Significant FLS improvements occurred at 1 week post SCI in the PEGylated IFN-beta-treated group but not at any other time point or with any other treatment approaches. These results suggest that this acute neuroprotective treatment strategy does not translate into long term behavioral recovery even when combined with forced exercise.

  3. Low-methoxyl lemon pectin attenuates inflammatory responses and improves intestinal barrier integrity in caerulein-induced experimental acute pancreatitis

    NARCIS (Netherlands)

    Sun, Yajun; He, Yue; Wang, Fei; Zhang, Hao; de Vos, Paul; Sun, Jia

    Scope: Acute pancreatitis (AP) is a common clinical acute abdominal disease. The intestinal injury associated with AP will aggravate the condition retroactively. This study investigates whether the low-methoxyl pectin (LMP) isolated from lemon could attenuate AP and associated intestinal injury.

  4. Suppressor of cytokine signaling 1 protects rat pancreatic islets from cytokine-induced apoptosis through Janus kinase/signal transducers and activators of transcription pathway

    Institute of Scientific and Technical Information of China (English)

    SUN Qi; XIANG Ruo-lan; YANG Yan-li; FENG Kai; ZHANG Kui; DING Wen-yi

    2013-01-01

    Background Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling pathway involved in negative feedback loops.Although SOCS1 is an important intracellular suppressor of apoptosis in a variety of cell types,its role in cytokine-induced pancreatic β-cell apoptosis remains unclear.The present study investigated potential effects of SOCS1 on the cytokine-induced pancreatic β-cell apoptosis.Methods After successfully transfected with SOCS1/pEGFP-C1 or pEGFP-C1 plasmids to overexpress SOCS1,RINm5F (rat insulinoma cell line) cells were exposed to cytokines,interferon (IFN)-γ alone,IFN-γ+interleukin (IL)-1β,IFN-y+IL-1β+tumor necrosis factor (TNF)-α respectively.Pancreatic β-cell apoptosis was assessed by using MTT,FACS,and caspase-3 activity assays.Protein phosphorylation of Janus kinase 2 (JAK2) and signal transducers and activators of transcription 1 (STAT1) were verified by Western blotting and mRNA expression of inducible nitric oxide synthase (iNOS),NF-κB and Fas were analyzed by RT-PCR.Results Overexpression of SOCS1 in RINm5F cells was shown to attenuate IFN-γ alone,IFN-γ+IL-1β and IFN-γ+TNF-α+IL-1β mediated apoptosis.Phosphorylation of JAK2 and STAT1 significantly decreased in RINm5F cells which overexpressed SOCS1 protein.Overexpression of SOCS1 significantly suppressed cytokine-induced iNOS mRNA levels.Conclusion Overexpression of SOCS1 protects pancreatic islets from cytokine-induced cell apoptosis via the JAK2/STAT1 pathway.

  5. Autologous cytokine-induced killer cells therapy on the quality of life of patients with breast cancer after adjuvant chemotherapy: A prospective study

    Institute of Scientific and Technical Information of China (English)

    梁雪峰

    2013-01-01

    Objective To explore the effect of autologous cytokine-induced killer cells on the quality of life in patient with breast cancer who have already finished the adjuvant chemotherapy.Methods One hundred and twenty-eight postoperative patients with breast cancer who underwent anthracycline-based adjuvant chemotherapy were enrolled in this prospective study,and they were randomized into2 groups,i.e.,treatment group,which received the therapy of CIK cells transfusion,and control group,

  6. Effective activity of cytokine-induced killer cells against autologous metastatic melanoma including cells with stemness features.

    Science.gov (United States)

    Gammaitoni, Loretta; Giraudo, Lidia; Leuci, Valeria; Todorovic, Maja; Mesiano, Giulia; Picciotto, Franco; Pisacane, Alberto; Zaccagna, Alessandro; Volpe, Maria Giuseppa; Gallo, Susanna; Caravelli, Daniela; Giacone, Elena; Venesio, Tiziana; Balsamo, Antonella; Pignochino, Ymera; Grignani, Giovanni; Carnevale-Schianca, Fabrizio; Aglietta, Massimo; Sangiolo, Dario

    2013-08-15

    We investigate the unknown tumor-killing activity of cytokine-induced killer (CIK) cells against autologous metastatic melanoma and the elusive subset of putative cancer stem cells (mCSC). We developed a preclinical autologous model using same patient-generated CIK cells and tumor targets to consider the unique biology of each patient/tumor pairing. In primary tumor cell cultures, we visualized and immunophenotypically defined a putative mCSC subset using a novel gene transfer strategy that exploited their exclusive ability to activate the promoter of stemness gene Oct4. The CIK cells from 10 patients with metastatic melanoma were successfully expanded (median, 23-fold; range, 11-117). Primary tumor cell cultures established and characterized from the same patients were used as autologous targets. Patient-derived CIK cells efficiently killed autologous metastatic melanoma [up to 71% specific killing (n = 26)]. CIK cells were active in vivo against autologous melanoma, resulting in delayed tumor growth, increased necrotic areas, and lymphocyte infiltration at tumor sites. The metastatic melanoma cultures presented an average of 11.5% ± 2.5% putative mCSCs, which was assessed by Oct4 promoter activity and stemness marker expression (Oct4, ABCG2, ALDH, MITF). Expression was confirmed on mCSC target molecules recognized by CIK cells (MIC A/B; ULBPs). CIK tumor killing activity against mCSCs was intense (up to 71%, n = 4) and comparable with results reported against differentiated metastatic melanoma cells (P = 0.8). For the first time, the intense killing activity of CIK cells against autologous metastatic melanoma, including mCSCs, has been shown. These findings move clinical investigation of a new immunotherapy for metastatic melanoma, including mCSCs, closer. ©2013 AACR.

  7. Phase II/III Study of Radiofrequency Ablation Combined with Cytokine-Induced Killer Cells Treating Colorectal Liver Metastases

    Directory of Open Access Journals (Sweden)

    Xiaodong Li

    2016-11-01

    Full Text Available Purpose: This phase II/III, non-randomized clinical trial aimed to determine the efficacy and safety of the combination of radiofrequency ablation (RFA and cytokine-induced killer (CIK cells transfusion for patients with colorectal liver metastases (CRLMs. Experimental Design: A total of 60 eligible patients with CRLMs were enrolled and divided into Group A (RFA alone, n = 30 and Group B (RFA plus CIK, n = 30, and following enzyme-linked immunosorbent spot assay was performed in 8 patients with CEA > 50 ng/mL pre-RFA and 7 days post-RFA and CIK treatment, respectively. Results: The median progression-free survival (PFS times of Group A and Group B were 18.5 months and 23 months, respectively (P = 0.0336. The 3-year progression-free rates were 13.3% in Group A and 20.3% in Group B, respectively. The median overall survival time was 43 months in Group A, and not reached in Group B. The 3-year survival rates were 64.6% in Group A and 81.0% in Group B, respectively (P = 0.1187. Among the 8 patients with CEA > 50ng/mL, 6 had increase of circulating CEA-specific T cells after RFA (P = 0.010. After CIK cell therapy, the number of CEA-specific T cells increased in all the 8 patients comparing with that pre-treatment (P = 0.001 and in 7 patients comparing with that post-RFA (P = 0.028. Conclusions: We firstly confirm that the combination of RFA and CIK cells boosts CEA-specific T cell response and shows to be an efficacious and safe treatment modality for patients with CRLMs.

  8. Curative Effects of Dendritic Cells Combined with Cytokine-Induced Killer Cells in Patients with Malignant Pericardial Effusion

    Science.gov (United States)

    Wang, Hongmin; Cui, Yuzhong; Wang, Sheng; Zhao, Rusen; Sun, Ming

    2016-01-01

    Background To determine the effects of dendritic cells (DCs) and cytokine-induced killer (CIK) cells in patients with malignant pericardial effusion. Material/Methods All patients underwent pericardial puncture and indwelling catheter insertion. After pericardial drainage, the 16 patients in the treatment group received an infusion of 20 mL DCs and CIK cells (>1.0×1010 cells) and 500,000 U interleukin (IL)-2 for 3 successive days. The 15 control-group patients received 30 mg/m2 cisplatin and 500,000 U IL-2 for 3 successive days. The treatment effects were assessed using imaging data. Results The total efficiency and complete remission rates were higher in the treatment group than in the control group at 4 weeks (total efficiency: 87.50% vs. 73.33%; complete remission: 62.50% vs. 46.67%) and 3 months after the treatment (total efficiency: 81.25% vs. 66.67%; complete remission: 50.00% vs. 40.00%; P<0.05 for all). In both groups, the Karnofsky scores for quality of life improved after treatment. However, the curative effects were better in the treatment group than in the control group (P<0.05). The following adverse reactions occurred: fever, 6 treatment-group patients and 3 control-group patients; chest pain, 2 treatment-group patients and 7 control-group patients; gastrointestinal reactions, 1 treatment-group patient and 6 control-group patients; and bone marrow suppression, 1 treatment-group patient and 5 control-group patients. The between-group differences in adverse reactions were significant (P<0.05). Conclusions The combination of DCs and CIK cells effectively treated malignant pericardial effusion, produced few side effects, and improved the patients’ quality of life. PMID:27806024

  9. Influence of autologous dendritic cells on cytokine-induced killer cell proliferation, cell phenotype and antitumor activity in vitro.

    Science.gov (United States)

    Cao, Jingsong; Chen, Cong; Wang, Yuhuan; Chen, Xuecheng; Chen, Zeying; Luo, Xiaoling

    2016-09-01

    Dendritic cell (DCs) are essential antigen processing and presentation cells that play a key role in the immune response. In this study, DCs were co-cultured with cytokine-induced killer cells (DC-CIKs) in vitro to detect changes in cell proliferation, cell phenotype and cell cytotoxicity. The results revealed that the DCs were suitable for co-culture with CIKs at day 7, and that cell quantity of DC-CIKs was lower than that of CIKs until day 11, but it was significantly improved to 1.17-fold that of CIKs at day 13. Flow cytometry was used to detect the cell phenotype of CIKs and DC-CIKs. Compared with CIKs at day 13, the percentage of CD3(+), CD3(+)CD4(+), CD3(+)CD8(+) and CD3(+)CD56(+) T cells in DC-CIKs was significantly improved 1.02, 1.79, 1.26 and 2.44-fold, respectively. In addition, trypan blue staining analysis demonstrated that the cell viability of CIKs and DC-CIKs was 96% and 98%, respectively. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis verified that CIK and DC-CIK cytotoxicity in Hela cells was 58% and 80%, respectively, with a significant difference. Taken together, our results indicate that the cell proliferation, cell phenotype and antitumor activity of CIKs were all enhanced following co-culture with DCs in vitro. These results are likely to be useful for DC-CIK application in antitumor therapies.

  10. Multivariate statistical data analysis as a tool to analyze ex vivo expansion dynamics of cytokine-induced killer cells.

    Science.gov (United States)

    Zanon, Cristina; Stocchero, Matteo; Albiero, Elena; Castegnaro, Silvia; Chieregato, Katia; Madeo, Domenico; Rodeghiero, Francesco; Astori, Giuseppe

    2014-07-01

    Cytokine-induced killer (CIK) cells, obtained after mononucleated cell stimulation with interferon-γ, interleukin-2, and anti-CD3 antibody, are constituted by CD3(+) CD56(+) (CIK) cells and a minority of natural killer (NK; CD3(-) CD56(+) ) cells and T-lymphocytes (CD3(+) CD56(-) ) with antitumor effect against hematological malignancies, thus representing a promising immunotherapy strategy. To ensure in vivo antitumor activity it is mandatory to maximize the percentage of CD3(+) 56(+) effector cells, which is highly variable depending on the starting sample and the harvesting day. Based on cytofluorimetric data, we have retrospectively applied multivariate statistical data analysis (MVDA) to 30 expansions building mathematical models able to predict the expansion fate and the optimal CIK harvesting day. Cell phenotype was monitored during culture; multivariate batch statistical process control was applied to monitor cell expansion and orthogonal projections to latent structures to predict CIK percentage. Ten expansions had CD3(+) CD56(+) cells ≥ 40% (good batches) and 20 had CD3(+) CD56(+) cells ≤ 40%. In 36.7%, CD3(+) CD56(+) cells reached the highest concentration at day 17 and the others at day 21. We built a highly predictive regression model for estimating CD3(+) CD56(+) cells during culture. Three variables resulted highly informative: NK % at day 0, cytotoxic T-lymphocytes % (CTLs, CD3(+) CD8(+) ) at day 4, and CIK % at day 7. "Good batches" are characterized by a high percentage of CTLs and CD3(+) CD56(+) cells at day 4 and day 7, respectively. By applying MVDA it is possible to optimize CIK expansion, deciding the optimal cell harvesting day. A predictive role for CTL and CIK was evidenced. © 2013 Clinical Cytometry Society.

  11. Acute immune-inflammatory responses to a single bout of aerobic exercise in smokers; the effect of smoking history and status.

    Directory of Open Access Journals (Sweden)

    Tegan Emma Kastelein

    2015-12-01

    Full Text Available This study examined the acute immune and inflammatory responses to exercise in smokers compared to non-smokers, and further, the effect of smoking history on these immune-inflammatory responses. Fifty four recreationally active males who were either smokers (SM; n=27 or non-smokers (NS; n=27; were allocated into either young (YSM, YNS or middle-aged groups (MSM, MNS based on smoking status. Participants were matched for fitness and smoking habits and following familiarisation and baseline testing, undertook an exercise protocol that involved 40min of cycle ergometry at 50% of VO2peak. Venous blood was obtained pre and post (0min,1h, 4h exercise to measure circulating leukocytes and inflammatory markers interleukin (IL-6, IL-1β, IL-1ra and monocyte chemoattractant protein-1 (MCP-1. Compared to MNS, MSM showed elevated basal concentrations of MCP-1 which were increased with a longer smoking history (P<0.05. In response to exercise, YSM demonstrated an amplified IL-6 response from immediately- to 1h-post compared to YNS. Further, IL-1ra in YSM was elevated above that of YNS across all time points (P<0.05. The MSM group had higher IL-1β at baseline when compared to YSM, although IL-1ra was greater for YSM at baseline (P<0.05. Finally, the post-exercise leukocyte response was greater in MSM compared to YSM and non-smokers (P<0.05. In conclusion, smoker’s exhibit elevated MCP-1 and IL-1β which seems to be evident with a longer smoking history (~15years. Further, the differences in exercise-induced inflammatory responses noted in YSM may be indicative tobacco smoke exposure priming circulating leukocytes to amplify inflammatory responses.

  12. Inflammatory cytokines imbalance in the very early phase of acute coronary syndrome: correlations with angiographic findings and in-hospital events.

    Science.gov (United States)

    Brunetti, Natale Daniele; Munno, Irene; Pellegrino, Pier Luigi; Ruggero, Vincenzo; Correale, Michele; De Gennaro, Luisa; Cuculo, Andrea; Campanale, Erasmo Giulio; Di Biase, Matteo

    2011-02-01

    The aim of this study is to investigate the release of some inflammatory cytokines (Cks) during the very early phase (first 24 h) of acute coronary syndrome (ACS). Twenty-six consecutive subjects admitted to coronary care unit with ACS underwent serial blood sampling in order to evaluate concentrations of interleukin (IL)-2, IL-10, IL-18, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. Blood samples were taken within 6 h after onset of chest pain (T₀), at 12 h (T₁), and at 24 h (T₂). Patients were thus divided into four groups comparing pro-inflammatory Ck release (IL-2, TNF-α, and IFN-γ) and anti-inflammatory activity (IL-10). Clinical features, risk factors, incidence of adverse events, and coronary angiography findings were compared with Ck activation. Ck levels were significantly increased if compared with baseline. Subjects with marked inflammatory response showed a higher incidence of left anterior descending coronary disease (IL-2, p < 0.001; TNF-α and IFN-γ, p < 0.05) and more often incurred early complications (IL-2, p < 0.05; IFN-γ, p < 0.001). A correlation was detectable between IL-18 levels and myocardial enzyme release (creatine kinase, r = 0.47; lactate dehydrogenase, r = 0.54; troponin I, r = 0.58; p < 0.05). TNF-α levels were associated with a worse prognosis at follow-up (Log rank, p < 0.05). A Ck activation characterizes the early phase of ACS. Early inflammatory reaction seems to correlate with coronary disease and adverse events.

  13. Reações inflamatórias leptomeníngeas em neurocirurgia Acute inflammatory leptomeningeal reactions in neurosurgery

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    A. Gama da Rocha

    1971-03-01

    Full Text Available Revisão de 840 casos de pacientes submetidos a intervenções neurocirúrgicas na Unidade de Neurologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo durante 5 anos (1962-1967 para verificar a incidência de reações inflamatórias leptomeníngeas (RIL no pós-operatório. Em 106 casos (12,6% foi demonstrada a ocorrência de RIL. O diagnóstico de RIL foi comprovado pelo quadro liquórico; em apenas um caso êle resultou dos achados do exame necroscópico exclusivamente. Analisando os 105 casos em que o LCR foi estudado verificou-se ser a hipertermia, a cefaléia, os sinais meníngeos e as alterações da consciência os sintomas que com mais freqüência sugeriam o diagnóstico; este foi comprovado em média 10 dias após o ato cirúrgico, mediante o exame do LCR. Baseando -se nas alterações do LCR os casos foram divididos em três grupos: RIL provavelmente asséptica (72 casos, RIL provavelmente séptica (26 casos, RIL sépticas (7 casos. Em 59 casos associava-se à RIL hemorragia sub-aracnóidea, dado considerado indicativo de gravidade, pois dos 24 pacientes que vieram a falecer, 20 apresentavam hemorragia sub-aracnóidea e RIL.Data concerning to 840 patients submitted to neurosurgical operations during 5 years (1962-1967 were reviewed in order to verify the occurrence of acute inflammatory leptomeningeal reactions (RIL in the immediate post -operative period. It was verified that RIL occurred in 106 cases (12,6%. In one case the demonstration was made at the necroscopic examination; in 105 cases the demonstration was based in the cerebrospinal fluid (CSF examination. Clinical and CSF data concerning to the last 105 cases were studied. It was shown that fever, headache, meningism and changes in consciousness were the symptoms that most commonly suggested the diagnosis. Symptoms were more conspicuous about the tenth day (mean of the post-operative period. Considering the CSF changes found, the cases were

  14. Derivation of a T2-weighted MRI total colonic inflammation score (TCIS) for assessment of patients with severe acute inflammatory colitis - a preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Hafeez, Rehana; Boulos, Paul [University College London Hospitals NHS Trust, Department of Surgery, London (United Kingdom); Punwani, Shonit; Halligan, Steve [University College London, Centre for Medical Imaging, London (United Kingdom); University College London Hospitals NHS Trust, Department of Specialist X-ray, Level 2 podium, London (United Kingdom); Pendse, Doug [University College London, Centre for Medical Imaging, London (United Kingdom); Bloom, Stuart [University College London Hospitals NHS Trust, Department of Gastroenterology, London (United Kingdom); Taylor, Stuart A. [University College London, Centre for Medical Imaging, London (United Kingdom); University College London Hospitals NHS Trust, Department of Specialist X-ray, Level 2 podium, London (United Kingdom)

    2011-02-15

    To derive an MRI score for assessing severity, therapeutic response and prognosis in acute severe inflammatory colitis. Twenty-one patients with acute severe colitis underwent colonic MRI after admission and again (n = 16) after median 5 days of treatment. Using T2-weighted images, two radiologists in consensus graded segmental haustral loss, mesenteric and mural oedema, mural thickness, and small bowel and colonic dilatation producing a total colonic inflammatory score (TCIS, range 6-95). Pre- and post-treatment TCIS were compared, and correlated with CRP, stool frequency, and number of inpatient days (therapeutic response marker). Questionnaire assessment of patient worry, satisfaction and discomfort graded 1 (bad) to 7 (good) was administered Admission TCIS correlated significantly with CRP (Kendall's tau=0.45, 95% confidence interval [CI] 0.11-0.79, p = 0.006), and stool frequency (Kendall's tau 0.39, 95% CI 0.14-0.64, p = 0.02). TCIS fell after treatment (median [22 range 15-31]) to median 20 [range 8-25], p = 0.01. Admission TCIS but not CRP or stool frequency was correlated with length of inpatient stay (Kendall's tau 0.40, 95% CI 0.11-0.69, p = 0.02). Patients reported some discomfort (median score 4) during MRI. MRI TCIS falls after therapy, correlates with existing markers of disease severity, and in comparison may better predict therapeutic response. (orig.)

  15. Cytokine-induced impairment of short-chain fatty acid oxidation and viability in human colonic epithelial cells

    DEFF Research Database (Denmark)

    Pedersen, G; Saermark, T; Horn, T;

    2000-01-01

    Pro-inflammatory cytokines may directly influence the viability and metabolic function of colonic epithelial cells (CEC) as an early event in the development of inflammatory bowel disease. We report here that TNF-alpha+IFN-gamma induced a synergistic, concentration-dependent decline in butyrate o...

  16. Effects of budesonide and N-acetylcysteine on acute lung hyperinflation, inflammation and injury in rats.

    Science.gov (United States)

    Jansson, Anne-Helene; Eriksson, Christina; Wang, Xiangdong

    2005-08-01

    Leukocyte activation and production of inflammatory mediators and reactive oxygen species are important in the pathogenesis of lipopolysaccharide (LPS)-induced acute lung injury. The present study investigated acute lung hyperinflation, edema, and lung inflammation 4 h after an intratracheal instillation of LPS (0.5, 2.5, 5, 10, 50, 100, 500, 1000, and 5000 microg/ml/kg). Effects of budesonide, an inhaled anti-inflammatory corticosteroids, and N-acetylcysteine (NAC), an antioxidant, were evaluated in Wistar rats receiving either low (2.5 microg/ml/kg) or high (50 microg/ml/kg) concentrations of LPS. This study demonstrates that LPS in a concentration-dependent pattern induces acute lung hyperinflation measured by excised lung gas volume (25-45% above control), lung injury indicated by increased lung weight (10-60%), and lung inflammation characterized by the infiltration of leukocytes (40-14000%) and neutrophils (80-17000%) and the production of cytokines (up to 2700%) and chemokines (up to 350%) in bronchoalveolar lavage fluid (BALF). Pretreatment with NAC partially prevented tumor necrosis factor alpha (TNFalpha) production induced by the low concentration of LPS, while pretreatment with budesonide totally prevented the increased production of TNFalpha, interleukin (IL)-1beta, IL-6, and monocyte chemoattractive protein (MCP)-1 after LPS challenge at both low and high concentrations. Budesonide failed to prevent BALF levels of macrophage inflammatory protein (MIP)-2 and cytokine-induced neutrophil chemoattractant 1 (GRO/CINC-1) as well as lung hyperinflation induced by both low and high concentrations of LPS. Pretreatment with budesonide totally prevented the formation of lung edema at the low concentration of LPS and had partial effects on acute lung injury and leukocyte influx at the high concentrations. Thus, our data indicate that therapeutic effects of budesonide and NAC are dependent upon the severity of the disease.

  17. Effects of rosuvastatin and atorvastatin on inflammatory factors and left ventricular remodeling in patients with non-ST segment elevation acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Yun Zhou; Le Qu; Xiao-Li Zhu

    2016-01-01

    Objective:To explore the effects of rosuvastatin and atorvastatin on inflammatory factors and left ventricular remodeling in patients with non-ST segment elevation acute myocardial. Methods:A total of 100 cases patients of NSTEMI were selected that they were admitted during January 2013 to December 2014 and randomly divided into observer group and control group, each of 50 cases. Patients were given a comprehensive treatment of myocardial infarction, the control group was given the treatment of rosuvastatin and the observer group was given the treatment of atorvastatin over the same period, compared the related indicators of serum inflammatory factors and left ventricular remodeling after treatment in two groups. Results:The observer group serum TNF- , IL-6, hs-CRP levels were significantly lower than the control group in the treatment of 1 month, 3 months. The observer group was treated for 1 month, 3 months LVEF was significantly higher than the control group, and LVEDD, LVESD, PWT was significantly lower than the control group. The observer group was treated for 1 month, 3 months AngⅡ, PⅢNP, NT-proBNP level was significantly lower than the control group.Conclusions:The rosuvastatin is better than the atorvastatin in improving the level of NSTEMI inflammatory factors, prevention of left ventricular remodeling.

  18. Suppression of P2X7/NF-κB pathways by Schisandrin B contributes to attenuation of lipopolysaccharide-induced inflammatory responses in acute lung injury.

    Science.gov (United States)

    Cai, Zhiyong; Liu, Jindi; Bian, Hongliang; Cai, Jinlan; Zhu, Gendi

    2016-04-01

    The aim of the present study was to assess the effects and mechanisms of Schisandrin B (SchB) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS (1 mg/kg), and SchB (25, 50, and 75 mg/kg) was injected 1 h before LPS challenge by gavage. After 12 h, bronchoalveolar lavage fluid (BALF) samples and lung tissues were collected. Histological studies demonstrated that SchB attenuated LPS-induced interstitial edema, hemorrhage, and infiltration of neutrophils in the lung tissue. SchB pretreatment at doses of 25, 50, and 75 mg/kg was shown to reduce LPS-induced lung wet-to-dry weight ratio and lung myeloperoxidase activity. In addition, pretreatment with SchB lowered the number of inflammatory cells and pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in BALF. The mRNA and protein expression levels of nuclear factor kappa B (NF-κB) signaling-related molecules activated by P2X7 were investigated to determine the molecular mechanism of SchB. The findings presented here suggest that the protective mechanism of SchB may be attributed partly to the decreased production of pro-inflammatory cytokines through the inhibition of P2X7/NF-κB activation.

  19. The molecular mechanisms of the hepatoprotective effect of gomisin A against oxidative stress and inflammatory response in rats with carbon tetrachloride-induced acute liver injury.

    Science.gov (United States)

    Teraoka, Ryutaro; Shimada, Tsutomu; Aburada, Masaki

    2012-01-01

    Oxidative damage and inflammation are implicated in the pathogenesis of liver injury and fibrosis. In the present study, we investigated the molecular mechanism by which gomisin A conferred a hepatoprotective effect, focusing on its antioxidant and anti-inflammatory effects using rats with carbon tetrachloride (CCl(4))-induced acute liver injury. Pretreatment with gomisin A prior to the administration of CCl(4) markedly prevented an increase in alanine aminotransferase, aspartate aminotransferase, and histological hepatic lesions. Gomisin A was also associated with a decrease in hepatic lipid peroxidation, and increased superoxide dismutase activity, suggesting that gomisin A has an antioxidant effect. In addition gomisin A treatment ameliorated mRNA levels of CCl(4)-induced inflammatory mediators, including tumor necrosis factor-α, interleukin-1β and inducible nitric oxide (NO) synthase, and the protein levels of transcriptional upregulator nuclear factor kappa B (NF-κB) and phospho-inhibitor of NF-κB (IκB). Furthermore, α-smooth muscle actin (α-SMA), a myofibroblast marker, was also inhibited by gomisin A treatment. These results suggest that gomisin A inhibits the oxidative stress and activation of NF-κB, leading to down-regulation of pro-inflammatory mediators and amelioration of fibrogenesis.

  20. Effect of Atorvastatin intensive therapy on the serum inflammatory factors, platelet activity and fibrinolytic activity in patients with acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    Xiao-Li Zhu; Yun Zhou; Fang Liu

    2016-01-01

    Objective:To observe the effect of Atorvastatin intensive therapy on the serum inflammatory factors, platelet activity and fibrinolytic activity in patients with acute coronary syndrome (ACS).Methods:A total of 92 patients with ACS were randomly divided into observation group (47 cases) and control group (45 cases). The control group was given Atorvastatin (10 mg/d) based on the conventional therapy, while the observation group was given Atorvastatin at an intensive dose (40 mg/d) based on the conventional therapy. Half a month later, the changes of IL-6, IL-8, hs-CRP, TNF-α, TXB2, GMP-140, PAI-1 and t-PA were observed and compared between the two groups.Results:After treatment, the inflammatory factors (IL-6, IL-8, hs-CRP and TNF-α) and the indicators of platelet activity (TXB2, GMP-140 and PAI-1) were obviously decreased, while the indicator of fibrinolytic activity (t-PA) was apparently increased in the two groups. Besides, the amplitudes of change referring to these indicators in the observation group were bigger than those in the control group after treatment, and the differences were statistically significant.Conclusion: The intensive therapy with the administration of Atorvastatin at a dose of 40 mg/d was better than the conventional therapy (Atorvastatin: 10 mg/d) in aspects of reducing inflammatory factors, inhibiting platelet activity and correcting the high coagulation state of fibrinolytic system.

  1. Acute kidney injury and inflammatory immune reconstitution syndrome in mixed genotype (A/E) hepatitis B virus co-infection in HIV-associated lymphoma.

    Science.gov (United States)

    Tajima, Katsushi; Kohno, Kei; Shiono, Yosuke; Suzuki, Ikuko; Kato, Yuichi; Hiroshima, Yuki; Yamamoto, Masakazu; Ohtake, Hiroya; Iwaba, Akiko; Yamakawa, Mitsunori; Kato, Takeo

    2013-01-01

    We report a first case of HIV-associated lymphoma (HAL) presenting with acute kidney injury (AKI) and inflammatory immune reconstitution syndrome (IRIS). A 39-year-old male, treated with nonsteroidal anti-inflammatory drugs (NSAIDs) for one month prior to admission, developed AKI, left testicular tumor, and recurrent swelling of the right parotid gland. A resected testicular tumor exhibited features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Renal biopsy showed hydro-degeneration of renal tubules, interstitial inflammatory cells, and a small number of lymphoma cells in the sub-capsule, compatible with acute interstitial nephritis. His renal dysfunction rapidly recovered following chemotherapy and combination antiretroviral therapy (cART). He developed pneumonia concomitantly with a decrease in HIV-RNA level and an increase in CD4+ cells after the first cycle of chemotherapy, which spontaneously resolved after the second cycle of chemotherapy without additional anti-infection drugs; thus, his pneumonia fulfilled the diagnostic criteria for IRIS. We suggest that IRIS may frequently develop during chemotherapy for HAL, but may be overlooked. He was coinfected with hepatitis B virus (HBV), which genotypes known as is associated with liver-related mortality and response to antiviral therapy; recently, an intimate interplay between HIV and HBV in the onset of lymphoma has been reported. Therefore, we addressed the HBV genotype in the patient. The analysis revealed that he exhibited a mixed genotype (A/E) not native to Japan and primarily found in Europe and North America or West Africa. These findings suggest that universal vaccination for juveniles against HBV is warranted in Japan.

  2. Role of parathyroid hormone-related protein in the pro-inflammatory and pro-fibrogenic response associated with acute pancreatitis.

    Science.gov (United States)

    Bhatia, Vandanajay; Kim, Sung O K; Aronson, Judith F; Chao, Celia; Hellmich, Mark R; Falzon, Miriam

    2012-04-10

    Pancreatitis is a common and potentially lethal necro-inflammatory disease with both acute and chronic manifestations. Current evidence suggests that the accumulated damage incurred during repeated bouts of acute pancreatitis (AP) can lead to chronic disease, which is associated with an increased risk of pancreatic cancer. While parathyroid hormone-related protein (PTHrP) exerts multiple effects in normal physiology and disease states, its function in pancreatitis has not been previously addressed. Here we show that PTHrP levels are transiently elevated in a mouse model of cerulein-induced AP. Treatment with alcohol, a risk factor for both AP and chronic pancreatitis (CP), also increases PTHrP levels. These effects of cerulein and ethanol are evident in isolated primary acinar and stellate cells, as well as in the immortalized acinar and stellate cell lines AR42J and irPSCc3, respectively. Ethanol sensitizes acinar and stellate cells to the PTHrP-modulating effects of cerulein. Treatment of acinar cells with PTHrP (1-36) increases expression of the inflammatory mediators interleukin-6 (IL-6) and intracellular adhesion protein (ICAM-1), suggesting a potential autocrine loop. PTHrP also increases apoptosis in AR42J cells. Stellate cells mediate the fibrogenic response associated with pancreatitis; PTHrP (1-36) increases procollagen I and fibronectin mRNA levels in both primary and immortalized stellate cells. The effects of cerulein and ethanol on levels of IL-6 and procollagen I are suppressed by the PTH1R antagonist, PTHrP (7-34). Together these studies identify PTHrP as a potential mediator of the inflammatory and fibrogenic responses associated with alcoholic pancreatitis. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Expression and Significance of Toll-like Receptor 2, 4 of Peripheral Blood Mononuclear Cells in Acute Abdomen Patients Associated with Systemic Inflammatory Response Syndrome

    Institute of Scientific and Technical Information of China (English)

    XIONG Jing; WANG Yang; ZHU Zhonghua; LIU Jianshe

    2006-01-01

    The changes of Toll-like receptor (TLR) 2, 4 of peripheral blood mononuclear cells (PBMCs) in the acute abdomen patients associated with systemic inflammatory response syndrome (SIRS) and their potential significance were explored. A clinical study was performed on 103 acute abdomen patients in whom 65 were associated with SIRS. Forty healthy individuals served as normal controls. The mRNA expression of TLR2, 4 was detected by RT-PCR, and the expression of TNF-αand IL-6 by ELISA. The level of plasma endotoxin, hospital stay and mortality were measured. It was found that the endotoxin level was increased to varying degrees in all the acute abdomen patients, and the endotoxin level was and hospital stay longer in SIRS group than in non-SIRS group (P<0.01).TLR2 mRNA, TLR4 mRNA, IL-6 and TNF-α could be detected with low value in normal controls,but they were up-regulated markedly on the 1 st day after admission. Then TLR4 mRNA, IL-6 and TNF-α were decreased gradually, but TLR2 mRNA maintained at a high level till the 5th day. These indexes above in SIRS group were higher than those in non-SIRS group (P<0.01). The results of correlation analysis revealed the expression of TLR2, 4 mRNA was positively correlated with the levels of TNF-α and IL-6, and the hospital stay. The results of Logistic regression demonstrated that overexpression of TLR2, 4 mRNA might result in higher risk of multiple organ dysfunction syndrome (MODS). It was concluded that in the acute abdomen patients associated with SIRS, the expression of TLR2, 4 in PBMCs was increased markedly, suggesting that TLR might play an important role in the pathogenesis of acute abdomen associated with SIRS.

  4. P2X3 Receptors Mediate Visceral Hypersensitivity during Acute Chemically-Induced Colitis and in the Post-Inflammatory Phase via Different Mechanisms of Sensitization

    Science.gov (United States)

    Deiteren, Annemie; van der Linden, Laura; de Wit, Anouk; Ceuleers, Hannah; Buckinx, Roeland; Timmermans, Jean-Pierre; Moreels, Tom G.; Pelckmans, Paul A.; De Man, Joris G.; De Winter, Benedicte Y.

    2015-01-01

    Objectives Experiments using P2X3 knock-out mice or more general P2X receptor antagonists suggest that P2X3 receptors contribute to visceral hypersensitivity. We aimed to investigate the effect of the selective P2X3 antagonist A-317491 on visceral sensitivity under physiological conditions, during acute colitis and in the post-inflammatory phase of colitis. Methods Trinitrobenzene sulphonic-acid colitis was monitored by colonoscopy: on day 3 to confirm the presence of colitis and then every 4 days, starting from day 10, to monitor convalescence and determine the exact timepoint of endoscopic healing in each rat. Visceral sensitivity was assessed by quantifying visceromotor responses to colorectal distension in controls, rats with acute colitis and post-colitis rats. A-317491 was administered 30 min prior to visceral sensitivity testing. Expression of P2X3 receptors (RT-PCR and immunohistochemistry) and the intracellular signalling molecules cdk5, csk and CASK (RT-PCR) were quantified in colonic tissue and dorsal root ganglia. ATP release in response to colorectal distension was measured by luminiscence. Results Rats with acute TNBS-colitis displayed significant visceral hypersensitivity that was dose-dependently, but not fully, reversed by A-317491. Hypersenstivity was accompanied by an increased colonic release of ATP. Post-colitis rats also displayed visceral hypersensitivity that was dose-dependently reduced and fully normalized by A-317491 without increased release of ATP. A-317491 did not modify visceral sensitivity in controls. P2X3 mRNA and protein expression in the colon and dorsal root ganglia were similar in control, acute colitis and post-colitis groups, while colonic mRNA expression of cdk5, csk and CASK was increased in the post-colitis group only. Conclusions These findings indicate that P2X3 receptors are not involved in sensory signaling under physiological conditions whereas they modulate visceral hypersensitivity during acute TNBS-colitis and even

  5. P2X3 receptors mediate visceral hypersensitivity during acute chemically-induced colitis and in the post-inflammatory phase via different mechanisms of sensitization.

    Directory of Open Access Journals (Sweden)

    Annemie Deiteren

    Full Text Available Experiments using P2X3 knock-out mice or more general P2X receptor antagonists suggest that P2X3 receptors contribute to visceral hypersensitivity. We aimed to investigate the effect of the selective P2X3 antagonist A-317491 on visceral sensitivity under physiological conditions, during acute colitis and in the post-inflammatory phase of colitis.Trinitrobenzene sulphonic-acid colitis was monitored by colonoscopy: on day 3 to confirm the presence of colitis and then every 4 days, starting from day 10, to monitor convalescence and determine the exact timepoint of endoscopic healing in each rat. Visceral sensitivity was assessed by quantifying visceromotor responses to colorectal distension in controls, rats with acute colitis and post-colitis rats. A-317491 was administered 30 min prior to visceral sensitivity testing. Expression of P2X3 receptors (RT-PCR and immunohistochemistry and the intracellular signalling molecules cdk5, csk and CASK (RT-PCR were quantified in colonic tissue and dorsal root ganglia. ATP release in response to colorectal distension was measured by luminiscence.Rats with acute TNBS-colitis displayed significant visceral hypersensitivity that was dose-dependently, but not fully, reversed by A-317491. Hypersenstivity was accompanied by an increased colonic release of ATP. Post-colitis rats also displayed visceral hypersensitivity that was dose-dependently reduced and fully normalized by A-317491 without increased release of ATP. A-317491 did not modify visceral sensitivity in controls. P2X3 mRNA and protein expression in the colon and dorsal root ganglia were similar in control, acute colitis and post-colitis groups, while colonic mRNA expression of cdk5, csk and CASK was increased in the post-colitis group only.These findings indicate that P2X3 receptors are not involved in sensory signaling under physiological conditions whereas they modulate visceral hypersensitivity during acute TNBS-colitis and even more so in the post-inflammatory

  6. Thymoglobulin, interferon-γ and interleukin-2 efficiently expand cytokine-induced killer (CIK cells in clinical-grade cultures

    Directory of Open Access Journals (Sweden)

    Corallo Maria

    2010-12-01

    Full Text Available Abstract Background Cytokine-induced killer (CIK cells are typically differentiated in vitro with interferon (IFN-γ and αCD3 monoclonal antibodies (mAb, followed by the repeated provision of interleukin (IL-2. It is presently unknown whether thymoglobulin (TG, a preparation of polyclonal rabbit γ immunoglobulins directed against human thymocytes, can improve the generation efficiency of CIK cells compared with αCD3 mAb in a clinical-grade culture protocol. Methods Peripheral blood mononuclear cells (PBMC from 10 healthy donors and 4 patients with solid cancer were primed with IFN-γ on day 0 and low (50 ng/ml, intermediate (250 ng/ml and high (500 ng/ml concentrations of either αCD3 mAb or TG on day 1, and were fed with IL-2 every 3 days for 21 days. Aliquots of cells were harvested weekly to monitor the expression of representative members of the killer-like immunoglobulin receptor (KIR, NK inhibitory receptor, NK activating receptor and NK triggering receptor families. We also quantified the frequency of bona fide regulatory T cells (Treg, a T-cell subset implicated in the down-regulation of anti-tumor immunity, and tested the in vitro cytotoxic activity of CIK cells against NK-sensitive, chronic myeloid leukaemia K562 cells. Results CIK cells expanded more vigorously in cultures supplemented with intermediate and high concentrations of TG compared with 50 ng/ml αCD3 mAb. TG-driven CIK cells expressed a constellation of NK activating/inhibitory receptors, such as CD158a and CD158b, NKp46, NKG2D and NKG2A/CD94, released high quantities of IL-12p40 and efficiently lysed K562 target cells. Of interest, the frequency of Treg cells was lower at any time-point compared with PBMC cultures nurtured with αCD3 mAb. Cancer patient-derived CIK cells were also expanded after priming with TG, but they expressed lower levels of the NKp46 triggering receptor and NKG2D activating receptor, thus manifesting a reduced ability to lyse K562 cells

  7. Antitumor activities of human autologous cytokine-induced killer (CIK) cells against hepatocellular carcinoma cells in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Fu-Sheng Wang; Ming-Xu Liu; Bing Zhang; Ming Shi; Zhou-Yun Lei; Wen-Bing Sun; Qing-You Du; Ju-Mei Chen

    2002-01-01

    AIM: To characterize the anticancer function of cytokine-induced killer cells (CIK) and develop an adoptiveimmunotherapy for the patients with primary hepatocellularcarcinoma (HCC), we evaluated the proliferation rate,phenotype and the antitumor activity of human CIK cellsfrom healthy donors and HCC patients in vitro and in vivo.METHODS: Peripheral blood mononuclear cells (PBMC) fronhealthy donors and patients with primary HCC were incubatedin vitro and induced into ClK cells in the presence of variouscytokines such as interferon-gamma (IFN-γ), interleukin-1(IL-1), IL-2, and monoclonal antibody (mAb) against CD3.The phenotype and characterization of CIK cells wereidentified by flow cytometric analysis. The cytotoxicity of CIKcells was determined by 51 Cr release assay.RESULTS: The CIK cells were shown to be a heterogeneouspopulation with different cellular phenotypes. Thepercentage of CD3+/CD56+ positive cells, the dominanteffector cells, in total CIK cells from healthy donors andHCC patients, significantly increased from 0.1-0.13 % at day0 to 19.0-20.5 % at day 21 incubation, which suggested thatthe CD3+ CD56+ positive cells proliferated faster than othercell populations of CIK cells in the protocol used in thisstudy. After 28 day in vitro incubation, the ClK cells frompatients with HCC and healthy donors increased by morethan 300-fold and 500-fold in proliferation cell number,respectively. CIK cells originated from HCC patientspossessed a higher in vitro antitumor cytotoxic activity onautologous HCC cells than the autologous lymphokine-activated killer (LAK) cells and PBMC cells. In in vivoanimal experiment, CIK cells had stronger effects on theinhibition of tumor growth in Balb/c nude mice bearing BEL-7402-producing tumor than LAK cells (mean inhibitory rate,84.7 % vs 52.8 %, P < 0.05) or PBMC (mean inhibitoryrate, 84.7% vs37.1%, P<0.01).CONCLUSION: Autologous CIK cells are of highly efficientcytotoxic effector cells against primary hepatocellularcarcinoma

  8. Alpha-Lipoic Acid Alleviates Acute Inflammation and Promotes Lipid Mobilization During the Inflammatory Response in White Adipose Tissue of Mice.

    Science.gov (United States)

    Guo, Jun; Gao, Shixing; Liu, Zhiqing; Zhao, Ruqian; Yang, Xiaojing

    2016-10-01

    Recently, white adipose tissue has been shown to exhibit immunological activity, and may play an important role in host defense and protection against bacterial infection. Αlpha-lipoic acid (α-LA) has been demonstrated to function as an anti-inflammatory and anti-oxidant agent. However, its influence on the inflammatory response and metabolic changes in white adipose tissue remains unknown. We used male C57BL/6 mice as models to study the effect of α-LA on the inflammatory response and metabolic changes in white adipose tissue after stimulation with lipopolysaccharide (LPS). The non-esterified fatty acid content was measured by an automatic biochemical analyzer. The expression of inflammation-, lipid- and energy metabolism-related genes and proteins was determined by quantitative real-time polymerase chain reaction and western blotting. The results indicated that α-LA significantly decreased the epididymis fat weight index and the non-esterified fatty acid content in plasma compared with the control group. LPS significantly increased the expression of inflammation genes and α-LA reduced their expression. The LPS-induced expression of nuclear factor-κB protein was decreased by α-LA. Regarding lipid metabolism, α-LA significantly counteracted the inhibitory effects of LPS on the expression of hormone-sensitive lipase gene and protein. α-LA evidently increased the gene expression of fatty acid transport protein 1 and cluster of differentiation 36. Regarding energy metabolism, α-LA significantly increased the expression of most of mitochondrial DNA-encoded genes compared with the control and LPS group. Accordingly, α-LA can alleviate acute inflammatory response and this action may be related with the promotion of lipid mobilization in white adipose tissue.

  9. Surfactant proteins SP-B and SP-C and their precursors in bronchoalveolar lavages from children with acute and chronic inflammatory airway disease

    Directory of Open Access Journals (Sweden)

    Winter Tobias

    2008-04-01

    Full Text Available Abstract Background The surfactant proteins B (SP-B and C (SP-C are important for the stability and function of the alveolar surfactant film. Their involvement and down-regulation in inflammatory processes has recently been proposed, but their level during neutrophilic human airway diseases are not yet known. Methods We used 1D-electrophoresis and Western blotting to determine the concentrations and molecular forms of SP-B and SP-C in bronchoalveolar lavage (BAL fluid of children with different inflammatory airway diseases. 21 children with cystic fibrosis, 15 with chronic bronchitis and 14 with pneumonia were included and compared to 14 healthy control children. Results SP-B was detected in BAL of all 64 patients, whereas SP-C was found in BAL of all but 3 children; those three BAL fluids had more than 80% neutrophils, and in two patients, who were re-lavaged later, SP-C was then present and the neutrophil count was lower. SP-B was mainly present as a dimer, SP-C as a monomer. For both qualitative and quantitative measures of SP-C and SP-B, no significant differences were observed between the four evaluated patient groups. Conclusion Concentration or molecular form of SP-B and SP-C is not altered in BAL of children with different acute and chronic inflammatory lung diseases. We conclude that there is no down-regulation of SP-B and SP-C at the protein level in inflammatory processes of neutrophilic airway disease.

  10. Effects of Ketamine on Levels of Inflammatory Cytokines IL-6, IL-1β, and TNF-α in the Hippocampus of Mice Following Acute or Chronic Administration.

    Science.gov (United States)

    Li, Yanning; Shen, Ruipeng; Wen, Gehua; Ding, Runtao; Du, Ao; Zhou, Jichuan; Dong, Zhibin; Ren, Xinghua; Yao, Hui; Zhao, Rui; Zhang, Guohua; Lu, Yan; Wu, Xu

    2017-01-01

    Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile, ketamine has been shown to modulate the levels of inflammatory cytokines. We hypothesized that the effects of ketamine on the central nervous system are associated with inflammatory cytokines. Therefore, we set out to establish acute and chronic ketamine administration models in C57BL/6 mice, to evaluate spatial recognition memory and emotional response, to analyze the changes in the levels of the inflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the mouse hippocampus, employing behavioral tests, Western blot, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunohistochemistry. Our results showed that ketamine at the dose of 60 mg/kg induced spatial recognition memory deficit and reduced anxiety-like behaviors in mice after chronic administration. Moreover, we found that ketamine increased the hippocampal levels of IL-6 and IL-1β after single, multiple and long-term administration in a dose-dependent manner. However, the expression level of TNF-α differed in the mouse hippocampus under different conditions. Single administration of ketamine increased the level of TNF-α, whereas multiple and long-term administration decreased it significantly. We considered that TNF-α expression could be controlled by a bi-directional regulatory pathway, which was associated with the dose and duration of ketamine administration. Our results suggest that the alterations in the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α may be involved in the neurotoxicity of ketamine.

  11. Pregnane X Receptor Activation Attenuates Inflammation-Associated Intestinal Epithelial Barrier Dysfunction by Inhibiting Cytokine-Induced Myosin Light-Chain Kinase Expression and c-Jun N-Terminal Kinase 1/2 Activation.

    Science.gov (United States)

    Garg, Aditya; Zhao, Angela; Erickson, Sarah L; Mukherjee, Subhajit; Lau, Aik Jiang; Alston, Laurie; Chang, Thomas K H; Mani, Sridhar; Hirota, Simon A

    2016-10-01

    The inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with a complex etiology. IBD is thought to arise in genetically susceptible individuals in the context of aberrant interactions with the intestinal microbiota and other environmental risk factors. Recently, the pregnane X receptor (PXR) was identified as a sensor for microbial metabolites, whose activation can regulate the intestinal epithelial barrier. Mutations in NR1I2, the gene that encodes the PXR, have been linked to IBD, and in animal models, PXR deletion leads to barrier dysfunction. In the current study, we sought to assess the mechanism(s) through which the PXR regulates barrier function during inflammation. In Caco-2 intestinal epithelial cell monolayers, tumor necrosis factor-α/interferon-γ exposure disrupted the barrier and triggered zonula occludens-1 relocalization, increased expression of myosin light-chain kinase (MLCK), and activation of c-Jun N-terminal kinase 1/2 (JNK1/2). Activation of the PXR [rifaximin and [[3,5-Bis(1,1-dimethylethyl)-4-hydroxyphenyl]ethenylidene]bis-phosphonic acid tetraethyl ester (SR12813); 10 μM] protected the barrier, an effect that was associated with attenuated MLCK expression and JNK1/2 activation. In vivo, activation of the PXR [pregnenolone 16α-carbonitrile (PCN)] attenuated barrier disruption induced by toll-like receptor 4 activation in wild-type, but not Pxr-/-, mice. Furthermore, PCN treatment protected the barrier in the dextran-sulfate sodium model of experimental colitis, an effect that was associated with reduced expression of mucosal MLCK and phosphorylated JNK1/2. Together, our data suggest that the PXR regulates the intestinal epithelial barrier during inflammation by modulating cytokine-induced MLCK expression and JNK1/2 activation. Thus, targeting the PXR may prove beneficial for the treatment of inflammation-associated barrier disruption in the context of IBD.

  12. The CD14+CD16+ inflammatory monocyte subset displays increased mitochondrial activity and effector function during acute Plasmodium vivax malaria.

    Directory of Open Access Journals (Sweden)

    Lis R V Antonelli

    2014-09-01

    Full Text Available Infection with Plasmodium vivax results in strong activation of monocytes, which are important components of both the systemic inflammatory response and parasite control. The overall goal of this study was to define the role of monocytes during P. vivax malaria. Here, we demonstrate that P. vivax-infected patients display significant increase in circulating monocytes, which were defined as CD14(+CD16- (classical, CD14(+CD16(+ (inflammatory, and CD14loCD16(+ (patrolling cells. While the classical and inflammatory monocytes were found to be the primary source of pro-inflammatory cytokines, the CD16(+ cells, in particular the CD14(+CD16(+ monocytes, expressed the highest levels of activation markers, which included chemokine receptors and adhesion molecules. Morphologically, CD14(+ were distinguished from CD14lo monocytes by displaying larger and more active mitochondria. CD14(+CD16(+ monocytes were more efficient in phagocytizing P. vivax-infected reticulocytes, which induced them to produce high levels of intracellular TNF-α and reactive oxygen species. Importantly, antibodies specific for ICAM-1, PECAM-1 or LFA-1 efficiently blocked the phagocytosis of infected reticulocytes by monocytes. Hence, our results provide key information on the mechanism by which CD14(+CD16(+ cells control parasite burden, supporting the hypothesis that they play a role in resistance to P. vivax infection.

  13. Thoracic epidural analgesia inhibits the neuro-hormonal but not the acute inflammatory stress response after radical retropubic prostatectomy

    NARCIS (Netherlands)

    Fant, F.; Tina, E.; Sandblom, D.; Andersson, S. -O.; Magnuson, A.; Hultgren-Hornkvist, E.; Axelsson, K.; Gupta, A.

    2013-01-01

    Background. Epidural anaesthesia and analgesia has been shown to suppress the neurohormonal stress response, but its role in the inflammatory response is unclear. The primary aim was to assess whether the choice of analgesic technique influences these processes in patients undergoing radical retropu

  14. Acute toxicity and surgical complications after preoperative (chemo)radiation therapy for rectal cancer in patients with inflammatory bowel disease

    NARCIS (Netherlands)

    Bosch, S.L.; Rooijen, S.J. van; Bökkerink, G.M.J.; Braam, H.J.; Derikx, L.A.A.P.; Poortmans, P.M.P.; Marijnen, C.A.; Nagtegaal, I.D.; Wilt, J.H.W. de

    2017-01-01

    PURPOSE: Preoperative therapy reduces local recurrences and may facilitate surgery in rectal cancer patients. However, in patients with inflammatory bowel disease (IBD) this treatment is often withheld due to the perceived risk of excessive side-effects, even though evidence is limited. The purpose

  15. Acute inflammatory response to a foreign body in Calomys callosus Perfil de migração celular agudo induzido pela presença de corpo estranho em Calomys callosus

    OpenAIRE

    André Kipnis; Loanda Carvalho Santa Ana-Limongi; Luciano Schneider Silva; Ana Paula Junqueira-Kipnis

    2008-01-01

    Calomys callosus are wild rodents present in the Brazilian savannas that were adapted to the laboratorial conditions. These animals are resistant to infections that induce chronic inflammatory responses (Trypanosoma cruzi and Paracoccidioides brasiliensis). The objective of this work was to characterize the acute inflammatory reaction, prompted by the subcutaneous implementation of a foreign body. Twenty seven <...

  16. Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 Pathway.

    Science.gov (United States)

    Zhang, Xiang-Sheng; Li, Wei; Wu, Qi; Wu, Ling-Yun; Ye, Zhen-Nan; Liu, Jing-Peng; Zhuang, Zong; Zhou, Meng-Liang; Zhang, Xin; Hang, Chun-Hua

    2016-08-12

    Toll-like receptor 4 (TLR4) has been proven to play a critical role in neuroinflammation and to represent an important therapeutic target following subarachnoid hemorrhage (SAH). Resveratrol (RSV), a natural occurring polyphenolic compound, has a powerful anti-inflammatory property. However, the underlying molecular mechanisms of RSV in protecting against early brain injury (EBI) after SAH remain obscure. The purpose of this study was to investigate the effects of RSV on the TLR4-related inflammatory signaling pathway and EBI in rats after SAH. A prechiasmatic cistern SAH model was used in our experiment. The expressions of TLR4, high-mobility group box 1 (HMGB1), myeloid differentiation factor 88 (MyD88), and nuclear factor-κB (NF-κB) were evaluated by Western blot and immunohistochemistry. The expressions of Iba-1 and pro-inflammatory cytokines in brain cortex were determined by Western blot, immunofluorescence staining, or enzyme-linked immunosorbent assay. Neural apoptosis, brain edema, and neurological function were further evaluated to investigate the development of EBI. We found that post-SAH treatment with RSV could markedly inhibit the expressions of TLR4, HMGB1, MyD88, and NF-κB. Meanwhile, RSV significantly reduced microglia activation, as well as inflammatory cytokines leading to the amelioration of neural apoptosis, brain edema, and neurological behavior impairment at 24 h after SAH. However, RSV treatment failed to alleviate brain edema and neurological deficits at 72 h after SAH. These results indicated that RSV treatment could alleviate EBI after SAH, at least in part, via inhibition of TLR4-mediated inflammatory signaling pathway.

  17. Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 Pathway

    Directory of Open Access Journals (Sweden)

    Xiang-Sheng Zhang

    2016-08-01

    Full Text Available Toll-like receptor 4 (TLR4 has been proven to play a critical role in neuroinflammation and to represent an important therapeutic target following subarachnoid hemorrhage (SAH. Resveratrol (RSV, a natural occurring polyphenolic compound, has a powerful anti-inflammatory property. However, the underlying molecular mechanisms of RSV in protecting against early brain injury (EBI after SAH remain obscure. The purpose of this study was to investigate the effects of RSV on the TLR4-related inflammatory signaling pathway and EBI in rats after SAH. A prechiasmatic cistern SAH model was used in our experiment. The expressions of TLR4, high-mobility group box 1 (HMGB1, myeloid differentiation factor 88 (MyD88, and nuclear factor-κB (NF-κB were evaluated by Western blot and immunohistochemistry. The expressions of Iba-1 and pro-inflammatory cytokines in brain cortex were determined by Western blot, immunofluorescence staining, or enzyme-linked immunosorbent assay. Neural apoptosis, brain edema, and neurological function were further evaluated to investigate the development of EBI. We found that post-SAH treatment with RSV could markedly inhibit the expressions of TLR4, HMGB1, MyD88, and NF-κB. Meanwhile, RSV significantly reduced microglia activation, as well as inflammatory cytokines leading to the amelioration of neural apoptosis, brain edema, and neurological behavior impairment at 24 h after SAH. However, RSV treatment failed to alleviate brain edema and neurological deficits at 72 h after SAH. These results indicated that RSV treatment could alleviate EBI after SAH, at least in part, via inhibition of TLR4-mediated inflammatory signaling pathway.

  18. Improved early diagnosis of acute inflammatory skeletal-articular diseases in children: A two-radiopharmaceutical approach

    Energy Technology Data Exchange (ETDEWEB)

    Handmaker, H.; Giammona, S.T.

    1984-05-01

    The febrile child with a painful bone or joint still presents a difficult pediatric diagnostic problem. Acute hematogenous osteomyelitis, septic arthritis, and cellulitis are the most common causes of this symptom. Thirty-seven patients with these disorders were studied. Because findings from technetium-99m phosphate bone scans and roentgenograms are often normal in patients in the early stages of acute hematogenous osteomyelitis, children suspected of having this disorder were tested using gallium-67 citrate scans in addition to the other diagnostic procedures. The increased diagnostic accuracy of this approach over that of bone scan and roentgenogram studies alone was observed in the children with fever and bone or joint pain.

  19. Rapid cooling after acute hyperthermia alters intestinal tissue morphology and increases the systemic inflammatory response in pigs

    Science.gov (United States)

    Acute hyperthermia can result in mortality if recovery is not appropriately managed. The study objective was to determine the effects of heatstroke recovery methods on the physiological response in pigs. In four repetitions, 36 male pigs (88.7 ± 1.6 kg BW) were exposed to thermoneutral conditions (T...

  20. Anti-RAGE antibody selectively blocks acute systemic inflammatory responses to LPS in serum, liver, CSF and striatum.

    Science.gov (United States)

    Gasparotto, Juciano; Ribeiro, Camila Tiefensee; Bortolin, Rafael Calixto; Somensi, Nauana; Fernandes, Henrique Schaan; Teixeira, Alexsander Alves; Guasselli, Marcelo Otavio Rodrigues; Agani, Crepin Aziz Jose O; Souza, Natália Cabral; Grings, Mateus; Leipnitz, Guilhian; Gomes, Henrique Mautone; de Bittencourt Pasquali, Matheus Augusto; Dunkley, Peter R; Dickson, Phillip W; Moreira, José Claudio Fonseca; Gelain, Daniel Pens

    2017-05-01

    Systemic inflammation induces transient or permanent dysfunction in the brain by exposing it to soluble inflammatory mediators. The receptor for advanced glycation endproducts (RAGE) binds to distinct ligands mediating and increasing inflammatory processes. In this study we used an LPS-induced systemic inflammation model in rats to investigate the effect of blocking RAGE in serum, liver, cerebrospinal fluid (CSF) and brain (striatum, prefrontal cortex, ventral tegmental area and substantia nigra). Intraperitoneal injection of RAGE antibody (50μg/kg) was followed after 1h by a single LPS (5mg/kg) intraperitoneal injection. Twenty-four hours later, tissues were isolated for analysis. RAGE antibody reduced LPS-induced inflammatory effects in both serum and liver; the levels of proinflammatory cytokines (TNF-α, IL-1β) were decreased and the phosphorylation/activation of RAGE downstream targets (ERK1/2, IκB and p65) in liver were significantly attenuated. RAGE antibody prevented LPS-induced effects on TNF-α and IL-1β in CSF. In striatum, RAGE antibody inhibited increases in IL-1β, Iba-1, GFAP, phospho-ERK1/2 and phospho-tau (ser202), as well as the decrease in synaptophysin levels. These effects were caused by systemic RAGE inhibition, as RAGE antibody did not cross the blood-brain barrier. RAGE antibody also prevented striatal lipoperoxidation and activation of mitochondrial complex II. In conclusion, blockade of RAGE is able to inhibit inflammatory responses induced by LPS in serum, liver, CSF and brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Comparison of Growth and the Cytokines Induced by Pathogenic Yersinia enterocolitica Bio-Serotypes 3/O: 3 and 2/O: 9.

    Science.gov (United States)

    Yang, Haoshu; Gu, Wenpeng; Qiu, Haiyan; Sun, Guixiang; Liang, Junrong; Li, Kewei; Xiao, Yuchun; Duan, Ran; Jing, Huaiqi; Wang, Xin

    2017-01-01

    Pathogenic Yersinia enterocolitica is widely distributed in China where the primary bio-serotypes are 3/O: 3 and 2/O: 9. Recently, the distribution of 2/O: 9 strains are being gradually replaced by 3/O: 3 strains where presently 3/O: 3 strains are the major pathogenic Y. enterocolitica in China. To identify the growth conditions and cytokines induced by Y. enterocolitica and providing some clues for this shift, we performed competitive growth in vitro and in vivo for these two bio-serotype strains; and we also compared the cytokines induced by them in infected BALB/C mice. We found 2/O: 9 strains grew more in vitro, while 3/O: 3 strains grew more in vivo regardless of using single cultures or mixed cultures. The cytokines induced by the two strains were similar: interleukin-6 (IL-6), IL-9, IL-13, granulocyte colony-stimulating factor (G-CSF), chemokines (KC), monocyte chemotactic protein 1 (MCP-1), macrophage inflammation protein-1α (MIP-1α), tumor necrosis factor-α (TNF-α), and RANTES were statistically up-regulated upon activation of normal T cells compared to the control. The cytokine values were higher in mixed infections than in single infections except for IL-6, G-CSF, and KC. The data illustrated the different growth of pathogenic Y. enterocolitica bio-serotype 3/O: 3 and 2/O: 9 in vitro and in vivo, and the cytokine changes induced by the two strains in infected BALB/C mice. The growth comparisons of two strains maybe reflect the higher pathogenic ability or resistance to host immune response for Y. enterocolitica bio-serotype 3/O: 3 and maybe it as one of the reason for bacteria shift.

  2. Expression of acute phase proteins and inflammatory cytokines in mouse mammary gland following Staphylococcus aureus challenge and in response to milk accumulation

    DEFF Research Database (Denmark)

    Nazemi, Sasan; Aalbæk, Bent; Kjelgaard-Hansen, Mads

    2014-01-01

    We used a mouse model of pathogenic (Staphylococcus aureus) and non-pathogenic (teat sealing) mammary inflammation to investigate mRNA expression of several inflammatory cytokines and acute phase proteins (APP) in mammary tissue and liver, and the appearance of some of these factors in plasma...... in combination might provide a tool for diagnostic discrimination between mastitis caused by pathogenic invasion and milk accumulation, and hence allow for better targeting of antibiotic therapy. In comparison with mammary expression, expression of cytokines in liver tissue was up-regulated to a similar...... or lesser extent, whilst expression of APP was up-regulated to a much greater extent. The first appearance of increased cytokine and APP concentrations in plasma and of milk amyloid A (MAA) in milk occurred in advance of the measurable up-regulation of expression, hence their origin cannot be stated...

  3. 2-Chloroadenosine (2-CADO) treatment modulates the pro-inflammatory immune response to prevent acute lung inflammation in BALB/c mice suffering from Klebsiella pneumoniae B5055-induced pneumonia.

    Science.gov (United States)

    Kumar, Vijay; Harjai, Kusum; Chhibber, Sanjay

    2010-06-01

    Acute lung inflammation (ALI) is a life-threatening pathology and can develop during the course of several clinical conditions such as pneumonia, acid aspiration or sepsis. Adenosine plays a significant role in controlling acute inflammation via binding to A(2A) receptors on inflammatory cells, i.e. neutrophils or macrophages. The present study was designed to evaluate the anti-inflammatory and immunomodulatory effects of 2-chloroadenosine (2-CADO), alone or in combination with amoxicillin/clavulanic acid (AMC), in Klebsiella pneumoniae B5055-induced acute lung infection in mice. Acute lung infection in mice was induced by directly instilling the selected dose (10(4) colony-forming units/mL) of bacteria intranasally. Histopathological examination of the lungs was performed to reveal neutrophil infiltration into the lung alveoli. In addition to the major pro-inflammatory cytokines tumour necrosis factor-alpha (TNFalpha) and interleukin (IL)-1alpha, levels of the anti-inflammatory cytokine IL-10 were also determined. Intranasal instillation of bacteria caused profound neutrophil infiltration into the lung alveoli as well as a significant increase in the levels of pro-inflammatory mediators (i.e. TNFalpha and IL-1alpha). However, intravenous administration of 2-CADO 10 microg/kg/day, alone or in combination with an antibiotic (i.e. AMC), significantly decreased neutrophil infiltration into the lung alveoli. A significant decrease in TNFalpha and IL-1alpha along with elevation of IL-10 levels in the lung homogenate of mice with acute lung infection was observed upon treatment with 2-CADO alone, with no significant decrease in bacterial counts. Moreover, in combination with AMC, 2-CADO exhibited its immunomodulatory action in acute lung infection and prevented ALI, whilst an antibacterial action was exhibited by AMC.

  4. Ginkgo biloba extracts attenuate lipopolysaccharide-induced inflammatory responses in acute lung injury by inhibiting the COX-2 and NF-κB pathways.

    Science.gov (United States)

    Yao, Xin; Chen, Nan; Ma, Chun-Hua; Tao, Jing; Bao, Jian-An; Zong-Qi, Cheng; Chen, Zu-Tao; Miao, Li-Yan

    2015-01-01

    In the present study, we analyzed the role of Ginkgo biloba extract in lipopolysaccharide(LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS. G. biloba extract (12 and 24 mg·kg(-1)) and dexamethasone (2 mg·kg(-1)), as a positive control, were given by i.p. injection. The cells in the bronchoalveolar lavage fluid (BALF) were counted. The degree of animal lung edema was evaluated by measuring the wet/dry weight ratio. The superoxidase dismutase (SOD) and myeloperoxidase (MPO) activities were assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators, tumor necrosis factor-a, interleukin-1b, and interleukin-6, were assayed by enzyme-linked immunosorbent assay. Pathological changes of lung tissues were observed by H&E staining. The levels of NF-κB p65 and COX-2 expression were detected by Western blotting. Compared to the LPS group, the treatment with the G. biloba extract at 12 and 24 mg·kg(-1) markedly attenuated the inflammatory cell numbers in the BALF, decreased NF-κB p65 and COX-2 expression, and improved SOD activity, and inhibited MPO activity. The histological changes of the lungs were also significantly improved. The results indicated that G. biloba extract has a protective effect on LPS-induced acute lung injury in mice. The protective mechanism of G. biloba extract may be partly attributed to the inhibition of NF-κB p65 and COX-2 activation.

  5. Cytokine-induced killer cell combination with TACE in the treatment of hepatocellular cancers:a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Biao Chen; Ximing Xu; Miao Xiang; Jiao Yang; Tingting Yu; Yi Hu

    2013-01-01

    Objective:The aim of the study was to evaluate the ef icacy and safety of cytokine-induced kil er (CIK) cellcombined with transcatheter arterial chemoembolization (TACE) therapy in the treatment of hepatocellular carcinoma (HCC). Methods:Randomized control ed trials (RCTs) on CIK cells combination with TACE based-therapy were identified by elec-tronic searches in the Cochrane Library, MEDLINE, Pubmed, Wanfang, VIP, CNKI and other electronic databases. We in-cluded any RCTs evaluating CIK cellcombination with TACE for the treatment of hepatocellular cancers. The quality of RCTs meeting inclusion criteria was evaluated and data on short-term and long-term curative ef ects, quality of life, liver function and immunologic function were extracted. For quantitative data, we conducted meta-analysis with ReMan 5.1 software and the GRADE System was used to rate the level of evidence and strength of recommendation. For qualitative data, data mainly adopted descriptive methods. Results:The 9 RCTs involving 870 cases meeting the inclusion criteria were included. The meta-analysis showed significant survival benefit on 0.5-year survival rate (RR=1.51, 95%CI, 1.35-1.69, P<0.00001) in fa-vor of CIK based therapy. This ef ect was consistent at other prospective dates, including 1-year survival rate (RR=2.30, 95%CI, 1.94-2.72, P<0.00001), 2-year survival rate (RR=7.03, 95%CI, 3.83-12.91, P<0.0001). Meanwhile, the CIK-based group also demonstrated a significantly prolonged time-to-progression (TTP) (SD=1.62, 95%CI, 1.30-1.94, P<0.0001) and overal survival (OS) (SD=20.6, 95%CI, 20.2-21.18, P<0.0001). Moreover, a favored response rate (RR=CR+PR) (RR=2, 95%CI, 1.65-2.43, P<0.00001) and the quality of life improvement rate (KPS) (RR=1.76, 95%CI, 1.26-2.45, P=0.0008) were also observed in patients receiving CIK cells and TACE therapy. Furthermore, patients in the CIK group showed lower AFP (SD=-165.23, 95%CI,-178.51--151.94, P<0.00001), ALT (SD=-33.14, 95%CI,-40.30--36.37, P<0

  6. Cytokine-induced impairment of short-chain fatty acid oxidation and viability in human colonic epithelial cells

    DEFF Research Database (Denmark)

    Pedersen, G; Saermark, T; Horn, T

    2000-01-01

    Pro-inflammatory cytokines may directly influence the viability and metabolic function of colonic epithelial cells (CEC) as an early event in the development of inflammatory bowel disease. We report here that TNF-alpha+IFN-gamma induced a synergistic, concentration-dependent decline in butyrate...... oxidation, an essential energy supply, in HT-29 and DLD-1 cells. TNF-alpha+IFN-gamma induced a parallel profound decline in cell viability in HT-29 cells, but not in DLD-1 cells, where impairment of butyrate oxidation seemed to precede later occurrence of cell damage. TNF-alpha+INF-gamma induced CEC damage...

  7. Fetal Kidney Cells Can Ameliorate Ischemic Acute Renal Failure in Rats through Their Anti-Inflammatory, Anti-Apoptotic and Anti-Oxidative Effects.

    Science.gov (United States)

    Gupta, Ashwani Kumar; Jadhav, Sachin H; Tripathy, Naresh Kumar; Nityanand, Soniya

    2015-01-01

    Fetal kidney cells may contain multiple populations of kidney stem cells and thus appear to be a suitable cellular therapy for the treatment of acute renal failure (ARF) but their biological characteristics and therapeutic potential have not been adequately explored. We have culture expanded fetal kidney cells derived from rat fetal kidneys, characterized them and evaluated their therapeutic effect in an ischemia reperfusion (IR) induced rat model of ARF. The fetal kidney cells grew in culture as adherent spindle shaped/polygonal cells and expressed CD29, CD44, CD73, CD90, CD105, CD24 and CD133 markers. Administration of PKH26 labeled fetal kidney cells in ARF rats resulted in a significant decrease in the levels of blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin and decreased tubular necrosis in the kidney tissues (pkidney cells were observed to engraft around injured tubular cells, and there was increased proliferation and decreased apoptosis of tubular cells in the kidneys (pkidney tissues of ARF rats treated with fetal kidney cells had a higher gene expression of renotropic growth factors (VEGF-A, IGF-1, BMP-7 and bFGF) and anti-inflammatory cytokine (IL10); up regulation of anti-oxidative markers (HO-1 and NQO-1); and a lower Bax/Bcl2 ratio as compared to saline treated rats (pkidney cells express mesenchymal and renal progenitor markers, and ameliorate ischemic ARF predominantly by their anti-apoptotic, anti-inflammatory and anti-oxidative effects.

  8. Effect of acute sleep deprivation and recovery on Insulin-like Growth Factor-I responses and inflammatory gene expression in healthy men.

    Science.gov (United States)

    Chennaoui, Mounir; Drogou, Catherine; Sauvet, Fabien; Gomez-Merino, Danielle; Scofield, Denis E; Nindl, Bradley C

    2014-01-01

    Acute sleep deprivation in humans has been found to increase inflammatory markers and signaling pathways in the periphery through a possible Toll-like receptor 4 (TLR-4). In addition, short duration sleep has been associated with low circulating total Insulin-like Growth Factor-I (IGF-I) concentrations. We aimed to determine whether a total sleep deprivation (TSD) protocol with recovery altered whole-blood gene expression of the proinflammatory cytokines TNF-α and IL-6, as well as TLR-4 expression, and to examine the relationship with circulating concentrations of the IGF-I system. Twelve healthy men participated in a five-day TSD (two control nights followed by one night of sleep deprivation and one night of recovery). Blood was sampled at 0800, before and after sleep deprivation (D2 and D4), and after recovery (D5). It is shown that 25 h of sleep deprivation (D4) induced significant increases in mRNA levels of TNF-α and its soluble receptor R1 (Psleep deprivation in healthy subjects is sufficient to induce transient and reversible genomic expression of the pro-inflammatory cytokine TNF-α and its R1 receptor, and its mediator TLR-4, with a possible link to IGF-I axis inhibition.

  9. Artesunate ameliorates severe acute pancreatitis (SAP) in rats by inhibiting expression of pro-inflammatory cytokines and Toll-like receptor 4.

    Science.gov (United States)

    Cen, Yanyan; Liu, Chao; Li, Xiaoli; Yan, Zifei; Kuang, Mei; Su, Yujie; Pan, Xichun; Qin, Rongxin; Liu, Xin; Zheng, Jiang; Zhou, Hong

    2016-09-01

    Severe acute pancreatitis (SAP) is a severe clinical condition with significant morbidity and mortality. Multiple organs dysfunction (MOD) is the leading cause of SAP-related death. The over-release of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α is the underlying mechanism of MOD; however, there is no effective agent against the inflammation. Herein, artesunate (AS) was found to increase the survival of SAP rats significantly when injected with 3.5% sodium taurocholate into the biliopancreatic duct in a retrograde direction, improving their pancreatic pathology and decreasing serum amylase and pancreatic lipase activities along with substantially reduced pancreatic IL-1β and IL-6 release. In vitro, AS-pretreatment strongly inhibited IL-1β and IL-6 release and their mRNA expressions in the pancreatic acinar cells treated with lipopolysaccharide (LPS) but exerted little effect on TNF-α release. Additionally, AS reduced the mRNA expressions of Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) p65 as well as their protein expressions in the pancreatic acinar cells. In conclusion, our results demonstrated that AS could significantly protect SAP rats, and this protection was related to the reduction of digestive enzyme activities and pro-inflammatory cytokine expressions via inhibition of TLR4/NF-κB signaling pathway. Therefore, AS may be considered as a potential therapeutic agent against SAP.

  10. Heat-Processed Scutellariae Radix Enhances Anti-Inflammatory Effect against Lipopolysaccharide-Induced Acute Lung Injury in Mice via NF-κB Signaling

    Directory of Open Access Journals (Sweden)

    Yu Ock Shin

    2015-01-01

    Full Text Available The present study was conducted to examine whether heat-processed Scutellariae Radix has an ameliorative effect on lipopolysaccharide- (LPS- induced acute lung injury in mice. The effects of Scutellariae Radix heat-processed at 160°C (HSR were compared with those of nonheat-processed Scutellariae Radix (NSR. The LPS-treated group displayed a markedly decreased body weight and significantly increased lung weight; however, the administration of NSR or HSR improved both the body and lung weights. The increased oxidative stress and inflammatory biomarker levels in the serum and lung were reduced significantly with HSR. The reduced superoxide dismutase and catalase increased significantly by both NSR and HSR. Also, the dysregulated oxidative stress and inflammation were significantly ameliorated by NSR and HSR. The expression of inflammatory mediators and cytokines by nuclear factor-kappa B activation was modulated through inhibition of a nuclear factor kappa Bα degradation. Also, lung histological change was markedly suppressed by HSR rather than NSR. Overall, the ameliorative effects of HSR were superior to those when being nonheat-processed. The representative flavonoid contents of Scutellariae Radix that include baicalin, baicalein, and wogonin were greater by heat process. These data reveal heat-processed Scutellariae Radix may be a critical factor involved in the improvement of lung disorders caused by LPS.

  11. Usefulness of Serum Procalcitonin Levels in Predicting Tubo-Ovarian Abscess in Patients with Acute Pelvic Inflammatory Disease.

    Science.gov (United States)

    Erenel, Hakan; Yilmaz, Nevin; Oncul, Mahmut; Acikgoz, Abdullah Serdar; Karatas, Suat; Ayhan, Isil; Aslan, Berna; Tuten, Abdullah

    2016-09-03

    We aimed to investigate the clinical importance of serum procalcitonin (PCT) levels in the diagnosis of tubo-ovarian abscess (TOA). Patients diagnosed with pelvic inflammatory disease (PID; n = 36) and patients diagnosed with TOA (n = 42) were included in the study. Sociodemographic characteristics, laboratory and clinical parameters were compared between the 2 groups. Mean PCT level was higher in the TOA group (p = 0.004). Mean length of stay in hospital was longer in patients with TOA (p TOA. Serum PCT is a promising inexpensive marker for the diagnosis of TOA in PID patients.

  12. Metabotropic glutamate antagonists alone and in combination with morphine: comparison across two models of acute pain and a model of persistent, inflammatory pain.

    Science.gov (United States)

    Picker, Mitchell J; Daugherty, Dana; Henry, Fredrick E; Miller, Laurence L; Dykstra, Linda A

    2011-12-01

    The present study examined the effects of the mGluR1 antagonist JNJ16259685 (JNJ) and the mGluR5 antagonist 2-methyl-6-phenylethynylpyridine (MPEP) alone and in combination with morphine in two acute pain models (hotplate, warm water tail-withdrawal), and a persistent, inflammatory pain model (capsaicin). In the hotplate and warm water tail-withdrawal procedures, JNJ and MPEP were ineffective when administered alone. In both procedures, JNJ potentiated morphine antinociception. In the hotplate procedure, MPEP potentiated morphine antinociception at the highest dose examined, whereas in the warm water tail-withdrawal procedure MPEP attenuated morphine antinociception at a moderate dose and potentiated morphine antinociception at a high dose. For both JNJ and MPEP, the magnitude of this morphine potentiation was considerably greater in the hotplate procedure. In the capsaicin procedure, the highest dose of MPEP produced intermediate levels of antihyperalgesia and also attenuated the effects of a dose of morphine that produced intermediate levels of antihyperalgesia. In contrast, JNJ had no effect when administered alone in the capsaicin procedure and did not alter morphine-induced antihyperalgesia. The present findings suggest that the effects produced by mGluR1 and mGluR5 antagonists alone and in combination with morphine can be differentiated in models of both acute and persistent pain.

  13. The inflammatory cytokine, interleukin-1 beta, mediates loss of astroglial glutamate transport and drives excitotoxic motor neuron injury in the spinal cord during acute viral encephalomyelitis.

    Science.gov (United States)

    Prow, Natalie A; Irani, David N

    2008-05-01

    Astrocytes remove glutamate from the synaptic cleft via specific transporters, and impaired glutamate reuptake may promote excitotoxic neuronal injury. In a model of viral encephalomyelitis caused by neuroadapted Sindbis virus (NSV), mice develop acute paralysis and spinal motor neuron degeneration inhibited by the AMPA receptor antagonist, NBQX. To investigate disrupted glutamate homeostasis in the spinal cord, expression of the main astroglial glutamate transporter, GLT-1, was examined. GLT-1 levels declined in the spinal cord during acute infection while GFAP expression was preserved. There was simultaneous production of inflammatory cytokines at this site, and susceptible animals treated with drugs that blocked IL-1beta release also limited paralysis and prevented the loss of GLT-1 expression. Conversely, infection of resistant mice that develop mild paralysis following NSV challenge showed higher baseline GLT-1 levels as well as lower production of IL-1beta and relatively preserved GLT-1 expression in the spinal cord compared to susceptible hosts. Finally, spinal cord GLT-1 expression was largely maintained following infection of IL-1beta-deficient animals. Together, these data show that IL-1beta inhibits astrocyte glutamate transport in the spinal cord during viral encephalomyelitis. They provide one of the strongest in vivo links between innate immune responses and the development of excitotoxicity demonstrated to date.

  14. Solanum paranense Extracts and Solanine Present Anti-Inflammatory Activity in an Acute Skin Inflammation Model in Mice

    Directory of Open Access Journals (Sweden)

    Mariana Piana

    2017-01-01

    Full Text Available The aim of the study was to evaluate the anti-inflammatory activity of the S. paranense crude extract, S. paranense alkaloid fraction, and solanine alkaloid. These samples reduce the croton oil-induced ear edema in a dose-dependent manner and a maximum inhibition of 81%, 98%, and 80% in the doses of 1.0, 0.73, and 0.37 mg/ear, respectively. Moreover, the samples inhibit the MPO activity with an inhibition maximum of 51%, 40%, and 46% in the doses of 1.0, 0.73, and 0.37 mg/ear, respectively. Similar results were found for dexamethasone 0.10 mg/ear (positive control, which showed inhibitions of ear edema and MPO activity of 100% and 65%, respectively. These results found probably are related to the presence of solanine which is present in significant quantity in the alkaloid fraction and others as rutin and rosmarinic, chlorogenic, and gallic acids. These results support the use of S. paranense for the treatment of inflammatory skin disorders.

  15. Dynamics of Acute Local Inflammatory Response after Autologous Transplantation of Muscle-Derived Cells into the Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Anna Burdzinska

    2014-01-01

    Full Text Available The vast majority of myoblasts transplanted into the skeletal muscle die within the first week after injection. Inflammatory response to the intramuscular cell transfer was studied in allogeneic but not in autologous model. The aim of this study was to evaluate immune reaction to autotransplantation of myogenic cells and to assess its dynamics within the first week after injection. Muscle-derived cells or medium alone was injected into the intact skeletal muscles in autologous model. Tissue samples were collected 1, 3, and 7 days after the procedure. Our analysis revealed the peak increase of the gene expression of all evaluated cytokines (Il-1α, Il-1β, Il-6, Tgf-β, and Tnf-α at day 1. The mRNA level of analyzed cytokines normalized in subsequent time points. The increase of Il-β gene expression was further confirmed at the protein level. Analysis of the tissue sections revealed rapid infiltration of injected cell clusters with neutrophils and macrophages. The inflammatory infiltration was almost completely resolved at day 7. The survived cells were able to participate in the muscle regeneration process. Presented results demonstrate that autotransplanted muscle-derived cells induce classical early immune reaction in the site of injection which may contribute to cellular graft elimination.

  16. Alpinetin attenuates inflammatory responses by suppressing TLR4 and NLRP3 signaling pathways in DSS-induced acute colitis.

    Science.gov (United States)

    He, Xuexiu; Wei, Zhengkai; Wang, Jingjing; Kou, Jinhua; Liu, Weijian; Fu, Yunhe; Yang, Zhengtao

    2016-06-20

    Alpinetin, a composition of Alpinia katsumadai Hayata, has been reported to have a number of biological properties, such as antibacterial, antitumor and other important therapeutic activities. However, the effect of alpinetin on inflammatory bowel disease (IBD) has not yet been reported. The purpose of this study was to investigate the anti-inflammatory effect and mechanism of alpinetin on dextran sulfate sodium (DSS)-induced colitis in mice. In vivo, DSS-induced mice colitis model was established by giving mice drinking water containing 5% (w/v) DSS for 7 days. Alpinetin (25, 50 and 100 mg/kg) were administered once a day by intraperitoneal injection 3 days before DSS treatment. In vitro, phorbol myristate acetate (PMA)-differentiated monocytic THP-1 macrophages were treated with alpinetin and stimulated by lipopolysaccharide (LPS). The results showed that alpinetin significantly attenuated diarrhea, colonic shortening, histological injury, myeloperoxidase (MPO) activity and the expressions of tumor necrosis factor (TNF-α) and interleukin (IL-1β) production in mice. In vitro, alpinetin markedly inhibited LPS-induced TNF-α and IL-1β production, as well as Toll-like receptor 4 (TLR4) mediated nuclear transcription factor-kappaB (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome activation. In conclusion, this study demonstrated that alpinetin had protective effects on DSS-induced colitis and may be a promising therapeutic reagent for colitis treatment.

  17. Lipopolysaccharide binding protein and serum amyloid A secretion by human intestinal epithelial cells during the acute phase response.

    Science.gov (United States)

    Vreugdenhil, A C; Dentener, M A; Snoek, A M; Greve, J W; Buurman, W A

    1999-09-01

    The acute phase proteins LPS binding protein (LBP) and serum amyloid A (SAA) are produced by the liver and are present in the circulation. Both proteins have been shown to participate in the immune response to endotoxins. The intestinal mucosa forms a large surface that is continuously exposed to these microbial products. By secretion of antimicrobial and immunomodulating agents, the intestinal epithelium contributes to the defense against bacteria and their products. The aim of this study was to explore the influence of the inflammatory mediators TNF-alpha, IL-6, and IL-1beta on the release of LBP and SAA by intestinal epithelial cells (IEC). In addition, the induction of LBP and SAA release by cell lines of intestinal epithelial cells and hepatic cells was compared. The data obtained show that in addition to liver cells, IEC also expressed LBP mRNA and released bioactive LBP and SAA upon stimulation. Regulation of LBP and SAA release by IEC and hepatocytes was typical for class 1 acute phase proteins, although differences in regulation between the cell types were observed. Endotoxin did not induce LBP and SAA release. Glucocorticoids were demonstrated to strongly enhance the cytokine-induced release of LBP and SAA by IEC, corresponding to hepatocytes. The data from this study, which imply that human IEC can produce LBP and SAA, suggest a role for these proteins in the local defense mechanism of the gut to endotoxin. Furthermore, the results demonstrate that tissues other than the liver are involved in the acute phase response.

  18. Agmatine Protects against Zymosan-Induced Acute Lung Injury in Mice by Inhibiting NF-κB-Mediated Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Xuanfei Li

    2014-01-01

    Full Text Available Acute lung injury (ALI is characterized by overwhelming lung inflammation and anti-inflammation treatment is proposed to be a therapeutic strategy for ALI. Agmatine, a cationic polyamine formed by decarboxylation of L-arginine, is an endogenous neuromodulator that plays protective roles in diverse central nervous system (CNS disorders. Consistent with its neuromodulatory and neuroprotective properties, agmatine has been reported to have beneficial effects on depression, anxiety, hypoxic ischemia, Parkinson’s disease, and gastric disorder. In this study, we tested the effect of agmatine on the lung inflammation induced by Zymosan (ZYM challenge in mice. We found that agmatine treatment relieved ZYM-induced acute lung injury, as evidenced by the reduced histological scores, wet/dry weight ratio, and myeloperoxidase activity in the lung tissue. This was accompanied by reduced levels of TNF-α, IL-1β, and IL-6 in lung and bronchoalveolar lavage fluid and decreased iNOS expression in lung. Furthermore, agmatine inhibited the phosphorylation and degradation of IκB and subsequently blocked the activation of nuclear factor (NF-κB induced by Zymosan. Taken together, our results showed that agmatine treatment inhibited NF-κB signaling in lungs and protected mice against ALI induced by Zymosan, suggesting agmatine may be a potential safe and effective approach for the treatment of ALI.

  19. Increase in cholinergic modulation with pyridostigmine induces anti-inflammatory cell recruitment soon after acute myocardial infarction in rats.

    Science.gov (United States)

    Rocha, Juraci Aparecida; Ribeiro, Susan Pereira; França, Cristiane Miranda; Coelho, Otávio; Alves, Gisele; Lacchini, Silvia; Kallás, Esper Georges; Irigoyen, Maria Cláudia; Consolim-Colombo, Fernanda M

    2016-04-15

    We tested the hypothesis that an increase in the anti-inflammatory cholinergic pathway, when induced by pyridostigmine (PY), may modulate subtypes of lymphocytes (CD4+, CD8+, FOXP3+) and macrophages (M1/M2) soon after myocardial infarction (MI) in rats. Wistar rats, randomly allocated to receive PY (40 mg·kg(-1)·day(-1)) in drinking water or to stay without treatment, were followed for 4 days and then were subjected to ligation of the left coronary artery. The groups-denominated as the pyridostigmine-treated infarcted (IP) and infarcted control (I) groups-were submitted to euthanasia 3 days after MI; the heart was removed for immunohistochemistry, and the peripheral blood and spleen were collected for flow cytometry analysis. Noninfarcted and untreated rats were used as controls (C Group). Echocardiographic measurements were registered on the second day after MI, and heart rate variability was measured on the third day after MI. The infarcted groups had similar MI areas, degrees of systolic dysfunction, blood pressures, and heart rates. Compared with the I Group, the IP Group showed a significant higher parasympathetic modulation and a lower sympathetic modulation, which were associated with a small, but significant, increase in diastolic function. The IP Group showed a significant increase in M2 macrophages and FOXP3(+)cells in the infarcted and peri-infarcted areas, a significantly higher frequency of circulating Treg cells (CD4(+)CD25(+)FOXP3(+)), and a less extreme decrease in conventional T cells (CD25(+)FOXP3(-)) compared with the I Group. Therefore, increasing cholinergic modulation with PY induces greater anti-inflammatory cell recruitment soon after MY in rats.

  20. Mice deficient in interferon-gamma or interferon-gamma receptor 1 have distinct inflammatory responses to acute viral encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Eun-Young Lee

    Full Text Available Interferon (IFN-gamma is an important component of the immune response to viral infections that can have a role both in controlling virus replication and inducing inflammatory damage. To determine the role of IFN-gamma in fatal alphavirus encephalitis, we have compared the responses of wild type C57BL/6 (WTB6 mice with mice deficient in either IFN-gamma (GKO or the alpha-chain of the IFN-gamma receptor (GRKO after intranasal infection with a neuroadapted strain of sindbis virus. Mortalities of GKO and GRKO mice were similar to WTB6 mice. Both GKO and GRKO mice had delayed virus clearance from the brain and spinal cord, more infiltrating perforin(+ cells and lower levels of tumor necrosis factor (TNF-alpha and interleukin (IL-6 mRNAs than WTB6 mice. However, inflammation was more intense in GRKO mice than WTB6 or GKO mice with more infiltrating CD3(+ T cells, greater expression of major histocompatibility complex-II and higher levels of interleukin-17A mRNA. Fibroblasts from GRKO embryos did not develop an antiviral response after treatment with IFN-gamma, but showed increases in TNF-alpha, IL-6, CXCL9 and CXCL10 mRNAs although these increases developed more slowly and were less intense than those of WTB6 fibroblasts. These data indicate that both GKO and GRKO mice fail to develop an IFN-gamma-mediated antiviral response, but differ in regulation of the inflammatory response to infection. Therefore, GKO and GRKO cannot be considered equivalent when assessing the role of IFN-gamma in CNS viral infections.

  1. Variants of CEP68 Gene Are Associated with Acute Urticaria/Angioedema Induced by Multiple Non-Steroidal Anti-Inflammatory Drugs

    Science.gov (United States)

    Cornejo-García, José Antonio; Flores, Carlos; Plaza-Serón, María C.; Acosta-Herrera, Marialbert; Blanca-López, Natalia; Doña, Inmaculada; Torres, María J.; Mayorga, Cristobalina; Guéant-Rodríguez, Rosa M.; Ayuso, Pedro; Fernández, Javier; Laguna, José J.; Agúndez, José A. G.; García-Martín, Elena; Guéant, Jean-Louis; Canto, Gabriela; Blanca, Miguel

    2014-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are the most consumed drugs worldwide because of their efficacy and utility in the treatment of pain and inflammatory diseases. However, they are also responsible for an important number of adverse effects including hypersensitivity reactions. The most important group of these reactions is triggered by non-immunological, pharmacological mechanisms catalogued under the denomination of cross-intolerance (CRI), with acute urticaria/angioedema induced by multiple NSAIDs (MNSAID-UA) the most frequently associated clinical entity. A recent genome-wide association study identified the gene encoding the centrosomal protein of 68 KDa (CEP68) as the major locus associated with aspirin intolerance susceptibility in asthmatics. In this study, we aimed to assess the role of this locus in susceptibility to CRI to NSAIDs by examining 53 common gene variants in a total of 635 patients that were classified as MNSAID-UA (n = 399), airway exacerbations (n = 110) or blended pattern (n = 126), and 425 controls. We found in the MNSAID-UA group a number of variants (17) associated (lowest p-value = 1.13×10−6), including the non-synonymous Gly74Ser variant (rs7572857) previously associated with aspirin intolerance susceptibility in asthmatics. Although not being significant in the context of multiple testing, eight of these variants were also associated with exacerbated respiratory disease or blended reactions. Our results suggest that CEP68 gene variants may play an important role in MNSAID-UA susceptibility and, despite the different regulatory mechanisms involved depending on the specific affected organ, in the development of hypersensitivity reactions to NSAIDs. PMID:24618698

  2. Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw.

    Science.gov (United States)

    Costa, Barbara; Colleoni, Mariapia; Conti, Silvia; Parolaro, Daniela; Franke, Chiara; Trovato, Anna Elisa; Giagnoni, Gabriella

    2004-03-01

    Cannabidiol, the major non-psychoactive component of marijuana, has various pharmacological actions of clinical interest. It is reportedly effective as an anti-inflammatory and anti-arthritic in murine collagen-induced arthritis. The present study examined the anti-inflammatory and anti-hyperalgesic effects of cannabidiol, administered orally (5-40 mg/kg) once a day for 3 days after the onset of acute inflammation induced by intraplantar injection of 0.1 ml carrageenan (1% w/v in saline) in the rat. At the end of the treatment prostaglandin E2 (PGE2) was assayed in the plasma, and cyclooxygenase (COX) activity, production of nitric oxide (NO; nitrite/nitrate content), and of other oxygen-derived free radicals (malondialdehyde) in inflamed paw tissues. All these markers were significantly increased following carrageenan. Thermal hyperalgesia, induced by carrageenan and assessed by the plantar test, lasted 7 h. Cannabidiol had a time- and dose-dependent anti-hyperalgesic effect after a single injection. Edema following carrageenan peaked at 3 h and lasted 72 h; a single dose of cannabidiol reduced edema in a dose-dependent fashion and subsequent daily doses caused further time- and dose-related reductions. There were decreases in PGE2 plasma levels, tissue COX activity, production of oxygen-derived free radicals, and NO after three doses of cannabidiol. The effect on NO seemed to depend on a lower expression of the endothelial isoform of NO synthase. In conclusion, oral cannabidiol has a beneficial action on two symptoms of established inflammation: edema and hyperalgesia.

  3. Sulforaphane exerts anti-inflammatory effects against lipopolysaccharide-induced acute lung injury in mice through the Nrf2/ARE pathway.

    Science.gov (United States)

    Qi, Tianjie; Xu, Fei; Yan, Xixin; Li, Shuai; Li, Haitao

    2016-01-01

    Sulforaphane (1-isothiocyanate-4-methyl sulfonyl butane) is a plant extract (obtained from cruciferous vegetables, such as broccoli and cabbage) and is known to exert anticancer, antioxidant and anti-inflammatory effects. It stimulates the generation of human or animal cells, which is beneficial to the body. The aim of the current study was to determine whether sulforaphane protects against lipopolysaccharide (LPS)‑induced acute lung injury (ALI) through its anti-inflammatory effects, and to investigate the signaling pathways involved. For this purpose, male BALB/c mice were treated with sulforaphane (50 mg/kg) and 3 days later, ALI was induced by the administration of LPS (5 mg/kg) and we thus established the model of ALI. Our results revealed that sulforaphane significantly decreased lactate dehydrogenase (LDH) activity (as shown by LDH assay), the wet-to-dry ratio of the lungs and the serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) (measured by ELISA), as well as nuclear factor-κB protein expression in mice with LPS-induced ALI. Moreover, treatment with sulforaphane significantly inhibited prostaglandin E2 (PGE2) production, and cyclooxygenase-2 (COX-2), matrix metalloproteinase-9 (MMP-9) protein expression (as shown by western blot analysis), as well as inducible nitric oxide synthase (iNOS) activity in mice with LPS-induced ALI. Lastly, we noted that pre-treatment with sulforaphane activated the nuclear factor-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway in the mice with LPS-induced ALI. These findings demonstrate that sulforaphane exerts protective effects against LPS-induced ALI through the Nrf2/ARE pathway. Thus, sulforaphane may be a potential a candidate for use in the treatment of ALI.

  4. Plant derived aporphinic alkaloid S-(+-dicentrine induces antinociceptive effect in both acute and chronic inflammatory pain models: evidence for a role of TRPA1 channels.

    Directory of Open Access Journals (Sweden)

    Deise Prehs Montrucchio

    Full Text Available S-(+-dicentrine is an aporphinic alkaloid found in several plant species, mainly from Lauraceae family, which showed significant antinociceptive activity in an acute model of visceral pain in mice. In this work, we extended the knowledge on the antinociceptive properties of S-(+-dicentrine and showed that this alkaloid also attenuates mechanical and cold hypersensitivity associated with cutaneous inflammation induced by Complete Freund's Adjuvant in mice. Given orally, S-(+-dicentrine (100 mg/kg reversed CFA-induced mechanical hypersensitivity, evaluated as the paw withdrawal threshold to von Frey hairs, and this effect lasted up to 2 hours. S-(+-dicentrine also reversed CFA-induced cold hypersensitivity, assessed as the responses to a drop of acetone in the injured paw, but did not reverse the heat hypersensitivity, evaluated as the latency time to paw withdrawal in the hot plate (50°C. Moreover, S-(+-dicentrine (100 mg/kg, p.o. was effective in inhibit nociceptive responses to intraplantar injections of cinnamaldehyde, a TRPA1 activator, but not the responses induced by capsaicin, a TRPV1 activator. When administered either by oral or intraplantar routes, S-(+-dicentrine reduced the licking time (spontaneous nociception and increased the latency time to paw withdrawal in the cold plate (cold hypersensitivity, both induced by the intraplantar injection of cinnamaldehyde. Taken together, our data adds information about antinociceptive properties of S-(+-dicentrine in inflammatory conditions, reducing spontaneous nociception and attenuating mechanical and cold hypersensitivity, probably via a TRPA1-dependent mechanism. It also indicates that S-(+-dicentrine might be potentially interesting in the development of new clinically relevant drugs for the management of persistent pain, especially under inflammatory conditions.

  5. Variants of CEP68 gene are associated with acute urticaria/angioedema induced by multiple non-steroidal anti-inflammatory drugs.

    Directory of Open Access Journals (Sweden)

    José Antonio Cornejo-García

    Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs are the most consumed drugs worldwide because of their efficacy and utility in the treatment of pain and inflammatory diseases. However, they are also responsible for an important number of adverse effects including hypersensitivity reactions. The most important group of these reactions is triggered by non-immunological, pharmacological mechanisms catalogued under the denomination of cross-intolerance (CRI, with acute urticaria/angioedema induced by multiple NSAIDs (MNSAID-UA the most frequently associated clinical entity. A recent genome-wide association study identified the gene encoding the centrosomal protein of 68 KDa (CEP68 as the major locus associated with aspirin intolerance susceptibility in asthmatics. In this study, we aimed to assess the role of this locus in susceptibility to CRI to NSAIDs by examining 53 common gene variants in a total of 635 patients that were classified as MNSAID-UA (n = 399, airway exacerbations (n = 110 or blended pattern (n = 126, and 425 controls. We found in the MNSAID-UA group a number of variants (17 associated (lowest p-value = 1.13 × 10(-6, including the non-synonymous Gly74Ser variant (rs7572857 previously associated with aspirin intolerance susceptibility in asthmatics. Although not being significant in the context of multiple testing, eight of these variants were also associated with exacerbated respiratory disease or blended reactions. Our results suggest that CEP68 gene variants may play an important role in MNSAID-UA susceptibility and, despite the different regulatory mechanisms involved depending on the specific affected organ, in the development of hypersensitivity reactions to NSAIDs.

  6. Variants of CEP68 gene are associated with acute urticaria/angioedema induced by multiple non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    Cornejo-García, José Antonio; Flores, Carlos; Plaza-Serón, María C; Acosta-Herrera, Marialbert; Blanca-López, Natalia; Doña, Inmaculada; Torres, María J; Mayorga, Cristobalina; Guéant-Rodríguez, Rosa M; Ayuso, Pedro; Fernández, Javier; Laguna, José J; Agúndez, José A G; García-Martín, Elena; Guéant, Jean-Louis; Canto, Gabriela; Blanca, Miguel

    2014-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are the most consumed drugs worldwide because of their efficacy and utility in the treatment of pain and inflammatory diseases. However, they are also responsible for an important number of adverse effects including hypersensitivity reactions. The most important group of these reactions is triggered by non-immunological, pharmacological mechanisms catalogued under the denomination of cross-intolerance (CRI), with acute urticaria/angioedema induced by multiple NSAIDs (MNSAID-UA) the most frequently associated clinical entity. A recent genome-wide association study identified the gene encoding the centrosomal protein of 68 KDa (CEP68) as the major locus associated with aspirin intolerance susceptibility in asthmatics. In this study, we aimed to assess the role of this locus in susceptibility to CRI to NSAIDs by examining 53 common gene variants in a total of 635 patients that were classified as MNSAID-UA (n = 399), airway exacerbations (n = 110) or blended pattern (n = 126), and 425 controls. We found in the MNSAID-UA group a number of variants (17) associated (lowest p-value = 1.13 × 10(-6)), including the non-synonymous Gly74Ser variant (rs7572857) previously associated with aspirin intolerance susceptibility in asthmatics. Although not being significant in the context of multiple testing, eight of these variants were also associated with exacerbated respiratory disease or blended reactions. Our results suggest that CEP68 gene variants may play an important role in MNSAID-UA susceptibility and, despite the different regulatory mechanisms involved depending on the specific affected organ, in the development of hypersensitivity reactions to NSAIDs.

  7. Studies on the pathogenesis of acute inflammation. I. The inflammatory reaction to thermal injury as observed in the rabbit ear chamber.

    Science.gov (United States)

    ALLISON, F; SMITH, M R; WOOD, W B

    1955-12-01

    A special adaptation of the rabbit ear chamber has been devised to study in vivo, under high magnification, the acute inflammatory reaction to thermal injury. Systematic observations of the cellular response have led to the following conclusions. 1. Contrary to the commonly accepted view, vasodilatation does not always precede the adherence of leucocytes to vascular endothelium. 2. The fact that leucocytes often adhere to one another as well as to the endothelium indicates that the increased adhesiveness characteristic of the early stages of inflammation is not limited to the surfaces of the endothelial cells. 3. The sharing of erythrocytes and platelets in this increased stickiness suggests that a "plasma factor" is involved. There is indirect but as yet inconclusive evidence that the plasma factor may concern the clotting mechanism of the blood. 4. The adherence of leucocytes to the endothelium is usually first noted on the side of the vessel closest to the site of injury. This previously undescribed phenomenon of "unilateral sticking" is in keeping with the concept that the vascular reaction is caused by products of cellular damage which diffuse to the vessel from the site of injury. 5. Leucocytes always become adherent to the endothelium before penetrating the vessel wall. They often migrate about for some time on the endothelial surface before undergoing diapedesis. 6. Although no definite stomata are at any time visible in the endothelium, penetrating leucocytes may leave behind temporary defects through which other leucocytes and even erythrocytes may pass. 7. The diapedesis of leucocytes appears to depend primarily upon cellular motility. It may occur in static vessels where there is presumably little if any hydrostatic pressure. 8. The diapedesis of erythrocytes, on the other hand, is a passive process depending upon intravascular pressure. Its occurrence is greatly exaggerated in areas in which intravascular pressure becomes elevated. Such elevations

  8. Efficacy of cytokine-induced killer cell infusion as an adjuvant immunotherapy for hepatocellular carcinoma: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Yu R

    2017-03-01

    Full Text Available Ruili Yu,1 Bo Yang,2 Xiaohua Chi,3 Lili Cai,4 Cui Liu,5 Lei Yang,6 Xueyan Wang,1 Peifeng He,7 Xuechun Lu2 1Department of Allergy, Beijing Shijitan Hospital, Affiliated to Capital Medical University, 2Department of Geriatric Hematology, Chinese PLA General Hospital, 3Department of Pharmacy, Chinese PLA Rocket Force General Hospital, 4Department of Geriatric Laboratory Medicine, 5Department of Geriatric Ultrasound, 6Medical Department, Nanlou Clinic, Chinese PLA General Hospital, Beijing, 7School of Medical Information Management, Shanxi Medical University, Taiyuan, People’s Republic of China Abstract: This study was designed to evaluate the efficacy and safety of cytokine-induced killer (CIK cell-based immunotherapy as an adjuvant therapy for hepatocellular carcinoma (HCC. Published studies were identified by searching Medline, Cochrane, EMBASE, and Google Scholar databases with the keywords: cytokine-induced killer cell, hepatocellular carcinoma, and immunotherapy. The outcomes of interest were overall survival, progression-free survival, and disease-free survival. Eight randomized controlled trials (RCTs, six prospective studies, and three retrospective studies were included. The overall analysis revealed that patients in the CIK cell-treatment group had a higher survival rate (pooled hazard ratio (HR =0.594, 95% confidence interval [CI] =0.501–0.703, P<0.001. Patients treated with CIK cells in non-RCTs had a higher progression-free survival rate (pooled HR =0.613, 95% CI =0.510–0.738, P<0.001. However, CIK cell-treated patients in RCTs had progression-free survival rates similar to those of the control group (pooled HR =0.700, 95% CI =0.452–1.084, P=0.110. The comparison between pooled results of RCTs and non-RCTs regarding the progression-free survival rate did not reach statistical significance. Patients in the CIK cell-treatment group had lower rates of relapse in RCTs (pooled HR =0.635, 95% CI =0.514–0.784, P<0.001. Similar

  9. Sarcandra glabra combined with lycopene protect rats from lipopolysaccharide induced acute lung injury via reducing inflammatory response.

    Science.gov (United States)

    Liu, Tian-Yin; Chen, Shi-Biao

    2016-12-01

    Sarcandra glabra (Chinese name, Zhongjiefeng) is an important herb widely used in traditional Chinese medicine. Lycopene has been shown to be a powerful antioxidant. This study aims to test the hypothesis that Sarcandra glabra combined with lycopene protect rats from lipopolysaccharide (LPS) induced acute lung injury (ALI). Metabolomics approach combined with pathological inspection, serum biochemistry examination, enzyme-linked immunosorbent assay and western blotting were used to explore the protective effects of Sarcandra glabra and lycopene on LPS-induced ALI, and to elucidate the underlying mechanisms. Results showed that Sarcandra glabra and lycopene could significantly ameliorate LPS-induced histopathological injuries, improve the anti-oxidative activities of rats, decrease the levels of TNF-α and IL-6, suppress the activations of MAPK and transcription factor NF-κB and reverse the disturbed metabolism towards the normal status. Taken together, this integrated study revealed that Sarcandra glabra combined with lycopene had great potential in protecting rats from LPS-induced ALI, which would be helpful to guide the clinical medication.

  10. Fish Oil-Based Fat Emulsion Reduces Acute Kidney Injury and Inflammatory Response in Antibiotic-Treated Polymicrobial Septic Mice.

    Science.gov (United States)

    Shih, Juey-Ming; Shih, Yao-Ming; Pai, Man-Hui; Hou, Yu-Chen; Yeh, Chiu-Li; Yeh, Sung-Ling

    2016-03-15

    Acute kidney injury (AKI) is a common complication in sepsis. This study compared the effects of a fish oil-based with a mixed oil fat emulsion on remote renal injury in an antibiotic-treated septic murine model. Mice were randomly assigned to a normal control (NC) group and three septic groups. Sepsis was induced by cecal ligation and puncture (CLP). The antibiotic was injected intraperitoneally (IP) after CLP and then daily till the time of sacrifice. Three hours after antibiotic treatment, one of the septic groups was injected IP with a fish oil-based emulsion (FO), while the other two groups were given either a mixed oil emulsion (MO) or saline (SC). The septic groups were further divided into two separate time groups, with blood and kidneys samples collected at 24 h or 72 h post-CLP. The results showed that sepsis leads to the activation of neutrophils, T helper (Th)1/Th-2/Th-17 and Treg cells (p oil-based emulsion had decreased plasma NGAL by 22% and Treg by 33%. Furthermore, renal gene expressions of MyD88 and TLR4 reduced by 46% and 62%, respectively, whereas heat shock protein 70 and peroxisome proliferator-activated receptor-γ increased by 158% and 69%, respectively (p oil-based emulsion has favorable effects, maintaining blood T cell percentage, downregulating Treg expression, attenuating systemic and local inflammation and offering renal protection under conditions of antibiotic-treated polymicrobial sepsis.

  11. More pronounced effect of acute exercise-induced increase in circulating inflammatory markers in obese compared to lean subjects

    DEFF Research Database (Denmark)

    Christiansen, Tore; Paulsen, Søren Kildeberg; Bruun, Jens Meldgaard

    2010-01-01

    (55-60% of maximal heart rate). Blood samples were obtained at baseline (T0), after 60 minutes of bicycling (T=60), after 120 minutes of bicycling (T=120), whereas biopsies from AT and SM were obtained at T0 and T120. Results: Divided into weight-status, plasma levels of IL-8 and TNFα were at T=120......Objective: Exercise modulates the immune system and in young males acute exercise has been found associated with increased systemic level of infam-matory markers such as IL-6 and IL-8. In this study we investigated the impact of obesity on the exercise induced release of infammatory markers...... in circulation, and on gene expression on these infammatory marker in skeletal muscle (SM) and adipose tissue (AT) biopsies. Material and Methods: 15 lean males and females (BMI 22.4±2 kg/m2) and 16 obese males and females (BMI 31.6±3 kg/m2) exercised for 120 minutes by ergometer bicycling at moderate intensity...

  12. Proinflammatory cytokines induce bronchial hyperplasia and squamous metaplasia in smokers: implications for chronic obstructive pulmonary disease therapy.

    Science.gov (United States)

    Herfs, Michael; Hubert, Pascale; Poirrier, Anne-Lise; Vandevenne, Patricia; Renoux, Virginie; Habraken, Yvette; Cataldo, Didier; Boniver, Jacques; Delvenne, Philippe

    2012-07-01

    Tracheobronchial squamous metaplasia is common in smokers, and is associated with both airway obstruction in chronic obstructive pulmonary disease (COPD) and increased risk of lung cancer. Although this reversible epithelial replacement is almost always observed in association with chronic inflammation, the role of inflammatory mediators in the pathogenesis of squamous metaplasia remains unclear. In the present study, we investigated the implication of cigarette smoke-mediated proinflammatory cytokine up-regulation in the development and treatment of tracheobronchial epithelial hyperplasia and squamous metaplasia. Using immunohistological techniques, we showed a higher epithelial expression of TNF-α, IL-1β, and IL-6, as well as an activation of NF-κB and activator protein-1/mitogen-activated protein kinase signaling pathways in the respiratory tract of smoking patients, compared with the normal ciliated epithelium of nonsmoking patients. In addition, we demonstrated that these signaling pathways strongly influence the proliferation and differentiation state of in vitro-generated normal human airway epithelial basal cells. Finally, we exposed mice to cigarette smoke for 16 weeks, and demonstrated that anti-TNF-α (etanercept), anti-IL-1β (anakinra), and/or anti-IL-6R (tocilizumab) therapies significantly reduced epithelial hyperplasia and the development of squamous metaplasia. These data highlight the importance of soluble inflammatory mediators in the pathogenesis of tracheobronchial squamous metaplasia. Therefore, the administration of proinflammatory cytokine antagonists may have clinical applications in the management of patients with COPD.

  13. Non-Steroidal Anti-Inflammatory Drugs and Aspirin Therapy for the Treatment of Acute and Recurrent Idiopathic Pericarditis

    Directory of Open Access Journals (Sweden)

    Nicholas Schwier

    2016-03-01

    Full Text Available Aspirin (ASA and non-steroidal anti-inflammatory drugs (NSAIDs are a mainstay of therapy for the treatment of idiopathic pericarditis (IP. A comprehensive review consisting of pertinent clinical literature, pharmacokinetic, and pharmacodynamic considerations, has not been released in recent years. This review will facilitate the clinician’s understanding of pharmacotherapeutic considerations for using ASA/NSAIDs to treat IP. Data were compiled using clinical literature consisting of case reports, cohort data, retrospective and prospective studies, and manufacturer package inserts. ASA, ibuprofen, indometacin, and ketorolac relatively have the most evidence in the treatment of IP, provide symptomatic relief of IP, and should be tapered accordingly. ASA is the drug of choice in patients with coronary artery disease (CAD, heart failure (HF, or renal disease, but should be avoided in patients with asthma and nasal polyps, who are naïve to ASA therapy. Ibuprofen is an inexpensive and relatively accessible option in patients who do not have concomitant CAD, HF, or renal disease. Indometacin is not available over-the-counter in the USA, and has a relatively higher incidence of central nervous system (CNS adverse effects. Ketorolac is an intravenous option; however, clinicians must be mindful of the maximum dose that can be administered. While ASA/NSAIDs do not ameliorate the disease process of IP, they are part of first-line therapy (along with colchicine, for preventing recurrence of IP. ASA/NSAID choice should be dictated by comorbid conditions, tolerability, and adverse effects. Additionally, the clinician should be mindful of considerations such as tapering, high-sensitivity CRP monitoring, bleeding risk, and contraindications to ASA/NSAID therapy.

  14. Echocardiography, spirometry, and systemic acute-phase inflammatory proteins in smokers with COPD or CHF: an observational study.

    Directory of Open Access Journals (Sweden)

    Bianca Beghé

    Full Text Available Chronic obstructive pulmonary disease (COPD and chronic heart failure (CHF may coexist in elderly patients with a history of smoking. Low-grade systemic inflammation induced by smoking may represent the link between these 2 conditions. In this study, we investigated left ventricular dysfunction in patients primarily diagnosed with COPD, and nonreversible airflow limitation in patients primarily diagnosed with CHF. The levels of circulating high-sensitive C-reactive protein (Hs-CRP, pentraxin 3 (PTX3, interleukin-1β (IL-1 β, and soluble type II receptor of IL-1 (sIL-1RII were also measured as markers of systemic inflammation in these 2 cohorts. Patients aged ≥ 50 years and with ≥ 10 pack years of cigarette smoking who presented with a diagnosis of stable COPD (n=70 or stable CHF (n=124 were recruited. All patients underwent echocardiography, N-terminal pro-hormone of brain natriuretic peptide measurements, and post-bronchodilator spirometry. Plasma levels of Hs-CRP, PTX3, IL-1 β, and sIL-1RII were determined by using a sandwich enzyme-linked immuno-sorbent assay in all patients and in 24 healthy smokers (control subjects. Although we were unable to find a single COPD patient with left ventricular dysfunction, we found nonreversible airflow limitation in 34% of patients with CHF. On the other hand, COPD patients had higher plasma levels of Hs-CRP, IL1 β, and sIL-1RII compared with CHF patients and control subjects (p < 0.05. None of the inflammatory biomarkers was different between CHF patients and control subjects. In conclusion, although the COPD patients had no evidence of CHF, up to one third of patients with CHF had airflow limitation, suggesting that routine spirometry is warranted in patients with CHF, whereas echocardiography is not required in well characterized patients with COPD. Only smokers with COPD seem to have evidence of systemic inflammation.

  15. Anti-inflammatory effect of Moringa oleifera Lam. seeds on acetic acid-induced acute colitis in rats

    Directory of Open Access Journals (Sweden)

    Mohsen Minaiyan

    2014-02-01

    Full Text Available Objective: Anti-inflammatory, immuno-modulatory, and antioxidant properties of Moringa oleifera Lam. suggest that it might have beneficial effects on colitis. The present study was performed to investigate the anticolitis effect of Moringa oleifera seeds hydro-alcoholic extract (MSHE and its chloroform fraction (MCF on acetic acid-induced colitis in rats. Materials and Methods: Both MSHE and MCF with three increasing doses (50, 100, and 200 mg/kg were administered orally to separate groups of male Wistar rats, 2 h before ulcer induction (using acetic acid 4% and continued for 5 days. Prednisolone (4 mg/kg and normal saline (1 ml/kg were used in reference and control groups, respectively. All rats were sacrificed 24 h after the last dose (at day 6 and tissue injuries were assessed macroscopically and pathologically. Results: Extracts with three doses mentioned before were effective to reduce weight of distal colon (8 cm as a marker for inflammation and tissue edema. Three doses of MSHE and two greater doses of MCF (100 and 200 mg/kg were effective to reduce ulcer severity, area, and index as well as mucosal inflammation severity and extent, crypt damage, invasion involvement, total colitis index, and MPO activity compared with controls. MCF (50 mg/kg was not significantly effective in reducing evaluated parameters of colitis compared with controls. Conclusion: It is concluded that MSHE and MCF were both effective to treat experimental colitis and this might be attributed to their similar major components, biophenols and flavonoids. Since the efficacy was evident even in low doses of MSHE, presence of active constituents with high potency in seeds is persuasive.

  16. Mixed Lineage Kinase-3 Stabilizes and Functionally Cooperates with TRIBBLES-3 to Compromise Mitochondrial Integrity in Cytokine-induced Death of Pancreatic Beta Cells*

    Science.gov (United States)

    Humphrey, Rohan K.; Newcomb, Christina J.; Yu, Shu-Mei A.; Hao, Ergeng; Yu, Doris; Krajewski, Stan; Du, Keyong; Jhala, Ulupi S.

    2010-01-01

    Mixed lineage kinases (MLKs) have been implicated in cytokine signaling as well as in cell death pathways. Our studies show that MLK3 is activated in leukocyte-infiltrated islets of non-obese diabetic mice and that MLK3 activation compromises mitochondrial integrity and induces apoptosis of beta cells. Using an ex vivo model of islet-splenocyte co-culture, we show that MLK3 mediates its effects via the pseudokinase TRB3, a mammalian homolog of Drosophila Tribbles. TRB3 expression strongly coincided with conformational change and mitochondrial translocation of BAX. Mechanistically, MLK3 directly interacted with and stabilized TRB3, resulting in inhibition of Akt, a strong suppressor of BAX translocation and mitochondrial membrane permeabilization. Accordingly, attenuation of MLK3 or TRB3 expression each prevented cytokine-induced BAX conformational change and attenuated the progression to apoptosis. We conclude that MLKs compromise mitochondrial integrity and suppress cellular survival mechanisms via TRB3-dependent inhibition of Akt. PMID:20421299

  17. Fish Oil-Based Fat Emulsion Reduces Acute Kidney Injury and Inflammatory Response in Antibiotic-Treated Polymicrobial Septic Mice

    Directory of Open Access Journals (Sweden)

    Juey-Ming Shih

    2016-03-01

    Full Text Available Acute kidney injury (AKI is a common complication in sepsis. This study compared the effects of a fish oil-based with a mixed oil fat emulsion on remote renal injury in an antibiotic-treated septic murine model. Mice were randomly assigned to a normal control (NC group and three septic groups. Sepsis was induced by cecal ligation and puncture (CLP. The antibiotic was injected intraperitoneally (IP after CLP and then daily till the time of sacrifice. Three hours after antibiotic treatment, one of the septic groups was injected IP with a fish oil-based emulsion (FO, while the other two groups were given either a mixed oil emulsion (MO or saline (SC. The septic groups were further divided into two separate time groups, with blood and kidneys samples collected at 24 h or 72 h post-CLP. The results showed that sepsis leads to the activation of neutrophils, T helper (Th1/Th-2/Th-17 and Treg cells (p < 0.05. Plasma NGAL and mRNA expressions of renal MyD88 and TLR4 were also enhanced (p < 0.05. Compared to the SC group, the group given the fish oil-based emulsion had decreased plasma NGAL by 22% and Treg by 33%. Furthermore, renal gene expressions of MyD88 and TLR4 reduced by 46% and 62%, respectively, whereas heat shock protein 70 and peroxisome proliferator-activated receptor-γ increased by 158% and 69%, respectively (p < 0.05, at Day 3 after CLP. These results suggest that administration of a fish oil-based emulsion has favorable effects, maintaining blood T cell percentage, downregulating Treg expression, attenuating systemic and local inflammation and offering renal protection under conditions of antibiotic-treated polymicrobial sepsis.

  18. Vaginal Heparan Sulfate Linked to Neutrophil Dysfunction in the Acute Inflammatory Response Associated with Experimental Vulvovaginal Candidiasis

    Science.gov (United States)

    Yano, Junko; Noverr, Mairi C.

    2017-01-01

    ABSTRACT Despite acute inflammation by polymorphonuclear neutrophils (PMNs) during vulvovaginal candidiasis (VVC), clearance of Candida fails to occur. The purpose of this study was to uncover the mechanism of vaginal PMN dysfunction. Designs included assessing PMN migration, proinflammatory mediators, and tissue damage (by analysis of the activity of lactate dehydrogenase [LDH]) in mice susceptible (C3H/HeN-C57BL/6) or resistant (CD-1) to chronic VVC (CVVC-S or CVVC-R) and testing morphology-specific Candida albicans strains under conditions of preinduced PMN migration (CVVC-S mice) or PMN depletion (CVVC-R mice). In vitro designs included evaluation of C. albicans killing by elicited vaginal or peritoneal PMNs in standard or vaginal conditioned medium (VCM). Results showed that despite significant migration of PMNs and high levels of vaginal beta interleukin-1 (IL-1β) and alarmin S100A8, CVVC-S mice failed to reduce vaginal fungal burden irrespective of morphology or whether PMNs were present pre- or postinoculation, and had high LDH levels. In contrast, CVVC-R mice had reduced fungal burden and low LDH levels following PMN recruitment and IL-1β/S100A8 production, but maintained colonization in the absence of PMNs. Elicited vaginal and peritoneal PMNs showed substantial killing activity in standard media or VCM from CVVC-R mice but not in VCM from CVVC-S mice. The inhibitory effect of VCM from CVVC-S mice was unaffected by endogenous or exogenous estrogen and was ablated following depletion/neutralization of Mac-1 ligands using Mac-1+/+ PMNs or recombinant Mac-1. Heparan sulfate (HS) was identified as the putative inhibitor as evidenced by the rescue of PMN killing following heparanase treatment of VCM, as well as by inhibition of killing by purified HS. These results suggest that vaginal HS is linked to PMN dysfunction in CVVC-S mice as a competitive ligand for Mac-1. PMID:28292981

  19. Using the polymerase chain reaction coupled with denaturing gradient gel electrophoresis to investigate the association between bacterial translocation and systemic inflammatory response syndrome in predicted acute severe pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Callum B Pearce; Vitaly Zinkevich; Iwona Beech; Viera Funjika; Ana Garcia Ruiz; Afraa Aladawi; Hamish D Duncan

    2005-01-01

    AIM: To investigate the use of PCR and DGGE to investigate the association between bacterial translocation and systemic inflammatory response syndrome in predicted severe AP.METHODS: Patients with biochemical and clinical evidence of acute pancreatitis and an APACHE Ⅱ score ≥8 were enrolled. PCR and DGGE were employed to detect bacterial translocation in blood samples collected on d1,3, and 8 after the admission. Standard microbial blood cultures were taken when there was clinical evidence of sepsis or when felt to be clinically indicated by the supervising team.RESULTS: Six patients were included. Of all the patients investigated, only one developed septic complications;the others had uneventful illness. Bacteria were detected using PCR in 4 of the 17 collected blood samples. The patient with sepsis was PCR-positive in two samples (taken on d 1 and 3), despite three negative blood cultures. Using DGGE and specific primers, the bacteria in all blood specimens which tested positive for the presence of bacterial DNA were identified as E coli.CONCLUSION: Our study confirmed thatunlike traditional microbiological techniques, PCR can detect the presence of bacteria in the blood of patients with severe AP. Therefore, this latter method in conjunction with DGGE is potentially an extremely useful tool in predicting septic morbidity and evaluating patients with the disease. Further research using increased numbers of patients, in particular those patients with necrosis and sepsis, is required to assess the reliability of PCR and DGGE in the rapid diagnosis of infection in AP.

  20. Early Electrodiagnostic Features of Upper Extremity Sensory Nerves Can Differentiate Axonal Guillain-Barré Syndrome from Acute Inflammatory Demyelinating Polyneuropathy

    Science.gov (United States)

    Koo, Yong Seo; Shin, Ha Young; Kim, Jong Kuk; Nam, Tai-Seung; Shin, Kyong Jin; Bae, Jong-Seok; Suh, Bum Chun; Oh, Jeeyoung; Yoon, Byeol-A

    2016-01-01

    Background and Purpose Serial nerve conduction studies (NCSs) are recommended for differentiating axonal and demyelinating Guillain-Barré syndrome (GBS), but this approach is not suitable for early diagnoses. This study was designed to identify possible NCS parameters for differentiating GBS subtypes. Methods We retrospectively reviewed the medical records of 70 patients with GBS who underwent NCS within 10 days of symptom onset. Patients with axonal GBS and acute inflammatory demyelinating polyneuropathy (AIDP) were selected based on clinical characteristics and serial NCSs. An antiganglioside antibody study was used to increase the diagnostic certainty. Results The amplitudes of median and ulnar nerve sensory nerve action potentials (SNAPs) were significantly smaller in the AIDP group than in the axonal-GBS group. Classification and regression-tree analysis revealed that the distal ulnar sensory nerve SNAP amplitude was the best predictor of axonal GBS. Conclusions Early upper extremity sensory NCS findings are helpful in differentiating axonal-GBS patients with antiganglioside antibodies from AIDP patients. PMID:27819421

  1. Is abdominal CT useful for the management of patients with severe acute colitis complicating inflammatory bowel disease? A study in 54 consecutive patients.

    Science.gov (United States)

    Mege, D; Monsinjon, M; Zappa, M; Stefanescu, C; Treton, X; Maggiori, L; Bouhnik, Y; Panis, Y

    2017-04-01

    To evaluate the contribution of CT for the management of patients with severe acute exacerbation of colitis (SAC) complicating inflammatory bowel disease (IBD); in particular, its contribution to surgical decision making. All patients who were admitted to our institution for SAC complicating IBD were divided into two groups: group A (those who received surgical treatment); and group B (those who received medical treatment). Admission CT results were compared between groups. From 2006 to 2015, 54 patients [26 male; median age 39 (17-71) years] presenting with SAC were placed in either group A (n = 41; 76%) or group B (n = 13; 24%). Surgical patients in group A more frequently had altered general status (50 vs 17%; P = 0.01). Physical examination, Lichtiger score, endoscopic findings and laboratory results were similar between the groups. There was no significant difference in CT data between the groups with respect to extent of the colitis (pan-colitis in 54 and 69%, respectively, P = 0.35), median colonic thickness [10 (4-16) vs 8 (6-11) mm, P = 0.15], target enhancement (88 vs 77%, P = 0.38) and occurrence of toxic megacolon (2 vs 0%). Admission CT is not helpful in surgical decision making in SAC. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

  2. Comparative expression profile of NOD1/2 and certain acute inflammatory cytokines in thermal-stressed cell culture model of native and crossbred cattle

    Science.gov (United States)

    Bhanuprakash, V.; Singh, Umesh; Sengar, Gyanendra Singh; Raja, T. V.; Sajjanar, Basavraj; Alex, Rani; Kumar, Sushil; Alyethodi, R. R.; Kumar, Ashish; Sharma, Ankur; Kumar, Suresh; Bhusan, Bharat; Deb, Rajib

    2017-05-01

    Thermotolerance depends mainly on the health and immune status of the animals. The variation in the immune status of the animals may alter the level of tolerance of animals exposed to heat or cold stress. The present study was conducted to investigate the expression profile of two important nucleotide binding and oligomerization domain receptors (NLRs) (NOD1 and NOD2) and their central signalling molecule RIP2 gene during in vitro thermal-stressed bovine peripheral blood mononuclear cells (PBMCs) of native (Sahiwal) and crossbred (Sahiwal X HF) cattle. We also examined the differential expression profile of certain acute inflammatory cytokines in in vitro thermal-stressed PBMC culture among native and its crossbred counterparts. Results revealed that the expression profile of NOD1/2 positively correlates with the thermal stress, signalling molecule and cytokines. Present findings also highlighted that the expression patterns during thermal stress were comparatively superior among indigenous compared to crossbred cattle which may add references regarding the better immune adaptability of Zebu cattle.

  3. Comparative expression profile of NOD1/2 and certain acute inflammatory cytokines in thermal-stressed cell culture model of native and crossbred cattle

    Science.gov (United States)

    Bhanuprakash, V.; Singh, Umesh; Sengar, Gyanendra Singh; Raja, T. V.; Sajjanar, Basavraj; Alex, Rani; Kumar, Sushil; Alyethodi, R. R.; Kumar, Ashish; Sharma, Ankur; Kumar, Suresh; Bhusan, Bharat; Deb, Rajib

    2016-11-01

    Thermotolerance depends mainly on the health and immune status of the animals. The variation in the immune status of the animals may alter the level of tolerance of animals exposed to heat or cold stress. The present study was conducted to investigate the expression profile of two important nucleotide binding and oligomerization domain receptors (NLRs) (NOD1 and NOD2) and their central signalling molecule RIP2 gene during in vitro thermal-stressed bovine peripheral blood mononuclear cells (PBMCs) of native (Sahiwal) and crossbred (Sahiwal X HF) cattle. We also examined the differential expression profile of certain acute inflammatory cytokines in in vitro thermal-stressed PBMC culture among native and its crossbred counterparts. Results revealed that the expression profile of NOD1/2 positively correlates with the thermal stress, signalling molecule and cytokines. Present findings also highlighted that the expression patterns during thermal stress were comparatively superior among indigenous compared to crossbred cattle which may add references regarding the better immune adaptability of Zebu cattle.

  4. Modulation of Early Inflammatory Response by Different Balanced and Non-Balanced Colloids and Crystalloids in a Rodent Model of Endotoxemia

    Science.gov (United States)

    Voigtsberger, Stefanie; Urner, Martin; Hasler, Melanie; Roth Z'Graggen, Birgit; Booy, Christa; Spahn, Donat R.; Beck-Schimmer, Beatrice

    2014-01-01

    The use of hydroxyethyl starch (HES) in sepsis has been shown to increase mortality and acute kidney injury. However, the knowledge of the exact mechanism by which several fluids, especially starch preparations may impair end-organ function particularly in the kidney, is still missing. The aim of this study was to measure the influence of different crystalloid and colloid fluid compositions on the inflammatory response in the kidney, the liver and the lung using a rodent model of acute endotoxemia. Rats were anesthetized and mechanically ventilated. Lipopolysaccharide (5 mg/kg) was administered intravenously. After one hour crystalloids [lactate-buffered (RLac) or acetate-buffered (RAc)] were infused i.v. (30 ml/kg) in all groups. At 2 hours rats either received different crystalloids (75 ml/kg of RLac or RAc) or colloids (25 ml/kg of HES in saline or HES in RAc or gelatin in saline). Expression of messenger RNA for cytokine-induced neutrophil chemoattractant-1 (CINC-1), monocyte chemotactic protein-1 (MCP-1), necrosis factor α (TNFα) and intercellular adhesion molecule 1 (ICAM-1) was assessed in kidney, liver and lung tissue by real-time PCR after 4 hours. The use of acetate-buffered solutions was associated with a significantly higher expression of CINC-1 and TNFα mRNA in the liver, in the kidney and in the lung. Only marginal effects of gelatin and hydroxyethyl starch on mRNA expression of inflammatory mediators were observed. The study provides evidence that the type of buffering agent of different colloidal and crystalloid solutions might be a crucial factor determining the extent of early end-organ inflammatory response in sepsis. PMID:24709833

  5. Modulation of early inflammatory response by different balanced and non-balanced colloids and crystalloids in a rodent model of endotoxemia.

    Directory of Open Access Journals (Sweden)

    Stefanie Voigtsberger

    Full Text Available The use of hydroxyethyl starch (HES in sepsis has been shown to increase mortality and acute kidney injury. However, the knowledge of the exact mechanism by which several fluids, especially starch preparations may impair end-organ function particularly in the kidney, is still missing. The aim of this study was to measure the influence of different crystalloid and colloid fluid compositions on the inflammatory response in the kidney, the liver and the lung using a rodent model of acute endotoxemia. Rats were anesthetized and mechanically ventilated. Lipopolysaccharide (5 mg/kg was administered intravenously. After one hour crystalloids [lactate-buffered (RLac or acetate-buffered (RAc] were infused i.v. (30 ml/kg in all groups. At 2 hours rats either received different crystalloids (75 ml/kg of RLac or RAc or colloids (25 ml/kg of HES in saline or HES in RAc or gelatin in saline. Expression of messenger RNA for cytokine-induced neutrophil chemoattractant-1 (CINC-1, monocyte chemotactic protein-1 (MCP-1, necrosis factor α (TNFα and intercellular adhesion molecule 1 (ICAM-1 was assessed in kidney, liver and lung tissue by real-time PCR after 4 hours. The use of acetate-buffered solutions was associated with a significantly higher expression of CINC-1 and TNFα mRNA in the liver, in the kidney and in the lung. Only marginal effects of gelatin and hydroxyethyl starch on mRNA expression of inflammatory mediators were observed. The study provides evidence that the type of buffering agent of different colloidal and crystalloid solutions might be a crucial factor determining the extent of early end-organ inflammatory response in sepsis.

  6. Inhibition by rebamipide of cytokine-induced or lipopolysaccharide-induced chemokine synthesis in human corneal fibroblasts.

    Science.gov (United States)

    Fukuda, Ken; Ishida, Waka; Tanaka, Hiroshi; Harada, Yosuke; Fukushima, Atsuki

    2014-12-01

    The dry-eye drug rebamipide has mucin secretagogue activity in and anti-inflammatory effects on corneal epithelial cells. Corneal stromal fibroblasts (transdifferentiated keratocytes) function as immune modulators in the pathogenesis of chronic ocular allergic inflammation and in innate immune responses at the ocular surface. The possible anti-inflammatory effects of rebamipide on human corn