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Sample records for endotoxin-induced acute inflammatory

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

    International Nuclear Information System (INIS)

    Chen, Jiao; Shetty, Sreerama; Zhang, Ping; Gao, Rong; Hu, Yuxin; Wang, Shuxia; Li, Zhenyu; Fu, Jian

    2014-01-01

    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

  2. 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.

  3. Agent-based modeling of endotoxin-induced acute inflammatory response in human blood leukocytes.

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    Dong, Xu; Foteinou, Panagiota T; Calvano, Steven E; Lowry, Stephen F; Androulakis, Ioannis P

    2010-02-18

    Inflammation is a highly complex biological response evoked by many stimuli. A persistent challenge in modeling this dynamic process has been the (nonlinear) nature of the response that precludes the single-variable assumption. Systems-based approaches offer a promising possibility for understanding inflammation in its homeostatic context. In order to study the underlying complexity of the acute inflammatory response, an agent-based framework is developed that models the emerging host response as the outcome of orchestrated interactions associated with intricate signaling cascades and intercellular immune system interactions. An agent-based modeling (ABM) framework is proposed to study the nonlinear dynamics of acute human inflammation. The model is implemented using NetLogo software. Interacting agents involve either inflammation-specific molecules or cells essential for the propagation of the inflammatory reaction across the system. Spatial orientation of molecule interactions involved in signaling cascades coupled with the cellular heterogeneity are further taken into account. The proposed in silico model is evaluated through its ability to successfully reproduce a self-limited inflammatory response as well as a series of scenarios indicative of the nonlinear dynamics of the response. Such scenarios involve either a persistent (non)infectious response or innate immune tolerance and potentiation effects followed by perturbations in intracellular signaling molecules and cascades. The ABM framework developed in this study provides insight on the stochastic interactions of the mediators involved in the propagation of endotoxin signaling at the cellular response level. The simulation results are in accordance with our prior research effort associated with the development of deterministic human inflammation models that include transcriptional dynamics, signaling, and physiological components. The hypothetical scenarios explored in this study would potentially improve

  4. Erythropoietin augments the cytokine response to acute endotoxin-induced inflammation in humans

    DEFF Research Database (Denmark)

    Hojman, Pernille; Taudorf, Sarah; Lundby, Carsten

    2009-01-01

    in a human in vivo model of acute systemic low-grade inflammation, we measured circulating inflammatory mediators after intravenous administration of Escherichia coli endotoxin (LPS) bolus injection (0.1 ng/kg of body weight) in young healthy male subjects. The subjects were divided into three groups...... receiving either (1) LPS alone, (2) EPO alone (15,000 IE of rHuEPO) or (3) EPO and LPS. Endotoxin administration alone induced a 3-, 12- and 5-fold increase in plasma concentrations of TNF-alpha, IL-6 and IL-10, respectively, 3h after LPS challenge. When EPO was given prior to a bolus injection...... with endotoxin, the levels of TNF-alpha and IL-6 were enhanced by 5- and 40-fold, respectively, whereas the endotoxin-induced increase in IL-10 response was not influenced by EPO. In contrast to our hypothesis, we find that EPO augments the acute inflammatory effect....

  5. Anti-inflammatory effect of lycopene on endotoxin-induced uveitis in rats

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    Tuğba Göncü

    Full Text Available ABSTRACT Purpose: We evaluated the efficacy of lycopene, a dietary carotenoid and potent antioxidant, against ocular inflammation and oxidative stress in an experimental uveitis model. Methods: Endotoxin-induced uveitis (EIU was induced in Sprague-Dawley rats by a single subcutaneous injection of 200 μg lipopolysaccharide (LPS. Induction of EIU was preceded by daily intraperitoneal injection of 10 mg/kg lycopene for three consecutive days (Lycopene + LPS group or equivolume vehicle (Vehicle + LPS group. A positive control group received 1 mg/kg dexamethasone pretreatment (DEX + LPS, and a negative control group received daily vehicle injection but no LPS (Vehicle Control. Twenty-four hours after LPS or final vehicle administration, eyes were enucleated, and aqueous humor was collected for measurement of the number of infiltrating cells, total protein concentration, and levels of nitric oxide (NO, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, and oxidative stress markers. Inflammatory response severity was compared among groups clinically and histopathologically. Results: Infiltrating cell number, total protein concentration, and NO, TNF-α, and IL-6 levels were significantly elevated in the aqueous humor of Vehicle + LPS group rats compared to Vehicle Controls. Compared to the Vehicle + LPS group, lycopene pretreatment significantly reduced aqueous humor concentrations of oxidative stress markers, NO (0.29 ± 0.1 μM vs. 0.19 ± 0.1 μM, p=0.003, TNF-α (71.0 ± 22.3 ng/ml vs. 50.1 ± 2.1 ng/ml, p=0.043, and IL-6 (121.6 ± 3.0 pg/ml vs. 111.1 ± 5.6 pg/ml, p=0.008. Inflammatory score was also reduced (2.0 ± 0.0 vs. 0.4 ± 0.5, p=0.001. Lycopene reduced the infiltrating cell count and protein concentration, but differences did not reach significance. Most lycopene effects were equivalent to dexamethasone. Conclusions: Lycopene may aid in the clinical management of uveitis by suppressing inflammation and oxidative stress.

  6. Anti-inflammatory effect of lycopene on endotoxin-induced uveitis in rats.

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    Göncü, Tuğba; Oğuz, Elif; Sezen, Hatice; Koçarslan, Sezen; Oğuz, Halit; Akal, Ali; Adıbelli, Fatih Mehmet; Çakmak, Sevim; Aksoy, Nurten

    2016-01-01

    We evaluated the efficacy of lycopene, a dietary carotenoid and potent antioxidant, against ocular inflammation and oxidative stress in an experimental uveitis model. Endotoxin-induced uveitis (EIU) was induced in Sprague-Dawley rats by a single subcutaneous injection of 200 μg lipopolysaccharide (LPS). Induction of EIU was preceded by daily intraperitoneal injection of 10 mg/kg lycopene for three consecutive days (Lycopene + LPS group) or equivolume vehicle (Vehicle + LPS group). A positive control group received 1 mg/kg dexamethasone pretreatment (DEX + LPS), and a negative control group received daily vehicle injection but no LPS (Vehicle Control). Twenty-four hours after LPS or final vehicle administration, eyes were enucleated, and aqueous humor was collected for measurement of the number of infiltrating cells, total protein concentration, and levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and oxidative stress markers. Inflammatory response severity was compared among groups clinically and histopathologically. Infiltrating cell number, total protein concentration, and NO, TNF-α, and IL-6 levels were significantly elevated in the aqueous humor of Vehicle + LPS group rats compared to Vehicle Controls. Compared to the Vehicle + LPS group, lycopene pretreatment significantly reduced aqueous humor concentrations of oxidative stress markers, NO (0.29 ± 0.1 μM vs. 0.19 ± 0.1 μM, p=0.003), TNF-α (71.0 ± 22.3 ng/ml vs. 50.1 ± 2.1 ng/ml, p=0.043), and IL-6 (121.6 ± 3.0 pg/ml vs. 111.1 ± 5.6 pg/ml, p=0.008). Inflammatory score was also reduced (2.0 ± 0.0 vs. 0.4 ± 0.5, p=0.001). Lycopene reduced the infiltrating cell count and protein concentration, but differences did not reach significance. Most lycopene effects were equivalent to dexamethasone. Lycopene may aid in the clinical management of uveitis by suppressing inflammation and oxidative stress.

  7. An anti-interleukin-2 receptor drug attenuates T- helper 1 lymphocytes-mediated inflammation in an acute model of endotoxin-induced uveitis.

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    Salvador Mérida

    Full Text Available The aim of the present study was to evaluate the anti-inflammatory efficacy of Daclizumab, an anti-interleukin-2 receptor drug, in an experimental uveitis model upon a subcutaneous injection of lipopolysaccharide into Lewis rats, a valuable model for ocular acute inflammatory processes. The integrity of the blood-aqueous barrier was assessed 24 h after endotoxin-induced uveitis by evaluating two parameters: cell count and protein concentration in aqueous humors. The histopathology of all the ocular structures (cornea, lens, sclera, choroid, retina, uvea, and anterior and posterior chambers was also considered. Enzyme-linked immunosorbent assays of the aqueous humor samples were performed to quantify the levels of the different chemokine and cytokine proteins. Similarly, a biochemical analysis of oxidative stress-related markers was also assessed. The inflammation observed in the anterior chamber of the eyes when Daclizumab was administered with endotoxin was largely prevented since the aqueous humor protein concentration substantially lowered concomitantly with a significant reduction in the uveal and vitreous histopathological grading. Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon-γ, also significantly reduced with related anti-oxidant systems recovery. Daclizumab treatment in endotoxin-induced uveitis reduced Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon gamma, by about 60-70% and presented a preventive role in endotoxin-induced oxidative stress. This antioxidant protective effect of Daclizumab may be related to several of the observed Daclizumab effects in our study, including IL-6 cytokine regulatory properties and a substantial concomitant drop in INFγ. Concurrently, Daclizumab treatment triggered a significant reduction in both the uveal histopathological grading and protein concentration in aqueous humors, but not in cellular infiltration.

  8. MMP-3 Deficiency Alleviates Endotoxin-Induced Acute Inflammation in the Posterior Eye Segment

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    Inge Van Hove

    2016-11-01

    Full Text Available Matrix metalloproteinase-3 (MMP-3 is known to mediate neuroinflammatory processes by activating microglia, disrupting blood–central nervous system barriers and supporting neutrophil influx into the brain. In addition, the posterior part of the eye, more specifically the retina, the retinal pigment epithelium (RPE and the blood–retinal barrier, is affected upon neuroinflammation, but a role for MMP-3 during ocular inflammation remains elusive. We investigated whether MMP-3 contributes to acute inflammation in the eye using the endotoxin-induced uveitis (EIU model. Systemic administration of lipopolysaccharide induced an increase in MMP-3 mRNA and protein expression level in the posterior part of the eye. MMP-3 deficiency or knockdown suppressed retinal leukocyte adhesion and leukocyte infiltration into the vitreous cavity in mice subjected to EIU. Moreover, retinal and RPE mRNA levels of intercellular adhesion molecule 1 (Icam1, interleukin 6 (Il6, cytokine-inducible nitrogen oxide synthase (Nos2 and tumor necrosis factor α (Tnfα, which are key molecules involved in EIU, were clearly reduced in MMP-3 deficient mice. In addition, loss of MMP-3 repressed the upregulation of the chemokines monocyte chemoattractant protein (MCP-1 and (C-X-C motif ligand 1 (CXCL1. These findings suggest a contribution of MMP-3 during EIU, and its potential use as a therapeutic drug target in reducing ocular inflammation.

  9. Preventive and therapeutic anti-inflammatory effects of systemic and topical thalidomide on endotoxin-induced uveitis in rats.

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    Rodrigues, Gustavo Büchele; Passos, Giselle Fazzioni; Di Giunta, Gabriella; Figueiredo, Cláudia Pinto; Rodrigues, Eduardo Büchele; Grumman, Astor; Medeiros, Rodrigo; Calixto, João B

    2007-03-01

    The present study examined the outcomes of systemic or topical treatment with thalidomide, a compound that possesses anti-inflammatory, immunomodulatory and anti-angiogenic properties, in rats subjected to endotoxin-induced uveitis (EIU). The effects of thalidomide were evaluated on endotoxin-induced leucocyte and protein infiltration and also on the production of interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha in rat aqueous humour (AqH). Moreover, the actions of thalidomide were assessed on the cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) protein expression in retinal tissue. EIU was produced by a hindpaw injection of lipopolysaccharide (LPS), in male Wistar rats. Thalidomide (5, 25 and 50 mg/kg) was administered orally 1 h before LPS injection. In another set of experiments, to evaluate the therapeutic efficacy, 5% thalidomide was applied topically to both eyes at 6, 12 and 18 h after LPS administration. The oral pre-treatment with thalidomide decreased, in a dose-dependent manner, the number of inflammatory cells, the protein concentration, and the levels of IL-1beta and TNF-alpha in the AqH. Similar results were found in the AqH of rats that received a topical application of thalidomide. Furthermore, oral (50 mg/kg) and local (5%) thalidomide treatment also reduced expression of the pro-inflammatory proteins COX-2 and iNOS in the posterior segment of the eye. Thalidomide exhibited marked preventive and curative ocular effects in EIU in rats, a property that might be associated with its ability to inhibit the production of inflammatory cytokines and the expression of COX-2 and iNOS. This assembly of data provides additional molecular and functional insights into beneficial effects of thalidomide as an agent for the management of ocular inflammation.

  10. Molecular mechanisms of topical anti-inflammatory effects of lipoxin A(4) in endotoxin-induced uveitis.

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    Medeiros, Rodrigo; Rodrigues, Gustavo Büchele; Figueiredo, Cláudia Pinto; Rodrigues, Eduardo Büchele; Grumman, Astor; Menezes-de-Lima, Octavio; Passos, Giselle Fazzioni; Calixto, João Batista

    2008-07-01

    Lipoxin A(4) (LXA(4)) is a lipid mediator that plays an important role in inflammation resolution. We assessed the anti-inflammatory effect of LXA(4) on endotoxin-induced uveitis (EIU) in rats. The inflammatory cell number and levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), prostaglandin E(2) (PGE(2)), and protein, as well as expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF), in the anterior chamber of the eye were determined 24 h after lipopolysaccharide (LPS; 200 mug/paw) intradermal injection. The immunohistochemical reactivities of nuclear factor-kappaB (NF-kappaB) and c-Jun were also examined. Topical LXA(4) (1-10 ng/eye) pretreatment decreased the number of inflammatory cells and the protein leakage into the aqueous humor (AqH). In addition, topical LXA(4) (10 ng/eye) inhibited the LPS-induced production of IL-1beta, TNF-alpha, and PGE(2), and expression of COX-2 and VEGF. A decreased activation of NF-kappaB and c-Jun was also found in LXA(4)-treated eyes. It is very interesting that an anti-inflammatory effect was achieved even when LXA(4) (10 ng/eye) was applied topically after LPS challenge, as indicated by the reduction in the cellular and protein extravasations into the AqH. Moreover, topical treatment of corticosteroid prednisolone (200 mug/eye) beginning before or after LPS injection reduced all of the molecular and biochemical alterations promoted on EIU rats in an efficacy similar to that of LXA(4). Together, the present results provide clear evidence that pharmacological activation of LXA(4) signaling pathway potently reduces the EIU in rats. Therefore, LXA(4) stable analogs could represent promising agents for the management of ocular inflammatory diseases.

  11. Theissenolactone C Exhibited Ocular Protection of Endotoxin-Induced Uveitis by Attenuating Ocular Inflammatory Responses and Glial Activation

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    Fan-Li Lin

    2018-04-01

    Full Text Available The aim of this study was to investigate the effects of a natural component, theissenolactone C (LC53, on the ocular inflammation of experimental endotoxin-induced uveitis (EIU and its related mechanisms in microglia. Evaluation of the severity of anterior uveitis indicated that LC53 treatment significantly decreased iridal hyperemia and restored the clinical scores. Additionally, the deficient retina functions of electroretinography were improved by LC53. LC53 significantly reduced levels of tumor necrosis factor (TNF-α, monocyte chemoattractant protein-1, protein leakage and activation of matrix metalloproteinases in the anterior section during EIU. Moreover, LC53 treatment decreased the oxidative stress as well as neuroinflammatory reactivities of GFAP and Iba-1 in the posterior section. Furthermore, LC53 decreased the phosphorylation of p65, expression of HSP90, Bax, and cleaved-caspase-3 in EIU. According to the microglia studies, LC53 significantly abrogated the productions of TNF-α, PGE2, NO and ROS, as well as inducible NO synthase and cyclooxygenase-2 expression in LPS-stimulated microglial BV2 cells. The microglial activation of IKKβ, p65 phosphorylation and nuclear phosphorylated p65 translocation were strongly attenuated by LC53. On the other hand, LC53 exhibited the inhibitory effects on JNK and ERK MAPKs activation. Our findings indicated that LC53 exerted the ocular-protective effect through its inhibition on neuroinflammation, glial activation, and apoptosis in EIU, suggesting a therapeutic potential with down-regulation of the NF-κB signaling for uveitis and retinal inflammatory diseases.

  12. Endotoxin-induced monocytic microparticles have contrasting effects on endothelial inflammatory responses.

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    Beryl Wen

    Full Text Available Septic shock is a severe disease state characterised by the body's life threatening response to infection. Complex interactions between endothelial cells and circulating monocytes are responsible for microvasculature dysfunction contributing to the pathogenesis of this syndrome. Here, we intended to determine whether microparticles derived from activated monocytes contribute towards inflammatory processes and notably vascular permeability. We found that endotoxin stimulation of human monocytes enhances the release of microparticles of varying phenotypes and mRNA contents. Elevated numbers of LPS-induced monocytic microparticles (mMP expressed CD54 and contained higher levels of transcripts for pro-inflammatory cytokines such as TNF, IL-6 and IL-8. Using a prothrombin time assay, a greater reduction in plasma coagulation time was observed with LPS-induced mMP than with non-stimulated mMP. Co-incubation of mMP with the human brain endothelial cell line hCMEC/D3 triggered their time-dependent uptake and significantly enhanced endothelial microparticle release. Unexpectedly, mMP also modified signalling pathways by diminishing pSrc (tyr416 expression and promoted endothelial monolayer tightness, as demonstrated by endothelial impedance and permeability assays. Altogether, these data strongly suggest that LPS-induced mMP have contrasting effects on the intercellular communication network and display a dual potential: enhanced pro-inflammatory and procoagulant properties, together with protective function of the endothelium.

  13. Regulation of Lipolysis and Adipose Tissue Signaling during Acute Endotoxin-Induced Inflammation

    DEFF Research Database (Denmark)

    Rittig, Nikolaj; Bach, Ermina; Thomsen, Henrik Holm

    2016-01-01

    BACKGROUND: Lipolysis is accelerated during the acute phase of inflammation, a process being regulated by pro-inflammatory cytokines (e.g. TNF-α), stress-hormones, and insulin. The intracellular mechanisms remain elusive and we therefore measured pro- and anti-lipolytic signaling pathways...... to measure palmitate rate of appearance (Rapalmitate) and indirect calorimetry was performed to measure energy expenditures and lipid oxidation rates. A subcutaneous abdominal fat biopsy was obtained during both interventions and subjected to western blotting and qPCR quantifications. RESULTS: LPS caused...... a mean increase in serum free fatty acids (FFA) concentrations of 90% (CI-95%: 37-142, p = 0.005), a median increase in Rapalmitate of 117% (CI-95%: 77-166, penergy expenditure of 28% (CI-95%: 16-42, p...

  14. Effect of the Toll-Like Receptor 4 Antagonist Eritoran on Retinochoroidal Inflammatory Damage in a Rat Model of Endotoxin-Induced Inflammation

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    Feyzahan Ekici

    2014-01-01

    Full Text Available Purpose. We investigated the effect of eritoran, a Toll-like receptor 4 antagonist, on retinochoroidal inflammatory damage in an endotoxin-induced inflammatory rat model. Methods. Endotoxin-induced inflammatory model was obtained by intraperitoneal injection of 1.5 mg/kg lipopolysaccharide (LPS. Group 1 had control rats; in groups 2-3 LPS and 0.5 mg/kg sterile saline were injected; and in groups 4-5 LPS and 0.5 mg/kg eritoran were injected. Blood samples were taken and eyes were enucleated after 12 hours (h (groups 2 and 4 or 24 hours (Groups 3 and 5. Tumor necrosis factor-α (TNF-α and malondialdehyde (MDA levels in the serum and retinochoroidal tissue and nuclear factor kappa-B (NFκB levels in retinochoroidal tissue were determined. Histopathological examination was performed and retinochoroidal changes were scored. Results. Eritoran treatment resulted in lower levels of TNF-α, MDA, and NFκB after 12 h which became significant after 24 h. Serum TNF-α and retinochoroidal tissue NFκB levels were similar to control animals at the 24th h of the study. Eritoran significantly reversed histopathological damage after 24 h. Conclusions. Eritoran treatment resulted in less inflammatory damage in terms of serum and retinochoroidal tissue parameters.

  15. Comparison of acute effect of systemic versus intravitreal infliximab treatment in an experimental model of endotoxin-induced uveitis.

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    Yuksel, Erdem; Hasanreisoglu, Berati; Yuksel, Nilay; Yilmaz, Guldal; Ercin, Ugur; Bilgihan, Ayse

    2014-02-01

    In this study, we investigated the efficacy of systemic and intravitreal (IV) infliximab treatments and compared these 2 different treatment modalities in an experimental model of endotoxin-induced uveitis (EIU). Twenty-four white New Zealand rabbits were equally divided into 4 groups. Group 1 received IV injection of lipopolysaccharide (LPS), group 2 received IV injections of LPS and saline, group 3 received IV LPS and IV 2 mg/0.1 cc infliximab, and group 4 received IV LPS and 5 mg/kg intravenous infliximab. Inflammation was determined with objective and subjective tests. The subjective test was clinical determination of uveitis, the objective tests were determination of protein concentrations and tumor necrosis factor alpha (TNF-α) levels and histopathology. Clinical examination score was lower in group 3 and group 4 (4±0.6 and 3.5±1.6, respectively) when compared with group 1 (P=0.02; P=0.04, respectively) and group 2. In group 3 and 4, the aqueous and vitreous protein and TNF-α concentration measured significantly lower than group 1 and 2. In histopathologic examination, there was no statistically significant difference between group 1, 2, and 3 (3.5±0.5, 3.6±0.5, 3.6±0.5, respectively). However, the lowest histopathologic inflammation was determined in group 4 (2.5±0.5) (compared with group 1 and group 3, respectively; P=0.03; P=0.014). In a rabbit model of experimental EIU, intravenous administration of infliximab was more effective than IV route in an acute period.

  16. The effects of a selective inhibitor of c-Fos/activator protein-1 on endotoxin-induced acute kidney injury in mice

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    Miyazaki Hiroyuki

    2012-11-01

    Full Text Available Abstract Background Sepsis has been identified as the most common cause of acute kidney injury (AKI in intensive care units. Lipopolysaccharide (LPS induces the production of several proinflammatory cytokines including tumor necrosis factor (TNF-alpha, a major pathogenetic factor in septic AKI. c-Fos/activator protein (AP-1 controls the expression of these cytokines by binding directly to AP-1 motifs in the cytokine promoter regions. T-5224 is a new drug developed by computer-aided drug design that selectively inhibits c-Fos/AP-1 binding to DNA. In this study, we tested whether T-5224 has a potential inhibitory effect against LPS-induced AKI, by suppressing the TNF-alpha inflammatory response and other downstream effectors. Methods To test this hypothesis, male C57BL/6 mice at 7 weeks old were divided into three groups (control, LPS and T-5224 groups. Mice in the control group received saline intraperitoneally and polyvinylpyrrolidone solution orally. Mice in the LPS group were injected intraperitoneally with a 6 mg/kg dose of LPS and were given polyvinylpyrrolidone solution immediately after LPS injection. In the T-5224 group, mice were administered T-5224 orally at a dose of 300 mg/kg immediately after LPS injection. Serum concentrations of TNF-alpha, interleukin (IL-1beta, IL-6 and IL-10 were measured by ELISA. Moreover, the expression of intercellular adhesion molecule (ICAM-1 mRNA in kidney was examined by quantitative real-time RT-PCR. Finally, we evaluated renal histological changes. Results LPS injection induced high serum levels of TNF-alpha, IL-1beta and IL-6. However, the administration of T-5224 inhibited the LPS-induced increase in these cytokine levels. The serum levels of IL-10 in the LPS group and T-5224 group were markedly elevated compared with the control group. T-5224 also inhibited LPS-induced ICAM-1 mRNA expression. Furthermore histological studies supported an anti-inflammatory role of T-5224. Conclusions In endotoxin-induced

  17. Effects of morphine on the expression of cytokines and inflammatory mediators in a rabbit model of endotoxin-induced experimental uveitis

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    Kethye P. Ortencio

    2015-12-01

    Full Text Available ABSTRACT Purpose: To evaluate the effects of 1% morphine instillation on clinical parameters, aqueous humor turbidity, and expression levels of tumor necrosis factor alpha (TNF-α, interleukin-1 beta (IL-1beta, prostaglandin E2 (PGE2, and myeloperoxidase (MPO in rabbits with endotoxin-induced experimental uveitis. Methods: Twenty four New Zealand white rabbits were divided into four groups (n=6 each: control (CG, morphine (MG, naloxone (NG, and morphine-naloxone (MNG groups. Under dissociative anesthesia, 0.1 mL of solution containing 0.2 µg of lipopolysaccharide (LPS endotoxin from the Salmonella typhimurium cell wall was injected in the vitreous chamber. Clinical evaluations (conjunctical hyperemia, chemosis blepharospasm, and ocular discharge and laser flaremetry were performed before (baseline, and 10 and 20 hours after induction of uveitis. Rabbits were subsequently euthanized and eyes were enucleated to quantify expression levels of TNF-α, IL-1 beta, PGE2, and MPO. Results: No significant differences in clinical parameters and flare values were observed between the study groups. TNF-α and IL-1 beta levels increased significantly in the CG, MG, NG, and MNG groups compared to baseline (P0.05. Conclusions: Morphine has no effect on clinical parameters, flare, or expression levels of inflammatory mediators in a rabbit model of uveitis induced by intravitreal injection of LPS.

  18. Anti-inflammatory effect of cinnamaldehyde and linalool from the leaf essential oil of Cinnamomum osmophloeum Kanehira in endotoxin-induced mice.

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    Lee, Shih-Chieh; Wang, Shih-Yun; Li, Chien-Chun; Liu, Cheng-Tzu

    2018-01-01

    Cinnamomum osmophloeum Kanehira is a Taiwan native plant that belongs to genus Cinnamomum and is also known as pseudocinnamomum or indigenous cinnamon. Its leaf is traditionally used by local people in cooking and as folk therapy. We previously demonstrated the chemical composition and anti-inflammatory effect of leaf essential oil of Cinnamomum osmophloeum Kanehira of linalool chemotype in streptozotocin-induced diabetic rats and on endotoxin-injected mice. The aim of the present study is to evaluate whether cinnamaldehyde and linalool the active anti-inflammatory compounds in leaf essential oil of Cinnamomum osmophloeum Kanehira. Before the injection of endotoxin, C57BL/6 mice of the experimental groups were administered cinnamaldehyde (0.45 or 0.9 mg/kg body weight) or linalool (2.6 or 5.2 mg/kg body weight), mice of the positive control group were administered the leaf essential oil (13 mg/kg body weight), and mice of the negative group were administered vehicle (corn oil, 4 mL/kg body weight) by gavage every other day for two weeks. All mice received endotoxin (i.p. 10 mg/mL/kg body weight) the next day after the final administration and were killed 12 h after the injection. Normal control mice were pretreated with vehicle followed by the injection with saline. None of the treatment found to affect body weight or food or water intake of mice before the injection of endotoxin. Cinnamaldehyde and linalool were found significantly reversed endotoxin-induced body weight loss and lymphoid organ enlargement compared with vehicle (P essential oil, which was 0.9 mg/kg and 5.2 mg/kg, respectively, showed similar or slightly less inhibitory activity for most of these inflammatory parameters compared with that of the leaf essential oil. Our data confirmed the potential use of leaf essential oil of Cinnamomum osmophloeum Kanehira as an anti-inflammatory natural product and provide evidence for cinnamaldehyde and linalool as two potent agents for prophylactic use

  19. (−-Epigallocatechin gallate inhibits endotoxin-induced expression of inflammatory cytokines in human cerebral microvascular endothelial cells

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    Li Jieliang

    2012-07-01

    Full Text Available Abstract Background (−-Epigallocatechin gallate (EGCG is a major polyphenol component of green tea that has antioxidant activities. Lipopolysaccharide (LPS induces inflammatory cytokine production and impairs blood–brain barrier (BBB integrity. We examined the effect of EGCG on LPS-induced expression of the inflammatory cytokines in human cerebral microvascular endothelial cells (hCMECs and BBB permeability. Methods The expression of TNF-α, IL-1β and monocyte chemotactic protein-1 (MCP-1/CCL2 was determined by quantitative real time PCR (qRT-PCR and ELISA. Intercellular adhesion molecule 1 (ICAM-1 and vascular cell adhesion molecule (VCAM in hCMECs were examined by qRT-PCR and Western blotting. Monocytes that adhered to LPS-stimulated endothelial cells were measured by monocyte adhesion assay. Tight junctional factors were detected by qRT-PCR (Claudin 5 and Occludin and immunofluorescence staining (Claudin 5 and ZO-1. The permeability of the hCMEC monolayer was determined by fluorescence spectrophotometry of transmembrane fluorescin and transendothelial electrical resistance (TEER. NF-kB activation was measured by luciferase assay. Results EGCG significantly suppressed the LPS-induced expression of IL-1β and TNF-α in hCMECs. EGCG also inhibited the expression of MCP-1/CCL2, VCAM-1 and ICAM-1. Functional analysis showed that EGCG induced the expression of tight junction proteins (Occludin and Claudin-5 in hCMECs. Investigation of the mechanism showed that EGCG had the ability to inhibit LPS-mediated NF-κB activation. In addition, 67-kD laminin receptor was involved in the anti-inflammatory effect of EGCG. Conclusions Our results demonstrated that LPS induced inflammatory cytokine production in hCMECs, which could be attenuated by EGCG. These data indicate that EGCG has a therapeutic potential for endotoxin-mediated endothelial inflammation.

  20. Regulation of Lipolysis and Adipose Tissue Signaling during Acute Endotoxin-Induced Inflammation: A Human Randomized Crossover Trial.

    Directory of Open Access Journals (Sweden)

    Nikolaj Rittig

    Full Text Available Lipolysis is accelerated during the acute phase of inflammation, a process being regulated by pro-inflammatory cytokines (e.g. TNF-α, stress-hormones, and insulin. The intracellular mechanisms remain elusive and we therefore measured pro- and anti-lipolytic signaling pathways in adipocytes after in vivo endotoxin exposure.Eight healthy, lean, male subjects were investigated using a randomized cross over trial with two interventions: i bolus injection of saline (Placebo and ii bolus injection of lipopolysaccharide endotoxin (LPS. A 3H-palmitate tracer was used to measure palmitate rate of appearance (Rapalmitate and indirect calorimetry was performed to measure energy expenditures and lipid oxidation rates. A subcutaneous abdominal fat biopsy was obtained during both interventions and subjected to western blotting and qPCR quantifications.LPS caused a mean increase in serum free fatty acids (FFA concentrations of 90% (CI-95%: 37-142, p = 0.005, a median increase in Rapalmitate of 117% (CI-95%: 77-166, p<0.001, a mean increase in lipid oxidation of 49% (CI-95%: 1-96, p = 0.047, and a median increase in energy expenditure of 28% (CI-95%: 16-42, p = 0.001 compared with Placebo. These effects were associated with increased phosphorylation of hormone sensitive lipase (pHSL at ser650 in adipose tissue (p = 0.03, a trend towards elevated pHSL at ser552 (p = 0.09 and cAMP-dependent protein kinase A (PKA phosphorylation of perilipin 1 (PLIN1 (p = 0.09. Phosphatase and tensin homolog (PTEN also tended to increase (p = 0.08 while phosphorylation of Akt at Thr308 tended to decrease (p = 0.09 during LPS compared with Placebo. There was no difference between protein or mRNA expression of ATGL, G0S2, and CGI-58.LPS stimulated lipolysis in adipose tissue and is associated with increased pHSL and signs of increased PLIN1 phosphorylation combined with a trend toward decreased insulin signaling. The combination of these mechanisms appear to be the driving forces

  1. Systemic anti-tumor necrosis factor antibody treatment exacerbates endotoxin-induced uveitis in the rat

    NARCIS (Netherlands)

    de Vos, A. F.; van Haren, M. A.; Verhagen, C.; Hoekzema, R.; Kijlstra, A.

    1995-01-01

    Tumor necrosis factor is released in the circulation and aqueous humor during endotoxin-induced uveitis, and induces acute uveitis when injected intraocularly in rats. To elucidate the role of tumor necrosis factor in the development of endotoxin-induced uveitis we analysed the effect of

  2. Human Chorionic Gonadotropin Has Anti-Inflammatory Effects at the Maternal-Fetal Interface and Prevents Endotoxin-Induced Preterm Birth, but Causes Dystocia and Fetal Compromise in Mice1

    Science.gov (United States)

    Furcron, Amy-Eunice; Romero, Roberto; Mial, Tara N.; Balancio, Amapola; Panaitescu, Bogdan; Hassan, Sonia S.; Sahi, Aashna; Nord, Claire; Gomez-Lopez, Nardhy

    2016-01-01

    Human chorionic gonadotropin (hCG) is implicated in the maintenance of uterine quiescence by down-regulating myometrial gap junctions during pregnancy, and it was considered as a strategy to prevent preterm birth after the occurrence of preterm labor. However, the effect of hCG on innate and adaptive immune cells implicated in parturition is poorly understood. Herein, we investigated the immune effects of hCG at the maternal-fetal interface during late gestation, and whether this hormone can safely prevent endotoxin-induced preterm birth. Using immunophenotyping, we demonstrated that hCG has immune effects at the maternal-fetal interface (decidual tissues) by: 1) increasing the proportion of regulatory T cells; 2) reducing the proportion of macrophages and neutrophils; 3) inducing an M1 → M2 macrophage polarization; and 4) increasing the proportion of T helper 17 cells. Next, ELISAs were used to determine whether the local immune changes were associated with systemic concentrations of progesterone, estradiol, and/or cytokines (IFNgamma, IL1beta, IL2, IL4, IL5, IL6, IL10, IL12p70, KC/GRO, and TNFalpha). Plasma concentrations of IL1beta, but not progesterone, estradiol, or any other cytokine, were increased following hCG administration. Pretreatment with hCG prevented endotoxin-induced preterm birth by 44%, proving the effectiveness of this hormone as an anti-inflammatory agent. However, hCG administration alone caused dystocia and fetal compromise, as proven by Doppler ultrasound. These results provide insight into the mechanisms whereby hCG induces an anti-inflammatory microenvironment at the maternal-fetal interface during late gestation, and demonstrate its effectiveness in preventing preterm labor/birth. However, the deleterious effects of this hormone on mothers and fetuses warrant caution. PMID:27146032

  3. L-ascorbate attenuates the endotoxin-induced production of inflammatory mediators by inhibiting MAPK activation and NF-κB translocation in cortical neurons/glia Cocultures.

    Directory of Open Access Journals (Sweden)

    Ya-Ni Huang

    Full Text Available In response to acute insults to the central nervous system, such as pathogen invasion or neuronal injuries, glial cells become activated and secrete inflammatory mediators such as nitric oxide (NO, cytokines, and chemokines. This neuroinflammation plays a crucial role in the pathophysiology of chronic neurodegenerative diseases. Endogenous ascorbate levels are significantly decreased among patients with septic encephalopathy. Using the bacterial endotoxin lipopolysaccharide (LPS to induce neuroinflammation in primary neuron/glia cocultures, we investigated how L-ascorbate (vitamin C; Vit. C affected neuroinflammation. LPS (100 ng/ml induced the expression of inducible NO synthase (iNOS and the production of NO, interleukin (IL-6, and macrophage inflammatory protein-2 (MIP-2/CXCL2 in a time-dependent manner; however, cotreatment with Vit. C (5 or 10 mM attenuated the LPS-induced iNOS expression and production of NO, IL-6, and MIP-2 production. The morphological features revealed after immunocytochemical staining confirmed that Vit. C suppressed LPS-induced astrocytic and microglial activation. Because Vit. C can be transported into neurons and glia via the sodium-dependent Vit. C transporter-2, we examined how Vit. C affected LPS-activated intracellular signaling in neuron/glia cocultures. The results indicated the increased activation (caused by phosphorylation of mitogen-activated protein kinases (MAPKs, such as p38 at 30 min and extracellular signal-regulated kinases (ERKs at 180 min after LPS treatment. The inhibition of p38 and ERK MAPK suppressed the LPS-induced production of inflammatory mediators. Vit. C also inhibited the LPS-induced activation of p38 and ERK. Combined treatments of Vit. C and the inhibitors of p38 and ERK yielded no additional inhibition compared with using the inhibitors alone, suggesting that Vit. C functions through the same signaling pathway (i.e., MAPK as these inhibitors. Vit. C also reduced LPS-induced Iκ

  4. Effects of the immunomodulator, VGX-1027, in endotoxin-induced uveitis in Lewis rats

    DEFF Research Database (Denmark)

    Mangano, K; Sardesai, N Y; Quattrocchi, C

    2008-01-01

    VGX-1027 is a novel, low molecular weight, immunomodulatory compound that has shown efficacy against a variety of immuno-inflammatory disease models in animals including autoimmune diabetes in NOD mice, collagen-induced arthritis and chemically induced inflammatory colitis. Here, we have studied ...... the effects of VGX-1027 on the development of endotoxin-induced uveitis (EIU) in male Lewis rats, as a model of inflammatory ocular diseases in humans....

  5. Aldose reductase deficiency protects from autoimmune- and endotoxin-induced uveitis in mice.

    Science.gov (United States)

    Yadav, Umesh C S; Shoeb, Mohammed; Srivastava, Satish K; Ramana, Kota V

    2011-10-17

    To investigate the effect of aldose reductase (AR) deficiency in protecting the chronic experimental autoimmune (EAU) and acute endotoxin-induced uveitis (EIU) in c57BL/6 mice. The WT and AR-null (ARKO) mice were immunized with human interphotoreceptor retinoid-binding peptide (hIRPB-1-20), to induce EAU, or were injected subcutaneously with lipopolysaccharide (LPS; 100 μg) to induce EIU. The mice were killed on day 21 for EAU and at 24 hours for EIU, when the disease was at its peak, and the eyes were immediately enucleated for histologic and biochemical studies. Spleen-derived T-lymphocytes were used to study the antigen-specific immune response in vitro and in vivo. In WT-EAU mice, severe damage to the retinal wall, especially to the photoreceptor layer was observed, corresponding to a pathologic score of ∼2, which was significantly prevented in the ARKO or AR inhibitor-treated mice. The levels of cytokines and chemokines increased markedly in the whole-eye homogenates of WT-EAU mice, but not in ARKO-EAU mice. Further, expression of inflammatory marker proteins such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, and vascular cell adhesion molecule (VCAM)-1 was increased in the WT-EIU mouse eyes but not in the ARKO-EIU eyes. The T cells proliferated vigorously when exposed to the hIRPB antigen in vitro and secreted various cytokines and chemokines, which were significantly inhibited in the T cells isolated from the ARKO mice. These findings suggest that AR-deficiency/inhibition protects against acute as well as chronic forms of ocular inflammatory complications such as uveitis.

  6. Therapeutic Effects of Procainamide on Endotoxin-Induced Rhabdomyolysis in Rats.

    Science.gov (United States)

    Shih, Chih-Chin; Hii, Hiong-Ping; Tsao, Cheng-Ming; Chen, Shiu-Jen; Ka, Shuk-Man; Liao, Mei-Hui; Wu, Chin-Chen

    2016-01-01

    Overt systemic inflammatory response is a predisposing mechanism for infection-induced skeletal muscle damage and rhabdomyolysis. Aberrant DNA methylation plays a crucial role in the pathophysiology of excessive inflammatory response. The antiarrhythmic drug procainamide is a non-nucleoside inhibitor of DNA methyltransferase 1 (DNMT1) used to alleviate DNA hypermethylation. Therefore, we evaluated the effects of procainamide on the syndromes and complications of rhabdomyolysis rats induced by lipopolysaccharide (LPS). Rhabdomyolysis animal model was established by intravenous infusion of LPS (5 mg/kg) accompanied by procainamide therapy (50 mg/kg). During the experimental period, the changes of hemodynamics, muscle injury index, kidney function, blood gas, blood electrolytes, blood glucose, and plasma interleukin-6 (IL-6) levels were examined. Kidneys and lungs were exercised to analyze superoxide production, neutrophil infiltration, and DNMTs expression. The rats in this model showed similar clinical syndromes and complications of rhabdomyolysis including high levels of plasma creatine kinase, acute kidney injury, hyperkalemia, hypocalcemia, metabolic acidosis, hypotension, tachycardia, and hypoglycemia. The increases of lung DNMT1 expression and plasma IL-6 concentration were also observed in rhabdomyolysis animals induced by LPS. Treatment with procainamide not only inhibited the overexpression of DNMT1 but also diminished the overproduction of IL-6 in rhabdomyolysis rats. In addition, procainamide improved muscle damage, renal dysfunction, electrolytes disturbance, metabolic acidosis, hypotension, and hypoglycemia in the rats with rhabdomyolysis. Moreover, another DNMT inhibitor hydralazine mitigated hypoglycemia, muscle damage, and renal dysfunction in rhabdomyolysis rats. These findings reveal that therapeutic effects of procainamide could be based on the suppression of DNMT1 and pro-inflammatory cytokine in endotoxin-induced rhabdomyolysis.

  7. Therapeutic Effects of Procainamide on Endotoxin-Induced Rhabdomyolysis in Rats.

    Directory of Open Access Journals (Sweden)

    Chih-Chin Shih

    Full Text Available Overt systemic inflammatory response is a predisposing mechanism for infection-induced skeletal muscle damage and rhabdomyolysis. Aberrant DNA methylation plays a crucial role in the pathophysiology of excessive inflammatory response. The antiarrhythmic drug procainamide is a non-nucleoside inhibitor of DNA methyltransferase 1 (DNMT1 used to alleviate DNA hypermethylation. Therefore, we evaluated the effects of procainamide on the syndromes and complications of rhabdomyolysis rats induced by lipopolysaccharide (LPS. Rhabdomyolysis animal model was established by intravenous infusion of LPS (5 mg/kg accompanied by procainamide therapy (50 mg/kg. During the experimental period, the changes of hemodynamics, muscle injury index, kidney function, blood gas, blood electrolytes, blood glucose, and plasma interleukin-6 (IL-6 levels were examined. Kidneys and lungs were exercised to analyze superoxide production, neutrophil infiltration, and DNMTs expression. The rats in this model showed similar clinical syndromes and complications of rhabdomyolysis including high levels of plasma creatine kinase, acute kidney injury, hyperkalemia, hypocalcemia, metabolic acidosis, hypotension, tachycardia, and hypoglycemia. The increases of lung DNMT1 expression and plasma IL-6 concentration were also observed in rhabdomyolysis animals induced by LPS. Treatment with procainamide not only inhibited the overexpression of DNMT1 but also diminished the overproduction of IL-6 in rhabdomyolysis rats. In addition, procainamide improved muscle damage, renal dysfunction, electrolytes disturbance, metabolic acidosis, hypotension, and hypoglycemia in the rats with rhabdomyolysis. Moreover, another DNMT inhibitor hydralazine mitigated hypoglycemia, muscle damage, and renal dysfunction in rhabdomyolysis rats. These findings reveal that therapeutic effects of procainamide could be based on the suppression of DNMT1 and pro-inflammatory cytokine in endotoxin-induced rhabdomyolysis.

  8. Endotoxin induced chorioamnionitis prevents intestinal development during gestation in fetal sheep.

    Directory of Open Access Journals (Sweden)

    Tim G A M Wolfs

    Full Text Available Chorioamnionitis is the most significant source of prenatal inflammation and preterm delivery. Prematurity and prenatal inflammation are associated with compromised postnatal developmental outcomes, of the intestinal immune defence, gut barrier function and the vascular system. We developed a sheep model to study how the antenatal development of the gut was affected by gestation and/or by endotoxin induced chorioamnionitis.Chorioamnionitis was induced at different gestational ages (GA. Animals were sacrificed at low GA after 2d or 14d exposure to chorioamnionitis. Long term effects of 30d exposure to chorioamnionitis were studied in near term animals after induction of chorioamnionitis. The cellular distribution of tight junction protein ZO-1 was shown to be underdeveloped at low GA whereas endotoxin induced chorioamnionitis prevented the maturation of tight junctions during later gestation. Endotoxin induced chorioamnionitis did not induce an early (2d inflammatory response in the gut in preterm animals. However, 14d after endotoxin administration preterm animals had increased numbers of T-lymphocytes, myeloperoxidase-positive cells and gammadelta T-cells which lasted till 30d after induction of chorioamnionitis in then near term animals. At early GA, low intestinal TLR-4 and MD-2 mRNA levels were detected which were further down regulated during endotoxin-induced chorioamnionitis. Predisposition to organ injury by ischemia was assessed by the vascular function of third-generation mesenteric arteries. Endotoxin-exposed animals of low GA had increased contractile response to the thromboxane A2 mimetic U46619 and reduced endothelium-dependent relaxation in responses to acetylcholine. The administration of a nitric oxide (NO donor completely restored endothelial dysfunction suggesting reduced NO bioavailability which was not due to low expression of endothelial nitric oxide synthase.Our results indicate that the distribution of the tight

  9. The redistribution of granulocytes following E. coli endotoxin induced sepsis

    DEFF Research Database (Denmark)

    Toft, P; Lillevang, S T; Tønnesen, Else Kirstine

    1994-01-01

    Infusion of endotoxin elicits granulocytopenia followed by increased numbers of granulocytes in peripheral blood. The purpose of this study was to investigate the redistribution and sequestration of granulocytes in the tissues following E. coli endotoxin induced sepsis. From 16 rabbits granulocytes...

  10. The redistribution of granulocytes following E. coli endotoxin induced sepsis

    DEFF Research Database (Denmark)

    Toft, P; Lillevang, S T; Tønnesen, Else Kirstine

    1994-01-01

    Infusion of endotoxin elicits granulocytopenia followed by increased numbers of granulocytes in peripheral blood. The purpose of this study was to investigate the redistribution and sequestration of granulocytes in the tissues following E. coli endotoxin induced sepsis. From 16 rabbits granulocytes...... were isolated, labelled with Indium and reinjected intravenously. Eight rabbits received an infusion of E. coli endotoxin 2 micrograms kg-1 while eight received isotonic saline. The redistribution of granulocytes was imaged with a gamma camera and calculated with a connected computer before and 2 and 6...... hours after infusion of endotoxin or saline. Serum cortisol and interleukin-1 beta were measured. In another seven rabbits, respiratory burst activity and degranulation of granulocytes were measured prior to and from 5 min to 6 hours after infusion of E. coli endotoxin 2 micrograms kg-1 BW. Following...

  11. Chlorogenic acid ameliorates endotoxin-induced liver injury by promoting mitochondrial oxidative phosphorylation

    International Nuclear Information System (INIS)

    Zhou, Yan; Ruan, Zheng; Zhou, Lili; Shu, Xugang; Sun, Xiaohong; Mi, Shumei; Yang, Yuhui; Yin, Yulong

    2016-01-01

    Acute or chronic hepatic injury is a common pathology worldwide. Mitochondrial dysfunction and the depletion of adenosine triphosphate (ATP) play important roles in liver injury. Chlorogenic acids (CGA) are some of the most abundant phenolic acids in human diet. This study was designed to test the hypothesis that CGA may protect against chronic lipopolysaccharide (LPS)-induced liver injury by modulating mitochondrial energy generation. CGA decreased the activities of serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. The contents of ATP and adenosine monophosphate (AMP), as well as the ratio of AMP/ATP, were increased after CGA supplementation. The activities of enzymes that are involved in glycolysis were reduced, while those of enzymes involved in oxidative phosphorylation were increased. Moreover, phosphorylated AMP-activated protein kinase (AMPK), and mRNA levels of AMPK-α, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α), nuclear respiratory factor 1, and mitochondrial DNA transcription factor A were increased after CGA supplementation. Collectively, these findings suggest that the hepatoprotective effect of CGA might be associated with enhanced ATP production, the stimulation of mitochondrial oxidative phosphorylation and the inhibition of glycolysis. - Highlights: • Dietary supplementation with chlorogenic acid (CGA) improved endotoxin-induced liver injury. • Chlorogenic acid enhances ATP increase and shifts energy metabolism, which is correlated with up-regulation AMPK and PGC-1α. • The possible mechanism of CGA on mitochondrial biogenesis was correlated with up-regulation AMPK and PGC-1α.

  12. Chlorogenic acid ameliorates endotoxin-induced liver injury by promoting mitochondrial oxidative phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yan [State Key Laboratory of Food Science and Technology and School of Food Science, Nanchang University, Nanchang 330047 (China); College of Food Safety, Guizhou Medical University, Guiyang 550025 (China); Ruan, Zheng, E-mail: ruanzheng@ncu.edu.cn [State Key Laboratory of Food Science and Technology and School of Food Science, Nanchang University, Nanchang 330047 (China); Zhou, Lili; Shu, Xugang [State Key Laboratory of Food Science and Technology and School of Food Science, Nanchang University, Nanchang 330047 (China); Sun, Xiaohong [College of Food Safety, Guizhou Medical University, Guiyang 550025 (China); Mi, Shumei; Yang, Yuhui [State Key Laboratory of Food Science and Technology and School of Food Science, Nanchang University, Nanchang 330047 (China); Yin, Yulong, E-mail: yinyulong@isa.ac.cn [State Key Laboratory of Food Science and Technology and School of Food Science, Nanchang University, Nanchang 330047 (China); Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125 (China)

    2016-01-22

    Acute or chronic hepatic injury is a common pathology worldwide. Mitochondrial dysfunction and the depletion of adenosine triphosphate (ATP) play important roles in liver injury. Chlorogenic acids (CGA) are some of the most abundant phenolic acids in human diet. This study was designed to test the hypothesis that CGA may protect against chronic lipopolysaccharide (LPS)-induced liver injury by modulating mitochondrial energy generation. CGA decreased the activities of serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. The contents of ATP and adenosine monophosphate (AMP), as well as the ratio of AMP/ATP, were increased after CGA supplementation. The activities of enzymes that are involved in glycolysis were reduced, while those of enzymes involved in oxidative phosphorylation were increased. Moreover, phosphorylated AMP-activated protein kinase (AMPK), and mRNA levels of AMPK-α, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α), nuclear respiratory factor 1, and mitochondrial DNA transcription factor A were increased after CGA supplementation. Collectively, these findings suggest that the hepatoprotective effect of CGA might be associated with enhanced ATP production, the stimulation of mitochondrial oxidative phosphorylation and the inhibition of glycolysis. - Highlights: • Dietary supplementation with chlorogenic acid (CGA) improved endotoxin-induced liver injury. • Chlorogenic acid enhances ATP increase and shifts energy metabolism, which is correlated with up-regulation AMPK and PGC-1α. • The possible mechanism of CGA on mitochondrial biogenesis was correlated with up-regulation AMPK and PGC-1α.

  13. The ocular endothelin system: a novel target for the treatment of endotoxin-induced uveitis with bosentan.

    Science.gov (United States)

    Keles, Sadullah; Halici, Zekai; Atmaca, Hasan Tarik; Yayla, Muhammed; Yildirim, Kenan; Ekinci, Metin; Akpinar, Erol; Altuner, Durdu; Cakici, Ozgur; Bayraktutan, Zafer

    2014-05-15

    We compared the anti-inflammatory effects of bosentan and dexamethasone in endotoxin-induced uveitis (EIU). Endotoxin-induced uveitis was induced by subcutaneous injection of lipopolysaccharide (LPS, 200 μg) in Wistar rats. Rats were divided randomly into 10 groups (n = 6). Bosentan at doses of 50 and 100 mg/kg were administered orally 1 hour before and 12 hours after LPS injection, and dexamethasone was administered by intraperitoneally 30 minutes before and 30 minutes after LPS injection at a dose of 1 mg/kg. Data were collected at two time points for each control and treatment; animals were killed at either 3 or 24 hours after LPS injection. Histopathologic evaluation and aqueous humour measurements of TNF-α level were performed, and endothelin-1 (ET-1), inducible nitric oxide synthase (iNOS), and endothelin receptor A and B (EDNRA and B) expression were analyzed. The group treated with 100 mg/kg bosentan at 24 hours displayed significantly milder uveitis and fewer inflammatory cells compared to LPS-injected animals, and there were similar findings in the dexamethasone-treated group at 24 hours. The TNF-α levels in the dexamethasone treatment group were lower than those in the LPS-induced uveitis control group (P treatment groups at 3 and 24 hours after LPS administration. Bosentan treatment at doses of 50 and 100 mg/kg significantly decreased iNOS expression compared to LPS-injected animals (P treatment groups was statistically significantly lower than that in the LPS-induced uveitis control group at 3 and 24 hours after LPS administration (P < 0.05). Bosentan reduces intraocular inflammation and has similar effects as dexamethasone in a rat model of EIU. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  14. Effects of hyper- and hypo- thyroidism on oxidative stress of the eye in experimental acute anterior uveitis.

    Science.gov (United States)

    Bilgihan, K; Bilgihan, A; Diker, S; Ataoglu, O; Dolapci, M; Akata, F; Hasanreisôglu, B; Turkozkan, N

    1996-02-01

    Glutathione peroxidase activities and malondialdehyde levels were measured in the homogenated anterior segment of rat eyes with endotoxin induced acute anterior uveitis in euthyroid, hyperthyroid and hypothyroid rats. Malondialdehyde concentrations were found to be significantly increased (p 0.05). These results suggest that excess or deficiency of the thyroid hormones cause alterations in the malondialdehyde levels and glutathione peroxidase activities of the rat eyes in endotoxin induced uveitis, and hyperthyroidism may increase the oxidative stress in endotoxin induced acute anterior uveitis.

  15. Prevention of endotoxin-induced uveitis in rats by benfotiamine, a lipophilic analogue of vitamin B1.

    Science.gov (United States)

    Yadav, Umesh C S; Subramanyam, Sumitra; Ramana, Kota V

    2009-05-01

    To study the amelioration of ocular inflammation in endotoxin-induced uveitis (EIU) in rats by benfotiamine, a lipid-soluble analogue of thiamine. EIU in Lewis rats was induced by subcutaneous injection of lipopolysaccharide (LPS) followed by treatment with benfotiamine. The rats were killed 3 or 24 hours after LPS injection, eyes were enucleated, aqueous humor (AqH) was collected, and the number of infiltrating cells, protein concentration, and inflammatory marker levels were determined. Immunohistochemical analysis of eye sections was performed to determine the expression of inducible-nitric oxide synthase (iNOS), cyclooxygenase (Cox)-2, protein kinase C (PKC), and transcription factor NF-kappaB. Infiltrating leukocytes, protein concentrations, and inflammatory cytokines and chemokines were significantly elevated in the AqH of EIU rats compared with control rats, and benfotiamine treatment suppressed these increases. Similarly increased expression of inflammatory markers iNOS and Cox-2 in ciliary body and retinal wall was also significantly inhibited by benfotiamine. The increased phosphorylation of PKC and the activation of NF-kappaB in the ciliary body and in the retinal wall of EIU rat eyes were suppressed by benfotiamine. These results suggest that benfotiamine suppresses oxidative stress-induced NF-kappaB-dependent inflammatory signaling leading to uveitis. Therefore, benfotiamine could be used as a novel therapeutic agent for the treatment of ocular inflammation, especially uveitis.

  16. Transvaginal sonography of acute pelvic inflammatory disease

    International Nuclear Information System (INIS)

    Choi, Jin Soo; Kim, Young Hwa; Shin, Hyung Chul; Han, Gun Soo; Kim, Il Young

    1999-01-01

    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.

  17. [Inflammatory biomarkers in ischemic acute coronary syndrome].

    Science.gov (United States)

    Domínguez-Rodríguez, Alberto; Abreu-González, Pedro

    2015-10-01

    Diagnosing acute coronary syndrome (ACS) in the emergency department is often a complex process. Inflammatory markers might be useful for the rapid assessment of a patient's overall risk and might also help predict future episodes. The clinical use of these biomarkers could potentially lower the number of emergency visits and help in the prevention of future adverse events. The aim of this review was to evaluate the clinical utility of markers of cardiovascular inflammation in emergency patients with ACS. Based on a critical analysis of a selection of the literature, we concluded that none of the biomarkers of cardiovascular inflammation would at present be useful for stratifying risk in emergency situations, aiding prognosis, or guiding therapy for patients with ACS.

  18. Influence of endotoxin-induced sepsis on the requirements of propofol-fentanyl infusion rate in pigs

    DEFF Research Database (Denmark)

    Bollen, Peter; Nielsen, Bjørn J; Toft, Palle

    2007-01-01

    Endotoxin-induced sepsis in pigs is a recognized experimental model for the study of human septic shock. Generally, pigs are brought into general anaesthesia before sepsis is induced. It is our experience that drug dosages of propofol and fentanyl need to be reduced during endotoxin-induced sepsis......, in order to prevent respiratory and cardiovascular depression, but the scientific evidence for this observation is lacking. Therefore, we measured the consumption of propofol and fentanyl at equal level of anaesthesia in pigs with (n = 5) and without (n = 5) endotoxin-induced sepsis, using the cerebral...... state index (CSI) as measure of anaesthetic depth. Infusion rates of propofol (P endotoxin-induced sepsis had an infusion rate of 2.2 mg/kg/hr (S.D. 0.5) for propofol and 12 microg/kg/hr (S.D. 2) for fentanyl, whereas...

  19. Inflammatory Cell Infiltrates in Acute and Chronic Thoracic Aortic Dissection.

    Science.gov (United States)

    Wu, Darrell; Choi, Justin C; Sameri, Aryan; Minard, Charles G; Coselli, Joseph S; Shen, Ying H; LeMaire, Scott A

    2013-12-01

    Thoracic aortic dissection (TAD) is a highly lethal cardiovascular disease. Injury to the intima and media allows pulsatile blood to enter the media, leading to dissection formation. Inflammatory cells then infiltrate the site of aortic injury to clear dead cells and damaged tissue. This excessive inflammation may play a role in aneurysm formation after dissection. Using immunohistochemistry, we compared aortic tissues from patients with acute TAD (n = 11), patients with chronic TAD (n = 35), and donor controls (n = 20) for the presence of CD68+ macrophages, neutrophils, mast cells, and CD3+ T lymphocytes. Tissue samples from patients with acute or chronic TAD generally had significantly more inflammatory cells in both the medial and adventitial layers than did the control samples. In tissues from patients with acute TAD, the adventitia had more of the inflammatory cells studied than did the media. The pattern of increase in inflammatory cells was similar in chronic and acute TAD tissues, except for macrophages, which were seen more frequently in the adventitial layer of acute TAD tissue than in the adventitia of chronic TAD tissue. The inflammatory cell content of both acute and chronic TAD tissue was significantly different from that of control tissue. However, the inflammatory cell profile of aneurysmal chronic TAD was similar to that of acute TAD. This may reflect a sustained injury response that contributes to medial degeneration and aneurysm formation.

  20. Nonsteroidal anti-inflammatory drugs for treatment of acute gout

    NARCIS (Netherlands)

    van Durme, Caroline M. P. G.; Wechalekar, Mihir D.; Landewé, Robert B. M.

    2015-01-01

    Are nonsteroidal anti-inflammatory drugs (NSAIDs) associated with better outcomes than cyclooxygenase inhibitors, glucocorticoids, IL-1 inhibitors or placebo in the treatment of acute gout? NSAIDs are not significantly associated with a difference in pain reduction compared with cyclooxygenase

  1. Diet-induced obesity attenuates endotoxin-induced cognitive deficits.

    Science.gov (United States)

    Setti, Sharay E; Littlefield, Alyssa M; Johnson, Samantha W; Kohman, Rachel A

    2015-03-15

    Activation of the immune system can impair cognitive function, particularly on hippocampus dependent tasks. Several factors such as normal aging and prenatal experiences can modify the severity of these cognitive deficits. One additional factor that may modulate the behavioral response to immune activation is obesity. Prior work has shown that obesity alters the activity of the immune system. Whether diet-induced obesity (DIO) influences the cognitive deficits associated with inflammation is currently unknown. The present study explored whether DIO alters the behavioral response to the bacterial endotoxin, lipopolysaccharide (LPS). Female C57BL/6J mice were fed a high-fat (60% fat) or control diet (10% fat) for a total of five months. After consuming their respective diets for four months, mice received an LPS or saline injection and were assessed for alterations in spatial learning. One month later, mice received a second injection of LPS or saline and tissue samples were collected to assess the inflammatory response within the periphery and central nervous system. Results showed that LPS administration impaired spatial learning in the control diet mice, but had no effect in DIO mice. This lack of a cognitive deficit in the DIO female mice is likely due to a blunted inflammatory response within the brain. While cytokine production within the periphery (i.e., plasma, adipose, and spleen) was similar between the DIO and control mice, the DIO mice failed to show an increase in IL-6 and CD74 in the brain following LPS administration. Collectively, these data indicate that DIO can reduce aspects of the neuroinflammatory response as well as blunt the behavioral reaction to an immune challenge. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Lipocalin 2 Suppresses Ocular Inflammation by Inhibiting the Activation of NF-κβ Pathway in Endotoxin-Induced Uveitis

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    Wenyi Tang

    2018-03-01

    Full Text Available Background/Aims: Lipocalin 2 (LCN2, an important mediator of a variety of cellular processes, is involved in regulating the inflammatory response, but its roles in different inflammatory diseases are controversial. Because the role of LCN2 in ocular inflammation has been unclear until now, we explored the function of LCN2 in lipopolysaccharide (LPS-induced ocular inflammation in vivo and in vitro. Methods: Endotoxin-induced uveitis (EIU was induced in male Sprague Dawley rats by the intravitreal injection of LPS. The expression and location of LCN2 in the retina were detected with western blotting and immunohistochemistry, respectively. We determined the clinical scores for anterior inflammation, quantified the infiltrated inflammatory cells, and measured the pro-inflammatory factors to determine the anti-inflammatory effects of LCN2 in EIU eyes. Cultured primary rat Müller cells were stimulated with LPS and the expression and secretion of LCN2 were measured with real-time PCR, western blotting, and an ELISA. After Müller cells were cotreated with LPS and LCN2 or PBS, the expression and secretion of TNF-α, IL-6, and MCP-1 were examined with realtime PCR, western blotting, and ELISAs. Western blotting and immunofluorescence were used to detect the phosphorylation and cellular distribution of nuclear factor kappaB (NF-κB subunit p65. Results: In EIU, the expression of LCN2 was significantly upregulated in the retina, especially in the outer nuclear layer (mainly composed of Müller cells. LPS stimulation of cultured Müller cells also markedly elevated LCN2 expression. Intravitreal injection of LCN2 significantly reduced the clinical scores, inflammatory infiltration, and protein leakage in EIU, which correlated with the reduced levels of proinflammatory factors in the aqueous humor and retina. LCN2 treatment also reduced the expression and secretion of TNF-α, IL-6, and MCP-1 in LPS-stimulated Müller cells. LCN2 inhibited the inflammatory

  3. Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans

    DEFF Research Database (Denmark)

    Starkie, Rebecca; Ostrowski, Sisse Rye; Jauffred, Sune

    2003-01-01

    and atherosclerosis. To test this hypothesis, we performed three experiments in which eight healthy males either rested (CON), rode a bicycle for 3 h (EX), or were infused with recombinant human IL-6 (rhIL-6) for 3 h while they rested. After 2.5 h, the volunteers received a bolus of Escherichia coli...... exercise and rhIL-6 infusion at physiological concentrations inhibit endotoxin-induced TNF-alpha production in humans. Hence, these data provide the first experimental evidence that physical activity mediates antiinflammatory activity and suggest that the mechanism include IL-6, which is produced...

  4. Effects of hydrogen-rich saline on endotoxin-induced uveitis

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    Wei-ming Yan

    2017-01-01

    Full Text Available The therapeutic effects of hydrogen-rich saline (HRS have been reported for a wide range of diseases mainly via selectively reducing the amount of reactive oxygen species. Oxidative stress plays an important role in the pathogenesis of uveitis and endotoxin-induced uveitis (EIU. In this study, we investigated whether HRS can mitigate EIU in rats. Sprague-Dawley rats were randomly divided into Norm group, Model group, HRS group, dexamethasone (DEX group, and rats in the latter three groups were injected with equal amount of lipopolysaccharide (LPS to induce EIU of different severities (by 1 mg/kg of LPS, or 1/8 mg/kg of LPS. Rats in HRS group were injected with HRS intraperitoneally at three different modes to purse an ameliorating effect of EIU (10 mL/kg of HRS immediately after injection of 1 mg/kg of LPS, 20 mL/kg of HRS once a day for 1 week before injection of 1 mg/kg of LPS and at 0, 0.5, 1, 2, 6, 8, 12 hours after LPS administration, or 20 mL/kg of HRS once a day for 1 week before injection of 1/8 mg/kg of LPS, and at 0, 0.5, 1, 2, 6, 8, 12, 24 hours and once a day for 3 weeks after LPS administration. Rats of DEX group were injected with 1 mL/kg of DEX solution intraperitoneally immediately after LPS administration. Rats in Norm and Model groups did not receive any treatment. All rats were examined under slit lamp microscope and graded according to the clinical signs of uveitis. Electroretinogram, quantitative analysis of protein in aqueous humor (AqH and histological examination of iris and ciliary body were also carried out. Our results showed that HRS did not obviously ameliorate the signs of uveitis under slit lamp examination and the inflammatory cells infiltration around iris and cilliary body of EIU induced by 1 mg/kg or 1/8 mg/kg of LPS (P > 0.05, while DEX significantly reduced the inflammation reflected by the above two indicators (P 0.05, while DEX had an obvious therapeutic effect (P < 0.05. However, HRS exerted an inhibition

  5. A Case Of Infectious Mononucleosis With Acute Inflammatory Demyelinating Polyradiculoneuropathy

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    Somani S K

    2003-01-01

    Full Text Available We report a case of Acute inflammatory demyelinating polyradiculo neuropathy (AIDP, following infectious mononucleosis. A 12 year old girl presented with acute flaccid quadriplegia with bilateral cervical lymphadenopathy and enlarged tonsils six weeks after a febrile illness. Cerebrospinal fluid revealed albuminocytological dissociation and electrophysiology showed evidence of axonal-demyelinating polyradiculoneuropathy. Heterophile antibody test was positive and lymph node biopsy showed non -specific reactive hyperplasia. She was managed conservatively with good outcome.

  6. Acute systemic inflammatory response after cardiac surgery in ...

    African Journals Online (AJOL)

    2017-09-03

    Sep 3, 2017 ... valve(s) replacement were enrolled, from a single center hospital, after informed consent was obtained. C-reactive ... Cite as: Gojo MKE, Prakaschandra R. Acute systemic inflammatory response after cardiac surgery in patients infected with human im- ..... Arroyo-Espliguero R, Avanzas P, Cosín-Sales J, Al-.

  7. Effect of Probiotic Administration on Acute Inflammatory Pain

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    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.

  8. Fucoidan Extracted from Fucus evanescens Prevents Endotoxin-Induced Damage in a Mouse Model of Endotoxemia

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    Tatyana A. Kuznetsova

    2014-01-01

    Full Text Available An important problem of treating patients with endotoxemia is to find drugs to reduce the negative effects of endotoxin on the organism. We tested fucoidan (sulfated polysaccharide from the brown alga Fucus evanescens as a potential drug in a mouse model of endotoxemia inducted by lipopolysaccharide (LPS. The survival time of mice injected with LPS increased under fucoidan treatment compared with the group of mice injected with LPS only. The preventive administration of fucoidan to mice with endotoxemia resulted in inhibition of increased levels of proinflammatory cytokines (TNFα and IL-6, as well as decreasing of the processes of hypercoagulability. The parenteral or per os administration of fucoidan resulted in decreasing the degree of microcirculatory disorders and secondary dystrophic-destructive changes in parenchymal organs of mice with endotoxemia. Taken together, these results demonstrate that fucoidan prevents endotoxin-induced damage in a mouse model of endotoxemia and increases the mice’s resistance to LPS.

  9. Effect of plasmapheresis on the immune system in endotoxin-induced sepsis

    DEFF Research Database (Denmark)

    Toft, P; Schmidt, R; Broechner, A C

    2008-01-01

    BACKGROUND: It has been proposed that plasmapheresis is most effective when applied early in Gram-negative sepsis. We therefore studied the effect of early plasmapheresis on immunity in experimental Escherichia coli endotoxin-induced sepsis. METHODS: 20 pigs received 30 microg/kg of E. coli...... endotoxin. 40 min later, half of the pigs were treated with plasmapheresis which lasted 4 h. The adhesion molecules, the oxidative burst, the number of neutrophils in blood and lungs, and cytokines were measured. RESULTS: Infusion of endotoxin was associated with activation of adhesion molecules increased...... oxidative burst, increased concentration of cytokine, and accumulation of granulocytes in lung tissue. Plasmapheresis reduced the oxidative burst, and there was a tendency towards a reduced accumulation of granulocytes in the lung. CONCLUSION: Though plasmapheresis was initiated early after the endotoxin...

  10. Acute urinary retention due to benign inflammatory nervous diseases.

    Science.gov (United States)

    Sakakibara, Ryuji; Yamanishi, Tomonori; Uchiyama, Tomoyuki; Hattori, Takamichi

    2006-08-01

    Both neurologists and urologists might encounter patients with acute urinary retention due to benign inflammatory nervous diseases. Based on the mechanism of urinary retention, these disorders can be divided into two subgroups: disorders of the peripheral nervous system (e.g., sacral herpes) or the central nervous system (e.g., meningitis-retention syndrome [MRS]). Laboratory abnormalities include increased herpes virus titers in sacral herpes, and increased myelin basic protein in the cerebrospinal fluid (CSF) in some cases with MRS. Urodynamic abnormality in both conditions is detrusor areflexia; the putative mechanism of it is direct involvement of the pelvic nerves in sacral herpes; and acute spinal shock in MRS. There are few cases with CSF abnormality alone. Although these cases have a benign course, management of the acute urinary retention is necessary to avoid bladder injury due to overdistension. Clinical features of sacral herpes or MRS differ markedly from those of the original "Elsberg syndrome" cases.

  11. Susceptibility to endotoxin induced uveitis is not reduced in mice deficient in BLT1, the high affinity leukotriene B4 receptor

    OpenAIRE

    Smith, J R; Subbarao, K; Franc, D T; Haribabu, B; Rosenbaum, J T

    2004-01-01

    Aim: To investigate the role of arachidonic acid derived chemotactic factor, LTB4, in the development of endotoxin induced uveitis (EIU), using mice deficient in the BLT1 gene which encodes the high affinity LTB4 receptor.

  12. Piroxicam Reverses Endotoxin-Induced Hypotension in Rats: Contribution of Vasoactive Eicosanoids and Nitric Oxide

    Science.gov (United States)

    Buharalioglu, C. Kemal; Korkmaz, Belma; Cuez, Tuba; Sahan-Firat, Seyhan; Sari, Ayşe Nihal; Malik, Kafait U.; Tunctan, Bahar

    2011-01-01

    Nitric oxide (NO) produced by inducible NO synthase (iNOS) is responsible for endotoxin-induced vascular hyporeactivity and hypotension resulting in multiple organ failure. Endotoxic shock is also characterized by decreased expression of constitutive cyclooxygenase (COX-1), cytochrome P450 (CYP) 4A and endothelial NOS (eNOS). Our previous studies demonstrated that dual inhibition of iNOS and COX with a selective COX-2 inhibitor, NS-398, or a non-selective COX inhibitor, indomethacin, restores blood pressure presumably due to increased production of 20-hydroxyeicosatetraenoic acid (20-HETE) derived from arachidonic acid (AA) by CYP4A in endotoxaemic rats. The aim of this study was to investigate the effects of piroxicam, a preferential COX-1 inhibitor, on the endotoxin-induced changes in blood pressure, expression of COX-1, inducible COX (COX-2), CYP4A1, eNOS, iNOS and heat shock protein 90 (hsp90), and production of PGI2, PGE2, 20-HETE and NO. Injection of endotoxin (10 mg/kg, i.p.) to male Wistar rats caused a fall in blood pressure and an increase in heart rate associated with elevated renal 6-keto-PGF1α and PGE2 levels as well as an increase in COX-2 protein expression. Endotoxin also caused an elevation in systemic and renal nitrite levels associated with increased renal iNOS protein expression. In contrast, systemic and renal 20-HETE levels and renal expression of eNOS, COX-1 and CYP4A1 were decreased in endotoxaemic rats. The effects of endotoxin, except for renal COX-1 and eNOS protein expression, were prevented by piroxicam (10 mg/kg, i.p.), given 1 hr after injection of endotoxin. Endotoxin did not change renal hsp90 protein expression. These data suggest that a decrease in the expression and activity of COX-2 and iNOS associated with an increase in CYP4A1 expression and 20-HETE synthesis contributes to the effect of piroxicam to prevent the hypotension during rat endotoxaemia. PMID:21463481

  13. Curcumin Protects Against the Acute Inflammatory Process in Irradiated Rats

    International Nuclear Information System (INIS)

    El-Ghazaly, M.A.; Nada, A.S.; Hegazy, M.E.; Kenawy, S.A.

    2010-01-01

    Nutraceuticals that provide medical or health benefits, including prevention and treatment of disease may be advantageous in inflammation and exposure to radiation. The aim of this study was to investigate the potential of curcumin to modulate, counteract or prevent the inflammatory response induced in irradiated and non-irradiated rats using the carrageenan air-pouch model as an acute model. Diclofenac was used as a reference standard non-steroidal anti-inflammatory drug (NSAID). Results indicated that exposure of rats to a single dose of gamma-radiation (6 Gy) before induction of inflammation increased production of prostaglandin E2 (PGE2), tumour necrosis factor-alpha (TNF-alpha) and malondialdehyde (MDA) levels in serum. Blood glutathione (GSH) was shown to be reduced in irradiated animals. Curcumin suppressed the elevated levels of TNF-alpha, PGE2 and MDA and was able to restore blood GSH levels. Reduction in liver contents of copper (Cu), zinc (Zn), selenium (Se) and iron (Fe) was recorded after irradiation of animals before induction of inflammation. Curcumin restored the hepatic concentrations of these trace elements. The present results suggest that irradiation of rats caused marked changes in the inflammatory response while curcumin suppressed the inflammatory response in both irradiated and control animals.

  14. Expression Profile of Cationic Amino Acid Transporters in Rats with Endotoxin-Induced Uveitis

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    Yung-Ray Hsu

    2016-01-01

    Full Text Available Purpose. The transcellular arginine transportation via cationic amino acid transporter (CAT is the rate-limiting step in nitric oxide (NO synthesis, which is crucial in intraocular inflammation. In this study, CAT isoforms and inducible nitric oxide synthase (iNOS expression was investigated in endotoxin-induced uveitis (EIU. Methods. EIU was induced in Lewis rats by lipopolysaccharide (LPS injection. In the treatment group, the rats were injected intraperitoneally with the proteasome inhibitor bortezomib before EIU induction. After 24 hours, leukocyte quantification, NO measurement of the aqueous humor, and histopathological examination were evaluated. The expression of CAT isoforms and iNOS was determined by reverse transcription-polymerase chain reaction, western blotting, and immunofluorescence staining. Nuclear factor-kappa B (NF-κB binding activity was evaluated by electrophoretic mobility shift assay. The mouse macrophage cell line RAW 264.7 was used to validate the in vivo findings. Results. LPS significantly stimulated iNOS, CAT-2A, and CAT-2B mRNA and protein expression but did not affect CAT-1 in EIU rats and RAW 264.7 cells. Bortezomib attenuated inflammation and inhibited iNOS, CAT-2A, and CAT-2B expression through NF-κB inhibition. Conclusions. CAT-2 and iNOS, but not CAT-1, are specifically involved in EIU. NF-κB is essential in the induction of CAT-2 and iNOS in EIU.

  15. Acute nonsteroidal anti-inflammatory drug-induced colitis

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    Massimo Tonolini

    2013-01-01

    Full Text Available Resulting from direct toxicity on the bowel mucosa, nonsteroidal anti-inflammatory drug (NSAID-induced colitis is an underestimated although potentially serious condition. Plain abdominal radiographs and multidetector computed tomography allow to identify a right-sided acute colitis with associated pericolonic inflammation, progressively diminished changes along the descending and sigmoid colon, and rectal sparing, consistent with the hypothesized pathogenesis of NSAID colitis. Increased awareness of this condition should reduce morbidity through both prevention and early recognition. High clinical suspicion and appropriate patient questioning, together with consistent instrumental findings, negative biochemistry, and stool investigations should help physicians not to miss this important diagnosis.

  16. Acute Inflammatory Demyelinating Neuropathy : Immunoglobulin And Immune Complex Profile

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    Shripad A

    2003-01-01

    Full Text Available Serum immunoglobulins (IgG, IgA and IgM and immune complexes IgG (IcG were measured in 58 cases of acute inflammatory demyelinating neuropathy, popularly known as Guillian Barre′ syndrome, and in 30 healthy controls using single radial immunodiffusion assay. Immunoglobulin and immune complex levels were significantly elevated in patients as compared to controls. The increased levels of immunoglobulins and immune complexes may contribute to the pathogenesis of the disease and provide rationale for therapeutic plasmapheresis.

  17. Clinical Significance of A Waves in Acute Inflammatory Demyelinating Polyradiculoneuropathy.

    Science.gov (United States)

    Lakshminarasimhan, Sindhuja; Venkatraman, Chandramouleeswaran; Vellaichamy, Kannan; Ranganathan, Lakshminarasimhan

    2018-05-25

    A wave is a late response recognized during recording of F waves. Though they might be seen in healthy subjects, their presence assumes significance in a patient presenting with polyradiculoneuropathy. In this prospective study, 75 patients with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) were enrolled. They were divided into two groups based on the presence or absence of A waves. Clinical features, electrophysiological parameters and extent of clinical recovery in short-term follow-up were analyzed. A waves were present in 49 out of 75 patients (65%). Most common pattern observed was multiple A waves. Prevalence of A waves was more in lower limb nerves than upper limb nerves. Occurrence of A waves correlated with the presence of conduction block. Patients with A waves had higher Hughes grade (P = 0.003) and lower Medical Research Council sum score at 6 weeks of follow-up (P = 0.04) as compared to patients without A waves. A waves are common in acute inflammatory demyelinating polyradiculoneuropathy form of Guillain Barre syndrome and are considered as a marker of demyelination. Long-term follow-up studies are required to ascertain their significance in prognostication and assessing recovery.

  18. Acute inflammatory thyromegaly following checkpoint inhibition: A new imaging entity?

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    Erik H. Middlebrooks, MD

    2018-02-01

    Full Text Available Immune checkpoint blockade (CPB utilizing such agents as ipilimumab, nivolumab, or pembrolizumab has revolutionized melanoma therapy and has seen continued utilization in numerous other malignancies in recent years. However, these agents come at the price of inflammatory immune-related adverse events. Despite the increasing recognition of biochemical thyroid dysfunction associated with CPB, information regarding potential imaging findings is sparse. We describe the first 2 cases of acute thyroiditis following CPB presenting as diffuse thyromegaly documented by computed tomography, ultrasound, and iodine uptake imaging. Given the rise in the use of CPB, it is important for radiologists to recognize potential imaging manifestations of therapy immune-related adverse events to avoid erroneous diagnosis and to prompt the biochemical investigation of thyroid function.

  19. Anti-inflammatory treatment for carditis in acute rheumatic fever.

    Science.gov (United States)

    Cilliers, Antoinette; Adler, Alma J; Saloojee, Haroon

    2015-05-28

    Rheumatic heart disease remains an important cause of acquired heart disease in developing countries. Although prevention of rheumatic fever and management of recurrences have been well established, optimal management of active rheumatic carditis remains unclear. This is an update of a review published in 2003, and previously updated in 2009 and 2012. To assess the effects, both harmful and beneficial, of anti-inflammatory agents such as aspirin, corticosteroids and other drugs in preventing or reducing further valvular damage in patients with acute rheumatic fever. We searched the Cochrane Central Register of Controlled Trials (2013, Issue 9 of 12), MEDLINE (Ovid, 1948 to 2013 October Week 1), EMBASE (Ovid, 1980 to 2013 Week 41) and Latin American Caribbean Health Sciences Literature (LILACS) (1982 to 17 October 2013). We last searched Index Medicus (1950 to April 2001) in 2001. We checked reference lists of identified studies and applied no language restrictions. Randomised controlled trials comparing anti-inflammatory agents (e.g. aspirin, steroids, immunoglobulins, pentoxifylline) versus placebo or controls, or comparing any of the anti-inflammatory agents versus one another, in adults and children with acute rheumatic fever diagnosed according to Jones, or modified Jones, criteria. The presence of cardiac disease one year after treatment was the major outcome criterion selected. Two review authors extracted data and assessed risk of bias using the methodology outlined in the Cochrane Handbook of Systematic Reviews of Interventions. Standard methodological procedures as expected by The Cochrane Collaboration were used. No new studies were included in this update. Eight randomised controlled trials involving 996 people were selected for inclusion in the review. Researchers compared several steroidal agents such as corticotrophin, cortisone, hydrocortisone, dexamethasone, prednisone and intravenous immunoglobulin versus aspirin, placebo or no treatment. Six

  20. Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability

    International Nuclear Information System (INIS)

    Li, E.J.; Cook, J.A.; Spicer, K.M.; Wise, W.C.; Rokach, J.; Halushka, P.V.

    1990-01-01

    Resistance to endotoxin in essential fatty acid-deficient (EFAD) rats is associated with reduced synthesis of certain arachidonic acid metabolites. It was hypothesized that EFAD rats would manifest decreased vascular permeability changes during endotoxemia as a consequence of reduced arachidonic acid metabolism. To test this hypothesis, changes in hematocrit (HCT) and mesenteric localization rate of technetium-labeled human serum albumin (99mTc-HSA) and red blood cells (99mTc-RBC) were assessed in EFAD and normal rats using gamma-camera imaging. Thirty minutes after Salmonella enteritidis endotoxin, EFAD rats exhibited less hemoconcentration as determined by % HCT than normal rats. Endotoxin caused a less severe change in permeability index in the splanchnic region in EFAD rats than in normal rats (1.2 +/- 0.6 x 10(-3)min-1 vs. 4.9 +/- 1.7 x 10(-3)min-1 respectively, P less than 0.05). In contrast to 99mTc-HSA, mesenteric localization of 99mTc-RBC was not changed by endotoxin in control or EFAD rats. Supplementation with ethyl-arachidonic acid did not enhance susceptibility of EFAD rats to endotoxin-induced splanchnic permeability to 99mTc-HSA. Leukotrienes have been implicated as mediators of increased vascular permeability in endotoxin shock. Since LTC3 formation has been reported to be increased in EFA deficiency, we hypothesized that LTC3 may be less potent than LTC4. Thus the effect of LTC3 on mean arterial pressure and permeability was compared to LTC4 in normal rats. LTC3-induced increases in peak mean arterial pressure were less than LTC4 at 10 micrograms/kg (39 +/- 5 mm Hg vs. 58 +/- 4 mm Hg respectively, P less than 0.05) and at 20 micrograms/kg (56 +/- 4 mm Hg vs. 75 +/- 2 mm Hg respectively, P less than 0.05). LY171883 (30 mg/kg), an LTD4/E4 receptor antagonist, attenuated the pressor effect of LTC4, LTD4, and LTC3

  1. 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.

  2. Topically applied standardized aqueous extract of Curcuma longa Linn. suppresses endotoxin-induced uveal inflammation in rats.

    Science.gov (United States)

    Agarwal, Renu; Gupta, S K; Agarwal, Puneet; Srivastava, Sushma

    2013-10-01

    Aqueous extract of C. longa when administered 4 h after induction of E. coli lipopolysaccharide-induced uveitis in rats showed significantly suppressed inflammation with a significantly lower mean clinical grade, histopathological grade and aqueous humor (AH) protein level compared to vehicle treated group. Although, prednisolone group showed significantly lower clinical grade, histopathological grades and AH protein levels compared to C. longa group, TNF-alpha levels did not differ significantly. Moreover, when the aqueous extract was administered starting from 3 days before induction of uveitis, the mean clinical and histopathological grade as well as AH protein and TNF-alpha levels were comparable to C. longa group when treatment was administered 4 h after induction of uveitis. It is concluded that topically applied standardized aqueous extract of C. longa suppresses endotoxin-induced uveitis in rats by reducing TNF-alpha activity.

  3. 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...

  4. The efficacy of intravitreal interferon alpha-2b for the treatment of experimental endotoxin-induced uveitis

    Directory of Open Access Journals (Sweden)

    Mehrdad Afarid

    2016-01-01

    Full Text Available Purpose: To study the efficacy of intravitreal interferon alpha-2b for endotoxin-induced uveitis. Materials and Methods: A total of 36 rabbits were randomly allocated to one of the three groups: (1 received interferon plus balanced-salt solution; (2 received lipopolysaccharide (LPS plus interferon; and (3 received LPS plus balanced-salt solution. Intraocular inflammation was evaluated by slit-lamp biomicroscopy (standardization of uveitis nomenclature grading, binocular indirect ophthalmoscopy (BIO score, and histopathology. Results: Group 2 showed significantly lower mean (±standard deviation anterior chamber reaction than Group 3 (3.1 ± 0.9 vs. 3.8 ± 0.4 on day 1 postinjection, lower vitreous cells on days 1 through 7 (day 1: 3.1 ± 0.9 vs. 3.8 ± 0.4; day 3: 2.1 ± 1.6 vs. 3.8 ± 0.4; day 7: 1.9 ± 1.3 vs. 3.6 ± 0.7, and lower BIO score on days 1-7 (day 1: 3.3 ± 1.2 vs. 4.4 ± 0.7; day 3: 3.0 ± 1.4 vs. 4.3 ± 0.9; day 7: 2.4 ± 1.4 vs. 3.7 ± 1.2. The protein content of anterior and vitreous aspirates was lower in Group 2 than 3 (1618.5 ± 411.4 vs. 2567.3 ± 330.8 and 2157.0 ± 283.3 vs. 3204.6 ± 259.5, respectively. Conclusion: Intravitreal interferon alpha-2b was effective in controlling endotoxin-induced uveitis.

  5. The efficacy of intravitreal interferon alpha-2b for the treatment of experimental endotoxin-induced uveitis.

    Science.gov (United States)

    Afarid, Mehrdad; Lashkarizadeh, Hamid; Ashraf, Mohammad J; Nowroozzadeh, Mohammad Hossein; Shafiee, Sayed M

    2016-05-01

    To study the efficacy of intravitreal interferon alpha-2b for endotoxin-induced uveitis. A total of 36 rabbits were randomly allocated to one of the three groups: (1) received interferon plus balanced-salt solution; (2) received lipopolysaccharide (LPS) plus interferon; and (3) received LPS plus balanced-salt solution. Intraocular inflammation was evaluated by slit-lamp biomicroscopy (standardization of uveitis nomenclature grading), binocular indirect ophthalmoscopy (BIO) score, and histopathology. Group 2 showed significantly lower mean (±standard deviation) anterior chamber reaction than Group 3 (3.1 ± 0.9 vs. 3.8 ± 0.4) on day 1 postinjection, lower vitreous cells on days 1 through 7 (day 1: 3.1 ± 0.9 vs. 3.8 ± 0.4; day 3: 2.1 ± 1.6 vs. 3.8 ± 0.4; day 7: 1.9 ± 1.3 vs. 3.6 ± 0.7), and lower BIO score on days 1-7 (day 1: 3.3 ± 1.2 vs. 4.4 ± 0.7; day 3: 3.0 ± 1.4 vs. 4.3 ± 0.9; day 7: 2.4 ± 1.4 vs. 3.7 ± 1.2). The protein content of anterior and vitreous aspirates was lower in Group 2 than 3 (1618.5 ± 411.4 vs. 2567.3 ± 330.8 and 2157.0 ± 283.3 vs. 3204.6 ± 259.5, respectively). Intravitreal interferon alpha-2b was effective in controlling endotoxin-induced uveitis.

  6. Effects of the immunomodulator, VGX-1027, in endotoxin-induced uveitis in Lewis rats

    DEFF Research Database (Denmark)

    Mangano, K; Sardesai, N Y; Quattrocchi, C

    2008-01-01

    VGX-1027 is a novel, low molecular weight, immunomodulatory compound that has shown efficacy against a variety of immuno-inflammatory disease models in animals including autoimmune diabetes in NOD mice, collagen-induced arthritis and chemically induced inflammatory colitis. Here, we have studied ...

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

    DEFF Research Database (Denmark)

    Andersson, Manne; Rubér, Marie; Ekerfelt, Christina

    2014-01-01

    BACKGROUND: The diagnosis of appendicitis is difficult and resource consuming. New inflammatory markers have been proposed for the diagnosis of appendicitis, but their utility in combination with traditional diagnostic variables has not been tested. Our objective is to explore the potential of new...... inflammatory markers for improving the diagnosis of appendicitis.METHODS: The diagnostic properties of the six most promising out of 21 new inflammatory markers (interleukin [IL]-6, chemokine ligand [CXCL]-8, chemokine C-C motif ligand [CCL]-2, serum amyloid A [SAA], matrix metalloproteinase [MMP]-9......, 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...

  8. Acute and chronic stress and the inflammatory response in hyperprolactinemic rats.

    Science.gov (United States)

    Ochoa-Amaya, J E; Malucelli, B E; Cruz-Casallas, P E; Nasello, A G; Felicio, L F; Carvalho-Freitas, M I R

    2010-01-01

    Prolactin (PRL), a hormone produced by the pituitary gland, has multiple physiological functions, including immunoregulation. PRL can also be secreted in response to stressful stimuli. During stress, PRL has been suggested to oppose the immunosuppressive effects of inflammatory mediators. Therefore, the aim of the present study was to analyze the effects of short- and long-term hyperprolactinemia on the inflammatory response in rats subjected to acute or chronic cold stress. Inflammatory edema was induced by carrageenan in male rats, and hyperprolactinemia was induced by injections of the dopamine receptor antagonist domperidone. The volume of inflammatory edema was measured by plethysmography after carrageenan injection. Additionally, the effects of hyperprolactinemia on body weight and serum corticosterone levels were evaluated. Five days of domperidone-induced hyperprolactinemia increased the volume of inflammatory edema. No differences in serum corticosterone levels were observed between groups. No significant differences were found among 30 days domperidone-induced hyperprolactinemic animals subjected to acute stress and the inflammatory response observed in chronic hyperprolactinemic animals subjected to chronic stress. The results suggest that short-term hyperprolactinemia has pro-inflammatory effects. Because such an effect was not observed in long-term hyperprolactinemic animals, PRL-induced tolerance seems likely. We suggest that short-term hyperprolactinemia may act as a protective factor in rats subjected to acute stress. These data suggest that hyperprolactinemia and stress interact differentially according to the time period. Copyright 2010 S. Karger AG, Basel.

  9. 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)

  10. Binding of /sup 125/I-labeled endotoxin to bovine, canine, and equine platelets and endotoxin-induced agglutination of canine platelets

    Energy Technology Data Exchange (ETDEWEB)

    Meyers, K.M.; Boehme, M.; Inbar, O.

    1982-10-01

    Endotoxin from Escherichia coli O127:B8, Salmonella abortus-equi and S minnesota induced clumping of some canine platelets (PLT) at a final endotoxin concentration of 1 microgram/ml. Endotoxin-induced clumping of canine PLT was independent of PLT energy-requiring processes, because clumping was observed with canine PLT incubated with 2-deoxy-D-glucose and antimycin A. The PLT responded to adenosine diphosphate before, but not after, incubation with the metabolic inhibitors. Endotoxin induced a slight and inconsistant clumping of bovine and equine PLT at high (mg/ml) endotoxin concentration. High-affinity binding sites could not be demonstrated on canine, bovine, and equine PLT, using /sup 125/I-labeled E coli O127:B8 endotoxin. Nonspecific binding was observed and appeared to be due primarily to an extraneous coat on the PLT surface that was removed by gel filtration. The endotoxin that was bound to PLT did not appear to modify PLT function. An attempt to identify plasma proteins that bound physiologically relevant amounts of endotoxin was not successful. The significance of the endotoxin-induced clumping or lack of it on the pathophysiology of endotoxemia is discussed.

  11. Binding of 125I-labeled endotoxin to bovine, canine, and equine platelets and endotoxin-induced agglutination of canine platelets

    International Nuclear Information System (INIS)

    Meyers, K.M.; Boehme, M.; Inbar, O.

    1982-01-01

    Endotoxin from Escherichia coli O127:B8, Salmonella abortus-equi and S minnesota induced clumping of some canine platelets (PLT) at a final endotoxin concentration of 1 microgram/ml. Endotoxin-induced clumping of canine PLT was independent of PLT energy-requiring processes, because clumping was observed with canine PLT incubated with 2-deoxy-D-glucose and antimycin A. The PLT responded to adenosine diphosphate before, but not after, incubation with the metabolic inhibitors. Endotoxin induced a slight and inconsistant clumping of bovine and equine PLT at high (mg/ml) endotoxin concentration. High-affinity binding sites could not be demonstrated on canine, bovine, and equine PLT, using 125 I-labeled E coli O127:B8 endotoxin. Nonspecific binding was observed and appeared to be due primarily to an extraneous coat on the PLT surface that was removed by gel filtration. The endotoxin that was bound to PLT did not appear to modify PLT function. An attempt to identify plasma proteins that bound physiologically relevant amounts of endotoxin was not successful. The significance of the endotoxin-induced clumping or lack of it on the pathophysiology of endotoxemia is discussed

  12. MODERN MANAGEMENT OF ACUTE RESPIRATORY INFECTIONS IN CHILDREN. RECOURSES OF SYSTEM ANTI INFLAMMATORY TREATMENT

    Directory of Open Access Journals (Sweden)

    O.V. Zaitseva

    2008-01-01

    Full Text Available A problem of etiology and pathogenesis of acute respiratory infections in children are observed in this article. Modern approach to management of its treatment in pediatric patients, including often ailing children, is described. Authors give characteristics to main directions of treatment of obstructive syndrome. An experience of anti-inflammatory therapy with fenspiride (eurespal in children of different age is summa ized in this article.Key words: often ailing children, acute respiratory infections, bronchoobstructive syndrome, anti-inflammatory treatment, fenspiride.

  13. 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.

  14. 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 volunteers...... on 3 separate days with 7-day intervals. They received either (1) subcutaneous infiltration with ketamine in the burn area (local treatment) and contralateral placebo injections, or (2) subcutaneous ketamine contralateral to the burn (systemic treatment) and placebo in the burn area, or (3) placebo...... hyperalgesia. Local ketamine infiltration reduced pain during the burn injury compared with systemic treatment and placebo (P ketamine treatment compared with placebo immediately after injection (P

  15. 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.

  16. The role of genital chlamydial infection in acute pelvic inflammatory ...

    African Journals Online (AJOL)

    The result showed that 11.1 per cent of women with acute PID were infected with Chlamydia trachomatis as compared to 4.3 per cent in the control group (odds ratio 2.75: 95% confidence interval (CI), 0.7-11.7). Neiserria gonorrhoeae was not detected in either of the two groups. Trichomoniasis (10% in PID cases and no ...

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

    Energy Technology Data Exchange (ETDEWEB)

    El Hentour, Kim; Millet, Ingrid; Pages-Bouic, Emmanuelle; Curros-Doyon, Fernanda; Taourel, Patrice [Lapeyronie Hospital, Department of Medical Imaging, Montpellier (France); Molinari, Nicolas [UMR 5149 IMAG, CHU, Department of Medical Information and Statistics, Montpellier (France)

    2018-02-15

    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. (orig.)

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

    International Nuclear Information System (INIS)

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

    2018-01-01

    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. (orig.)

  19. 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

    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 known about

  20. 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

  1. Myeloid Heme Oxygenase-1 Regulates the Acute Inflammatory Response to Zymosan in the Mouse Air Pouch

    Directory of Open Access Journals (Sweden)

    Rita Brines

    2018-01-01

    Full Text Available Heme oxygenase-1 (HO-1 is induced by many stimuli to modulate the activation and function of different cell types during innate immune responses. Although HO-1 has shown anti-inflammatory effects in different systems, there are few data on the contribution of myeloid HO-1 and its role in inflammatory processes is not well understood. To address this point, we have used HO-1M-KO mice with myeloid-restricted deletion of HO-1 to specifically investigate its influence on the acute inflammatory response to zymosan in vivo. In the mouse air pouch model, we have shown an exacerbated inflammation in HO-1M-KO mice with increased neutrophil infiltration accompanied by high levels of inflammatory mediators such as interleukin-1β, tumor necrosis factor-α, and prostaglandin E2. The expression of the degradative enzyme matrix metalloproteinase-3 (MMP-3 was also enhanced. In addition, we observed higher levels of serum MMP-3 in HO-1M-KO mice compared with control mice, suggesting the presence of systemic inflammation. Altogether, these findings demonstrate that myeloid HO-1 plays an anti-inflammatory role in the acute response to zymosan in vivo and suggest the interest of this target to regulate inflammatory processes.

  2. Leucocytes labelled with In-111-oxine in acute inflammatory processes

    International Nuclear Information System (INIS)

    Herranz, R.; Lomena, F.; Fernandez, R.M.; Del Rio, L.; Piera, C.; Vida, F.; Setoain, J.

    1982-01-01

    We used autologous leucocytes labelled with In-111-Oxine to diagnose inflammatory processes, located or scattered, in 60 patients. In 46 there was suspected located infection focus. Gammagraphy was abnormal in 38 cases (83%), 28 abdominally located (87%), 5 thorax located (71%) and 5 of several locations. In other 14 cases there was clinic suspicion of infection without located septic focus. In 5 of them gammagraphy was interpreted as positive but only in 3 patients it was found abdominal located abscess. The two other cases are considered as false positive ones. In the 9 remaining, with negative gammagraphy there was no clinic confirmation nor other diagnostic methods of abscess existence. In this paper we checked high sensitivity of leucocytes In-111-Oxine to diagnose and locate infectious focuses. In our casuistry there was only a false negative and two false positive ones

  3. Vasorelaxing Action of the Kynurenine Metabolite, Xanthurenic Acid: The Missing Link in Endotoxin-Induced Hypotension?

    Directory of Open Access Journals (Sweden)

    Carmine Vecchione

    2017-05-01

    Full Text Available The kynurenine pathway of tryptophan metabolism is activated by pro-inflammatory cytokines. L-kynurenine, an upstream metabolite of the pathway, acts as a putative endothelium-derived relaxing factor, and has been hypothesized to play a causative role in the pathophysiology of inflammation-induced hypotension. Here, we show that xanthurenic acid (XA, the transamination product of 3-hydroxykynurenine, is more efficacious than L-kynurenine in causing relaxation of a resistance artery, but fails to relax pre-contracted aortic rings. In the mesenteric artery, XA enhanced activating phosphorylation of endothelial nitric oxide synthase (NOS, and the relaxing action of XA was abrogated by pharmacological inhibition of NOS and endothelial-derived hyperpolarizing factor. Systemic injection of XA reduced blood pressure in mice, and serum levels of XA increased by several fold in response to a pulse with the endotoxin, lipopolysaccharide (LPS. LPS-induced hypotension in mice was prevented by pre-treatment with the kynurenine monooxygenase (KMO inhibitor, Ro-618048, which lowered serum levels of XA but enhanced serum levels of L-kynurenine. UPF 648, another KMO inhibitor, could also abrogate LPS-induced hypotension. Our data identify XA as a novel vasoactive compound and suggest that formation of XA is a key event in the pathophysiology of inflammation-induced hypotension.

  4. 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.

  5. The ultrasonographic findings of acute pelvic inflammatory disease

    International Nuclear Information System (INIS)

    Choi, Yeon Nam; Park, Jai Soung; Lee, Hae Kyung; Chung, Moo Chan; Lee, Beong Ho; Kim, Ki Jung

    1987-01-01

    Although ultrasonographic findings of female pelvic mass are frequently reported, those of acute PID are not well established. But differentiation of fluid collection and mass lesion of PID is exactly made by ultrasonography. We analysed the ultrasonographic findings in 26 cases of acute PID having satisfactory operative or histological proofs, examined at Soonchunhyang University Hospital from Oct. 1985 to Feb. 1987. The results were as follows: 1. The age was ranged from 17 years to 53 years of age and the majority was between 21 years and 50 years of age. 2. Ultrasonographic findings are classified to fluid collection in cul de sac 17, tuboovarian abscess, 7 pyosalpix 2, endometritis 1 and normal 2 cases. 3. In cases of pelvic mass formation, their ecnogenecity were cystic form in 6 cases (22%), mixed form in 19 cases (71%), solid form in 2 cases (7%), and shapes were mainly ovoid with irregular, ill-defined margin. The location of mass is unilateral in 17 cases (63%) bilateral in 10 cases (37%)

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

    International Nuclear Information System (INIS)

    Gold, R.P.; McClennan, B.L.; Rottenberg, R.R.

    1983-01-01

    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

  7. Low-dose dexamethasone-supplemented fluid resuscitation reverses endotoxin-induced acute renal failure and prevents cortical microvascular hypoxia

    NARCIS (Netherlands)

    Johannes, Tanja; Mik, Egbert G.; Klingel, Karin; Dieterich, Hans-Jürgen; Unertl, Klaus E.; Ince, Can

    2009-01-01

    There is growing evidence that impairment in intrarenal oxygenation and hypoxic injury might contribute to the pathogenesis of septic renal failure. An important molecule known to act on the renal microvascular tone and therefore consequently being involved in the regulation of intrarenal oxygen

  8. Important role of platelets in modulating endotoxin-induced lung inflammation in CFTR-deficient mice.

    Directory of Open Access Journals (Sweden)

    Caiqi Zhao

    Full Text Available Mutation of CFTR (cystic fibrosis transmembrane conductance regulator leads to cystic fibrosis (CF. Patients with CF develop abnormalities of blood platelets and recurrent lung inflammation. However, whether CFTR-mutated platelets play a role in the development of lung inflammation is elusive. Therefore, we intratracheally challenged wildtype and F508del (a common type of CFTR mutation mice with LPS to observe changes of F508del platelets in the peripheral blood and indexes of lung inflammation (BAL neutrophils and protein levels. Furthermore, we investigated whether or not and how F508del platelets modulate the LPS-induced acute lung inflammation by targeting anti-platelet aggregation, depletion of neutrophils, reconstitution of bone marrow or neutrophils, blockade of P-selectin glycoprotein ligand-1 (PSGL-1, platelet activating factor (PAF, and correction of mutated CFTR trafficking. We found that LPS-challenged F508del mice developed severe thrombocytopenia and had higher levels of plasma TXB2 coincided with neutrophilic lung inflammation relative to wildtype control. Inhibition of F508del platelet aggregation or depletion of F508del neutrophils diminished the LPS-induced lung inflammation in the F508del mice. Moreover, wildtype mice reconstituted with either F508del bone marrow or neutrophils developed worse thrombocytopenia. Blocking PSGL-1, platelet activating factor (PAF, or rectifying trafficking of mutated CFTR in F508del mice diminished and alveolar neutrophil transmigration in the LPS-challenged F508del mice. These findings suggest that F508del platelets and their interaction with neutrophils are requisite for the development of LPS-induced lung inflammation and injury. As such, targeting platelets might be an emerging strategy for dampening recurrent lung inflammation in cystic fibrosis patients.

  9. Dehydroepiandrosterone in relation to other adrenal hormones during an acute inflammatory stressful disease state compared with chronic inflammatory disease: role of interleukin-6 and tumour necrosis factor.

    Science.gov (United States)

    Straub, Rainer H; Lehle, Karin; Herfarth, Hans; Weber, Markus; Falk, Werner; Preuner, Jurgen; Scholmerich, Jurgen

    2002-03-01

    Serum levels of dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS) are low in chronic inflammatory diseases, although the reasons are unexplained. Furthermore, the behaviour of serum levels of these hormones during an acute inflammatory stressful disease state is not well known. In this study in patients with an acute inflammatory stressful disease state (13 patients undergoing cardiothoracic surgery) and patients with chronic inflammation (61 patients with inflammatory bowel diseases (IBD)) vs. 120 controls, we aimed to investigate adrenal hormone shifts looking at serum levels of DHEA in relation to other adrenal hormones. Furthermore, we tested the predictive role of serum tumour necrosis factor (TNF) and interleukin-6 (IL-6) for a change of serum levels of DHEA in relation to other adrenal hormones. The molar ratio of serum levels of DHEA/androstenedione (ASD) was increased in patients with an acute inflammatory stressful disease state and was decreased in patients with chronic inflammation. The molar ratio of serum levels of DHEAS/DHEA was reduced during an acute inflammatory stressful disease state and was increased in patients with chronic inflammation. A multiple linear regression analysis revealed that elevated serum levels of TNF were associated with a high ratio of serum levels of DHEA/ASD in all groups (for IL-6 in patients with an acute inflammatory stressful disease state only), and, similarly, elevated serum levels of TNF were associated with a high ratio of serum levels of DHEAS/DHEA only in IBD (for IL-6 only in healthy subjects). This study indicates that changes of serum levels of DHEA in relation to serum levels of other adrenal hormones are completely different in patients with an acute inflammatory stressful disease state compared with patients with chronic inflammation. The decrease of serum levels of DHEAS and DHEA is typical for chronic inflammation and TNF and IL-6 play a predictive role for these changes.

  10. Characterizing the inflammatory tissue response to acute myocardial infarction by clinical multimodality noninvasive imaging.

    Science.gov (United States)

    Wollenweber, Tim; Roentgen, Philipp; Schäfer, Andreas; Schatka, Imke; Zwadlo, Caroline; Brunkhorst, Thomas; Berding, Georg; Bauersachs, Johann; Bengel, Frank M

    2014-09-01

    Myocardial infarction (MI) triggers a systemic inflammatory response which determines subsequent healing. Experimentally, cardiac positron emission tomography and magnetic resonance imaging have been used successfully to obtain mechanistic insights. We explored the translational potential in patients early after MI. Positron emission tomography/computed tomography and cardiac magnetic resonance were performed in 15 patients sources of inflammatory cells. Positron emission tomography and cardiac magnetic resonance multimodality characterization of the acutely infarcted, inflamed myocardium may provide multiparametric end points for clinical studies aiming at support of infarct healing. © 2014 American Heart Association, Inc.

  11. INFLAMMATORY MARKERS IN ACUTE ISCHAEMIC STROKE IN RELATION TO CLINICAL SEVERITY AND EARLY OUTCOME

    Directory of Open Access Journals (Sweden)

    S. Gopi

    2018-01-01

    Full Text Available BACKGROUND Biochemical markers of inflammation could be useful to predict severity of stroke in acute phase. Stroke is the third cause of mortality and the first cause of disability. Recent literature have demonstrated that inflammation contributes to all phases of atherosclerosis. The results of researchers suggest that atherosclerosis is an inflammatory disease. The aim of the study is to assess the1. Level of peripheral inflammatory markers in acute ischaemic stroke and their relation to severity of acute stroke. 2. Value of inflammatory markers in predicting the short-term outcome and disability at the end of six months. MATERIALS AND METHODS This is a prospective case control study for 6 months done from September 2014 to August 2016 in 100 patients of acute ischaemic stroke within first 5 days of symptom onset in comparison >18 years of age with 50 age and sex matched controls. Blood samples for all cases and controls were sent for erythrocyte sedimentation rate, Neutrophil-to-Lymphocyte Ratio (NLR, hs-C-reactive protein, mean platelet volume, serum ferritin, serum albumin and S. gamma-glutamyl transferase at admission. RESULTS The mean values of ESR, NLR, hs-CRP in all the cases are higher when compared to the controls and are statistically significant, whereas the mean values of MPV, S. ferritin, S. albumin and GGT in cases are lower when compared to controls, but are within normal range and difference is statistically significant except ferritin. ESR, hs-CRP has significant correlation with severity of acute ischaemic stroke. The mean values of these markers increased with increase in severity. Serum albumin has significant correlation with severity of acute ischaemic stroke with mean values of these markers decreasing with increase in severity of stroke. There is no significant correlation of the inflammatory markers in present study with the short-term outcome. CONCLUSION Inflammation plays an important role in the pathogenesis of non

  12. Chronic Disseminated Candidiasis Complicated by Immune Reconstitution Inflammatory Syndrome in Child with Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Olga Zając-Spychała

    2016-01-01

    Full Text Available Hepatosplenic candidiasis also known as chronic disseminated candidiasis is a rare manifestation of invasive fungal infection typically observed in patients with acute leukemia in prolonged, deep neutropenia. Immune reconstitution inflammatory syndrome (IRIS is an inflammatory disorder triggered by rapid resolution of neutropenia. Diagnosis and treatment of IRIS are still challenging due to a variety of clinical symptoms, lack of certain diagnostic criteria, and no standards of treatment. The diagnosis of IRIS is even more difficult in patients with hematological malignancies complicated by “probable” invasive fungal infection, when fungal pathogen is still uncertain. We report a case of probable hepatic candidiasis in 4-year-old boy with acute lymphoblastic leukemia. Despite proper antifungal therapy, there was no clinical and radiological improvement, so diagnosis of Candida-related IRIS was made and corticosteroid therapy was added to antifungal treatment achieving prompt resolution of infection symptoms.

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

    OpenAIRE

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

    2016-01-01

    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 ca...

  14. Current possibilities of anti-inflammatory therapy in children with acute respiratory diseases

    OpenAIRE

    E. E. Lokshina; O. V. Zaytseva

    2017-01-01

    The paper gives an update on the pathogenesis of acute respiratory diseases, the basis for which is inflammation of the airway mucosal lining. It reflects the results of a comparative clinical trial of the efficacy and safety of the anti-inflammatory drug fenspiride used in the combination therapy for respiratory diseases in children. The findings allow one to recommend the use of fenspiride to treat this condition in children.

  15. Current possibilities of anti-inflammatory therapy in children with acute respiratory diseases

    Directory of Open Access Journals (Sweden)

    E. E. Lokshina

    2017-01-01

    Full Text Available The paper gives an update on the pathogenesis of acute respiratory diseases, the basis for which is inflammation of the airway mucosal lining. It reflects the results of a comparative clinical trial of the efficacy and safety of the anti-inflammatory drug fenspiride used in the combination therapy for respiratory diseases in children. The findings allow one to recommend the use of fenspiride to treat this condition in children.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Diagnosis of acute inflammatory conditions in children and adolescents using In-111 oxine white blood cells

    International Nuclear Information System (INIS)

    Gainey, M.A.; McDougall, I.R.

    1984-01-01

    In-111 oxine labeled white cells were used to diagnose acute inflammatory conditions in 42 children and adolescents, aged 6 weeks to 19 years. In 43 scans where a clinical correlation could be made, the test had a sensitivity of 81% and a specificity of 94%. There were no adverse reactions. For children the dose of In-111 recommended is 10-12 mu Ci/kg body weight to a maximum of 500 mu Ci

  18. Evaluation of Some Inflammatory and Biochemical Markers in Acute Coronary Syndrome

    International Nuclear Information System (INIS)

    Abdel-Messeih, PH.L.; Nossier, N.M.; Mansour, H.H.

    2012-01-01

    The term acute coronary syndrome (ACS) encompasses a range of thrombotic coronary artery diseases, including unstable angina (UA) and both ST-segment elevation (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). Bio markers play an important role in the diagnosis of non-ST-elevation ACS (NSTE-ACS) including unstable angina and non-STEMI. Among these, cardiac troponin and creatine phosphokinase myocardial band appeared to be the most sensitive and specific markers of myocardial injury. The important role of inflammatory processes in the development and progression of atherosclerosis has been clearly established. Different circulating inflammatory bio markers indicating the instability of atherosclerotic plaque have been identified and serve as diagnostic tools for the identification of patients with unstable angina or acute myocardial infarction and to identify risk patients. The present study was carried out on twenty patients with (NSTE-ACS). The level of serum troponin I (cTnI), creatine phosphokinase-total (CPK-T), myocardial band of creatine phosphokinase (CPK-MB), pregnancy associated plasma protein-A (PAPP-A) and highly sensitive C-reactive protein (hsCRP) were determined. The results showed increase in the level of cardiac bio markers (cTnI, CPK-MB, CPK-T) and inflammatory markers (PAPP-A, hsCRP). It could be concluded that the increase in inflammatory markers correlate especially PAPP-A in NSTE-ACS with the increase of cardiac bio markers

  19. Identification of health problems in patients with acute inflammatory arthritis, using the International Classification of Functioning, Disability and Health (ICF).

    Science.gov (United States)

    Zochling, J; Grill, E; Scheuringer, M; Liman, W; Stucki, G; Braun, J

    2006-01-01

    To identify the most common health problems experienced by patients with acute inflammatory arthritis using the International Classification of Functioning, Disability and Health (ICF), and to provide empirical data for the development of an ICF Core Set for acute inflammatory arthritis. Cross-sectional survey of patients with acute inflammatory arthritis of two or more joints requiring admission to an acute hospital. The second level categories of the ICF were used to collect information on patients' health problems. Relative frequencies of impairments, limitations and restrictions in the study population were reported for the ICF components Body Functions, Body Structures, and Activities and Participations. For the component Environmental Factors absolute and relative frequencies of perceived barriers or facilitators were reported. In total, 130 patients were included in the survey. The mean age of the population was 59.9 years (median age 63.0 years), 75% of the patients were female. Most had rheumatoid arthritis (57%) or early inflammatory polyarthritis (22%). Fifty-four second-level ICF categories had a prevalence of 30% or more: 3 (8%) belonged to the component Body Structures and 10 (13%) to the component Body Functions. Most categories were identified in the components Activities and Participation (19; 23%) and Environmental Factors (22; 56%). Patients with acute inflammatory arthritis can be well described by ICF categories and components. This study is the first step towards the development of an ICF Core Set for patients with acute inflammatory arthritis.

  20. Type 2 diabetes mellitus with early phase acute inflammatory protein on serum protein electrophoresis

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    ET Tuladhar

    2012-03-01

    Full Text Available Background: The onset of Type 2 diabetes has been associated with low grade systemic inflammation. The inflammatory status has been studied by measuring acute phase reactant proteins like hsCRP, α1- antitrypsin, α1-acid glycoprotein, ceruloplasmin, fibrinogen. Most of these acute phase reactants form α1 and α2 bands on electropherogram of serum proteins. The aim of this study was to evaluate inflammatory status in controlled and uncontrolled type 2 diabetes using cellulose acetate electrophoresis and to find the impact of glycemic status as indicated by HbA1c on inflammation process. Materials and Methods: Serum protein electrophoresis was done on serum samples of 60 cases of Diabetes [controlled and uncontrolled] using cellulose acetate paper technique. The electropherogram obtained was stained with Ponseu S and then quantitated using densitometer. Glycemic status was studied by HbA1c analysis. The density of α1and α2 bands in electropherogram were correlated with HbA1c level. Result: A significant increase in the percentage of α1 and α2 band proteins (0.765 and 0.716, p<0.001 were found with the increasing level of HbA1c. With cutoff of HbA1c 7% (American Diabetic Association recommended, the α1 and α2 serum proteins concentration are significantly higher (p<0.001 in uncontrolled diabetes mellitus compared to controlled diabetes mellitus Conclusion: Cellulose acetate electrophoresis of serum proteins show early phase acute inflammatory status in uncontrolled type 2 diabetes mellitus. The process of systemic inflammation worsens with uncontrolled glycemia as indicated by HbA1c. Inflammatory status should be studied adjunct to glycemic status. DOI: http://dx.doi.org/10.3126/jpn.v2i3.6024 JPN 2012; 2(3: 211-214

  1. Intratracheal synthetic CpG oligodeoxynucleotide causes acute lung injury with systemic inflammatory response

    Directory of Open Access Journals (Sweden)

    Hasegawa Naoki

    2009-09-01

    Full Text Available Abstract Bacterial genome is characterized by frequent unmethylated cytosine-phosphate-guanine (CpG motifs. Deleterious effects can occur when synthetic oligodeoxynucleotides (ODN with unmethylated CpG dinucleotides (CpG-ODN are administered in a systemic fashion. We aimed to evaluate the effect of intratracheal CpG-ODN on lung inflammation and systemic inflammatory response. C57BL/6J mice received intratracheal administration of CpG-ODN (0.01, 0.1, 1.0, 10, or 100 μM or control ODN without CpG motif. Bronchoalveolar lavage (BAL fluid was obtained 3 or 6 h or 1, 2, 7, or 14 days after the instillation and subjected to a differential cell count and cytokine measurement. Lung permeability was evaluated as the BAL fluid-to-plasma ratio of the concentration of human serum albumin that was injected 1 h before euthanasia. Nuclear factor (NF-κB DNA binding activity was also evaluated in lung homogenates. Intratracheal administration of 10 μM or higher concentration of CpG-ODN induced significant inflammatory cell accumulation into the airspace. The peak accumulation of neutrophils and lymphocytes occurred 1 and 2 days after the CpG-ODN administration, respectively. Lung permeability was increased 1 day after the 10 μM CpG-ODN challenge. CpG-ODN also induced nuclear translocation of NF-κB and upregulation of various inflammatory cytokines in BAL fluid and plasma. Histopathology of the lungs and liver revealed acute lung injury and liver damage with necrosis, respectively. Control ODN without CpG motif did not induce any inflammatory change. Since intratracheal CpG-ODN induced acute lung injury as well as systemic inflammatory response, therapeutic strategies to neutralize bacterial DNA that is released after administration of bactericidal agents should be considered.

  2. The mathematical pathogenetic factors analysis of acute inflammatory diseases development of bronchopulmonary system among infants

    Directory of Open Access Journals (Sweden)

    G. O. Lezhenko

    2017-10-01

    Full Text Available The purpose. To study the factor structure and to establish the associative interaction of pathogenetic links of acute diseases development of the bronchopulmonary system in infants.Materials and methods. The examination group consisted of 59 infants (average age 13.8 ± 1.4 months sick with acute inflammatory bronchopulmonary diseases. Also we tested the level of 25-hydroxyvitamin D (25(ОНD, vitamin D-binding protein, hBPI, cathelicidin LL-37, ß1-defensins, lactoferrin in blood serum with the help of immunoenzymometric analysis. Selection of prognostically important pathogenetic factors of acute bronchopulmonary disease among infants was conducted using ROC-analysis. The procedure for classifying objects was carried out using Hierarchical Cluster Analysis by the method of Centroid-based clustering. Results. Based on the results of the ROC-analysis were selected 15 potential predictors of the development of acute inflammatory diseases of the bronchopulmonary system among infants. The factor analysis made it possible to determine the 6 main components . The biggest influence in the development of the disease was made by "the anemia factor", "the factor of inflammation", "the maternal factor", "the vitamin D supply factor", "the immune factor" and "the phosphorus-calcium exchange factor” with a factor load of more than 0.6. The performed procedure of hierarchical cluster analysis confirmed the initial role of immuno-inflammatory components. The conclusions. The highlighted factors allowed to define a group of parameters, that must be influenced to achieve a maximum effect in carrying out preventive and therapeutic measures. First of all, it is necessary to influence the "the anemia factor" and "the calcium exchange factor", as well as the "the vitamin D supply factor". In other words, to correct vitamin D deficiency and carry out measures aimed at preventing the development of anemia. The prevention and treatment of the pathological course of

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

    International Nuclear Information System (INIS)

    Park, Seong Jin; Lee, Hae Kyung; Yi, Bum Ha; Kim, Hyun Cheol

    2005-01-01

    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

  4. Effects of the immunomodulator, VGX-1027, in endotoxin-induced uveitis in Lewis ratsTumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease

    DEFF Research Database (Denmark)

    Mangano, K.; Sardesai, N.Y.; Quattrocchi, C.

    2008-01-01

    BACKGROUND AND PURPOSE: VGX-1027 is a novel, low molecular weight, immunomodulatory compound that has shown efficacy against a variety of immuno-inflammatory disease models in animals including autoimmune diabetes in NOD mice, collagen-induced arthritis and chemically induced inflammatory colitis...... with VGX-1027 counteracts the uveitis-inducing effect of LPS in rats and suggests that this drug may have potential in the treatment of immuno-inflammatory conditions of the eye in humans Udgivelsesdato: 2008/11....... Here, we have studied the effects of VGX-1027 on the development of endotoxin-induced uveitis (EIU) in male Lewis rats, as a model of inflammatory ocular diseases in humans. EXPERIMENTAL APPROACH: EIU was induced by a single footpad injection of 200 microg lipopolysaccharide (LPS). Groups of rats were......, immunological and histological signs of EIU. KEY RESULTS: The rats treated with VGX-1027 within 6 h after LPS challenge exhibited milder clinical, histological and laboratory signs of EIU than those treated with vehicle. CONCLUSION AND IMPLICATIONS: This study provides the first evidence that systemic treatment...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Kaspar, Felix; Jelinek, Herbert F.; Perkins, Steven; Al-Aubaidy, Hayder A.; deJong, Bev; Butkowski, Eugene

    2016-01-01

    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. PMID:27212809

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

    Science.gov (United States)

    Kaspar, Felix; Jelinek, Herbert F; Perkins, Steven; Al-Aubaidy, Hayder A; deJong, Bev; Butkowski, Eugene

    2016-01-01

    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. Cohort study with repeated-measures design. 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. 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). 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.

  8. Comparison of acute ozone-induced nasal and pulmonary inflammatory responses

    Energy Technology Data Exchange (ETDEWEB)

    Hotchkiss, J A; Harkema, J R; Sun, J D; Henderson, R F

    1988-12-01

    The present study was designed to compare the effects of acute ozone exposure in the nose and lungs of rats. Rats were exposed to 0.0, 0.12, 0.80, or 1.5 ppm O{sub 3} for 6 h and were sacrificed immediately, 3,18, 42, or 66 h after exposure. Cellular inflammatory responses were assessed by quantitating polymorphonuclear neutrophils (PMN) recovered by nasal lavage (NL) and bronchoalveolar lavage (BAL) and morphometric quantitation of PMN within the nasal mucosa and pulmonary centriacinar region. Rats exposed to 0.12 ppm O{sub 3} had a transient nasal PMN response 18 h after exposure but no increase in pulmonary PMN. Rats exposed to 0.8 ppm O{sub 3} had a marked increase in nasal PMN immediately after exposure but the number of PMN within the nasal cavity decreased as the number of pulmonary PMN increased with time after exposure. Rats exposed to 1.5 ppm O{sub 3} had an increase in pulmonary PMN beginning 3 h post-exposure, but no increase in nasal PMN at any time. Our results suggest that at high O{sub 3} concentrations, the acute nasal inflammatory response is attenuated by a simultaneous, competing, inflammatory response within the lung. (author)

  9. Comparison of acute ozone-induced nasal and pulmonary inflammatory responses

    International Nuclear Information System (INIS)

    Hotchkiss, J.A.; Harkema, J.R.; Sun, J.D.; Henderson, R.F.

    1988-01-01

    The present study was designed to compare the effects of acute ozone exposure in the nose and lungs of rats. Rats were exposed to 0.0, 0.12, 0.80, or 1.5 ppm O 3 for 6 h and were sacrificed immediately, 3,18, 42, or 66 h after exposure. Cellular inflammatory responses were assessed by quantitating polymorphonuclear neutrophils (PMN) recovered by nasal lavage (NL) and bronchoalveolar lavage (BAL) and morphometric quantitation of PMN within the nasal mucosa and pulmonary centriacinar region. Rats exposed to 0.12 ppm O 3 had a transient nasal PMN response 18 h after exposure but no increase in pulmonary PMN. Rats exposed to 0.8 ppm O 3 had a marked increase in nasal PMN immediately after exposure but the number of PMN within the nasal cavity decreased as the number of pulmonary PMN increased with time after exposure. Rats exposed to 1.5 ppm O 3 had an increase in pulmonary PMN beginning 3 h post-exposure, but no increase in nasal PMN at any time. Our results suggest that at high O 3 concentrations, the acute nasal inflammatory response is attenuated by a simultaneous, competing, inflammatory response within the lung. (author)

  10. Effect of peripheral morphine in a human model of acute inflammatory pain

    DEFF Research Database (Denmark)

    Lillesø, J; Hammer, N A; Pedersen, J L

    2000-01-01

    Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo-controlled, th......Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo......-controlled, three-way crossover design in a human model of acute inflammatory pain (heat injury). We studied 18 healthy volunteers who each received morphine locally (2 mg), morphine systemically (2 mg), or placebo on three separate study days. The subjects received morphine infiltration subcutaneously (s.c.). 1 h......, but local morphine infiltration neither reduced pain during the burn, nor primary or secondary hyperalgesia to mechanical and heat stimuli after the burn. In conclusion, peripherally applied morphine had no acute antinociceptive effects in this human model of acute inflammatory pain....

  11. The inflammatory response plays a major role in the acute radiation syndrome induced by fission radiation

    International Nuclear Information System (INIS)

    Agay, D.; Chancerelle, Y.; Hirodin, F.; Mathieu, J.; Multon, E.; Van Uye, A.; Mestries, J.C.

    1997-01-01

    At high dose rates, both gamma and neutron irradiation induce an acute inflammatory syndrome with huge intercellular communication disorders. This inflammatory syndrome evolves in two phases, separated by a latency phase. During the prodromal phase, the molecular and cellular lesions induced by free radicals trigger an initial response which associates cellular repair and multicellular interactions involving both humoral and nervous communications. A large part of perturbations constitute a non specific inflammatory syndrome and clinically silent coagulation disorders which are linked by common intercellular mediators. All these perturbations are rapidly reversible and there is no correlation between the radiation dose and the severity of the response. During the manifest-illness phase, both inflammatory and coagulation disorders resume, slightly preceding the clinical symptoms. Biochemical symptoms are moderate in the animals which will survive, but they escape regulatory mechanisms in those which will die, giving rise to a vicious circle. These biochemical disorders are largely responsible for the death. With lower dose rates, it cannot be excluded that great cellular communication disorders take place at the tissue level, with limited blood modifications. This aspect should be taken into account for the optimization of cytokine therapies. (authors)

  12. TREATMENT OF ACUTE INFLAMMATORY DISEASES ACCOMPANIED BY THROAT IRRITATION AND PAIN

    Directory of Open Access Journals (Sweden)

    M. I. Petrovskaya

    2013-01-01

    Full Text Available Pathogenetically, prescription of local action drugs containing a wide spectrum antiseptic is reasonable for the upper respiratory tract diseases accompanied by throat irritation and pain. It should be noted that such drugs are very popular among parents; however, most of these drugs may have a range of side effects, which considerably complicate their use in children. That is why the right choice of local action drugs for the acute inflammatory diseases accompanied by throat irritation and pain is a guarantee of treatment efficacy and high compliance. This article examines pharmacological qualities of an antiseptic-containing local action drug permitted to use in children over 4 years of age.

  13. The effect of obesity on inflammatory cytokine and leptin production following acute mental stress.

    Science.gov (United States)

    Caslin, H L; Franco, R L; Crabb, E B; Huang, C J; Bowen, M K; Acevedo, E O

    2016-02-01

    Obesity may contribute to cardiovascular disease (CVD) risk by eliciting chronic systemic inflammation and impairing the immune response to additional stressors. There has been little assessment of the effect of obesity on psychological stress, an independent risk factor for CVD. Therefore, it was of interest to examine interleukin-6, tumor necrosis factor-α, interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1Ra), and leptin following an acute mental stress task in nonobese and obese males. Twenty college-aged males (21.3 ± 0.56 years) volunteered to participate in a 20-min Stroop color-word and mirror-tracing task. Subjects were recruited for obese (body mass index: BMI > 30) and nonobese (BMI stress task elicited an increase in heart rate, catecholamines, and IL-1β in all subjects. Additionally, acute mental stress increased cortisol concentrations in the nonobese group. There was a significant reduction in leptin in obese subjects 30 min posttask compared with a decrease in nonobese subjects 120 min posttask. Interestingly, the relationship between the percent change in leptin and IL-1Ra at 120 min posttask in response to an acute mental stress task was only observed in nonobese individuals. This is the first study to suggest that adiposity in males may impact leptin and inflammatory signaling mechanisms following acute mental stress. © 2015 Society for Psychophysiological Research.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Acrolein inhalation suppresses lipopolysaccharide-induced inflammatory cytokine production but does not affect acute airways neutrophilia.

    Science.gov (United States)

    Kasahara, David Itiro; Poynter, Matthew E; Othman, Ziryan; Hemenway, David; van der Vliet, Albert

    2008-07-01

    Acrolein is a reactive unsaturated aldehyde that is produced during endogenous oxidative processes and is a major bioactive component of environmental pollutants such as cigarette smoke. Because in vitro studies demonstrate that acrolein can inhibit neutrophil apoptosis, we evaluated the effects of in vivo acrolein exposure on acute lung inflammation induced by LPS. Male C57BL/6J mice received 300 microg/kg intratracheal LPS and were exposed to acrolein (5 parts per million, 6 h/day), either before or after LPS challenge. Exposure to acrolein either before or after LPS challenge did not significantly affect the overall extent of LPS-induced lung inflammation, or the duration of the inflammatory response, as observed from recovered lung lavage leukocytes and histology. However, exposure to acrolein after LPS instillation markedly diminished the LPS-induced production of several inflammatory cytokines, specifically TNF-alpha, IL-12, and the Th1 cytokine IFN-gamma, which was associated with reduction in NF-kappaB activation. Our data demonstrate that acrolein exposure suppresses LPS-induced Th1 cytokine responses without affecting acute neutrophilia. Disruption of cytokine signaling by acrolein may represent a mechanism by which smoking contributes to chronic disease in chronic obstructive pulmonary disease and asthma.

  16. Analysis of clinical application on determining serum inflammatory cytokines levels in patients with acute coronary syndrome

    International Nuclear Information System (INIS)

    Luo Wenhao; Bai Yun; Yang Yongqing

    2011-01-01

    Objective: To evaluate analysis of clinical application on determining serum inflammatory cytokines levels in patients with acute coronary syndrome (ACS). Methods: The levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), high-sensitive C-reaction protein (hs-CRP) (with high-sensitive enzyme immunoassay) and tumor necrosis factor-α (TNF-α) (with radioimmunoassay) in serum were determined in 112 patients with ACS, 32 patients with stable angina pectoris (SAP) and 42 normal controls as well as did compared analysis. Results: The serum IL-1β, IL-6, IL-8, TNF-α and hs-CRP levels in 112 patients with ACS were obviously higher than those in 42 controls (P all 0.05), serum hs-CRP level was increased only (P<0.05). The serum IL-1β, IL-6, IL-8, TNF-α and hs-CRP levels in 46 patients with acute myocardial infraction (AMI) were prominently higher than those in 66 patients with unstable angina pectoris (UAP) and in 32 patients with SAP. The serum IL-1β, IL-6, IL-8, TNF-α and hs-CRP levels with advanced degree SAP, UAP and AMI were increased. Conclusion: In the severity of the patients with SAP, UAP, AMI, the determination of serum inflammatory cytokines level were a good and important index, so that it was referential for heart coronary events happened. (authors)

  17. [The possibility of acute inflammatory reaction affects the development of pressure ulcers in bedridden elderly patients].

    Science.gov (United States)

    Matsuyama, N; Takano, K; Mashiko, T; Jimbo, S; Shimetani, N; Ohtani, H

    1999-11-01

    To test the hypothesis that acute inflammatory reaction associates with the development of pressure ulcers in bedridden elderly patients, 40 hospitalized elderly patients suffering from bacterial pneumonia, cerebrovascular disease, and femoral bone fracture were enrolled in this study. All of them were divided into two groups with pressure ulcers (group P; 17 patients) and without one (group N; 23 patients). The blood samples were taken from them within 5 days after the patients being bedridden. Although no significant difference exist in pressure ulcer risk factors (age, gender, Braden scale, underlying diseases, blood pressure, and heart rate) between the two groups, white blood cell, plasma C-reactive protein and fibrinogen in group P increased significantly as compared with those in group N. Besides number of platelets and maximum platelet aggregation rate were significantly higher in group P than in group N. Serum albumin and hemoglobin of both groups decreased after being bedridden, especially hemoglobin in group P was significantly lower than that in group N. While the concentration of serum IL-6 did not indicate a significant difference between both the groups, serum IL-1 beta increased significantly in group P. In conclusion, we suggested that acute inflammatory reaction releasing proinflammatory cytokines affected the development of pressure ulcer in bedridden elderly patients.

  18. Adoptively transferred dendritic cells restore primary cell-mediated inflammatory competence to acutely malnourished weanling mice.

    Science.gov (United States)

    Hillyer, Lyn; Whitley, Charlene; Olver, Amy; Webster, Michelle; Steevels, Tessa; Woodward, Bill

    2008-02-01

    Immune depression associated with prepubescent malnutrition underlies a staggering burden of infection-related morbidity. This investigation centered on dendritic cells as potentially decisive in this phenomenon. C57BL/6J mice, initially 19 days old, had free access for 14 days to a complete diet or to a low-protein formulation that induced wasting deficits of protein and energy. Mice were sensitized by i.p. injection of sheep red blood cells on day 9, at which time one-half of the animals in each dietary group received a simultaneous injection of 10(6) syngeneic dendritic cells (JAWS II). All mice were challenged with the immunizing antigen in the right hind footpad on day 13, and the 24-hour delayed hypersensitivity response was assessed as percentage increase in footpad thickness. The low-protein diet reduced the inflammatory immune response, but JAWS cells, which exhibited immature phenotypic and functional characteristics, increased the response of both the malnourished group and the controls. By contrast, i.p. injection of 10(6) syngeneic T cells did not influence the inflammatory immune response of mice subjected to the low-protein protocol. Antigen-presenting cell numbers limited primary inflammatory cell-mediated competence in this model of wasting malnutrition, an outcome that challenges the prevailing multifactorial model of malnutrition-associated immune depression. Thus, a new dendritic cell-centered perspective emerges regarding the cellular mechanism underlying immune depression in acute pediatric protein and energy deficit.

  19. Effect of Lavender (Lavandula angustifolia) Essential Oil on Acute Inflammatory Response

    Science.gov (United States)

    Cardia, Gabriel Fernando Esteves; Cavalcante, Heitor Augusto Otaviano; Cassarotti, Larissa Laila; Salvadego, Valter Eduardo Cocco; Spironello, Ricardo Alexandre; Bersani-Amado, Ciomar Aparecida

    2018-01-01

    Lavandula angustifolia is a plant of Lamiaceae family, with many therapeutic properties and biological activities, such as anticonvulsant, anxiolytic, antioxidant, anti-inflammatory, and antimicrobial activities. The aim of this study was to evaluate the effect of Lavandula angustifolia Mill. essential oil (LEO) on acute inflammatory response. LEO was analyzed using gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR) methods and showed predominance of 1,8-cineole (39.83%), borneol (22.63%), and camphor (22.12%). LEO at concentrations of 0.5, 1, 3, and 10 μg/ml did not present in vitro cytotoxicity. Additionally, LEO did not stimulate the leukocyte chemotaxis in vitro. The LEO topical application at concentrations of 0.25, 0.5, and 1 mg/ear reduced edema formation, myeloperoxidase (MPO) activity, and nitric oxide (NO) production in croton oil-induced ear edema model. In carrageenan-induced paw edema model, LEO treatment at doses of 75, 100, and 250 mg/kg reduced edema formation, MPO activity, and NO production. In dextran-induced paw edema model, LEO at doses of 75 and 100 mg/kg reduced paw edema and MPO activity. In conclusion, LEO presented anti-inflammatory activity, and the mechanism proposed of LEO seems to be, at least in part, involving the participation of prostanoids, NO, proinflammatory cytokines, and histamine. PMID:29743918

  20. 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 LD 50 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 IC 50 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. Reduced butyrylcholinesterase activity is an early indicator of trauma-induced acute systemic inflammatory response

    Directory of Open Access Journals (Sweden)

    Zivkovic AR

    2016-11-01

    Full Text Available Aleksandar R Zivkovic, Jochen Bender, Thorsten Brenner, Stefan Hofer,* Karsten Schmidt* Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany *These authors contributed equally to this work Purpose: Early diagnosis of systemic inflammatory response syndrome is fundamentally important for an effective and a goal-directed therapy. Various inflammation biomarkers have been used in clinical and experimental practice. However, a definitive diagnostic tool for an early detection of systemic inflammation remains to be identified. Acetylcholine (Ach has been shown to play an important role in the inflammatory response. Serum cholinesterase (butyrylcholinesterase [BChE] is the major Ach hydrolyzing enzyme in blood. The role of this enzyme during inflammation has not yet been fully understood. This study tests whether a reduction in the BChE activity could indicate the onset of the systemic inflammatory response upon traumatic injury. Patients and methods: This observational study measured BChE activity in patients with traumatic injury admitted to the emergency room by using point-of-care-test system (POCT. In addition, the levels of routine inflammation biomarkers during the initial treatment period were measured. Injury Severity Score was used to assess the trauma severity. Results: Altered BChE activity was correlated with trauma severity, resulting in systemic inflammation. Reduction in the BChE activity was detected significantly earlier compared to those of routinely measured inflammatory biomarkers. Conclusion: This study suggests that the BChE activity reduction might serve as an early indicator of acute systemic inflammation. Furthermore, BChE activity, measured using a POCT system, might play an important role in the early diagnosis of the trauma-induced systemic inflammation. Keywords: trauma, injury, early diagnostics, cholinergic, pseudocholinesterase, SIRS

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

    Directory of Open Access Journals (Sweden)

    Qi Ying Lean

    Full Text Available 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.

  7. Diagnostic transcranial magnetic stimulation in children with acute inflammatory demyelinating polyneuropathy

    Directory of Open Access Journals (Sweden)

    V. B. Voitenkov

    2016-01-01

    Full Text Available Objective of our work was to evaluate MEPs characteristics in children with acute inflammatory demyelinating polyneuropathy and evaluate usefulness of TMS as an additional diagnostic method in this disorder.Methods. 20 healthy children (7–14 years old, average 12 years, 7 females, 13 males without any signs of neurological disorders were enrolled as controls and 37 patients (8–13 years old, average 11 years, 19 females, 18 males with AIDP were enrolled as the main group. EMG and TMS were performed on 3–7 day from the onset of the first symptoms. Cortical and lumbar MEP`s latencies, shapes and amplitudes and CMCT were averaged and analyzed.Results. Significant differences between children with AIDP and controls on latencies of both cortical and lumbar MEPs were registered. Cortical MEPs shapes were disperse in 100% of the cases, and lumbar MEPs were disperse in 57% of the cases. Amplitudes changes for both lumbar and cortical MEPs were not significant.Conclusions. Diagnostic transcranial magnetic stimulation on the early stage of the acute demyelinating polyneuropathy in children may be implemented as the additional tool. Main finding in this population is lengthening of the latency of cortical and lumbar motor evoked potentials. Disperse shape of the lumbar MEPs may also be used as the early sign of the acute demyelization of the peripheral nerves.

  8. Acute inflammatory reaction in rats after intratracheal instillation of material collected from a nylon flocking plant.

    Science.gov (United States)

    Porter, D W; Castranova, V; Robinson, V A; Hubbs, A F; Mercer, R R; Scabilloni, J; Goldsmith, T; Schwegler-Berry, D; Battelli, L; Washko, R; Burkhart, J; Piacitelli, C; Whitmer, M; Jones, W

    1999-05-14

    fraction was much less active. Histological analysis of the lungs 1 d post-IT confirmed lung inflammation was occurring and tended to center around bronchioles. The results suggest that: (1) nylon flocking generates particles of respirable size that can interact with AM in the lung and can be detected in the lung 29 d after exposure, (2) the dust samples examined cause an inflammatory response, (3) water-extractable agent(s) from airborne dust contribute only minimally to the inflammatory response, and (4) the acute inflammatory response to these dusts is substantial when compared to other pathologic occupational dusts previously examined in our laboratory.

  9. Anti-inflammatory treatment and risk of depression in 91,842 patients with acute coronary syndrome and 91,860 individuals without acute coronary syndrome in Denmark

    DEFF Research Database (Denmark)

    Wium-Andersen, Ida Kim; Wium-Andersen, Marie Kim; Jørgensen, Martin Balslev

    2017-01-01

    Background We examined if treatment with acetylsalicylic acid (ASA), non-steroid anti-inflammatory drugs (NSAID), or statins after acute coronary syndrome (ACS) are associated with decreased risk of depression. Method This register-based cohort study included all individuals with a first...

  10. Emphysema induced by elastase enhances acute inflammatory pulmonary response to intraperitoneal LPS in rats.

    Science.gov (United States)

    da Fonseca, Lídia Maria Carneiro; Reboredo, Maycon Moura; Lucinda, Leda Marília Fonseca; Fazza, Thaís Fernanda; Rabelo, Maria Aparecida Esteves; Fonseca, Adenilson Souza; de Paoli, Flavia; Pinheiro, Bruno Valle

    2016-12-01

    Abnormalities in lungs caused by emphysema might alter their response to sepsis and the occurrence of acute lung injury (ALI). This study compared the extension of ALI in response to intraperitoneal lipopolysaccharide (LPS) injection in Wistar rats with and without emphysema induced by elastase. Adult male Wistar rats were randomized into four groups: control, emphysema without sepsis, normal lung with sepsis and emphysema with sepsis. Sepsis was induced, and 24 h later the rats were euthanised. The following analysis was performed: blood gas measurements, bronchoalveolar lavage (BAL), lung permeability and histology. Animals that received LPS showed significant increase in a lung injury scoring system, inflammatory cells in bronchoalveolar lavage (BAL) and IL-6, TNF-α and CXCL2 mRNA expression in lung tissue. Animals with emphysema and sepsis showed increased alveolocapillary membrane permeability, demonstrated by higher BAL/serum albumin ratio. In conclusion, the presence of emphysema induced by elastase increases the inflammatory response in the lungs to a systemic stimulus, represented in this model by the intraperitoneal injection of LPS. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

  11. Dynamics of inflammatory markers in post-acute stroke patients undergoing rehabilitation.

    Science.gov (United States)

    Manolescu, Bogdan Nicolae; Berteanu, Mihai; Dumitru, Luminița; Dinu, Horațiu; Iliescu, Alina; Fărcășanu, Ileana Cornelia; Oprea, Eliza; Vlădoiu, Suzana; Popa, Oana; Ianăș, Olga

    2011-12-01

    Stroke is a pathological condition associated with an enhanced inflammatory response that has a multifactorial etiology. We evaluated the dynamic of plasma concentrations of IL-1α, IL-6, IL-8, TNF-α, soluble form of intercellular adhesion molecule 1, and lipoprotein (a) [Lp(a)] during the rehabilitation of post-acute stroke patients (n = 20), in parallel with control subjects (n = 24). Stroke patients had significantly increased concentrations of IL-6, TNF-α, and Lp(a) when compared to healthy controls. It was found that the changes in the IL-6, IL-8, and TNF-α concentrations associated with the pathological condition were statistically significant (χ2 = 4.81, p = 0.028, χ2 = 10.40, p = 0.005 and χ2 = 6.73, p = 0.034, respectively). The decrease of Lp(a) during the rehabilitation had statistical significance (p = 0.043), while the decrease of IL-1α had marginal significance (p = 0.071). IL-1α, TNF-α, and Lp(a) concentrations were significantly negatively correlated with the Barthel index values, suggesting that the decrease of these inflammatory markers was beneficial for patients' recovery.

  12. Relationship between two blood stasis syndromes and inflammatory factors in patients with acute coronary syndrome.

    Science.gov (United States)

    Ma, Cai-Yun; Liu, Jing-Hua; Liu, Jian-Xun; Shi, Da-Zhuo; Xu, Zhen-Ye; Wang, Shao-Ping; Jia, Min; Zhao, Fu-Hai; Jiang, Yue-Rong; Ma, Qin; Peng, Hong-Yu; Lu, Yuan; Zheng, Ze; Ren, Feng-Xue

    2017-11-01

    To investigate the relationship between inflammatory factors and two Chinese medicine (CM) syndrome types of qi stagnation and blood stasis (QSBS) and qi deficiency and blood stasis (QDBS) in patients with acute coronary syndrome (ACS). Sixty subjects with ACS, whose pathogenesis changes belongs to qi disturbance blood stasis syndrome, were divided into 2 groups: 30 in the QSBS group and 30 in the QDBS group. The comparative analysis on them was carried out through comparing general information, coronary angiography and inflammatory factors including intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40) and lipoprotein-associated phospholipase A2 (Lp-PLA2). Compared with the QSBS group, Lp-PLA2 and YKL-40 levels in the QDBS group showed no-significant difference (P>0.05); ICAM-1 was significantly higher in the QDBS group than in the QSBS group in the pathological processes of qi disturbance and blood stasis syndrome of ACS (Psyndrome typing of QSBS and QDBS, which provides a research direction for standardization research of CM syndrome types.

  13. 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.

  14. Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice.

    Science.gov (United States)

    De Domenico, Ivana; Zhang, Tian Y; Koening, Curry L; Branch, Ryan W; London, Nyall; Lo, Eric; Daynes, Raymond A; Kushner, James P; Li, Dean; Ward, Diane M; Kaplan, Jerry

    2010-07-01

    Hepcidin is a peptide hormone that regulates iron homeostasis and acts as an antimicrobial peptide. It is expressed and secreted by a variety of cell types in response to iron loading and inflammation. Hepcidin mediates iron homeostasis by binding to the iron exporter ferroportin, inducing its internalization and degradation via activation of the protein kinase Jak2 and the subsequent phosphorylation of ferroportin. Here we have shown that hepcidin-activated Jak2 also phosphorylates the transcription factor Stat3, resulting in a transcriptional response. Hepcidin treatment of ferroportin-expressing mouse macrophages showed changes in mRNA expression levels of a wide variety of genes. The changes in transcript levels for half of these genes were a direct effect of hepcidin, as shown by cycloheximide insensitivity, and dependent on the presence of Stat3. Hepcidin-mediated transcriptional changes modulated LPS-induced transcription in both cultured macrophages and in vivo mouse models, as demonstrated by suppression of IL-6 and TNF-alpha transcript and secreted protein. Hepcidin-mediated transcription in mice also suppressed toxicity and morbidity due to single doses of LPS, poly(I:C), and turpentine, which is used to model chronic inflammatory disease. Most notably, we demonstrated that hepcidin pretreatment protected mice from a lethal dose of LPS and that hepcidin-knockout mice could be rescued from LPS toxicity by injection of hepcidin. The results of our study suggest a new function for hepcidin in modulating acute inflammatory responses.

  15. [Acute severe colitis with recto-vaginal fistula during treatment with non-steroidal anti-inflammatory agents].

    Science.gov (United States)

    Tissot, B; Lamy, A; Perraudeau, F; Manouvrier, J L; Imbert, Y

    2002-07-13

    We report the case of severe colitis occurring during treatment with non-steroid anti-inflammatories (NSAI). A 57 year-old woman was hospitalized for lumbar pain that had not been relieved by AINS, tramadol and then morphine. The patient presented with septic shock and peritonitis by rectal perforation, followed by acute rectorrhagia. The endoscopic aspect evoked Crohn's disease with a recto-vaginal fistula. Progression was further complicated by two episodes of collapse because of acute rectorrhagia, requiring hemostasis colectomy and abdominal-perineal amputation. The diagnosis retained was AINS-induced colitis complicated by acute colectasia on a fecaloma with recto-vaginal fistula.

  16. Voluntary Wheel Running Reduces the Acute Inflammatory Response to Liver Carcinogen in a Sex-specific Manner

    DEFF Research Database (Denmark)

    Bay, M L; Gehl, Julie; Pedersen, Bente Klarlund

    2017-01-01

    demonstrated to inhibit tumor growth, including diethylnitrosamine-(DEN)-induced hepatocarcinoma. Having observed a sex-dependent development of DEN-induced hepatocarcinoma, we aimed to evaluate the effect of exercise and sex on the acute inflammatory response to DEN. Thus, we randomized male and female mice...

  17. Imaging the inflammatory response to acute myocardial infarction in man using indium-111-labeled autologous platelets

    International Nuclear Information System (INIS)

    Davies, R.A.; Thakur, M.L.; Berger, H.J.; Wackers, F.J.T.; Gottschalk, A.; Zaret, B.L.

    1981-01-01

    The feasibility of imaging the inflammatory response to acute transmural myocardial infarction in man using indium-111 ( 111 In)-labeled autologous leukocytes was assessed in 36 patients. Indium-111 leukocytes were injected i.v. 18 to 112 hs after the onset of chest pain. Cardiac imaging was performed 24 hs later with a mobile gamma camera. Twenty-one patients had positive images and 15 had negative images. The percent of positive images increased as the interval between infarction and 111 In-leukocyte injection shortened; all patients injected within 24 hs of infarction had positive images. Patients with positive images were injected with 111 In leukocytes earlier after infarction and were younger than those with negative images. Several other parameters that could possibly have affected the imaging results were examined and were not significantly different in patients with positive and negative images. These included peak serum creatine kinase, location of infarction, incidence of pericarditis, use of antiinflammatory drugs or membrane-active antiarrhythmic drugs, peripheral leukocyte count, and cell labeling efficiency. The function of the labeled cells was similar in patients with positive and negative images. Six patients with acute infarction serving as controls and given free 111 In-oxine and six patients with stable coronary artery disease given 111 In-leukocytes all had negative cardiac images

  18. Expression of cyclin D{sub 1} during endotoxin-induced aleveolar type II cell hyperplasia in rat lung and the detection of apoptotic cells during the remodeling process

    Energy Technology Data Exchange (ETDEWEB)

    Tesfaigzi, J.; Wood, M.B.; Johnson, N.F.

    1995-12-01

    Our studies have shown that endotoxin intratracheally instilled into the rat lung induces proliferation of alveolar type II cells. In that study, the alveolar type II cells. In that study, the alveolar type II cell hyperplasia occurred 2 d after instillation of endotoxin and persisted for a further 2 d. After hyperplasia, the lung remodeled and returned to a normal state within 24-48 h. Understanding the mechanisms involved in the remodeling process of this transient hyperplasia may be useful to identify molecular changes that are altered in neoplasia. The purpose of the present study was to corroborate induction of epithelial cell hyperplasia by endotoxin and to delineate mechanisms involved in tissue remodeling after endotoxin-induced alveolar type II cell hyperplasia. In conclusion, immonostaining with cyclin D1 and cytokeratin shows that endotoxin induced epithelial cell proliferation and resulted in hyperplasia in the lung which persisted through 4 d post-instillation.

  19. 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.

  20. Activation of Inflammatory and Pro-Thrombotic Pathways in Acute Stress Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Timothy P. Fitzgibbons

    2017-08-01

    Full Text Available Stress cardiomyopathy (SCM is a unique cardiac disorder that more often occurs in women. SCM presents in a similar fashion as acute myocardial infarction (AMI, with chest pain, ECG changes, and congestive heart failure. The primary distinguishing feature is the absence of thrombotic coronary occlusion in SCM. How this reduction in cardiac function occurs in the absence of coronary occlusion remains unknown. Therefore, we tested the hypothesis that a targeted proteomic comparison of patients with acute SCM and AMI might identify relevant mechanistic differences. Blood was drawn in normal controls (n = 6, women with AMI (n = 12, or women with acute SCM (n = 15. Two-week follow-up samples were available in AMI (n = 4 and SCM patients (n = 11. Relative concentrations of 1,310 serum proteins were measured in each of the 48 samples using the SOMAscan assay. Women with AMI had greater myocyte necrosis, as reflected by a higher peak troponin I concentration (AMI 32.03 ± 29.46 vs. SCM 2.68 ± 2.6 ng/ml, p < 0.05. AMI and SCM patients had equivalent reductions in left ventricular ejection fraction [LVEF (% 39 ± 12 vs. 37 ± 12, p = 0.479]. In follow-up, women with SCM had a greater improvement in cardiac function [LVEF (% 60 ± 7 vs. 45 ± 13, p < 0.001]. No differentially expressed proteins were detected (absolute log2-fold change >1; q < 0.05 between AMI and SCM in the acute or recovery phase. However, when we compared normal controls to patients with AMI, there was differential expression of 35 proteins. When we compared normal controls to patients with SCM, 45 proteins were differentially expressed. In comparison to normal controls, biological processes such as complement, coagulation, and inflammation were activated in both AMI and SCM. There were four proteins that showed a non-significant trend to be increased in acute SCM vs. AMI (netrin-1, follistatin-like 3, kallikrein 7

  1. Metformin reduces the endotoxin-induced down-regulation of apolipoprotein E gene expression in macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Stavri, Simona; Trusca, Violeta G.; Simionescu, Maya; Gafencu, Anca V., E-mail: anca.gafencu@icbp.ro

    2015-05-29

    The atheroprotective role of macrophage-derived apolipoprotein E (apoE) is well known. Our previous reports demonstrated that inflammatory stress down-regulates apoE expression in macrophages, aggravating atherogenesis. Metformin, extensively used as an anti-diabetic drug, has also anti-inflammatory properties, and thus confers vascular protection. In this study, we questioned whether metformin could have an effect on apoE expression in macrophages in normal conditions or under lipopolysaccharide (LPS)-induced stress. The results showed that metformin slightly increases the apoE expression only at high doses (5–10 mM). Low doses of metformin (1–3 mM) significantly reduce the LPS down-regulatory effect on apoE expression in macrophages. Our experiments demonstrated that LPS-induced NF-κB binds to the macrophage-specific distal regulatory element of apoE gene, namely to the multienhancer 2 (ME.2) and its 5′-deletion fragments. The NF-κB binding on ME.2 and apoE promoter has a down-regulatory effect. In addition, data revealed that metformin impairs NF-κB nuclear translocation, and thus, improves the apoE levels in macrophages under inflammatory stress. The positive effect of metformin in the inflammatory states, its clinical safety and low cost, make this drug a potential adjuvant in the therapeutic strategies for atherosclerosis. - Highlights: • High doses of metformin slightly increase apoE expression in macrophages. • Low doses of metformin up-regulate apoE gene in endotoxin-stressed macrophages. • Metformin reduces the negative effect of LPS on apoE expression by NF-κB inhibition.

  2. Metformin reduces the endotoxin-induced down-regulation of apolipoprotein E gene expression in macrophages

    International Nuclear Information System (INIS)

    Stavri, Simona; Trusca, Violeta G.; Simionescu, Maya; Gafencu, Anca V.

    2015-01-01

    The atheroprotective role of macrophage-derived apolipoprotein E (apoE) is well known. Our previous reports demonstrated that inflammatory stress down-regulates apoE expression in macrophages, aggravating atherogenesis. Metformin, extensively used as an anti-diabetic drug, has also anti-inflammatory properties, and thus confers vascular protection. In this study, we questioned whether metformin could have an effect on apoE expression in macrophages in normal conditions or under lipopolysaccharide (LPS)-induced stress. The results showed that metformin slightly increases the apoE expression only at high doses (5–10 mM). Low doses of metformin (1–3 mM) significantly reduce the LPS down-regulatory effect on apoE expression in macrophages. Our experiments demonstrated that LPS-induced NF-κB binds to the macrophage-specific distal regulatory element of apoE gene, namely to the multienhancer 2 (ME.2) and its 5′-deletion fragments. The NF-κB binding on ME.2 and apoE promoter has a down-regulatory effect. In addition, data revealed that metformin impairs NF-κB nuclear translocation, and thus, improves the apoE levels in macrophages under inflammatory stress. The positive effect of metformin in the inflammatory states, its clinical safety and low cost, make this drug a potential adjuvant in the therapeutic strategies for atherosclerosis. - Highlights: • High doses of metformin slightly increase apoE expression in macrophages. • Low doses of metformin up-regulate apoE gene in endotoxin-stressed macrophages. • Metformin reduces the negative effect of LPS on apoE expression by NF-κB inhibition

  3. Role of macrophage migration inhibitory factor (MIF in allergic and endotoxin-induced airway inflammation in mice

    Directory of Open Access Journals (Sweden)

    M. Korsgren

    2000-01-01

    Full Text Available Macrophage migration inhibitory factor (MIF has recently been forwarded as a critical regulator of inflammatory conditions, and it has been hypothesized that MIF may have a role in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD. Hence, we examined effects of MIF immunoneutralization on the development of allergen-induced eosinophilic inflammation as well as on lipopolysaccaride (LPS-induced neutrophilic inflammation in lungs of mice. Anti-MIF serum validated with respect to MIF neutralizing capacity or normal rabbit serum (NRS was administered i.p. repeatedly during allergen aerosol exposure of ovalbumin (OVA-immunized mice in an established model of allergic asthma, or once before instillation of a minimal dose of LPS into the airways of mice, a tentative model of COPD. Anti-MIF treatment did not affect the induced lung tissue eosinophilia or the cellular composition of bronchoalveolar lavage fluid (BALF in the asthma model. Likewise, anti-MIF treatment did not affect the LPS-induced neutrophilia in lung tissue, BALF, or blood, nor did it reduce BALF levels of tumor necrosis factor-α (TNF-α and macrophage inflammatory protein–1 α (MIP–1 α. The present data suggest that MIF is not critically important for allergen-induced eosinophilic, and LPS-induced neutrophilic responses in lungs of mice. These findings do not support a role of MIF inhibition in the treatment of inflammatory respiratory diseases.

  4. 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

    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...... 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....... Treatment of rats with anti-MIP-1 beta Ab significantly decreased vascular permeability by 37% (p = 0.012), reduced neutrophil recruitment into lung by 65% (p = 0.047), and suppressed levels of TNF-alpha in bronchoalveolar lavage fluids by 61% (p = 0.008). Treatment of rats with anti-rat MCP-1 or anti...

  5. De Novo Endotoxin-Induced Production of Antibodies against the Bile Salt Export Pump Associated with Bacterial Infection following Major Hepatectomy

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    Kun-Ming Chan

    2018-01-01

    Full Text Available Background. Clinically severe infection-related inflammation after major liver resection may cause hyperbilirubinemia. This study aims to clarify the impact of bacterial infection and endotoxins on the hepatobiliary transporter system and to explore possible mechanisms of endotoxin-related postoperative hyperbilirubinemia. Method. Mice that underwent major hepatectomy with removal of at least 70% of liver volume were exposed to lipopolysaccharide (LPS at different dosages. Subsequently, hepatobiliary transporter compounds related to bile salt excretion were further investigated. Results. The expression of genes related to hepatobiliary transporter compounds was not significantly different in the liver tissue of mice after major hepatectomy and LPS exposure. However, bile salt export pump (BSEP protein expression within the liver tissue of mice treated with LPS after major hepatectomy was relatively weaker and was even further reduced in the high-dose LPS group. The formation of antibodies against the BSEP in response to endotoxin exposure was also detected. Conclusion. This study illustrates a possible mechanism whereby the dysfunction of hepatobiliary transporter systems caused by endotoxin-induced autoantibodies may be involved in the development of postoperative jaundice associated with bacterial infection after major hepatectomy.

  6. Platelet-activating factor acether (PAF-acether) involvement in acute inflammatory and pain processes.

    Science.gov (United States)

    Bonnet, J; Loiseau, A M; Orvoen, M; Bessin, P

    1981-12-01

    PAF-acether is a potent aggregating agent released by various cells involved in acute inflammatory process. In this paper, exogenous PAF-acether has been investigated for its ability to generate signs of inflammation (edema measured by plethysmometry) and hyperalgesia (Randall-Sellito test) by standard subplantar injection in the rat paw. From 0.005 microgram. PAF-acether induced significant edema of the paw, maximal 1 hour after injection; it was dose-dependent from 0.1 to 5 microgram. Significant dose-dependent hyperalgesia occurred from 1.25 microgram; it reached a plateau from 2 to 4 hours after injection. Both phenomena were long-lasting (greater than 6 h). PAF-acether was 1.5 to 10 times stronger than PGI2 and PGE2 in inducing edema, pain, and in increasing vascular permeability. We investigated the interaction of miscellaneous drugs with the edema and the hyperalgesia caused by 2.5 microgram of PAF-acether. Non-steroidal anti-inflammatory (NSAI) drugs exerted only moderate effects on the edema without affecting hyperalgesia. Edema was highly reduced by various agents: prednisolone, L-cysteine, anti-calcic drugs, theophylline, PGI2, salbutamol, clonidine. All of them, except clonidine, and in contrast to NSAI drugs, were more potent on PAF-acether edema than on kaolin edema; a possible link between these agents is their ability to increase cyclic AMP levels in the cells and consequently to reduce lysosomal enzyme release. PAF-acether itself, injected intra-peritoneally, inhibited PAF-acether edema without preventing pain, at doses inactive on arterial pressure and hematocrit, but inducing marked gastric mucosal damage. Among the drugs tested, including analgesics, only PGI2 and imidazole improved PAF-induced hyperalgesia, showing a dissociation between edema and hyperalgesia not only in their induction (doses of PAF required, time course of the phenomena), but in the drugs able to antagonize their development too.

  7. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. 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.

  9. 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...

  10. Giant Inflammatory Fibroid Polyp of the Hepatic Flexure of Colon Presenting with an Acute Abdomen

    Directory of Open Access Journals (Sweden)

    Ashish Lal Shrestha

    2016-01-01

    Full Text Available Background. Inflammatory Fibroid Polyp (IFP of the colon is an exceedingly rare condition. Since 1952 till now only 32 cases have been reported worldwide of which only 5 were giant (>4 cm polyps mostly found in the caecum (15 cases with only 3 in the descending colon. Case Presentation. A 36-year-old female with no previous illness presented to the emergency unit with an acute onset pain over the right hypochondrium for 3 days associated with intermittent fever and anorexia. As she had evidence of localized peritonitis she underwent a diagnostic laparoscopy and subsequently an exploratory laparotomy. A mass measuring 8 × 7 × 5 cm arising from the hepatic flexure of colon was noted. Right hemicolectomy with ileotransverse anastomosis was performed. The mass was subsequently reported to be IFP. Conclusion. IFP is a very rare condition with clinical presentation depending upon its size and location. Definitive diagnosis is possible with histopathological examination of tissue aided by immunohistochemical studies. Surgical resection has been the most common method of treatment especially for large and giant colonic IFPs owing to challenges in terms of diagnosis and technical difficulties associated with endoscopic methods.

  11. Lack of pro-inflammatory cytokine mobilization predicts poor prognosis in patients with acute heart failure.

    Science.gov (United States)

    Vistnes, M; Høiseth, A D; Røsjø, H; Nygård, S; Pettersen, E; Søyseth, V; Hurlen, P; Christensen, G; Omland, T

    2013-03-01

    The aim of this study was to gain insight in the inflammatory response in acute heart failure (AHF) by assessing (1) plasma cytokine profiles and (2) prognostic value of circulating cytokines in AHF patients. Plasma levels of 26 cytokines were quantified by multiplex protein arrays in 36 patients with congestive AHF, characterized by echocardiographic, radiologic, and clinical examinations on admission, during hospitalization and at discharge. Recurrent AHF leading to death or readmission constituted the combined end point, and all patients were followed for 120 days after discharge. Levels of 15 of the measured cytokines were higher in AHF than in healthy subjects (n=22) on admission. Low levels of MCP-1, IL-1β and a low IL-1β/IL-1ra ratio predicted fatal and non-fatal AHF within 120 days. Patients with low circulating levels of IL-1β had lower left ventricular ejection fraction and higher levels of N-terminal pro-B-type natriuretic peptide, while patients with low levels of MCP-1 had higher E/E' and inferior caval vein diameter, than patients with high levels. Immune activation, reflected in increased cytokine levels, is present in AHF patients. Interestingly, failure to increase secretion of IL-1β and MCP-1 during AHF is associated with poor outcome. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. 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.

  13. Anti-inflammatory activity and sub-acute toxicity of artemetin.

    Science.gov (United States)

    Sertié, J A; Basile, A C; Panizza, S; Matida, A K; Zelnik, R

    1990-02-01

    The 5-hydroxy-3,6,7,3',4'-pentamethoxyflavone (artemetin) from Cordia verbenacea DC (Boraginaceae) showed marked anti-inflammatory activity using various experimental models in rats. Artemetin significantly inhibited carrageenin-induced paw edema following oral doses from 30.4 to 153.9 mg.kg-1. The doses of 102.6 and 153.9 mg.kg-1 showed an inhibitory effect similar to that of 50.0 mg.kg-1 of calcium phenylbutazone. The ED50 value of artemetin in rats was estimated to be 67.07 mg.kg-1. Repeated administration of artemetin at doses of 67.07 mg.kg-1 for a 6-day period reduced granuloma formation with a response comparable to that of 20.0 mg.kg-1 of calcium phenylbutazone. This same dose of artemetin also reduced the vascular permeability to intracutaneous histamine. Sub-acute toxicological experiments indicated a very low toxicity.

  14. Endotoxin-induced basal respiration alterations of renal HK-2 cells: A sign of pathologic metabolism down-regulation

    Energy Technology Data Exchange (ETDEWEB)

    Quoilin, C., E-mail: cquoilin@ulg.ac.be [Laboratory of Biomedical Spectroscopy, Department of Physics, University of Liege, 4000 Liege (Belgium); Mouithys-Mickalad, A. [Center of Oxygen Research and Development, Department of Chemistry, University of Liege, 4000 Liege (Belgium); Duranteau, J. [Department of Anaesthesia and Surgical ICU, CHU Bicetre, University Paris XI Sud, 94275 Le Kremlin Bicetre (France); Gallez, B. [Biomedical Magnetic Resonance Group, Louvain Drug Research Institute, Universite catholique de Louvain, 1200 Brussels (Belgium); Hoebeke, M. [Laboratory of Biomedical Spectroscopy, Department of Physics, University of Liege, 4000 Liege (Belgium)

    2012-06-29

    Highlights: Black-Right-Pointing-Pointer A HK-2 cells model of inflammation-induced acute kidney injury. Black-Right-Pointing-Pointer Two oximetry methods: high resolution respirometry and ESR spectroscopy. Black-Right-Pointing-Pointer Oxygen consumption rates of renal cells decrease when treated with LPS. Black-Right-Pointing-Pointer Cells do not recover normal respiration when the LPS treatment is removed. Black-Right-Pointing-Pointer This basal respiration alteration is a sign of pathologic metabolism down-regulation. -- Abstract: To study the mechanism of oxygen regulation in inflammation-induced acute kidney injury, we investigate the effects of a bacterial endotoxin (lipopolysaccharide, LPS) on the basal respiration of proximal tubular epithelial cells (HK-2) both by high-resolution respirometry and electron spin resonance spectroscopy. These two complementary methods have shown that HK-2 cells exhibit a decreased oxygen consumption rate when treated with LPS. Surprisingly, this cellular respiration alteration persists even after the stress factor was removed. We suggested that this irreversible decrease in renal oxygen consumption after LPS challenge is related to a pathologic metabolic down-regulation such as a lack of oxygen utilization by cells.

  15. H2S Attenuates LPS-Induced Acute Lung Injury by Reducing Oxidative/Nitrative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Hong-Xia Zhang

    2016-12-01

    Full Text Available Background: Hydrogen sulfide (H2S, known as the third endogenous gaseous transmitter, has received increasing attention because of its diverse effects, including angiogenesis, vascular relaxation and myocardial protection.We aimed to investigate the role of H2S in oxidative/nitrative stress and inflammation in acute lung injury (ALI induced by endotoxemia. Methods: Male ICR mice were divided in six groups: (1 Control group; (2 GYY4137treatment group; (3 L-NAME treatment group; (4 lipopolysaccharide (LPS treatment group; (5 LPS with GYY4137 treatment group; and (6 LPS with L-NAME treatment group. The lungs were analysed by histology, NO production in the mouse lungs determined by modified Griess (Sigma-Aldrich reaction, cytokine levels utilizing commercialkits, and protein abundance by Western blotting. Results: GYY4137, a slowly-releasing H2S donor, improved the histopathological changes in the lungs of endotoxemic mice. Treatment with NG-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase (NOS inhibitor, increased anti-oxidant biomarkers such as thetotal antioxidant capacity (T-AOC and theactivities of catalase (CAT and superoxide dismutase (SOD but decreased a marker of peroxynitrite (ONOO- action and 3-nitrotyrosine (3-NT in endotoxemic lung. L-NAME administration also suppressed inflammation in endotoxemic lung, as evidenced by the decreased pulmonary levels of interleukin (IL-6, IL-8, and myeloperoxidase (MPO and the increased level of anti-inflammatory cytokine IL-10. GYY4137 treatment reversed endotoxin-induced oxidative/nitrative stress, as evidenced by a decrease in malondialdehyde (MDA, hydrogenperoxide (H2O2 and 3-NT and an increase in the antioxidant biomarker ratio of reduced/oxidized glutathione(GSH/GSSG ratio and T-AOC, CAT and SOD activity. GYY4137 also attenuated endotoxin-induced lung inflammation. Moreover, treatment with GYY4137 inhibited inducible NOS (iNOS expression and nitric oxide (NO production in the

  16. MODERN INSIGHTS INTO THE ROLE OF HEMORHEOLOGICAL DEVIATIONS AND FUNCTIONAL STATUS OF THE ENDOTHELIAL TISSUE IN THE PATHOGENESIS OF ACUTE INFLAMMATORY LUNG AND BRONCHIAL DISEASES AMONG CHILDREN

    Directory of Open Access Journals (Sweden)

    A.V. Mozhaev

    2007-01-01

    Full Text Available Disorders of the endothelial tissue and hemorheology function build up one of the pathogenic bases to form the acute inflammatory abnormality of the respiratory tract among children. The overview highlights the information on the role and disorders of the erythrocyte clumping and plasticity, blood viscosity and function of the endothelial tissue as a response to the acute respiratory infections among children.Key words: endothelial dysfunction, hemorheology, hemorheological deviations, acute respiratory infections, acute bronchopulmonary diseases, children.

  17. Cheongsangbangpung-tang ameliorated the acute inflammatory response via the inhibition of NF-κB activation and MAPK phosphorylation.

    Science.gov (United States)

    Kim, Seon Young; Park, Sang Mi; Hwangbo, Min; Lee, Jong Rok; Byun, Sung Hui; Ku, Sae Kwang; Cho, Il Je; Kim, Sang Chan; Jee, Seon Young; Park, Sook Jahr

    2017-01-13

    Cheongsangbangpung-tang (CBT) is a traditional herbal formula used in Eastern Asia to treat heat-related diseases and swellings in the skin. The present study was conducted to evaluate the anti-inflammatory effects of cheongsangbangpung-tang extract (CBTE) both in vitro and in vivo. The in vitro effects of CBTE on the lipopolysaccharide (LPS)-induced production of inflammation-related proteins were examined in RAW 264.7 cells. The levels of nitric oxide (NO) were measured with the Griess reagent. Inflammatory cytokines and prostaglandin E 2 (PGE 2 ) were detected using the enzyme-linked immunosorbent assay (ELISA) method. Inflammation-related proteins were detected by Western blot. The effect of CBTE on acute inflammation in vivo was evaluated using carrageenan (CA)-induced paw oedema. To evaluate the anti-inflammatory effect, paw oedema volume, thickness of the dorsum and ventrum pedis skin, number of infiltrated inflammatory cells, and number of COX-2-, iNOS-immunoreactive cells were measured. In an in vitro study, CBTE inhibited the production of NO and PGE 2 and also decreased the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) activity, interleukin (IL)-1β, IL-6 and tumuor necrosis factor-α. In LPS-activated macrophages, nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) signalling is a pivotal pathway in the inflammatory process. These plausible molecular mechanisms increased the phosphorylation of I-κBα, while the activation of NF-κB and the phosphorylation of MAPK by LPS were blocked by CBTE treatment. In our in vivo study, a CA-induced acute oedematous paw inflammation rat model was used to evaluate the anti-inflammatory effect of CBTE. CBTE significantly reduced the increases in paw swelling, skin thicknesses, infiltrated inflammatory cells and iNOS-, COX-2 positive cells induced by CA injection. Based on these results, CBTE should favourably inhibit the acute inflammatory response through

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Lycopene rich extract from red guava (Psidium guajava L.) displays anti-inflammatory and antioxidant profile by reducing suggestive hallmarks of acute inflammatory response in mice.

    Science.gov (United States)

    Vasconcelos, Andreanne G; Amorim, Adriany das G N; Dos Santos, Raimunda C; Souza, Jessica Maria T; de Souza, Luan Kelves M; Araújo, Thiago de S L; Nicolau, Lucas Antonio D; de Lima Carvalho, Lucas; de Aquino, Pedro Everson A; da Silva Martins, Conceição; Ropke, Cristina D; Soares, Pedro Marcos G; Kuckelhaus, Selma Aparecida S; Medeiros, Jand-Venes R; Leite, José Roberto de S A

    2017-09-01

    This study investigated the anti-inflammatory activity of the extract (LEG) and purified (LPG) lycopene from guava (Psidium guajava L.), as well as some mechanisms possibly involved in this effect. The anti-inflammatory activity was initially assessed using paw edema induced by Carrageenan, Dextran, Compound 48/80, Histamine and Prostaglandin E2 in Swiss mice. A peritonitis model was used to evaluate neutrophil migration, the activity of myeloperoxidase (MPO) and reduced glutathione (GSH) concentration; while the effect on the expression of iNOS, COX-2 and NF-κB, was assessed by immunohistochemistry analysis. Results showed that oral and intraperitoneal administration of LEG and LPG inhibited inflammation caused by carrageenan. LPG (12.5mg/kg p.o.) significantly inhibited the edema formation induced by different phlogistic agents and immunostaining for iNOS, COX-2 and NF-κB. Leukocytes migration in paw tissue and peritoneal cavity was reduced, as well as MPO concentration, whereas GSH levels increased. Thus, lycopene-rich extract from red guava has beneficial effect on acute inflammation, offering protection against the consequences of oxidative stress by downregulating inflammatory mediators and inhibiting gene expression involved in inflammation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  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. 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

  2. Mechanism of cigarette smoke condensate-induced acute inflammatory response in human bronchial epithelial cells

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    Mohapatra Shyam S

    2002-07-01

    Full Text Available Abstract Background To demonstrate the involvement of tobacco smoking in the pathophysiology of lung disease, the responses of pulmonary epithelial cells to cigarette smoke condensate (CSC — the particulate fraction of tobacco smoke — were examined. Methods The human alveolar epithelial cell line A549 and normal human bronchial epithelial cells (NHBEs were exposed to 0.4 μg/ml CSC, a concentration that resulted in >90% cell survival and Results NHBEs exposed to CSC showed increased expression of the inflammatory mediators sICAM-1, IL-1β, IL-8 and GM-CSF, as determined by RT-PCR. CSC-induced IL-1β expression was reduced by PD98059, a blocker of mitogen-actived protein kinase (MAPK kinase (MEK, and by PDTC, a NFκB inhibitor. Analysis of intracellular signaling pathways, using antibodies specific for phosphorylated MAPKs (extracellular signal-regulated kinase [ERK]-1/2, demonstrated an increased level of phosphorylated ERK1/2 with increasing CSC concentration. Nuclear localization of phosphorylated ERK1/2 was seen within 30 min of CSC exposure and was inhibited by PD98059. Increased phosphorylation and nuclear translocation of IκB was also seen after CSC exposure. A549 cells transfected with a luciferase reporter plasmid containing a NFκB-inducible promoter sequence and exposed to CSC (0.4 μg/ml or TNF-α (50 ng/ml had an increased reporter activity of approximately 2-fold for CSC and 3.5-fold for TNF-α relative to untreated controls. Conclusion The acute phase response of NHBEs to cigarette smoke involves activation of both MAPK and NFκB.

  3. Extracellular histones play an inflammatory role in acid aspiration-induced acute respiratory distress syndrome.

    Science.gov (United States)

    Zhang, Yanlin; Wen, Zongmei; Guan, Li; Jiang, Ping; Gu, Tao; Zhao, Jinyuan; Lv, Xin; Wen, Tao

    2015-01-01

    Systemic inflammation is a key feature in acid aspiration-induced acute respiratory distress syndrome (ARDS), but the factors that trigger inflammation are unclear. The authors hypothesize that extracellular histones, a newly identified inflammatory mediator, play important roles in the pathogenesis of ARDS. The authors used a hydrochloric acid aspiration-induced ARDS model to investigate whether extracellular histones are pathogenic and whether targeting histones are protective. Exogenous histones and antihistone antibody were administered to mice. Heparin can bind to histones, so the authors studied whether heparin could protect from ARDS using cell and mouse models. Furthermore, the authors analyzed whether extracellular histones are clinically involved in ARDS patients caused by gastric aspiration. Extracellular histones in bronchoalveolar lavage fluid of acid-treated mice were significantly higher (1.832 ± 0.698) at 3 h after injury than in sham-treated group (0.63 ± 0.153; P = 0.0252, n = 5 per group). Elevated histones may originate from damaged lung cells and neutrophil infiltration. Exogenous histones aggravated lung injury, whereas antihistone antibody markedly attenuated the intensity of ARDS. Notably, heparin provided a similar protective effect against ARDS. Analysis of plasma from ARDS patients (n = 21) showed elevated histones were significantly correlated with the degree of ARDS and were higher in nonsurvivors (2.723 ± 0.2933, n = 7) than in survivors (1.725 ± 0.1787, P = 0.006, n = 14). Extracellular histones may play a contributory role toward ARDS by promoting tissue damage and systemic inflammation and may become a novel marker reflecting disease activity. Targeting histones by neutralizing antibody or heparin shows potent protective effects, suggesting a potentially therapeutic strategy.

  4. Significant Acute Kidney Injury Due to Non-steroidal Anti-inflammatory Drugs: Inpatient Setting

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    Mehul Dixit

    2010-04-01

    Full Text Available In the United States non-steroidal anti-inflammatory drugs (NSAID are freely available over-the-counter. Because of the adverse effects on the kidneys and the popularity of these drugs, unregulated use of NSAIDs is an under recognized and potentially dangerous problem. Fifteen inpatients, mean age of 15.2 ± 2.3 years (five males, 10 females, were referred to nephrology for acute kidney injury. All patients admitted to taking ibuprofen and six also consumed naproxen. None of the patients had underlying renal diseases at the time of admission. Nine patients had proteinuria and 12 had hematuria (including one with gross hematuria. One patient had nephrotic syndrome but the condition resolved spontaneously without steroids and has remained in remission for four years. Two patients required dialysis. Only one of the dialyzed patients required steroid therapy for recovery of renal function. The mean duration of hospitalization was 7.4 ± 5.5 days. The serum creatinine peaked at 4.09 ± 4.24 (range 1.2-15.3 mg/dL. All patients recovered renal function with normalization of serum creatinine to 0.71 ± 0.15 mg/dL. The estimated GFR (glomerular filtration rate at peak of renal failure was 38.2 ± 20.5 mL/min but did improve to a baseline of 134 ± 26.2 mL/min (range 89-177, p < 0.01. However, the duration from onset to normalization of serum creatinine was 37 ± 42 days indicating that majority of patients had abnormal renal function for a prolonged period. In conclusion, NSAIDs pose a significant risk of renal failure for significant duration and as an entity may be under recognized.

  5. An intense and short-lasting burst of neutrophil activation differentiates early acute myocardial infarction from systemic inflammatory syndromes.

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    Norma Maugeri

    Full Text Available BACKGROUND: Neutrophils are involved in thrombus formation. We investigated whether specific features of neutrophil activation characterize patients with acute coronary syndromes (ACS compared to stable angina and to systemic inflammatory diseases. METHODS AND FINDINGS: The myeloperoxidase (MPO content of circulating neutrophils was determined by flow cytometry in 330 subjects: 69 consecutive patients with acute coronary syndromes (ACS, 69 with chronic stable angina (CSA, 50 with inflammation due to either non-infectious (acute bone fracture, infectious (sepsis or autoimmune diseases (small and large vessel systemic vasculitis, rheumatoid arthritis. Four patients have also been studied before and after sterile acute injury of the myocardium (septal alcoholization. One hundred thirty-eight healthy donors were studied in parallel. Neutrophils with normal MPO content were 96% in controls, >92% in patients undergoing septal alcoholization, 91% in CSA patients, but only 35 and 30% in unstable angina and AMI (STEMI and NSTEMI patients, compared to 80%, 75% and 2% of patients with giant cell arteritis, acute bone fracture and severe sepsis. In addition, in 32/33 STEMI and 9/21 NSTEMI patients respectively, 20% and 12% of neutrophils had complete MPO depletion during the first 4 hours after the onset of symptoms, a feature not observed in any other group of patients. MPO depletion was associated with platelet activation, indicated by P-selectin expression, activation and transactivation of leukocyte β2-integrins and formation of platelet neutrophil and -monocyte aggregates. The injection of activated platelets in mice produced transient, P-selectin dependent, complete MPO depletion in about 50% of neutrophils. CONCLUSIONS: ACS are characterized by intense neutrophil activation, like other systemic inflammatory syndromes. In the very early phase of acute myocardial infarction only a subpopulation of neutrophils is massively activated, possibly via

  6. 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.

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

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    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. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. 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.

  9. Increased levels of proteins of the acute inflammatory phase in the peritoneal fluid of women with advanced stages of endometriosis.

    Science.gov (United States)

    Polak, Grzegorz; Barczyński, Bartłomiej; Bednarek, Wiesława; Kwaśniewski, Wojciech; Wertell, Iwona; Derewianka-Polak, Magdalena; Makara-Studzińska, Marta; Kotarski, Jan

    2015-06-01

    Most investigators agree that endometriosis is associated with a state of subclinical, non-infectious peritoneal inflammation. The objective of the study was to assess concentrations of two markers of the acute inflammatory phase proteins, haptoglobin and ceruloplasmin, in peritoneal fluid of endometriotic women. 229 women who underwent diagnostic or therapeutic laparoscopy were included in the study Minimal, mild, moderate and severe endometriosis according to ASRM was confirmed in 119 women (study groups), whereas 110 patients suffered from simple serous or dermoid ovarian cysts (reference groups). Haptoglobin and ceruloplasmin concentrations in the peritoneal fluid samples aspirated during laparoscopy were measured using commercially available radial immunodiffusion kits. The concentration of haptoglobin in the peritoneal fluid of women with endometriosis was significantly higher as compared to patients with serous and dermoid ovarian cysts. Significantly higher haptoglobin level was observed in patients with severe and moderate endometriosis as compared to women from both reference groups. No significant difference in the peritoneal fluid ceruloplasmin levels was found between patients with endometriosis and women from reference groups. However, it was noted that ceruloplasmin levels are higher in the subgroup of patients with severe endometriosis as compared to both reference groups and women with mild disease. Our results support the hypothesis that endometriosis is associated with subclinical inflammation within the peritoneal cavity It may be speculated that pro-inflammatory stimuli strong enough to cause an increase in acute inflammatory phase proteins peritoneal fluid concentrations are observed only in the advanced stages of the disease.

  10. Influence of sex and developmental stage on acute hepatotoxic and inflammatory responses to liver procarcinogens in the mouse

    International Nuclear Information System (INIS)

    Hanna, Daniel; Riedmaier, Ariane Emami; Sugamori, Kim S.; Grant, Denis M.

    2016-01-01

    The incidence of liver cancer is higher in men than in women. This sex difference is also observed in murine tumor induction models that result in the appearance of liver tumors in adult mice following their exposure on postnatal days 8 and/or 15 to carcinogens such as 4-aminobiphenyl (ABP) or diethylnitrosamine (DEN). Previous studies performed in adult mice showed that acute hepatotoxic and inflammatory responses to high-dose DEN exposure were greater in males than in females, leading to the suggestion that these responses could account for the sex difference in tumor development. We also recently observed that female but not male mice exposed postnatally to ABP had slightly increased expression of the antioxidant defense genes Nqo1 and Ggt1, which are regulated by the oxidative stress response protein nuclear factor erythroid 2-related factor 2 (NRF2), while expression of Hmox1 was increased in both sexes. The goal of the present study was therefore to compare selected acute hepatotoxic, inflammatory and oxidative stress defense responses to ABP, DEN, or the prototype hepatotoxicant carbon tetrachloride (CCl 4 ), in male and female mice exposed to these chemicals either postnatally or as adults. Exposure of adult mice to ABP, DEN or CCl 4 produced a 2-fold greater acute elevation in serum levels of the hepatotoxicity biomarker alanine aminotransferase (ALT) in males than in females, while levels of the inflammatory biomarker interleukin-6 (IL-6) showed no sex difference. However, treatment of immature mice with either ABP or DEN using standard tumor-inducing postnatal exposure protocols produced no increase in serum ALT or IL-6 levels in either males or females, while CCl 4 produced a 40-fold ALT elevation but with no sex difference. Basal expression of the NRF2-responsive gene Nqo1 was higher in adult females than in males, but there was no sex difference in basal expression of Ggt1 or Hmox1. Sexually immature animals showed no sex difference in basal

  11. 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

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

    Science.gov (United States)

    Wolkow, Alexander; Ferguson, Sally A; Vincent, Grace E; Larsen, Brianna; Aisbett, Brad; Main, Luana C

    2015-01-01

    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.

  13. MODERN INSIGHTS INTO THE ROLE OF HEMORHEOLOGICAL DEVIATIONS AND FUNCTIONAL STATUS OF THE ENDOTHELIAL TISSUE IN THE PATHOGENESIS OF ACUTE INFLAMMATORY LUNG AND BRONCHIAL DISEASES AMONG CHILDREN

    OpenAIRE

    A.V. Mozhaev; R.R. Shilyaev; M.R. Grineva; O.A. Pakhrova

    2007-01-01

    Disorders of the endothelial tissue and hemorheology function build up one of the pathogenic bases to form the acute inflammatory abnormality of the respiratory tract among children. The overview highlights the information on the role and disorders of the erythrocyte clumping and plasticity, blood viscosity and function of the endothelial tissue as a response to the acute respiratory infections among children.Key words: endothelial dysfunction, hemorheology, hemorheological deviations, acute ...

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

    Science.gov (United States)

    Roberts, S L; Hughes, H D; Burdick Sanchez, N C; Carroll, J A; Powell, J G; Hubbell, D S; Richeson, J T

    2015-08-01

    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 immunomodulation and whether concurrent oral administration of meloxicam (1 mg/kg BW) would alter these responses. On d -1, crossbred bull calves ( = 30; initial BW = 227.4 ± 10.3 kg) were fitted with indwelling jugular catheters and rectal temperature (RT) recording devices, placed into individual stanchions, and randomly assigned to 1 of 3 treatments. Treatment application occurred at h 0 and consisted of 1) intact bull calves treated with sham castration (CON), 2) bulls surgically castrated without meloxicam administration (CAS), and 3) bulls surgically castrated with oral meloxicam (1 mg/kg BW) administration (MEL). Blood samples were collected at 0.5-h intervals from h -2 to 4, 1.0-h intervals from h 4 to 8, and 12-h intervals from h 12 to 72. Serum was analyzed for cortisol and haptoglobin (Hp) concentrations using ELISA. Whole blood was analyzed for complete blood counts at -2, 0, 2, 4, 6, 8, 12, 24, 36, 48, 60, and 72 h, and RT was recorded in 5-min intervals. Postcastration RT was greatest for MEL (39.04), intermediate for CAS (38.99), and least for CON (38.93°C; ≤ 0.01). Serum cortisol was increased ( castration reduced the acute inflammatory response in castrates, as evidenced by a reduction in Hp and certain leukocyte concentrations; it also caused a delayed increase in RT. Further research is needed to determine if this reduced acute inflammatory response would equate to improved health and/or performance after castration.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Studies on the pathogenesis of fever. III. The leucocytic origin of endogenous pyrogen in acute inflammatory exudates.

    Science.gov (United States)

    KING, M K; WOOD, W B

    1958-02-01

    The evolution of an acute inflammatory exudate produced in rabbits by the intraperitoneal injection of saline has been described. Evidence has been presented that polymorphonuclear leucocytes release endogenous pyrogen into the cell-free fluid of the exudate. Leucocytes from such exudates have also been shown to release pyrogen into the surrounding medium during incubation in vitro at 37 degrees C. The results of parallel cytological studies have provided evidence which suggests that the leucocytes give up their pyrogen while functionally intact. These observations add further support to the hypothesis that polymorphonuclear leucocytes play a significant role in the pathogenesis of fever.

  17. 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.

  18. The effect of non-steroidal anti-inflammatory drugs on severity of acute pancreatitis and pancreatic necrosis.

    Science.gov (United States)

    Baxter, K A; Pucher, P H; Berry, D P; Elberm, H; Abu-Hilal, M; Marangoni, G; Hamady, Zzr

    2018-03-01

    Introduction Acute pancreatitis (AP) is a common emergency presentation and can be disabling. There is significant morbidity and mortality associated with AP, and it places a considerable burden on the healthcare system. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to have a protective effect in some elective contexts. This retrospective study aimed to evaluate the effect of NSAIDs on the course of AP and the severity of the disease. Methods A retrospective analysis was carried out of 324 patients admitted as an emergency with a diagnosis of AP to two UK hospitals. Patients were divided into two groups: those already taking NSAIDs for other co-morbidities and those not taking NSAIDs. Variables compared included: admission to a high dependency or intensive care unit; pancreatic necrosis; pseudocyst development; need for surgery; serum inflammatory markers; modified early warning scores on days 1, 3 and 5; length of stay; and mortality. Results Patients not taking NSAIDs were more likely to have a C-reactive protein level of ≥150mg/l (p=0.007). Patients in the NSAID group experienced less pancreatic necrosis (p=0.019) and lower rates of pseudocyst formation (p=0.010). Other variables showed no difference between the two groups, specifically length of stay and mortality. Conclusions Routine NSAID use may exert a protective effect on the development of AP, its severity, and complications. Therapeutic use of NSAIDs in acute presentations with pancreatitis should be further evaluated.

  19. Blockade of NMDA receptors decreased spinal microglia activation in bee venom induced acute inflammatory pain in rats.

    Science.gov (United States)

    Li, Li; Wu, Yongfang; Bai, Zhifeng; Hu, Yuyan; Li, Wenbin

    2017-03-01

    Microglial cells in spinal dorsal horn can be activated by nociceptive stimuli and the activated microglial cells release various cytokines enhancing the nociceptive transmission. However, the mechanisms underlying the activation of spinal microglia during nociceptive stimuli have not been well understood. In order to define the role of NMDA receptors in the activation of spinal microglia during nociceptive stimuli, the present study was undertaken to investigate the effect of blockade of NMDA receptors on the spinal microglial activation induced by acute peripheral inflammatory pain in rats. The acute inflammatory pain was induced by subcutaneous bee venom injection to the plantar surface of hind paw of rats. Spontaneous pain behavior, thermal withdrawal latency and mechanical withdrawal threshold were rated. The expression of specific microglia marker CD11b/c was assayed by immunohistochemistry and western blot. After bee venom treatment, it was found that rats produced a monophasic nociception characterized by constantly lifting and licking the injected hind paws, decreased thermal withdrawal latency and mechanical withdrawal threshold; immunohistochemistry displayed microglia with enlarged cell bodies, thickened, extended cellular processes with few ramifications, small spines, and intensive immunostaining; western blot showed upregulated expression level of CD11b/c within the period of hyperalgesia. Prior intrathecal injection of MK-801, a selective antagonist of NMDA receptors, attenuated the pain behaviors and suppressed up-regulation of CD11b/c induced by bee venom. It can be concluded that NMDA receptors take part in the mediation of spinal microglia activation in bee venom induced peripheral inflammatory pain and hyperalgesia in rats.

  20. Pregabalin reduces acute inflammatory and persistent pain associated with nerve injury and cancer in rat models of orofacial pain.

    Science.gov (United States)

    Hummig, Wagner; Kopruszinski, Caroline Machado; Chichorro, Juliana Geremias

    2014-01-01

    To assess the analgesic effect of pregabalin in orofacial models of acute inflammatory pain and of persistent pain associated with nerve injury and cancer, and so determine its effectiveness in controlling orofacial pains having different underlying mechanisms. Orofacial capsaicin and formalin tests were employed in male Wistar rats to assess the influence of pregabalin (or vehicle) pretreatment in acute pain models, and the results from these experiments were analyzed by one-way analysis of variance (ANOVA) followed by Newman Keuls post-hoc test. Pregabalin (or vehicle) treatment was also tested on the facial heat hyperalgesia that was evaluated in rats receiving injection of the inflammatory irritant carrageenan into the upper lip, as well as after constriction of the infraorbital nerve (a model of trigeminal neuropathic pain), or after inoculation of tumor cells into the facial vibrissal pad; two-way repeated measures ANOVA followed by Newman-Keuls post-hoc test was used to analyze data from these experiments. Facial grooming induced by capsaicin was abolished by pretreatment with pregabalin at 10 and 30 mg/kg. However, pregabalin failed to modify the first phase of the formalin response, but reduced the second phase at both doses (10 and 30 mg/kg). In addition, treatment of rats with pregabalin reduced the heat hyperalgesia induced by carrageenan, as well as by nerve injury and facial cancer. Pregabalin produced a marked antinociceptive effect in rat models of facial inflammatory pain as well as in facial neuropathic and cancer pain models, suggesting that it may represent an important agent for the clinical control of orofacial pain.

  1. Proinflammatory and anti-inflammatory cytokines present in the acute phase of experimental colitis treated with Saccharomyces boulardii.

    Science.gov (United States)

    Grijó, Nathália Nahas; Borra, Ricardo Carneiro; Sdepanian, Vera Lucia

    2010-09-01

    To study the proinflammatory and anti-inflammatory cytokines present in the acute phase of trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis treated with Saccharomyces boulardii. Thirty male Wistar rats were divided into three groups: (1) treated group--received Saccharomyces boulardii for 14 days; (2) non-treated group--received sodium chloride solution for 14 days; (3) control group. Colitis was induced on the seventh day of the study in the treated and the non-treated groups using TNBS (10 mg) dissolved in 50% ethanol. Quantification of cytokines, including interleukin (IL)-1beta (IL-1beta), IL-6, transforming growth factor-beta (TGF-beta), IL-10 and tumor necrosis factor-alpha (TNF-alpha), in the serum and colonic tissue collected on day 14 were carried out using an enzyme-linked immunosorbent assay (ELISA). The mean concentrations of TGF-beta in both the serum and the colonic tissue of the treated group were statistically higher than that of the control group. The mean concentration of TGF-beta in the colonic tissue of the non-treated group was also statistically higher than the control group. The group treated with Saccharomyces boulardii showed increased amounts of TGF-beta, an anti-inflammatory cytokine, during the acute phase of colitis. There were no differences in the amount of TNF-alpha, IL-1beta, IL-6, and IL-10 between the treated and the non-treated or the control groups during the acute phase of experimental colitis induced by TNBS.

  2. Phototherapy with low intensity laser in carrageenan-induced acute inflammatory process in mice paw - dosimetry studies

    International Nuclear Information System (INIS)

    Meneguzzo, Daiane Thais

    2010-01-01

    The importance of modulation of inflammation on the treatment of inflammatory diseases and the difficulty in determining the laser irradiation parameters has led us to study the effects of different protocols of phototherapy with low intensity laser (power, energy, time and place of irradiation) in the treatment and prevention of edema in acute inflammatory process using the experimental model of paw edema induced by carrageenan (CGN) in three strains of mice (Balb-c, Swiss and C57BL/6). The first stage of the study evaluated different combinations of energy (1J and 3J) with different powers (30, 60 and 100mW) in Balb-C mice paw irradiated 1 and 2h after injection of CGN. The second stage studied different combinations of location (foot, inguinal lymph nodes and both) and exposure time (2 and 1h before, 1h and immediately before the CGN, 1 and 2h and 3.5 and 4.5h after CGN) using fixed irradiation parameters (1J, 100mW, 35J/cm 2 , spot area of 0.028 cm 2 ). The third stage compared different strains of mice Balb-c and C57BL/6) in the best local and time parameters found in step 2. At all stages, we evaluated the change in paw volume by plethysmography and inflammatory infiltrate by histomorphometry or analysis of myeloperoxidase (MPO). The results showed that laser phototherapy treated and prevented edema and modulated the inflammatory process with paw and inguinal lymph nodes irradiations accordingly with the parameters and mice strain used. (author)

  3. Fidelity in Animal Modeling: Prerequisite for a Mechanistic Research Front Relevant to the Inflammatory Incompetence of Acute Pediatric Malnutrition.

    Science.gov (United States)

    Woodward, Bill

    2016-04-11

    Inflammatory incompetence is characteristic of acute pediatric protein-energy malnutrition, but its underlying mechanisms remain obscure. Perhaps substantially because the research front lacks the driving force of a scholarly unifying hypothesis, it is adrift and research activity is declining. A body of animal-based research points to a unifying paradigm, the Tolerance Model, with some potential to offer coherence and a mechanistic impetus to the field. However, reasonable skepticism prevails regarding the relevance of animal models of acute pediatric malnutrition; consequently, the fundamental contributions of the animal-based component of this research front are largely overlooked. Design-related modifications to improve the relevance of animal modeling in this research front include, most notably, prioritizing essential features of pediatric malnutrition pathology rather than dietary minutiae specific to infants and children, selecting windows of experimental animal development that correspond to targeted stages of pediatric immunological ontogeny, and controlling for ontogeny-related confounders. In addition, important opportunities are presented by newer tools including the immunologically humanized mouse and outbred stocks exhibiting a magnitude of genetic heterogeneity comparable to that of human populations. Sound animal modeling is within our grasp to stimulate and support a mechanistic research front relevant to the immunological problems that accompany acute pediatric malnutrition.

  4. Fidelity in Animal Modeling: Prerequisite for a Mechanistic Research Front Relevant to the Inflammatory Incompetence of Acute Pediatric Malnutrition

    Science.gov (United States)

    Woodward, Bill

    2016-01-01

    Inflammatory incompetence is characteristic of acute pediatric protein-energy malnutrition, but its underlying mechanisms remain obscure. Perhaps substantially because the research front lacks the driving force of a scholarly unifying hypothesis, it is adrift and research activity is declining. A body of animal-based research points to a unifying paradigm, the Tolerance Model, with some potential to offer coherence and a mechanistic impetus to the field. However, reasonable skepticism prevails regarding the relevance of animal models of acute pediatric malnutrition; consequently, the fundamental contributions of the animal-based component of this research front are largely overlooked. Design-related modifications to improve the relevance of animal modeling in this research front include, most notably, prioritizing essential features of pediatric malnutrition pathology rather than dietary minutiae specific to infants and children, selecting windows of experimental animal development that correspond to targeted stages of pediatric immunological ontogeny, and controlling for ontogeny-related confounders. In addition, important opportunities are presented by newer tools including the immunologically humanized mouse and outbred stocks exhibiting a magnitude of genetic heterogeneity comparable to that of human populations. Sound animal modeling is within our grasp to stimulate and support a mechanistic research front relevant to the immunological problems that accompany acute pediatric malnutrition. PMID:27077845

  5. Circadian time-dependent antioxidant and inflammatory responses to acute cadmium exposure in the brain of zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Jia-Lang, E-mail: zhengjialang@aliyun.com; Yuan, Shuang-Shuang; Wu, Chang-Wen; Lv, Zhen-Ming; Zhu, Ai-Yi

    2017-01-15

    Highlights: • Gene changed at mRNA, protein and activity levels between exposure time points. • ROS mediated antioxidant and inflammatory responses by Nrf2 and NF-κB. • The effect of time of day on Cd-induced toxicity should not be neglected in fish. - Abstract: Up to date, little information is available on effects of circadian rhythm on metal-induced toxicity in fish. In this study, zebrafish were acutely exposed to 0.97 mg L{sup −1} cadmium for 12 h either at ZT0 (the light intensity began to reached maximum) or at ZT12 (light intensity began to reached minimum) to evaluate the temporal sensitivity of oxidative stress and inflammatory responses in the brain of zebrafish. Profiles of responses of some genes at mRNA, protein and activity levels were different between ZT0 and ZT12 in the normal water. Exposure to Cd induced contrary antioxidant responses and similar inflammatory responses between ZT0 and ZT12. However, the number of inflammatory genes which were up-regulated was significantly greater at ZT12 than at ZT0. And, the up-regulated inflammatory genes were more responsive at ZT12 than at ZT0. At ZT12, antioxidant genes were down-regulated at mRNA, protein and activity levels. Contrarily, antioxidant genes were not affected at mRNA levels but activated at the protein and/or activity levels at ZT0. Reactive oxygen species (ROS) sharply increased and remained relatively stable when fish were exposed to Cd at ZT12 and ZT0, respectively. Positive correlations between ROS levels and mRNA levels of nuclear transcription factor κB (NF-κB) and between mRNA levels of NF-κB and its target genes were observed, suggesting that ROS may play an essential role in regulating the magnitude of inflammatory responses. Taken together, oxidative stress and immunotoxicity in the brain were more serious when fish were exposed to Cd in the evening than in the morning, highlighting the importance of circadian rhythm in Cd-induced neurotoxicity in fish.

  6. Circadian time-dependent antioxidant and inflammatory responses to acute cadmium exposure in the brain of zebrafish

    International Nuclear Information System (INIS)

    Zheng, Jia-Lang; Yuan, Shuang-Shuang; Wu, Chang-Wen; Lv, Zhen-Ming; Zhu, Ai-Yi

    2017-01-01

    Highlights: • Gene changed at mRNA, protein and activity levels between exposure time points. • ROS mediated antioxidant and inflammatory responses by Nrf2 and NF-κB. • The effect of time of day on Cd-induced toxicity should not be neglected in fish. - Abstract: Up to date, little information is available on effects of circadian rhythm on metal-induced toxicity in fish. In this study, zebrafish were acutely exposed to 0.97 mg L"−"1 cadmium for 12 h either at ZT0 (the light intensity began to reached maximum) or at ZT12 (light intensity began to reached minimum) to evaluate the temporal sensitivity of oxidative stress and inflammatory responses in the brain of zebrafish. Profiles of responses of some genes at mRNA, protein and activity levels were different between ZT0 and ZT12 in the normal water. Exposure to Cd induced contrary antioxidant responses and similar inflammatory responses between ZT0 and ZT12. However, the number of inflammatory genes which were up-regulated was significantly greater at ZT12 than at ZT0. And, the up-regulated inflammatory genes were more responsive at ZT12 than at ZT0. At ZT12, antioxidant genes were down-regulated at mRNA, protein and activity levels. Contrarily, antioxidant genes were not affected at mRNA levels but activated at the protein and/or activity levels at ZT0. Reactive oxygen species (ROS) sharply increased and remained relatively stable when fish were exposed to Cd at ZT12 and ZT0, respectively. Positive correlations between ROS levels and mRNA levels of nuclear transcription factor κB (NF-κB) and between mRNA levels of NF-κB and its target genes were observed, suggesting that ROS may play an essential role in regulating the magnitude of inflammatory responses. Taken together, oxidative stress and immunotoxicity in the brain were more serious when fish were exposed to Cd in the evening than in the morning, highlighting the importance of circadian rhythm in Cd-induced neurotoxicity in fish.

  7. 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...

  8. Detection of acute inflammatory bowel disease with Tc-99m-HSA-sucralfate scans

    International Nuclear Information System (INIS)

    Yip, T.C.; Houle, S.; Jeejeebhoy, K.N.

    1987-01-01

    Sucralfate binds to mucosal ulcerations. Twelve studies were performed in 11 patients with inflammatory bowel disease. Technetium-sucralfate was prepared in vitro and given orally. Images were obtained at 4-6, 24, and 48 hours. Persistent focal abnormalities or activity in the large bowel beyond 48 hours was interpreted as positive. Patients' charts were reviewed. Technetium-sucralfate was positive in ten of ten studies in nine patients with active disease, one with equivocal activity, and negative in one patient with inactive disease. Nine of 19 abnormal sites were detected with technetium-sucralfate and radiology or endoscopy; six of ten were detected with technetium-sucralfate only. Technetium-sucralfate is very sensitive in detecting active inflammatory bowel disease in individual patients

  9. Fibromyalgia: anti-inflammatory and stress responses after acute moderate exercise.

    Science.gov (United States)

    Bote, Maria Elena; Garcia, Juan Jose; Hinchado, Maria Dolores; Ortega, Eduardo

    2013-01-01

    Fibromyalgia (FM) is characterized in part by an elevated inflammatory status, and "modified exercise" is currently proposed as being a good therapeutic help for these patients. However, the mechanisms involved in the exercise-induced benefits are still poorly understood. The objective was to evaluate the effect of a single bout of moderate cycling (45 min at 55% VO2 max) on the inflammatory (serum IL-8; chemotaxis and O2 (-) production by neutrophils; and IL-1β, TNF-α, IL-6, IL-10, and IL-18 release by monocytes) and stress (cortisol; NA; and eHsp72) responses in women diagnosed with FM compared with an aged-matched control group of healthy women (HW). IL-8, NA, and eHsp72 were determined by ELISA. Cytokines released by monocytes were determined by Bio-Plex® system (LUMINEX). Cortisol was determined by electrochemoluminiscence, chemotaxis was evaluated in Boyden chambers and O2 (-) production by NBT reduction. In the FM patients, the exercise induced a decrease in the systemic concentration of IL-8, cortisol, NA, and eHsp72; as well as in the neutrophil's chemotaxis and O2 (-) production and in the inflammatory cytokine release by monocytes. This was contrary to the completely expected exercise-induced increase in all those biomarkers in HW. In conclusion, single sessions of moderate cycling can improve the inflammatory status in FM patients, reaching values close to the situation of aged-matched HW at their basal status. The neuroendocrine mechanism seems to be an exercise-induced decrease in the stress response of these patients.

  10. Fibromyalgia: anti-inflammatory and stress responses after acute moderate exercise.

    Directory of Open Access Journals (Sweden)

    Maria Elena Bote

    Full Text Available Fibromyalgia (FM is characterized in part by an elevated inflammatory status, and "modified exercise" is currently proposed as being a good therapeutic help for these patients. However, the mechanisms involved in the exercise-induced benefits are still poorly understood. The objective was to evaluate the effect of a single bout of moderate cycling (45 min at 55% VO2 max on the inflammatory (serum IL-8; chemotaxis and O2 (- production by neutrophils; and IL-1β, TNF-α, IL-6, IL-10, and IL-18 release by monocytes and stress (cortisol; NA; and eHsp72 responses in women diagnosed with FM compared with an aged-matched control group of healthy women (HW. IL-8, NA, and eHsp72 were determined by ELISA. Cytokines released by monocytes were determined by Bio-Plex® system (LUMINEX. Cortisol was determined by electrochemoluminiscence, chemotaxis was evaluated in Boyden chambers and O2 (- production by NBT reduction. In the FM patients, the exercise induced a decrease in the systemic concentration of IL-8, cortisol, NA, and eHsp72; as well as in the neutrophil's chemotaxis and O2 (- production and in the inflammatory cytokine release by monocytes. This was contrary to the completely expected exercise-induced increase in all those biomarkers in HW. In conclusion, single sessions of moderate cycling can improve the inflammatory status in FM patients, reaching values close to the situation of aged-matched HW at their basal status. The neuroendocrine mechanism seems to be an exercise-induced decrease in the stress response of these patients.

  11. Differential intrathecal inflammatory markers in acute optic neuritis and later conversion to multiple sclerosis

    DEFF Research Database (Denmark)

    Olesen, Mads Nikolaj; Soelberg, Kerstin; Nilsson, Anna Christine

    Background: Optic neuritis (ON) is often an early inflammatory, demyelinating event of multiple sclerosis (MS). We proffer that cytokine and chemokine profiles may (a) differ between patients with MS-related ON and those with non-MS-related ON and (b) predict conversion to MS in patients presenting......-up compared to those who had not. These findings are of potential relevance to our understanding of the pathogenesis of MS and may predict conversion of ON to MS....

  12. Inflammatory role and prognostic value of platelet chemokines in acute coronary syndrome

    NARCIS (Netherlands)

    Blanchet, X.; Cesarek, K.; Brandt, J.; Herwald, H.; Teupser, D.; Küchenhoff, H.; Karshovska, E.; Mause, S. F.; Siess, W.; Wasmuth, H.; Soehnlein, O.; Koenen, R. R.; Weber, C.; von Hundelshausen, P.

    2014-01-01

    Activated platelets and neutrophils exacerbate atherosclerosis. Platelets release the chemokines CXCL4, CXCL4L1 and CCL5, whereas myeloperoxidase (MPO) and azurocidin are neutrophil-derived. We investigated whether plasma levels of these platelet and neutrophil mediators are affected by the acute

  13. Warfarin affects acute inflammatory response induced by subcutaneous polyvinyl sponge implantation in rats.

    Science.gov (United States)

    Mirkov, Ivana; Popov Aleksandrov, Aleksandra; Demenesku, Jelena; Ninkov, Marina; Mileusnic, Dina; Kataranovski, Dragan; Kataranovski, Milena

    2017-09-01

    Warfarin (WF) is an anticoagulant which also affects physiological processes other than hemostasis. Our previous investigations showed the effect of WF which gained access to the organism via skin on resting peripheral blood granulocytes. Based on these data, the aim of the present study was to examine whether WF could modulate the inflammatory processes as well. To this aim the effect of WF on the inflammatory response induced by subcutaneous sponge implantation in rats was examined. Warfarin-soaked polyvinyl sponges (WF-sponges) were implanted subcutaneously and cell infiltration into sponges, the levels of nitric oxide (NO) and inflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6) production by sponge cells were measured as parameters of inflammation. T cell infiltration and cytokine interferon-γ (IFN-γ), interleukin-17 (IL-17) and interleukin-10 (IL-10) were measured at day 7 post implantation. Warfarin exerted both stimulatory and suppressive effects depending on the parameter examined. Flow cytometry of cells recovered from sponges showed higher numbers of granulocytes (HIS48 + cells) at days 1 and 3 post implantation and CD11b + cells at day 1 compared to control sponges. Cells from WF-sponges had an increased NO production (Griess reaction) at days 1 and 7. In contrast, lower levels of TNF (measured by ELISA) production by cells recovered from WF-soaked sponges were found in the early (day one) phase of reaction with unchanged levels at other time points. While IL-6 production by cells recovered from WF-soaked sponges was decreased at day 1, it was increased at day 7. Higher T cell numbers were noted in WF sponges at day 7 post implantation, and recovered cells produced more IFN-γ and IL-17, while IL-10 production remained unchanged. Warfarin affects some of the parameters of inflammatory reaction induced by subcutaneous polyvinyl sponge implantation. Differential (both stimulatory as well as inhibitory) effects of WF on

  14. Role of inflammatory markers as predictors of laparotomy in patients presenting with acute abdomen.

    Science.gov (United States)

    Dias, Brendan H; Rozario, Anthony P; Olakkengil, Santosh A

    2015-10-01

    There is a need for an ideal indicator of surgery in patients presenting with acute abdomen. Several markers have been analysed, but the search still continues as none have proven effective. This study aimed to analyse and compare the predictive value of plasma procalcitonin (PCT) strip test in patients presenting with acute abdomen and identify a useful cut-off value to differentiate patients that would benefit with surgery from those that require conservative management. A prospective study was conducted in the department of general surgery from June 2012 to June 2013. Plasma PCT was estimated by the semi-quantitative strip test. The levels of plasma PCT and other routinely used markers of inflammation were analysed and compared. Of the total of 58 patients, 44 patients (76%) were men with a mean age of 45 years. Forty patients required emergency surgical intervention. A plasma PCT value of >0.5 ng/mL at admission was 80% sensitive and 100% specific for predicting need for antibiotics in patients with acute abdomen that were managed conservatively. The mean plasma PCT value in the patients undergoing surgery (5.0-10.0 ng/mL) was significantly more than in those managed conservatively (0.5-2.0 ng/mL). Using receiver operating characteristic (ROC) curves a cut-off for plasma PCT of >5.0 ng/mL was 75% sensitive and 100% specific for considering surgical intervention in patients presenting with acute abdomen. Plasma PCT (value >5 ng/mL) could be used as an adjunct to clinical examination to predict requirement of surgery in patients presenting with acute abdomen. © 2015 Royal Australasian College of Surgeons.

  15. Short-Term High- and Moderate-Intensity Training Modifies Inflammatory and Metabolic Factors in Response to Acute Exercise

    Directory of Open Access Journals (Sweden)

    Fabio Santos Lira

    2017-10-01

    Full Text Available Purpose: To compare the acute and chronic effects of high intensity intermittent training (HIIT and steady state training (SST on the metabolic profile and inflammatory response in physically active men.Methods: Thirty recreationally active men were randomly allocated to a control group (n = 10, HIIT group (n = 10, or SST group (n = 10. For 5 weeks, three times per week, subjects performed HIIT (5 km 1-min at 100% of maximal aerobic speed interspersed by 1-min passive recovery or SST (5 km at 70% of maximal aerobic speed while the control group did not perform training. Blood samples were collected at fasting (~12 h, pre-exercise, immediately post, and 60 min post-acute exercise session (pre- and post-5 weeks training. Blood samples were analyzed for glucose, non-ester fatty acid (NEFA, and cytokine (IL-6, IL-10, and TNF-α levels through a three-way analysis (group, period, and moment of measurement with repeated measures in the second and third factors.Results: The results showed an effect of moment of measurement (acute session with greater values to TNF-α and glucose immediately post the exercise when compared to pre exercise session, independently of group or training period. For IL-6 there was an interaction effect for group and moment of measurement (acute session the increase occurred immediately post-exercise session and post-60 min in the HIIT group while in the SST the increase was observed only 60 min post, independently of training period. For IL-10, there was an interaction for training period (pre- and post-training and moment of measurement (acute session, in which in pre-training, pre-exercise values were lower than immediately and 60 min post-exercise, in post-training period pre-exercise values were lower than immediately post-exercise and immediately post-exercise lower than 60 min post, it was also observed that values immediately post-exercise were lower pre- than post-training, being all results independently of intensity

  16. Relationship between Cardiac Troponin and Thrombo-Inflammatory Molecules in Prediction of Outcome after Acute Ischemic Stroke

    DEFF Research Database (Denmark)

    Csecsei, Peter; Pusch, Gabriella; Ezer, Erzsebet

    2018-01-01

    BACKGROUND: In patients with acute ischemic stroke (AIS) without cardiovascular complications, we investigated the association of serum concentration of cardiac troponin (high-sensitivity cardiac troponin T [hs-cTnT]) with thrombo-inflammatory markers. METHODS: Thirty-five patients with first......-ever AIS were prospectively examined. Serum hs-cTnT was measured 6 and 24 hours after stroke, whereas S100B, high-sensitivity C-reactive protein (hsCRP), soluble CD40 ligand, tissue plasminogen activator (tPA), monocyte chemoattractant protein-1 (MCP-1), and P-selectin were measured 6 and 72 hours after...... stroke. Severity of stroke was assessed by the National Institutes of Health Stroke Scale (NIHSS) on admission, 24 hours later, and at discharge. RESULTS: Concentration of MCP-1 at 6 hours was higher in the serum of patients with worsened NIHSS by 24 hours (P = .009). Concentration of hs-cTnT at both 6...

  17. 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

  18. Mild hypothermia increases pulmonary anti-inflammatory response during protective mechanical ventilation in a piglet model of acute lung injury.

    Science.gov (United States)

    Cruces, Pablo; Erranz, Benjamín; Donoso, Alejandro; Carvajal, Cristóbal; Salomón, Tatiana; Torres, María Fernanda; Díaz, Franco

    2013-11-01

    The effects of mild hypothermia (HT) on acute lung injury (ALI) are unknown in species with metabolic rate similar to that of humans, receiving protective mechanical ventilation (MV). We hypothesized that mild hypothermia would attenuate pulmonary and systemic inflammatory responses in piglets with ALI managed with a protective MV. Acute lung injury (ALI) was induced with surfactant deactivation in 38 piglets. The animals were then ventilated with low tidal volume, moderate positive end-expiratory pressure (PEEP), and permissive hypercapnia throughout the experiment. Subjects were randomized to HT (33.5°C) or normothermia (37°C) groups over 4 h. Plasma and tissue cytokines, tissue apoptosis, lung mechanics, pulmonary vascular permeability, hemodynamic, and coagulation were evaluated. Lung interleukin-10 concentrations were higher in subjects that underwent HT after ALI induction than in those that maintained normothermia. No difference was found in other systemic and tissue cytokines. HT did not induce lung or kidney tissue apoptosis or influence lung mechanics or markers of pulmonary vascular permeability. Heart rate, cardiac output, oxygen uptake, and delivery were significantly lower in subjects that underwent HT, but no difference in arterial lactate, central venous oxygen saturation, and coagulation test was observed. Mild hypothermia induced a local anti-inflammatory response in the lungs, without affecting lung function or coagulation, in this piglet model of ALI. The HT group had lower cardiac output without signs of global dysoxia, suggesting an adaptation to the decrease in oxygen uptake and delivery. Studies are needed to determine the therapeutic role of HT in ALI. © 2013 John Wiley & Sons Ltd.

  19. Adiposity moderates links from early adversity and depressive symptoms to inflammatory reactivity to acute stress during late adolescence.

    Science.gov (United States)

    Chiang, Jessica J; Bower, Julienne E; Irwin, Michael R; Taylor, Shelley E; Fuligni, Andrew J

    2017-11-01

    Both early adversity and depression are associated with heightened inflammation. However, few studies have focused on inflammatory reactivity to psychosocial stress and examined adiposity as a potential moderator. Yet, repeated heightened inflammatory reactivity over time is thought to contribute to low-grade chronic inflammation and adipose tissue is a key source of pro-inflammatory cytokines. The purpose of the present study was to examine whether early adversity and depressive symptoms were related to stress-induced inflammation and whether these associations varied by total body and abdominal adiposity as measured by body mass index (BMI) and waist circumference (WC) in a sample of late adolescents. Participants reported on their early family environment and current depressive symptoms, had their height, weight, and WC assessed for adiposity markers, and provided blood samples for IL-6 assessment before and after a standardized laboratory stress task. No main effect of early adversity on IL-6 reactivity to acute stress was observed. However, significant interactions between early adversity and BMI and WC emerged. Greater exposure to early adversity was associated with greater IL-6 responses only among adolescents with higher BMI or WC. The same pattern of findings was observed for depressive symptoms. Additionally, moderated mediation analyses indicated that among adolescents with greater adiposity, early adversity indirectly influenced IL-6 reactivity via current depressive symptoms. These findings contribute to our understanding of vulnerability factors that may amplify the associations between early adversity and depressive symptoms and inflammation during relatively early stages of life. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Acute deviations from long-term trait depressive symptoms predict systemic inflammatory activity.

    Science.gov (United States)

    Rohleder, Nicolas; Miller, Gregory E

    2008-07-01

    Depressive symptoms increase morbidity and mortality from coronary heart disease and systemic inflammation has been proposed as the underlying mechanism. While higher levels of inflammatory mediators have been found in dysphoric individuals, it is not known whether long-term or short-term mood changes are responsible for this phenomenon. A sample of 65 young women provided weekly web-based self-ratings of depressive mood over a period of 20 weeks using the CES-D, and systemic inflammation was assessed by measuring plasma interleukin-6 (IL-6) and C-reactive protein (CRP) before and after the observation period. CES-D ratings were used to develop state and trait indicators of depressed mood and evaluate their relationship with inflammatory mediators. Hierarchical linear regressions controlling for baseline inflammation, age, and BMI revealed that trait levels of depressive symptoms were not associated with IL-6 (beta=0.09; n.s.) and CRP (beta=0.01; n.s.) concentrations after the observation period. In contrast, state levels of depressive symptoms were associated with changes in IL-6, but not CRP, particularly when they were indexed as the disparity between a person's trait level of symptoms and her CES-D score just prior to IL-6 assessment (beta=0.35; p=0.03). These results lead us to conclude that in young women, state, rather than trait depressed mood stimulates peripheral inflammation as measured by IL-6. This pattern suggests that in this age group, fast-reacting inflammatory mediators such as IL-6 probably respond to short-term changes, for example, in stress hormones or stress hormone sensitivity, rather than long-term dysregulations of allostatic mechanisms.

  1. 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....... The duration and quality of blocks were evaluated by the sympatogalvanic skin response and skin temperature. Bilateral heat injuries were produced on the medial surfaces of the calves with a 50 x 25 mm thermode (47 degrees C, 7 min) 45 min after the blocks. Pain intensity induced by heat, pain thresholds...... between sympathetic block and placebo for pain or mechanical allodynia during injury, or pain thresholds, pain responses to heat, or areas of secondary hyperalgesia after the injury. The comparisons were done for the period when the block was effective. CONCLUSION: Sympathetic nerve block did not change...

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

    Science.gov (United States)

    Joe, Bina; Nagaraju, Anitha; Gowda, Lalitha R; Basrur, Venkatesha; Lokesh, Belur R

    2014-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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 and...

  5. 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 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

  6. Co-ordinate but disproportionate activation of apoptotic, regenerative and inflammatory pathways characterizes the liver response to acute amebic infection.

    Science.gov (United States)

    Pelosof, Lorraine C; Davis, Paul H; Zhang, Zhi; Zhang, Xiaochun; Stanley, Samuel L

    2006-03-01

    The liver has the remarkable ability to respond to injury with repair and regeneration. The protozoan parasite Entamoeba histolytica is the major cause of liver abscess worldwide. We report a transcriptional analysis of the response of mouse liver to E. histolytica infection, the first study looking at acute liver infection by a non-viral pathogen. Focusing on early time points, we identified 764 genes with altered transcriptional levels in amebic liver abscess. The response to infection is rapid and complex, with concurrent increased expression of genes linked to host defence through IL-1, TLR2, or interferon-induced pathways, liver regeneration via activation of IL-6 pathways, and genes associated with programmed cell death possibly through TNFalpha or Fas pathways. A comparison of amebic liver infection with the liver response to partial hepatectomy or toxins reveals striking similarities between amebic liver abscess and non-infectious injury in key components of the liver regeneration pathways. However, the response in amebic liver abscess is biased towards apoptosis when compared with acute liver injury from hepatectomy, toxins, or other forms of liver infection. E. histolytica infection of the liver simultaneously activates inflammatory, regenerative and apoptotic pathways, but the sum of these early responses is biased towards programmed cell death.

  7. 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

  8. Acute oral toxicity and anti-inflammatory activity of hydroalcoholic extract from Lampaya medicinalis Phil in rats.

    Science.gov (United States)

    Morales, Glauco; Paredes, Adrián; Olivares, Alberto; Bravo, Jaime

    2014-03-26

    Algesia and inflammation are related with several pathological conditions. It is known that many drugs available for the treatment of these problems cause unwanted side effects. This study was aimed at evaluating acute toxicity and anti-inflammatory activity of Lampaya medicinalis Phil. (Verbenaceae) widely used in the folk medicine of Northern Chile against rheumatism, arthritis and body joints pain. Oral administration of hydroalcoholic extract (HAE) at the highest dose of 3000 mg/ Kg body weight resulted in no mortalities or evidence of significant behavioral changes. Histological examination revealed normal architecture and no significant adverse effects were observed on the liver, kidney, heart, lung or ovaries and testicles. The results suggest that the oral administration of hydroalcoholic extract (HAE) from Lampaya medicinalis did not produce any toxic effect in rats. Hydroalcoholic extract (HAE) significantly inhibited the carrageenan-induced rat paw edema in dose - response relationship, at test doses of 37.5, 75, 150 and 300 mg/Kg body weight. Maximum inhibition (61.98 ± 2.69%) was noted at 300 mg/Kg after 2 h of drug treatment carrageenan induced paw edema, whereas indomethacin produced 47.90 ± 1.16% of inhibition. The inhibitory values of edema at 3 h postcarrageenan were 31.04 ± 0.75%, 40.51 ± 2.36%, 48.97 ± 1.14% and 56.87 ± 0.41% for 37.5, 75, 150, and 300 mg/kg of extract respectively. Indomethacin (10 mg/Kg) gave a percentage inhibition of 49.44 ± 1.44. HAE (300 and 150 mg/kg) induced an anti-inflammatory effect greater than (or comparable) with the effect of indomethacin from 2nd to 4th hours of the experiment. Our results reveal for first time that compounds contained in the hydroalcoholic extract of Lampaya medicinalis Phil exert anti-inflammatory effect and the oral administration is safe and non toxic up to dose level 3000 mg/kg body weight. The anti-inflammatory activity may be associated with the presence of flavonoids. These

  9. Acute oral toxicity and anti-inflammatory activity of hydroalcoholic extract from Lampaya medicinalis Phil in rats

    Directory of Open Access Journals (Sweden)

    Glauco Morales

    2014-01-01

    Full Text Available BACKGROUND: Algesia and inflammation are related with several pathological conditions. It is known that many drugs available for the treatment of these problems cause unwanted side effects. This study was aimed at evaluating acute toxicity and anti-inflammatory activity of Lampaya medicinalis Phil. (Verbenaceae widely used in the folk medicine of Northern Chile against rheumatism, arthritis and body joints pain. RESULTS: Oral administration of hydroalcoholic extract (HAE at the highest dose of 3000 mg/ Kg body weight resulted in no mortalities or evidence of significant behavioral changes. Histological examination revealed normal architecture and no significant adverse effects were observed on the liver, kidney, heart, lung or ovaries and testicles. The results suggest that the oral administration of hydroalcoholic extract (HAE from Lampaya medicinalis did not produce any toxic effect in rats. Hydroalcoholic extract (HAE significantly inhibited the carrageenan-induced rat paw edema in dose - response relationship, at test doses of 37.5, 75, 150 and 300 mg/Kg body weight. Maximum inhibition (61.98 ± 2.69% was noted at 300 mg/Kg after 2 h of drug treatment carrageenan induced paw edema, whereas indomethacin produced 47.90 ± 1.16% of inhibition. The inhibitory values of edema at 3 h postcarrageenan were 31.04±0.75%, 40.51 ± 2.36%, 48.97 ± 1.14% and 56.87 ± 0.41% for 37.5, 75, 150, and 300 mg/kg of extract respectively. Indomethacin (10 mg/Kg gave a percentage inhibition of 49.44 ± 1.44. HAE (300 and 150 mg/kg induced an anti-inflammatory effect greater than (or comparable with the effect of indomethacin from 2nd to 4th hours of the experiment. CONCLUSIONS: Our results reveal for first time that compounds contained in the hydroalcoholic extract ofLampaya medicinalis Phil exert anti-inflammatory effect and the oral administration is safe and non toxic up to dose level 3000 mg/kg body weight. The anti-inflammatory

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

    Directory of Open Access Journals (Sweden)

    Jonathan E McDunn

    2008-02-01

    Full Text Available 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.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.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 background, gender, and pathogen. Prospective clinical trials are indicated

  11. Neonatal overfeeding attenuates acute central pro-inflammatory effects of short-term high fat diet

    Directory of Open Access Journals (Sweden)

    Guohui eCai

    2015-01-01

    Full Text Available Neonatal obesity predisposes individuals to obesity throughout life. In rats, neonatal overfeeding also leads to early accelerated weight gain that persists into adulthood. The phenotype is associated with dysfunction in a number of systems including paraventricular nucleus of the hypothalamus (PVN responses to psychological and immune stressors. However, in many cases weight gain in neonatally overfed rats stabilizes in early adulthood so the animal does not become more obese as it ages. Here we examined if neonatal overfeeding by suckling rats in small litters predisposes them to exacerbated metabolic and central inflammatory disturbances if they are also given a high fat diet in later life. In adulthood we gave the rats normal chow, 3 days, or 3 weeks high fat diet (45% kcal from fat and measured peripheral indices of metabolic disturbance. We also investigated hypothalamic microglial changes, as an index of central inflammation, as well as PVN responses to lipopolysaccharide (LPS. Surprisingly, neonatal overfeeding did not predispose rats to the metabolic effects of a high fat diet. Weight changes and glucose metabolism were unaffected by the early life experience. However, short term (3 day high fat diet was associated with more microglia in the hypothalamus and a markedly exacerbated PVN response to LPS in control rats; effects not seen in the neonatally overfed. Our findings indicate neonatally overfed animals are not more susceptible to the adverse metabolic effects of a short-term high fat diet but may be less able to respond to the central effects.

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

    DEFF Research Database (Denmark)

    Pedersen, J L; Kehlet, H

    1998-01-01

    as significant for all variables with fewer than 12 subjects in a cross-over design (2alpha = 5% and power = 80%). Between-day comparisons demanded up to 25 subjects to detect changes of the same magnitude. The burns caused mild to moderate pain (VAS: mean 29, SD 14) and the subjects (all right-handed) were more......The aim of the study was to examine reproducibility of primary and secondary hyperalgesia in a psychophysical model of human inflammatory pain. Mild burns were produced on the crura of 12 volunteers with a 50 x 25 mm thermode (47 degrees C, 7 min). Assessments of (i) cold and warm detection...... 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...

  13. Anti-irritant and anti-inflammatory effects of glycerol and xylitol in sodium lauryl sulphate-induced acute irritation.

    Science.gov (United States)

    Szél, E; Polyánka, H; Szabó, K; Hartmann, P; Degovics, D; Balázs, B; Németh, I B; Korponyai, C; Csányi, E; Kaszaki, J; Dikstein, S; Nagy, K; Kemény, L; Erős, G

    2015-12-01

    Glycerol is known to possess anti-irritant and hydrating properties and previous studies suggested that xylitol may also have similar effects. Our aim was to study whether different concentrations of these polyols restore skin barrier function and soothe inflammation in sodium lauryl sulphate (SLS)-induced acute irritation. The experiments were performed on male SKH-1 hairless mice. The skin of the dorsal region was exposed to SLS (5%) for 3 h alone or together with 5% or 10% of glycerol respectively. Further two groups received xylitol solutions (8.26% and 16.52% respectively) using the same osmolarities, which were equivalent to those of the glycerol treatments. The control group was treated with purified water. Transepidermal water loss (TEWL) and skin hydration were determined. Microcirculatory parameters of inflammation were observed by means of intravital videomicroscopy (IVM). Furthermore, accumulation of neutrophil granulocytes and lymphocytes, the expression of inflammatory cytokines and SLS penetration were assessed, as well. Treatment with the 10% of glycerol and both concentrations of xylitol inhibited the SLS-induced elevation of TEWL and moderated the irritant-induced increase in dermal blood flow and in the number of leucocyte-endothelial interactions. All concentrations of the applied polyols improved hydration and prevented the accumulation of lymphocytes near the treatment site. At the mRNA level, neither glycerol nor xylitol influenced the expression of interleukin-1 alpha. However, expression of interleukin-1 beta was significantly decreased by the 10% glycerol treatment, while expression of tumour necrosis factor-alpha decreased upon the same treatment, as well as in response to xylitol. Higher polyol treatments decreased the SLS penetration to the deeper layers of the stratum corneum. Both of the analysed polyols exert considerable anti-irritant and anti-inflammatory properties, but the effective concentration of xylitol is lower than that of

  14. 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.

  15. Physiologic and systemic acute phase inflammatory responses in young horses repeatedly infected with cyathostomins and Strongylus vulgaris.

    Science.gov (United States)

    Andersen, U V; Reinemeyer, C R; Toft, N; Olsen, S N; Jacobsen, S; Nielsen, M K

    2014-03-17

    Migrating Strongylus vulgaris and encysted cyathostomin larvae cause a localized inflammatory response in horses. It is unknown whether these larvae elicit a systemic acute phase response (APR), evidenced by changes in serum amyloid A (SAA), haptoglobin (Hp), iron (Fe), albumin, or albumin/globulin (A/G) ratio. In this study, 28 horses were randomly allocated to receive either pyrantel tartrate or a pelleted placebo formulation in their daily feed. Concurrent with treatment, all the horses were administered 5000 pyrantel-susceptible cyathostomin infective larvae once daily, 5 days a week, for 24 weeks. Beginning in the fifth week, the horses also received 25 S. vulgaris larvae once weekly for the remainder of the study. At regular biweekly intervals, fecal samples were collected for quantitative egg counts, and whole blood and serum samples were collected for measurement of packed cell volume, total protein, albumin, globulin, A/G ratio, SAA, Hp, and Fe. On days 161-164, all the horses were euthanatized and necropsied. Samples were collected for enumeration of total luminal worm burdens, encysted cyathostomin larval populations, and migrating S. vulgaris larvae. Concentrations of Hp, Fe, and A/G ratio were associated significantly with strongyle burdens. Only treated male horses had significant increases in serum albumin. Larval S. vulgaris did not associate with Fe, whereas Fe was associated negatively with both total cyathostomin burdens and encysted L4s. The A/G ratios differed significantly between the two treatment groups. Significant differences between groups and individual time points were also observed for Hp and Fe, whereas SAA concentrations remained low throughout the study. In general, this study illustrated that experimental inoculations with S. vulgaris and cyathostomins may be associated with changes in Hp, Fe, and serum proteins, but not with SAA. Overall, these changes suggest that mixed strongyle infections elicit a mild acute phase reaction

  16. 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

  17. 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...

  18. 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

  19. Design, synthesis, and structure-activity relationships of 2-benzylidene-1-indanone derivatives as anti-inflammatory agents for treatment of acute lung injury.

    Science.gov (United States)

    Xiao, Siyang; Zhang, Wenxin; Chen, Hongjin; Fang, Bo; Qiu, Yinda; Chen, Xianxin; Chen, Lingfeng; Shu, Sheng; Zhang, Yali; Zhao, Yunjie; Liu, Zhiguo; Liang, Guang

    2018-01-01

    The purpose of this study was to design and synthesize novel 2-benzylidene-1-indanone derivatives for treatment of acute lung injury. A series of 39 novel 2-benzylidene-indanone structural derivatives were synthesized and evaluated for anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated murine primary macrophages. Most of the obtained compounds effectively inhibited the LPS-induced expression of IL-6 and TNF-α. The most active compound, 8f , was found to significantly reduce LPS-induced pulmonary inflammation, as reflected by reductions in the concentration of total protein, inflammatory cell count, as well as the lung wet/dry ratio in bronchoalveolar lavage (BAL) fluid. Furthermore, 8f effectively inhibited mRNA expression of several inflammatory cytokines after LPS challenge in vitro and in vivo. Administration of 8f also blocked LPS-induced activation of the proinflammatory NF-κB/MAPK signaling pathway. The simple synthetic preparation and biological properties of these derivatives make these 2-benzylidene-indanone scaffolds promising new entities for the development of anti-inflammatory therapeutics for the treatment of acute lung injury.

  20. Design, synthesis, and structure–activity relationships of 2-benzylidene-1-indanone derivatives as anti-inflammatory agents for treatment of acute lung injury

    Science.gov (United States)

    Chen, Hongjin; Fang, Bo; Qiu, Yinda; Chen, Xianxin; Chen, Lingfeng; Shu, Sheng; Zhang, Yali; Zhao, Yunjie; Liu, Zhiguo; Liang, Guang

    2018-01-01

    Purpose The purpose of this study was to design and synthesize novel 2-benzylidene-1-indanone derivatives for treatment of acute lung injury. Methods A series of 39 novel 2-benzylidene-indanone structural derivatives were synthesized and evaluated for anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated murine primary macrophages. Results Most of the obtained compounds effectively inhibited the LPS-induced expression of IL-6 and TNF-α. The most active compound, 8f, was found to significantly reduce LPS-induced pulmonary inflammation, as reflected by reductions in the concentration of total protein, inflammatory cell count, as well as the lung wet/dry ratio in bronchoalveolar lavage (BAL) fluid. Furthermore, 8f effectively inhibited mRNA expression of several inflammatory cytokines after LPS challenge in vitro and in vivo. Administration of 8f also blocked LPS-induced activation of the proinflammatory NF-κB/MAPK signaling pathway. Conclusion The simple synthetic preparation and biological properties of these derivatives make these 2-benzylidene-indanone scaffolds promising new entities for the development of anti-inflammatory therapeutics for the treatment of acute lung injury. PMID:29719375

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

    International Nuclear Information System (INIS)

    Okunieff, Paul; Xu Jianhua; Hu Dongping; Liu Weimin; Zhang Lurong; Morrow, Gary; Pentland, Alice; Ryan, Julie L.; Ding, Ivan M.D.

    2006-01-01

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

  2. In vitro progesterone modulation on bacterial endotoxin-induced production of IL-1β, TNFα, IL-6, IL-8, IL-10, MIP-1α, and MMP-9 in pre-labor human term placenta.

    Science.gov (United States)

    Garcia-Ruíz, G; Flores-Espinosa, P; Preciado-Martínez, E; Bermejo-Martínez, L; Espejel-Nuñez, A; Estrada-Gutierrez, G; Maida-Claros, R; Flores-Pliego, A; Zaga-Clavellina, Veronica

    2015-10-07

    During human pregnancy, infection/inflammation represents an important factor that increases the risk of developing preterm labor. The purpose of this study was to determine if pre-treatment with progesterone has an immunomodulatory effect on human placenta production of endotoxin-induced inflammation and degradation of extracellular matrix markers. Placentas were obtained under sterile conditions from pregnancies delivered at term before the onset of labor by cesarean section. Explants from central cotyledons of 10 human placentas were pre-treated with different concentrations of progesterone (0.01, 01, 1.0 μM) and then stimulated with 1000 ng/mL of LPS of Escherichia coli. Cytokines TNFα, IL-1β, IL-6, IL-8, MIP-1α, IL-10 concentrations in the culture medium were then measured by specific ELISA. Secretion profile of MMP-9 was evaluated by ELISA and zymogram. Statistical differences were determined by one-way ANOVA followed by the appropriate ad hoc test; P progesterone significantly blunted (73, 56, 56, 75, 25, 48 %) the secretion of TNF-α, IL-1β, IL-6, IL-8, MIP-1α, IL-10, respectively. The MMP-9 induced by LPS treatment was inhibited only with the highest concentration of progesterone. Mifepristone (RU486) blocked the immunosuppressive effect of progesterone. The present results support the concept that progesterone could be part of the compensatory mechanism that limits the inflammation-induced cytotoxic effects associated with an infection process during gestation.

  3. Acute Immune-Inflammatory Responses to a Single Bout of Aerobic Exercise in Smokers; The Effect of Smoking History and Status

    Science.gov (United States)

    Kastelein, Tegan Emma; Duffield, Rob; Marino, Frank E.

    2015-01-01

    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 familiarization and baseline testing, undertook an exercise protocol that involved 40 min of cycle ergometry at 50% of VO2peak. Venous blood was obtained pre- and post- (0 min, 1, and 4 h) 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 exercise, YSM demonstrated an amplified IL-6 response from immediately- to 1 h-post compared to YNS. Furthermore, IL-1ra in YSM was elevated above that of YNS across all time points (P exercise leukocyte response was greater in MSM compared to YSM and non-smokers (P smoking history (~15 years). Furthermore, the differences in exercise-induced inflammatory responses noted in YSM may be indicative tobacco smoke exposure priming circulating leukocytes to amplify inflammatory responses. PMID:26779179

  4. Effect of Dan seven soft capsule adjuvant therapy on serum inflammatory factors, coagulation function and blood rheology indexes in patients with acute hemorrhagic cerebrovascular disease

    Directory of Open Access Journals (Sweden)

    Shu-Hua Gui

    2017-08-01

    Full Text Available Objective: To investigate the effect of Dan seven soft capsule on the treatment of acute hemorrhagic cerebrovascular disease and the influence of serum inflammatory factors, coagulation function and blood rheology indexes. Methods: A total of 112 cases of patients with acute hemorrhagic cerebrovascular disease, according to the random data table were divided into the control group (n=57 and observation group (n=55, the patients in the control group received routine treatment combined with edaravone, on the basis of the treatment of the control group, the observation group was treated with Dan seven soft capsule. The serum levels of inflammatory factors, coagulation function and blood rheology indexes were compared between the two groups before and after treatment. Results: Before treatment, there were no significant difference in the inflammatory factors (hs-CRP, TNF-α and IL-6, blood coagulation function (FIB, PT and APTT and hemorheology (high cut whole blood viscosity, low cut whole blood viscosity and plasma viscosity levels between the control group and observation group. Compared with the levels of the same group before treatment, two groups of hs-CRP, TNF-α, IL-6, FIB, high cut whole blood viscosity, low cut whole blood viscosity and plasma viscosity level after treatment were significantly decreased, and levels in the observation group were significantly lower than those in the control group; Compared with the group before treatment, the levels of PT and APTT in the two groups were significantly increased, and the observation group was significantly higher than the control group. Conclusion: Dan seven soft capsule in the treatment of acute hemorrhagic cerebrovascular disease can effectively reduce the level of serum inflammatory factors, improve coagulation function and blood rheology index, it has an important clinical value.

  5. Endogenous acute phase serum amyloid A lacks pro-inflammatory activity, contrasting the two recombinant variants that activate human neutrophils through different receptors

    Directory of Open Access Journals (Sweden)

    Karin eChristenson

    2013-04-01

    Full Text Available Most notable among the acute phase proteins is serum amyloid A (SAA, levels of which can increase 1000-fold during infections, aseptic inflammation, and/or trauma. Chronically elevated SAA levels are associated with a wide variety of pathological conditions, including obesity and rheumatic diseases. Using a recombinant hybrid of the two human SAA isoforms (SAA1 and 2 that does not exist in vivo, numerous in vitro studies have given rise to the notion that acute phase SAA is a pro-inflammatory molecule with cytokine-like properties. It is however unclear whether endogenous acute phase SAA per se mediates pro-inflammatory effects. We tested this in samples from patients with inflammatory arthritis and in a transgenic mouse model that expresses human SAA1. Endogenous human SAA did not drive production of pro-inflammatory IL-8/KC in either of these settings. Human neutrophils derived from arthritis patients displayed no signs of activation, despite being exposed to severely elevated SAA levels in circulation, and SAA-rich sera also failed to activate cells in vitro. In contrast, two recombinant SAA variants (the hybrid SAA and SAA1 both activated human neutrophils, inducing L-selectin shedding, production of reactive oxygen species, and production of IL-8. The hybrid SAA was approximately 100-fold more potent than recombinant SAA1. Recombinant hybrid SAA and SAA1 activated neutrophils through different receptors, with recombinant SAA1 being a ligand for formyl peptide receptor 2 (FPR2. We conclude that even though recombinant SAAs can be valuable tools for studying neutrophil activation, they do not reflect the nature of the endogenous protein.

  6. Design, synthesis, and structure–activity relationships of 2-benzylidene-1-indanone derivatives as anti-inflammatory agents for treatment of acute lung injury

    Directory of Open Access Journals (Sweden)

    Xiao S

    2018-04-01

    Full Text Available Siyang Xiao,1,* Wenxin Zhang,1,* Hongjin Chen,1 Bo Fang,1 Yinda Qiu,2 Xianxin Chen,1 Lingfeng Chen,1 Sheng Shu,1 Yunjie Zhao,1 Zhiguo Liu,1 Guang Liang1 1Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China; 2College of Life and Environmental Science, Wenzhou University, Wenzhou, Zhejiang, China *These authors contributed equally to this work Purpose: The purpose of this study was to design and synthesize novel 2-benzylidene-1-indanone derivatives for treatment of acute lung injury. Methods: A series of 39 novel 2-benzylidene-indanone structural derivatives were synthesized and evaluated for anti-inflammatory activity in lipopolysaccharide (LPS-stimulated murine primary macrophages. Results: Most of the obtained compounds effectively inhibited the LPS-induced expression of IL-6 and TNF-α. The most active compound, 8f, was found to significantly reduce LPS-induced pulmonary inflammation, as reflected by reductions in the concentration of total protein, inflammatory cell count, as well as the lung wet/dry ratio in bronchoalveolar lavage (BAL fluid. Furthermore, 8f effectively inhibited mRNA expression of several inflammatory cytokines after LPS challenge in vitro and in vivo. Administration of 8f also blocked LPS-induced activation of the proinflammatory NF-κB/MAPK signaling pathway. Conclusion: The simple synthetic preparation and biological properties of these derivatives make these 2-benzylidene-indanone scaffolds promising new entities for the development of anti-inflammatory therapeutics for the treatment of acute lung injury. Keywords: indanone, acute lung injury, drug design, anti-inflammation, synthesis

  7. Zingerone suppresses liver inflammation induced by antibiotic mediated endotoxemia through down regulating hepatic mRNA expression of inflammatory markers in Pseudomonas aeruginosa peritonitis mouse model.

    Directory of Open Access Journals (Sweden)

    Lokender Kumar

    Full Text Available Antibiotic-induced endotoxin release is associated with high mortality rate even when appropriate antibiotics are used for the treatment of severe infections in intensive care units. Since liver is involved in systemic clearance and detoxification of endotoxin hence it becomes a primary target organ for endotoxin mediated inflammation. Currently available anti-inflammatory drugs give rise to serious side effects. Hence, there is an urgent need for safe and effective anti-inflammatory therapy. It is likely that anti-inflammatory phytochemicals and neutraceutical agents may have the potential to reduce the endotoxin mediated inflammation and complications associated with endotoxin release. Keeping this in mind, the present study was planned to evaluate the hepatoprotective potential of zingerone (active compound of zingiber officinale against liver inflammation induced by antibiotic mediated endotoxemia. The selected antibiotics capable of releasing high content of endotoxin were employed for their in vivo efficacy in P.aeruginosa peritonitis model. Released endotoxin induced inflammation and zingerone as co-anti-inflammatory therapy significantly reduced inflammatory response. Improved liver histology and reduced inflammatory markers MDA, RNI, MPO, tissue damage markers (AST, ALT, ALP and inflammatory cytokines (MIP-2, IL-6 and TNF-α were indicative of therapeutic potential of zingerone. The mechanism of action of zingerone may be related to significant inhibition of the mRNA expression of inflammatory markers (TLR4, RelA, NF-kB2, TNF- α, iNOS, COX-2 indicating that zingerone interferes with cell signalling pathway and suppresses hyper expression of cell signaling molecules of inflammatory pathway. Zingerone therapy significantly protected liver from endotoxin induced inflammatory damage by down regulating biochemical as well as molecular markers of inflammation. In conclusion, this study provides evidence that zingerone is a potent anti-inflammatory

  8. Zingerone suppresses liver inflammation induced by antibiotic mediated endotoxemia through down regulating hepatic mRNA expression of inflammatory markers in Pseudomonas aeruginosa peritonitis mouse model.

    Science.gov (United States)

    Kumar, Lokender; Chhibber, Sanjay; Harjai, Kusum

    2014-01-01

    Antibiotic-induced endotoxin release is associated with high mortality rate even when appropriate antibiotics are used for the treatment of severe infections in intensive care units. Since liver is involved in systemic clearance and detoxification of endotoxin hence it becomes a primary target organ for endotoxin mediated inflammation. Currently available anti-inflammatory drugs give rise to serious side effects. Hence, there is an urgent need for safe and effective anti-inflammatory therapy. It is likely that anti-inflammatory phytochemicals and neutraceutical agents may have the potential to reduce the endotoxin mediated inflammation and complications associated with endotoxin release. Keeping this in mind, the present study was planned to evaluate the hepatoprotective potential of zingerone (active compound of zingiber officinale) against liver inflammation induced by antibiotic mediated endotoxemia. The selected antibiotics capable of releasing high content of endotoxin were employed for their in vivo efficacy in P.aeruginosa peritonitis model. Released endotoxin induced inflammation and zingerone as co-anti-inflammatory therapy significantly reduced inflammatory response. Improved liver histology and reduced inflammatory markers MDA, RNI, MPO, tissue damage markers (AST, ALT, ALP) and inflammatory cytokines (MIP-2, IL-6 and TNF-α) were indicative of therapeutic potential of zingerone. The mechanism of action of zingerone may be related to significant inhibition of the mRNA expression of inflammatory markers (TLR4, RelA, NF-kB2, TNF- α, iNOS, COX-2) indicating that zingerone interferes with cell signalling pathway and suppresses hyper expression of cell signaling molecules of inflammatory pathway. Zingerone therapy significantly protected liver from endotoxin induced inflammatory damage by down regulating biochemical as well as molecular markers of inflammation. In conclusion, this study provides evidence that zingerone is a potent anti-inflammatory

  9. A non-inflammatory form of immune competence prevails in acute pre-pubescent malnutrition: new evidence based on critical mRNA transcripts in the mouse.

    Science.gov (United States)

    Monk, Jennifer M; Richard, Cynthia L; Woodward, Bill

    2012-05-01

    The declining inflammatory immune competence of acute (i.e. wasting) pre-pubescent protein-energy malnutrition has been regarded as reflecting an unregulated immunological disintegration. Recent evidence, however, suggests that malnutrition stimulates a regulated immunological reconfiguration to achieve a non-inflammatory form of competence, perhaps offering protection against autoimmune reactions - the 'Tolerance Model'. Our objective was to determine the influence of acute pre-pubescent malnutrition on the expression of genes critical to tolerogenic regulation. Male and female C57BL/6J mice, initially 19 d old, consumed a complete purified diet either ad libitum (age-matched controls) or in restricted daily quantities (mimicking marasmus), or consumed an isoenergetic low-protein diet ad libitum (mimicking incipient kwashiorkor) for 14 d (six animals per dietary group). Gene expression in the spleen, typically an inflammatory organ, and in the small intestine, a site designed for non-inflammatory defence, was assessed by real-time quantitative RT-PCR, and normalised to β-actin. In the spleen of the malnourished groups, both IL-10 and transforming growth factor-β1 mRNA expression increased compared with controls (P 0.05). Moreover, forkhead box P3 mRNA expression, indicative of cell-based tolerogenic potential, was sustained in both the spleen and intestine of the malnourished groups (P>0.05). Thus, despite limited supplies of energy and substrates, the spleen shifted towards a non-inflammatory character and the intestine was sustained in this mode in advanced pre-pubescent weight loss. These findings provide the first support for the Tolerance Model at the level of mRNA transcript expression.

  10. 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.

  11. 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

    2007-07-01

    alpha-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 alpha-humulene and trans-caryophyllene on the acute inflammatory responses elicited by LPS. The biological activities of alpha-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-kappaB and up-regulated expression of kinin B(1) receptors. Treatment with either alpha-humulene or trans-caryophyllene effectively reduced neutrophil migration and activation of NF-kappaB induced by LPS in the rat paw. However, only alpha-humulene significantly reduced the increase in TNF-alpha and IL-1beta levels, paw oedema and the up-regulation of B(1) receptors following treatment with LPS. Both compounds failed to interfere with the activation of the MAP kinases, ERK, p38 and JNK. Both alpha-humulene and trans-caryophyllene inhibit the LPS-induced NF-kappaB activation and neutrophil migration, although only alpha-humulene had the ability to prevent the production of pro-inflammatory cytokines TNF-alpha and IL-1beta and the in vivo up-regulation of kinin B(1) receptors. These data provide additional molecular and functional insights into the beneficial effects of the sesquiterpenes alpha-humulene and trans-caryophyllene isolated from the essential oil of Cordia verbenacea as agents for the management of inflammatory diseases.

  12. Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats

    International Nuclear Information System (INIS)

    Marín-Prida, Javier; Pavón-Fuentes, Nancy; Llópiz-Arzuaga, Alexey; Fernández-Massó, Julio R.; Delgado-Roche, Liván; Mendoza-Marí, Yssel; Santana, Seydi Pedroso; Cruz-Ramírez, Alieski; Valenzuela-Silva, Carmen; Nazábal-Gálvez, Marcelo; Cintado-Benítez, Alberto; Pardo-Andreu, Gilberto L.; Polentarutti, Nadia; Riva, Federica; Pentón-Arias, Eduardo; Pentón-Rol, Giselle

    2013-01-01

    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 2 O 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 2 O 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

  13. Tylvalosin exhibits anti-inflammatory property and attenuates acute lung injury in different models possibly through suppression of NF-κB activation.

    Science.gov (United States)

    Zhao, Zhanzhong; Tang, Xiangfang; Zhao, Xinghui; Zhang, Minhong; Zhang, Weijian; Hou, Shaohua; Yuan, Weifeng; Zhang, Hongfu; Shi, Lijun; Jia, Hong; Liang, Lin; Lai, Zhi; Gao, Junfeng; Zhang, Keyu; Fu, Ling; Chen, Wei

    2014-07-01

    Tylvalosin, a new broad-spectrum, third-generation macrolides, may exert a variety of pharmacological activities. Here, we report on its anti-oxidative and anti-inflammatory activity in RAW 264.7 macrophages and mouse treated with lipopolysaccharide (LPS) as well as piglet challenged with porcine reproductive and respiratory syndrome virus (PRRSV). Tylvalosin treatment markedly decreased IL-8, IL-6, IL-1β, PGE2, TNF-α and NO levels in vitro and in vivo. LPS and PRRSV-induced reactive oxygen species (ROS) production, and the lipid peroxidation in mice lung tissues reduced after tylvalosin treatments. In mouse acute lung injury model induced by LPS, tylvalosin administration significantly attenuated tissues injury, and reduced the inflammatory cells recruitment and activation. The evaluated phospholipase A2 (PLA2) activity and the increased expressions of cPLA2-IVA, p-cPLA2-IVA and sPLA2-IVE were lowered by tylvalosin. Consistent with the mouse results, tylvalosin pretreatment attenuated piglet lung scores with improved growth performance and normal rectal temperature in piglet model induced by PRRSV. Furthermore, tylvalosin attenuated the IκBα phosphorylation and degradation, and blocked the NF-κB p65 translocation. These results indicate that in addition to its direct antimicrobial effect, tylvalosin exhibits anti-inflammatory property and attenuates acute lung injury through suppression of NF-κB activation. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. [The effect of partial liquid ventilation on inflammatory response in piglets with acute lung injury induced by lipopolysaccharide].

    Science.gov (United States)

    Tang, Jin; Zhang, Jie; Li, Xuguang; Guo, Zhongliang

    2014-02-01

    To evaluate the effect of partial liquid ventilation (PLV) on pro-inflammatory and anti-inflammatory factors change in lipopolysaccharide (LPS)-induced piglets acute lung injury (ALI). Twelve Shanghai white piglets were randomly divided into mechanical ventilation (MV) group (n=6) and PLV group (n=6). 60 μg×kg(-1)×h(-1) LPS were intravenous infused continuously for 2 hours to induce ALI model. PLV model was set on the basis of the MV by endotracheal injection of perfluorodecalin (PFC, 10 mL/kg). The hemodynamic and respiratory parameters such as mechanics and arterial blood gas analysis were monitored at basic condition and after lung injury establishment (0, 1, 2, 4 hours). The serum levels of interleukin (IL-1β, IL-6, IL-8, IL-10) and tumor necrosis factor-α (TNF-α) were dynamically monitored by enzyme linked immunosorbent assay (ELISA). A lung injury score was used to quantify lung tissues change under light microscopic observations. Ventilation and oxygenation function were improved gradually after PFC endotracheal injection in PLV group, and there were significant difference compared with MV group at 4 hours [heart rate (HR): 144 ± 6 beats/min vs. 179 ± 9 beats/min, respiratory rate (RR): 58 ± 4 beats/min vs. 77 ± 6 beats/min, mean arterial blood pressure (MAP): 99 ± 7 mmHg vs. 75 ± 29 mmHg, dynamic lung compliance (Cdyn): 1.9 ± 0.3 mL×cmH(2)O(-1)×kg(-1) vs. 1.2 ± 0.4 mL×cmH(2)O(-1)×kg(-1), tidal volume (VT): 7.8 ± 0.4 mL/kg vs. 5.8 ± 0.9 mL/kg, mean airway resistance (Raw): 20.5 ± 6.6 cmH(2)O×L(-1)×s(-1) vs. 35.2 ± 4.0 cmH(2)O×L(-1)×s(-1), mean airway pressure (Paw): 1.0 ± 0.5 cmH(2)O vs. 3.0 ± 0.9 cmH(2)O, ventilation efficacy index (VEI): 0.18 ± 0.02 vs. 0.08 ± 0.02, pH value: 7.386 ± 0.143 vs. 7.148 ± 0.165, arterial partial pressure of oxygen (PaO(2)): 121.8 ± 12.5 mmHg vs. 73.6 ± 10.9 mmHg, arterial partial pressure of carbon dioxide (PaCO(2)): 39.6 ± 20.3 mmHg vs. 66.8 ± 23.5 mmHg, oxygenation index (PaO(2)/FiO(2

  15. 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.

  16. Definition and quantification of acute inflammatory white matter injury in the immature brain by MRI/MRS at high magnetic field.

    Science.gov (United States)

    Lodygensky, Gregory A; Kunz, Nicolas; Perroud, Elodie; Somm, Emmanuel; Mlynarik, Vladimir; Hüppi, Petra S; Gruetter, Rolf; Sizonenko, Stéphane V

    2014-03-01

    Lipopolysaccharide (LPS) injection in the corpus callosum (CC) of rat pups results in diffuse white matter injury similar to the main neuropathology of preterm infants. The aim of this study was to characterize the structural and metabolic markers of acute inflammatory injury by high-field magnetic resonance imaging (MRI) magnetic resonance spectroscopy (MRS) in vivo. Twenty-four hours after a 1-mg/kg injection of LPS in postnatal day 3 rat pups, diffusion tensor imaging and proton nuclear magnetic spectroscopy ((1)H NMR) were analyzed in conjunction to determine markers of cell death and inflammation using immunohistochemistry and gene expression. MRI and MRS in the CC revealed an increase in lactate and free lipids and a decrease of the apparent diffusion coefficient. Detailed evaluation of the CC showed a marked apoptotic response assessed by fractin expression. Interestingly, the degree of reduction in the apparent diffusion coefficient correlated strongly with the natural logarithm of fractin expression, in the same region of interest. LPS injection further resulted in increased activated microglia clustered in the cingulum, widespread astrogliosis, and increased expression of genes for interleukin (IL)-1, IL-6, and tumor necrosis factor. This model was able to reproduce the typical MRI hallmarks of acute diffuse white matter injury seen in preterm infants and allowed the evaluation of in vivo biomarkers of acute neuropathology after inflammatory challenge.

  17. 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

  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; Fidel, Paul L

    2017-03-14

    worldwide. Despite an acute inflammatory response by neutrophils during infection, the response fails to reduce the organism. Instead, the response is considered a key process underlying the symptoms of vaginitis. Therefore, it is important to determine the mechanism(s) associated with the lack of vaginal neutrophil antifungal activity. The established mouse model of Candida vaginitis was used to uncover the mechanism of neutrophil dysfunction. Results revealed that heparan sulfate present in the vagina of mice susceptible to chronic vaginitis served as a competitive ligand for the receptor (Mac-1) necessary for fungal recognition and neutrophil-mediated killing. This inhibitory function of heparan sulfate, confirmed through several approaches, provides the first evidence to explain the lack of antifungal immune reactivity during vaginal candidiasis. This finding paves the way for design of therapeutic strategies to reduce/eliminate symptomatic vaginal candidiasis and restore quality of life to those affected. Copyright © 2017 Yano et al.

  19. Casticin, an active compound isolated from Vitex Fructus, ameliorates the cigarette smoke-induced acute lung inflammatory response in a murine model.

    Science.gov (United States)

    Lee, Hyeonhoon; Jung, Kyung-Hwa; Lee, Hangyul; Park, Soojin; Choi, Woosung; Bae, Hyunsu

    2015-10-01

    The aim of this study was to determine of the effect of casticin, as an anti-inflammatory agent, on an acute lung inflammation in vivo model established through exposure to cigarette smoke (CS). Casticin is a phytochemical from Vitex species such as Vitex rotundifolia and Vitex agnus-castus that was recently shown to exert an anti-inflammatory effect in vivo. To demonstrate the effects of casticin, C57BL/6 mice were whole-body exposed to mainstream CS or fresh air for two weeks and treated with 1, 2, and 10mg/kg casticin via an i.p. injection. Immune cell infiltrations and cytokine productions were assessed from bronchoalveolar lavage Fluid (BALF), and lung histological analysis was performed. Treatment with casticin was observed to significantly inhibit the numbers of total cells, neutrophils, macrophages, and lymphocytes and reduce the levels of proinflammatory cytokines and chemokines in the BALF. In addition, casticin significantly decreased the infiltration of peribronchial and perivascular inflammatory cells and the epithelium thickness. The results of this study indicate that casticin has significant effects on the lung inflammation induced by CS in a mouse model. According to these outcomes, casticin may have therapeutic potential in inflammatory lung diseases, such as chronic obstructive pulmonary disease (COPD). Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Nonsteroidal Anti-Inflammatory Drug without Antibiotics for Acute Viral Infection Increases the Empyema Risk in Children: A Matched Case-Control Study.

    Science.gov (United States)

    Le Bourgeois, Muriel; Ferroni, Agnès; Leruez-Ville, Marianne; Varon, Emmanuelle; Thumerelle, Caroline; Brémont, François; Fayon, Michael J; Delacourt, Christophe; Ligier, Caroline; Watier, Laurence; Guillemot, Didier

    2016-08-01

    To investigate the risk factors of empyema after acute viral infection and to clarify the hypothesized association(s) between empyema and some viruses and/or the use of nonsteroidal anti-inflammatory drugs (NSAIDs). A case-control study was conducted in 15 centers. Cases and controls were enrolled for a source population of children 3-15 years of age with acute viral infections between 2006 and 2009. Among 215 empyemas, 83 cases (children with empyema and acute viral infection within the 15 preceding days) were included, and 83 controls (children with acute viral infection) were matched to cases. Considering the intake of any drug within 72 hours after acute viral infection onset and at least 6 consecutive days of antibiotic use and at least 1 day of NSAIDs exposure, the multivariable analysis retained an increased risk of empyema associated with NSAIDs exposure (aOR 2.79, 95% CI 1.4-5.58, P = .004), and a decreased risk associated with antibiotic use (aOR 0.32, 95% CI 0.11-0.97, P = .04). The risk of empyema associated with NSAIDs exposure was greater for children not prescribed an antibiotic and antibiotic intake diminished that risk for children given NSAIDs. NSAIDs use during acute viral infection is associated with an increased risk of empyema in children, and antibiotics are associated with a decreased risk. The presence of antibiotic-NSAIDs interaction with this risk is suggested. These findings suggest that NSAIDs should not be recommended as a first-line antipyretic treatment during acute viral infections in children. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Targeted nanoparticles that mimic immune cells in pain control inducing analgesic and anti-inflammatory actions: a potential novel treatment of acute and chronic pain condition.

    Science.gov (United States)

    Hua, Susan; Cabot, Peter J

    2013-01-01

    The peripheral immune-derived opioid analgesic pathway has been well established as a novel target in the clinical pain management of a number of painful pathologies, including acute inflammatory pain, neuropathic pain, and rheumatoid arthritis. Our objective was to engineer targeted nanoparticles that mimic immune cells in peripheral pain control to deliver opioids, in particular loperamide HCl, specifically to peripheral opioid receptors to induce analgesic and anti-inflammatory actions for use in painful inflammatory conditions. This peripheral analgesic system is devoid of central opioid mediated side effects (e.g., respiratory depression, sedation, dependence, tolerance). A randomized, double blind, controlled animal trial. Thirty-six adult male Wistar rats (200 - 250 g) were randomly divided into 6 groups: loperamide HCl-encapsulated anti-ICAM-1 immunoliposomes, naloxone methiodide + loperamide HCl-encapsulated anti-ICAM-1 immunoliposomes, loperamide HCl-encapsulated liposomes, empty anti-ICAM-1 immunoliposomes, empty liposomes, and loperamide solution. Animals received an intraplantar injection of 150 μL Complete Freund's Adjuvant (CFA) into the right hindpaw and experiments were performed 5 days post-CFA injection, which corresponded to the peak inflammatory response. All formulations were administered intravenously via tail vein injection. The dose administered was 200 μL, which equated to 0.8 mg of loperamide HCl for the loperamide HCl treatment groups (sub-therapeutic dose). Naloxone methiodide (1 mg/kg) was administered via intraplantar injection, 15 minutes prior to loperamide-encapsulated anti-ICAM-1 immunoliposomes. An investigator blinded to the treatment administered assessed the time course of the antinociceptive and anti-inflammatory effects using a paw pressure analgesiometer and plethysmometer, respectively. Biodistribution studies were performed 5 days post-CFA injection with anti-ICAM-1 immunoliposomes and control liposomes via tail vein

  2. The Structural Basis for Endotoxin-induced Allosteric Regulation of the Toll-like Receptor 4 (TLR4) Innate Immune Receptor*

    Science.gov (United States)

    Paramo, Teresa; Piggot, Thomas J.; Bryant, Clare E.; Bond, Peter J.

    2013-01-01

    As part of the innate immune system, Toll-like receptor 4 (TLR4) recognizes bacterial cell surface lipopolysaccharide (LPS) by forming a complex with a lipid-binding co-receptor, MD-2. In the presence of agonist, TLR4·MD-2 dimerizes to form an active receptor complex, leading to initiation of intracellular inflammatory signals. TLR4 is of great biomedical interest, but its pharmacological manipulation is complicated because even subtle variations in the structure of LPS can profoundly impact the resultant immunological response. Here, we use atomically detailed molecular simulations to gain insights into the nature of the molecular signaling mechanism. We first demonstrate that MD-2 is extraordinarily flexible. The “clamshell-like” motions of its β-cup fold enable it to sensitively match the volume of its hydrophobic cavity to the size and shape of the bound lipid moiety. We show that MD-2 allosterically transmits this conformational plasticity, in a ligand-dependent manner, to a phenylalanine residue (Phe-126) at the cavity mouth previously implicated in TLR4 activation. Remarkably, within the receptor complex, we observe spontaneous transitions between active and inactive signaling states of Phe-126, and we confirm that Phe-126 is indeed the “molecular switch” in endotoxic signaling. PMID:24178299

  3. The structural basis for endotoxin-induced allosteric regulation of the Toll-like receptor 4 (TLR4) innate immune receptor.

    Science.gov (United States)

    Paramo, Teresa; Piggot, Thomas J; Bryant, Clare E; Bond, Peter J

    2013-12-20

    As part of the innate immune system, Toll-like receptor 4 (TLR4) recognizes bacterial cell surface lipopolysaccharide (LPS) by forming a complex with a lipid-binding co-receptor, MD-2. In the presence of agonist, TLR4·MD-2 dimerizes to form an active receptor complex, leading to initiation of intracellular inflammatory signals. TLR4 is of great biomedical interest, but its pharmacological manipulation is complicated because even subtle variations in the structure of LPS can profoundly impact the resultant immunological response. Here, we use atomically detailed molecular simulations to gain insights into the nature of the molecular signaling mechanism. We first demonstrate that MD-2 is extraordinarily flexible. The "clamshell-like" motions of its β-cup fold enable it to sensitively match the volume of its hydrophobic cavity to the size and shape of the bound lipid moiety. We show that MD-2 allosterically transmits this conformational plasticity, in a ligand-dependent manner, to a phenylalanine residue (Phe-126) at the cavity mouth previously implicated in TLR4 activation. Remarkably, within the receptor complex, we observe spontaneous transitions between active and inactive signaling states of Phe-126, and we confirm that Phe-126 is indeed the "molecular switch" in endotoxic signaling.

  4. Curcumin modulates the inflammatory response and inhibits subsequent fibrosis in a mouse model of viral-induced acute respiratory distress syndrome.

    Science.gov (United States)

    Avasarala, Sreedevi; Zhang, Fangfang; Liu, Guangliang; Wang, Ruixue; London, Steven D; London, Lucille

    2013-01-01

    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(7)pfu 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.

  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

    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

  6. Comparative efficacy and safety of the non-steroidal anti-inflammatory drugs nimesulide and diclofenac in patients with acute subdeltoid bursitis and bicipital tendinitis.

    Science.gov (United States)

    Wober, W; Rahlfs, V W; Büchl, N; Grässle, A; Macciocchi, A

    1998-01-01

    The efficacy and tolerability of nimesulide, a non-steroidal anti-inflammatory drug (NSAID) 100 mg twice daily were compared with diclofenac 75 mg b.i.d. in short term treatment of acute shoulder (acute subdeltoid bursitis and bicipital tendinitis) in adult patients. In this double-blind (double-dummy), randomised, parallel group study over two weeks, 122 patients were included. The Mann-Whitney statistics revealed therapeutic equivalence of both treatments with a slight superiority for nimesulide. The tolerability of nimesulide, judged by investigators and patients and analysed statistically, was superior to that of diclofenac. Thus, the benefit-risk relationship was better for the test drug than for the reference drug.

  7. Endotoxin-Induced Inflammation Suppresses the Effect of Melatonin on the Release of LH from the Ovine Pars Tuberalis Explants—Ex Vivo Study

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    Karolina Wojtulewicz

    2017-11-01

    Full Text Available The secretion of the hormone melatonin reliably reflects environmental light conditions. Among numerous actions, in seasonal breeders, melatonin may regulate the secretion of the gonadotropins acting via its corresponding receptors occurring in the Pars Tuberalis (PT. However, it was previously found that the secretory activity of the pituitary may be dependent on the immune status of the animal. Therefore, this study was designed to determine the role of melatonin in the modulation of luteinizing hormone (LH secretion from the PT explants collected from saline- and endotoxin-treated ewes in the follicular phase of the oestrous cycle. Twelve Blackhead ewes were sacrificed 3 h after injection with lipopolysaccharide (LPS; 400 ng/kg or saline, and the PTs were collected. Each PT was cut into 4 explants, which were then divided into 4 groups: I, incubated with ‘pure’ medium 199; II, treated with gonadotropin-releasing hormone (GnRH (100 pg/mL; III, treated with melatonin (10 nmol/mL; and IV, incubated with GnRH and melatonin. Melatonin reduced (p < 0.05 GnRH-induced secretion of LH only in the PT from saline-treated ewes. Explants collected from LPS-treated ewes were characterized by lower (p < 0.05 GnRH-dependent response in LH release. It was also found that inflammation reduced the gene expression of the GnRH receptor and the MT1 melatonin receptors in the PT. Therefore, it was shown that inflammation affects the melatonin action on LH secretion from the PT, which may be one of the mechanisms via which immune/inflammatory challenges disturb reproduction processes in animals.

  8. Anti-inflammatory and antioxidant effects of infliximab on acute lung injury in a rat model of intestinal ischemia/reperfusion.

    Science.gov (United States)

    Guzel, Ahmet; Kanter, Mehmet; Guzel, Aygul; Pergel, Ahmet; Erboga, Mustafa

    2012-06-01

    The purpose of this study was to investigate the role of infliximab on acute lung injury induced by intestinal ischemia/reperfusion (I/R). A total of 30 male Wistar albino rats were divided into three groups: sham, I/R and I/R+ infliximab; each group contain 10 animals. Sham group animals underwent laparotomy without I/R injury. After I/R groups animals underwent laparotomy, 1 h of superior mesenteric artery ligation were followed by 1 h of reperfusion. In the infliximab group, 3 days before I/R, infliximab (3 mg/kg) was administered by intravenously. All animals were sacrificed at the end of reperfusion and lung tissues samples were obtained for biochemical and histopathological investigation in all groups. To date, no more biochemical and histopathological changes on intestinal I/R injury in rats by infliximab treatment have been reported. Infliximab treatment significantly decreased the elevated tissue malondialdehyde levels and increased of reduced superoxide dismutase, and glutathione peroxidase enzyme activities in lung tissues samples. Intestinal I/R caused severe histopathological injury including edema, hemorrhage, increased thickness of the alveolar wall and a great number of inflammatory cells that infiltrated the interstitium and alveoli. Infliximab treatment significantly attenuated the severity of intestinal I/R injury. Furthermore, there is a significant reduction in the activity of inducible nitric oxide synthase and arise in the expression of surfactant protein D in lung tissue of acute lung injury induced by intestinal I/R with infliximab therapy. It was concluded that infliximab treatment might be beneficial in acute lung injury, therefore, shows potential for clinical use. Because of its anti-inflammatory and antioxidant effects, infliximab pretreatment may have protective effects in acute lung injury induced by intestinal I/R.

  9. The acute-phase response and serum amyloid A inhibit the inflammatory response to Acinetobacter baumannii Pneumonia

    NARCIS (Netherlands)

    Renckens, Rosemarijn; Roelofs, Joris J. T. H.; Knapp, Sylvia; de Vos, Alex F.; Florquin, Sandrine; van der Poll, Tom

    2006-01-01

    BACKGROUND: Acinetobacter baumannii is an emerging pathogen in nosocomial pneumonia. Trauma and postsurgical patients display a profound acute-phase protein response and are susceptible to pneumonia. METHODS: To study the way in which the acute-phase response induced by sterile tissue injury

  10. 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.

  11. Botulinum toxin-induced acute anterior uveitis in a patient with Behçet's disease under infliximab treatment: a case report.

    Science.gov (United States)

    Sasajima, Hirofumi; Yagi, Syunsuke; Osada, Hiromu; Zako, Masahiro

    2017-05-04

    Injections of lipopolysaccharide in animal models generate acute anterior uveitis (also known as endotoxin-induced uveitis), but the effects of lipopolysaccharide injection are unknown in humans. We describe an unusual case in which acute anterior uveitis was dramatically activated subsequent to botulinum toxin injection in a patient with Behçet's disease but the acute anterior uveitis was satisfactorily attenuated by infliximab. A 53-year-old Japanese man had normal ocular findings at his regularly scheduled appointment. He had been diagnosed as having incomplete-type Behçet's disease 11 years before. Three years after the diagnosis he was given systemic infusions of 5 mg/kg infliximab every 8 weeks and he had not experienced a uveitis attack for 8 years with no treatment other than infliximab. Two days after the eye examination, he received intracutaneous botulinum toxin injections to treat axillary hyperhidrosis on both sides. Three hours after the injections, he noted rapidly increasing floaters in his right eye. Four days after the injections, his right eye showed severe acute anterior uveitis with deteriorated aqueous flare and anterior vitreous opacity. He received his scheduled infliximab injection, and the right acute anterior uveitis immediately attenuated. Botulinum toxin may have clinical effects similar to those of lipopolysaccharide in endotoxin-induced uveitis models. To the best of our knowledge, this is the first report to suggest that botulinum toxin may trigger acute anterior uveitis, although the precise mechanism is still unclear.

  12. Anti-inflammatory activity of Albizia lebbeck Benth., an ethnomedicinal plant, in acute and chronic animal models of inflammation.

    Science.gov (United States)

    Babu, N Prakash; Pandikumar, P; Ignacimuthu, S

    2009-09-07

    Albizia lebbeck Benth. is used both in Indian traditional system and folk medicine to treat several inflammatory pathologies such as asthma, arthritis and burns. The aim of the present study was to evaluate the scientific basis of anti-inflammatory activity of different organic solvent extracts of Albizia lebbeck. The anti-inflammatory activity of Albizia lebbeck was studied using the carrageenan, dextran, cotton pellet and Freund's complete adjuvant induced rat models. The extracts obtained using petroleum ether, chloroform and ethanol were administered at the concentrations of 100, 200 and 400mg/kg body weight. The petroleum ether and ethanol extracts at 400mg/kg, showed maximum inhibition of inflammation induced by carrageenan (petroleum ether-48.6%; ethanol-59.57%), dextran (petroleum ether-45.99%; ethanol-52.93%), cotton pellet (petroleum ether-34.46%; ethanol-53.57%) and Freund's adjuvant (petroleum ether-64.97%; ethanol-68.57%). The marked inhibitory effect on paw edema shows that Albizia lebbeck possesses remarkable anti-inflammatory activity, supporting the folkloric usage of the plant to treat various inflammatory diseases.

  13. Effect of Atorvastatin intensive therapy on the serum inflammatory factors, platelet activity and fibrinolytic activity in patients with acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Xiao-Li Zhu

    2016-05-01

    Full Text Available 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 (10mg/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.

  14. A multi-centre cohort study evaluating the role of inflammatory markers in patient’s presenting with acute ureteric colic (MIMIC

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    T.T. Shah

    Full Text Available Background: Spontaneous Stone Passage (SSP rates in acute ureteric colic range from 47 to 75%. There is conflicting evidence on the role of raised inflammatory markers in acute ureteric colic. The use of an easily applicable biomarker that could predict SSP or need for intervention would improve the management of obstructing ureteric stones. Thus, there is a need to determine in an appropriately powered study, in patients who are initially managed conservatively, which factors at the time of acute admission can predict subsequent patient outcome such as SSP and the need for intervention. Particularly, establishing whether levels of white cell count (WBC at presentation are associated with likelihood of SSP or intervention may guide clinicians on the management of these patients’ stones. Design: Multi-center cohort study disseminated via the UK British Urology Researchers in Surgical Training (BURST and Australian Young Urology Researchers Organisation (YURO. Primary research question: What is the association between WBC and SSP in patients discharged from emergency department after initial conservative management? Patient population: Patients who have presented with acute renal colic with CT KUB evidence of a solitary ureteric stone. A minimum sample size of 720 patients across 15 centres will be needed. Hypothesis: A raised WBC is associated with decreased odds of spontaneous stone passage. Primary outcome: The occurrence of SSP within six months of presentation with acute ureteric colic (YES/NO. SSP was defined as absence of need for intervention to assist stone passage. Statistical analysis plan: A multivariable logistic regression model will be constructed, where the outcome of interest is SSP using data from patients who do not undergo intervention at presentation. A random effect will be used to account for clustering of patients within hospitals/institutions. The model will include adjustments for gender, age as control variables

  15. Atorvastatin along with imipenem attenuates acute lung injury in sepsis through decrease in inflammatory mediators and bacterial load.

    Science.gov (United States)

    Choudhury, Soumen; Kandasamy, Kannan; Maruti, Bhojane Somnath; Addison, M Pule; Kasa, Jaya Kiran; Darzi, Sazad A; Singh, Thakur Uttam; Parida, Subhashree; Dash, Jeevan Ranjan; Singh, Vishakha; Mishra, Santosh Kumar

    2015-10-15

    Lung is one of the vital organs which is affected during the sequential development of multi-organ dysfunction in sepsis. The purpose of the present study was to examine whether combined treatment with atorvastatin and imipenem could attenuate sepsis-induced lung injury in mice. Sepsis was induced by caecal ligation and puncture. Lung injury was assessed by the presence of lung edema, increased vascular permeability, increased inflammatory cell infiltration and cytokine levels in broncho-alveolar lavage fluid (BALF). Treatment with atorvastatin along with imipenem reduced the lung bacterial load and pro-inflammatory cytokines (IL-1β and TNFα) level in BALF. The markers of pulmonary edema such as microvascular leakage and wet-dry weight ratio were also attenuated. This was further confirmed by the reduced activity of MPO and ICAM-1 mRNA expression, indicating the lesser infiltration and adhesion of inflammatory cells to the lungs. Again, expression of mRNA and protein level of iNOS in lungs was also reduced in the combined treatment group. Based on the above findings it can be concluded that, combined treatment with atorvastatin and imipenem dampened the inflammatory response and reduced the bacterial load, thus seems to have promising therapeutic potential in sepsis-induced lung injury in mice. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. 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.

  17. A hot water extract of turmeric (Curcuma longa) suppresses acute ethanol-induced liver injury in mice by inhibiting hepatic oxidative stress and inflammatory cytokine production.

    Science.gov (United States)

    Uchio, Ryusei; Higashi, Yohei; Kohama, Yusuke; Kawasaki, Kengo; Hirao, Takashi; Muroyama, Koutarou; Murosaki, Shinji

    2017-01-01

    Turmeric ( Curcuma longa ) is a widely used spice that has various biological effects, and aqueous extracts of turmeric exhibit potent antioxidant activity and anti-inflammatory activity. Bisacurone, a component of turmeric extract, is known to have similar effects. Oxidative stress and inflammatory cytokines play an important role in ethanol-induced liver injury. This study was performed to evaluate the influence of a hot water extract of C. longa (WEC) or bisacurone on acute ethanol-induced liver injury. C57BL/6 mice were orally administered WEC (20 mg/kg body weight; BW) or bisacurone (60 µg/kg BW) at 30 min before a single dose of ethanol was given by oral administration (3·0 g/kg BW). Plasma levels of aspartate aminotransferase and alanine aminotransferase were markedly increased in ethanol-treated mice, while the increase of these enzymes was significantly suppressed by prior administration of WEC. The increase of alanine aminotransferase was also significantly suppressed by pretreatment with bisacurone. Compared with control mice, animals given WEC had higher hepatic tissue levels of superoxide dismutase and glutathione, as well as lower hepatic tissue levels of thiobarbituric acid-reactive substances, TNF-α protein and IL-6 mRNA. These results suggest that oral administration of WEC may have a protective effect against ethanol-induced liver injury by suppressing hepatic oxidation and inflammation, at least partly through the effects of bisacurone.

  18. Effects of melatonin on the acute inflammatory response associated with endoscopic retrograde cholangiopancreatography: A randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Hernández-Velázquez, B; Camara-Lemarroy, C R; González-González, J A; García-Compean, D; Monreal-Robles, R; Cordero-Pérez, P; Muñoz-Espinosa, L E

    2016-01-01

    Endoscopic retrograde cholangiopancreatography (ERCP) is associated with an acute inflammatory response and melatonin has a variety of immunomodulatory and antioxidant effects studied experimentally in pancreatobiliary pathology. The aim of our study was to evaluate the effects of peri-procedural administration of melatonin on the inflammatory response and lipid peroxidation associated with ERCP. In this proof-of-concept clinical trial, 37 patients with a high probability of choledocholithiasis were randomized to receive peri-procedure (ERCP) melatonin or placebo. We measured the serum concentration of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), lipid peroxidation, amylase, and liver function tests 24h before and after the procedure. We found no pre-procedure or post-procedure differences between the melatonin group or the placebo group (P>.05) in the serum concentrations of TNF-alpha (melatonin: 153.8 vs. 149.4ng/m; placebo: 103.5 vs. 107.3ng/ml), IL-6 (melatonin: 131.8 vs. 133.3ng/ml; placebo: 177.8 vs. 197.8ng/ml), or VEGF (melatonin: 157.3 vs. 157.8pg/ml; placebo: 97.3 vs. 97.8pg/ml), or in relation to lipid peroxidation (melatonin: 39.2 vs. 72.3μg/ml; placebo: 66.4 vs. 90.5μg/ml). After ERCP, a significant decrease in the AST, ALT, and total bilirubin levels was found only in the melatonin group (P<.05). The administration of melatonin was safe and tolerable. Melatonin is safe and tolerable in patients undergoing ERCP, but it does not appear to affect inflammatory cytokine concentrations or lipid peroxidation. Copyright © 2016 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  19. Cortical Astrocytes Acutely Exposed to the Monomethylarsonous Acid (MMAIII) Show Increased Pro-inflammatory Cytokines Gene Expression that is Consistent with APP and BACE-1: Over-expression.

    Science.gov (United States)

    Escudero-Lourdes, C; Uresti-Rivera, E E; Oliva-González, C; Torres-Ramos, M A; Aguirre-Bañuelos, P; Gandolfi, A J

    2016-10-01

    Long-term exposure to inorganic arsenic (iAs) through drinking water has been associated with cognitive impairment in children and adults; however, the related pathogenic mechanisms have not been completely described. Increased or chronic inflammation in the brain is linked to impaired cognition and neurodegeneration; iAs induces strong inflammatory responses in several cells, but this effect has been poorly evaluated in central nervous system (CNS) cells. Because astrocytes are the most abundant cells in the CNS and play a critical role in brain homeostasis, including regulation of the inflammatory response, any functional impairment in them can be deleterious for the brain. We propose that iAs could induce cognitive impairment through inflammatory response activation in astrocytes. In the present work, rat cortical astrocytes were acutely exposed in vitro to the monomethylated metabolite of iAs (MMA III ), which accumulates in glial cells without compromising cell viability. MMA III LD 50 in astrocytes was 10.52 μM, however, exposure to sub-toxic MMA III concentrations (50-1000 nM) significantly increased IL-1β, IL-6, TNF-α, COX-2, and MIF-1 gene expression. These effects were consistent with amyloid precursor protein (APP) and β-secretase (BACE-1) increased gene expression, mainly for those MMA III concentrations that also induced TNF-α over-expression. Other effects of MMA III on cortical astrocytes included increased proliferative and metabolic activity. All tested MMA III concentrations led to an inhibition of intracellular lactate dehydrogenase (LDH) activity. Results suggest that MMA III induces important metabolic and functional changes in astrocytes that may affect brain homeostasis and that inflammation may play a major role in cognitive impairment-related pathogenicity in As-exposed populations.

  20. Similar Anti-Inflammatory Acute Responses from Moderate-Intensity Continuous and High-Intensity Intermittent Exercise

    Directory of Open Access Journals (Sweden)

    Carolina Cabral-Santos, José Gerosa-Neto, Daniela Sayuri Inoue, Valéria Leme Gonçalves Panissa, Luís Alberto Gobbo, Alessandro Moura Zagatto, Eduardo Zapaterra Campos, Fábio Santos Lira

    2015-12-01

    Full Text Available The purpose of this study was to compare the effect of high-intensity intermittent exercise (HIIE versus volume matched steady state exercise (SSE on inflammatory and metabolic responses. Eight physically active male subjects completed two experimental sessions, a 5-km run on a treadmill either continuously (70% vVO2max or intermittently (1:1 min at vVO2max. Blood samples were collected at rest, immediately, 30 and 60 minutes after the exercise session. Blood was analyzed for glucose, non-ester fatty acid (NEFA, uric acid, lactate, cortisol, and cytokines (IL-6, IL-10 and TNF-α levels. The lactate levels exhibited higher values immediately post-exercise than at rest (HIIE 1.34 ± 0.24 to 7.11 ± 2.85, and SSE 1.35 ± 0.14 to 4.06±1.60 mmol·L-1, p 0.05. Cortisol, IL-6, IL-10 and TNF-α levels showed time-dependent changes under the different conditions (p < 0.05, however, the area under the curve of TNF-α in the SSE were higher than HIIE (p < 0.05, and the area under the curve of IL-6 in the HIIE showed higher values than SSE (p < 0.05. In addition, both exercise conditions promote increased IL-10 levels and IL-10/TNF-α ratio (p < 0.05. In conclusion, our results demonstrated that both exercise protocols, when volume is matched, promote similar inflammatory responses, leading to an anti-inflammatory status; however, the metabolic responses are different.

  1. Acrolein Inhalation Suppresses Lipopolysaccharide-Induced Inflammatory Cytokine Production but Does Not Affect Acute Airways Neutrophilia1

    OpenAIRE

    Kasahara, David Itiro; Poynter, Matthew E.; Othman, Ziryan; Hemenway, David; van der Vliet, Albert

    2008-01-01

    Acrolein is a reactive unsaturated aldehyde that is produced during endogenous oxidative processes and is a major bioactive component of environmental pollutants such as cigarette smoke. Because in vitro studies demonstrate that acrolein can inhibit neutrophil apoptosis, we evaluated the effects of in vivo acrolein exposure on acute lung inflammation induced by LPS. Male C57BL/6J mice received 300 μg/kg intratracheal LPS and were exposed to acrolein (5 parts per million, 6 h/day), either befo...

  2. Anti-inflammatory effect of diclofenac diethylammonium gel on acute phase of ligature induced periodontitis in rats

    OpenAIRE

    Botelho, Marco A.; Paixão, Mônica S.; Rachid, Ítalo; Bannet, Leonard Edward; Patrus, Ana Helena; Mattos, Thiago Borges; Queiroz, Dinalva; Ruela, Ronaldo; Costa, Jose M. C; Quintans Júnior, Lucindo José

    2010-01-01

    This study aimed to evaluate the effect of a diclofenac diethylammonium gel 10 mg/g (DD) on acute phase of ligature induced periodontitis model in rats. Experimental Periodontitis Disease (EPD) was induced in 30 Wistar rats subjected to ligature placement on left molars. Animals were treated with (DD), immediately after (EPD) induction. Saline-based gel (SG) was utilized as negative control and DD gel 10 mg/g was the tested substance. Animals were randomly assigned into the groups. The period...

  3. Effects of Prolastin C (Plasma-Derived Alpha-1 Antitrypsin) on the acute inflammatory response in patients with ST-segment elevation myocardial infarction (from the VCU-alpha 1-RT pilot study)

    NARCIS (Netherlands)

    Abbate, A.; Tassell, B.W. Van; Christopher, S.; Abouzaki, N.A.; Sonnino, C.; Oddi, C.; Carbone, S.; Melchior, R.D.; Gambill, M.L.; Roberts, C.S.; Kontos, M.C.; Peberdy, M.A.; Toldo, S.; Vetrovec, G.W.; Biondi-Zoccai, G.; Dinarello, C.A.

    2015-01-01

    Alpha-1 antitrypsin (AAT) has broad anti-inflammatory and immunomodulating properties in addition to inhibiting serine proteases. Administration of human plasma-derived AAT is protective in models of acute myocardial infarction in mice. The objective of this study was to determine the safety and

  4. Huperzine A ameliorates damage induced by acute myocardial infarction in rats through antioxidant, anti-apoptotic and anti-inflammatory mechanisms.

    Science.gov (United States)

    Sui, Xizhong; Gao, Changqing

    2014-01-01

    Huperzine A (HupA), an alkaloid used in traditional Chinese medicine and isolated from Huperzia serrata, has been shown to possess diverse biological activities. The present study was undertaken to evaluate the cardioprotective potential of HupA in myocardial ischemic damage using a rat model of acute myocardial infarction. HupA significantly diminished the infarct size and inhibited the activities of myocardial enzymes, including creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT). A significantly reduced activity of malondialdehyde (MDA) and elevated activities of superoxide dismutase (SOD), of the non-enzymatic scavenger enzyme, glutathione (GSH), as well as of glutathione peroxidase (GSH-PX) were found in the HupA-treated groups. Furthermore, decreased protein levels of caspase-3 and Bax, and increased levels of Bcl-2 were observed in the infarcted hearts of the rats treated with various concentrations of HupA. In addition, treatment with HupA markedly inhibited the expression of the nuclear factor-κB (NF-κB) subunit p65, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). These findings suggest that the cardioprotective potential of HupA is associated with its antioxidant, anti-apoptotic and anti-inflammatory properties in acute myocardial infarction in rats.

  5. Circulating microparticles in acute diabetic Charcot foot exhibit a high content of inflammatory cytokines, and support monocyte-to-osteoclast cell induction.

    Science.gov (United States)

    Pasquier, Jennifer; Thomas, Binitha; Hoarau-Véchot, Jessica; Odeh, Tala; Robay, Amal; Chidiac, Omar; Dargham, Soha R; Turjoman, Rebal; Halama, Anna; Fakhro, Khalid; Menzies, Robert; Jayyousi, Amin; Zirie, Mahmoud; Al Suwaidi, Jassim; Rafii, Arash; Malik, Rayaz A; Talal, Talal; Abi Khalil, Charbel

    2017-11-27

    Circulating microparticles (MPs) are major mediators in cardiovascular complications of type 2 diabetes (T2D); however, their contribution to Charcot foot (CF) disease is not known. Here, we purified and assessed the origin, concentration and content of circulating MPs from 33 individuals: 11 with T2D and acute CF, 11 T2D patients with equivalent neuropathy and 11 non-diabetic controls. First, we demonstrated that there were no differences in the distribution of MPs of endothelial, platelet origin among the 3 groups. However, MPs from leukocytes and monocytes origin were increased in CF patients. Moreover, we demonstrated that monocytes-derived MPs originated more frequently from intermediate and non-classical monocytes in CF patients. Five cytokines (G-CSF, GM-CSF, IL-1-ra, IL-2 and IL-16) were significantly increased in MPs from acute CF patients. Applying ingenuity pathways analysis, we found that those cytokines interacted well and induced the activation of pathways that are involved in osteoclast formation. Further, we treated THP-1 monocytes and monocytes sorted from healthy patients with CF-derived MPs during their differentiation into osteoclasts, which increased their differentiation into multinucleated osteoclast-like cells. Altogether, our study suggests that circulating MPs in CF disease have a high content of inflammatory cytokines and could increase osteoclast differentiation in vitro.

  6. Curcumin attenuates acute inflammatory injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway in experimental traumatic brain injury

    Science.gov (United States)

    2014-01-01

    Background Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to substantial neuronal damage and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of thiscascade. In the current study, we tested the hypothesis that curcumin, a phytochemical compound with potent anti-inflammatory properties that is extracted from the rhizome Curcuma longa, alleviates acute inflammatory injury mediated by TLR4 following TBI. Methods Neurological function, brain water content and cytokine levels were tested in TLR4-/- mice subjected to weight-drop contusion injury. Wild-type (WT) mice were injected intraperitoneally with different concentrations of curcumin or vehicle 15 minutes after TBI. At 24 hours post-injury, the activation of microglia/macrophages and TLR4 was detected by immunohistochemistry; neuronal apoptosis was measured by FJB and TUNEL staining; cytokines were assayed by ELISA; and TLR4, MyD88 and NF-κB levels were measured by Western blotting. In vitro, a co-culture system comprised of microglia and neurons was treated with curcumin following lipopolysaccharide (LPS) stimulation. TLR4 expression and morphological activation in microglia and morphological damage to neurons were detected by immunohistochemistry 24 hours post-stimulation. Results The protein expression of TLR4 in pericontusional tissue reached a maximum at 24 hours post-TBI. Compared with WT mice, TLR4-/- mice showed attenuated functional impairment, brain edema and cytokine release post-TBI. In addition to improvement in the above aspects, 100 mg/kg curcumin treatment post-TBI significantly reduced the number of TLR4-positive microglia/macrophages as well as inflammatory mediator release and neuronal apoptosis in WT mice. Furthermore, Western blot analysis indicated that the levels of TLR4 and its known downstream effectors (MyD88, and NF-κB) were also decreased after curcumin treatment. Similar outcomes were observed in the microglia and

  7. Solanum paranense Extracts and Solanine Present Anti-Inflammatory Activity in an Acute Skin Inflammation Model in Mice

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    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.

  8. Effects of edaravone combined with hyperbaric oxygen on cerebral vascular dynamics, oxidative stress products and inflammatory factors in patients with acute cerebral hemorrhage

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    Xia Li

    2017-10-01

    Full Text Available Objective: To investigate the effect of edaravone combined with hyperbaric oxygen therapy on cerebral vasculature, oxidative stress and inflammatory cytokines in patients with acute cerebral hemorrhage (ACH. Methods: A total of 96 patients with ACH were divided into control group (n=48 and observation group (n=48 according to the random number table. Both groups were treated routinely. On this basis, the control group was treated with edaravone injection, and the observation group was treated with edaravone injection combined with hyperbaric oxygen therapy. The change of cerebrovascular dynamics, oxidative stress products and inflammatory factors were examined in all subjects before and after treatment. Results: There were no significant differences in cerebrovascular function between the two groups before treatment. After treatment, the levels of Vmean and Qmean in both groups were significantly higher than those before treatment. The levels of Vmean and Qmean in the observation group were higher than those of the control group after treatment. There was no significant difference in serum oxidative stress between the two groups before treatment. After treatment, the levels of SOD in two groups were significantly higher than those before treatment. The level of SOD in the observation group was higher than that in the control group after treatment. After treatment, the levels of MDA in the two groups were significantly lower than that before treatment. The level of MDA in the observation group was lower than that of the control group after treatment. There were no significant differences in the level of serum inflammatory factors between the two groups before treatment. After treatment, the level of TNF-α and IL-1β in two groups were significantly lower than before treatment. The level of TNF-α and IL-1β in the observation group was lower than those of the control group after treatment. Conclusion: Edaravone combined with hyperbaric oxygen

  9. Severe Sepsis and Acute Myocardial Dysfunction in an Adolescent with Chlamydia Trachomatis Pelvic Inflammatory Disease: A Case Report.

    Science.gov (United States)

    Morgan, Ashley M; Roden, R Claire; Matson, Steven C; Wallace, Grant M; Lange, Hannah L H; Bonny, Andrea E

    2018-04-01

    Although generally asymptomatic, severe Chlamydia trachomatis (C. trachomatis) infections have been documented. C. trachomatis has been associated with myocarditis as well as sepsis. A 19-year-old girl with type 1 diabetes mellitus developed sudden-onset mental status change and shock after resolution of diabetic ketoacidosis. Abdominal and pelvic imaging showed uterine and adnexal inflammation, and pelvic examination confirmed a diagnosis of pelvic inflammatory disease. The patient was intubated, required vasopressor support, and developed severe biventricular myocardial dysfunction. Infectious myocarditis workup was negative. Nucleic acid amplification testing from vaginal discharge was positive for C. trachomatis and Trichomonas vaginalis and negative for Neisseria gonorrhoeae. C. trachomatis should be considered in the workup of septic shock, particularly in populations at high risk for sexually transmitted infections. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  10. Systemic oxidative-nitrosative-inflammatory stress during acute exercise in hypoxia; implications for microvascular oxygenation and aerobic capacity.

    Science.gov (United States)

    Woodside, John D S; Gutowski, Mariusz; Fall, Lewis; James, Philip E; McEneny, Jane; Young, Ian S; Ogoh, Shigehiko; Bailey, Damian M

    2014-12-01

    Exercise performance in hypoxia may be limited by a critical reduction in cerebral and skeletal tissue oxygenation, although the underlying mechanisms remain unclear. We examined whether increased systemic free radical accumulation during hypoxia would be associated with elevated microvascular deoxygenation and reduced maximal aerobic capacity (V̇O2 max ). Eleven healthy men were randomly assigned single-blind to an incremental semi-recumbent cycling test to determine V̇O2 max in both normoxia (21% O2) and hypoxia (12% O2) separated by a week. Continuous-wave near-infrared spectroscopy was employed to monitor concentration changes in oxy- and deoxyhaemoglobin in the left vastus lateralis muscle and frontal cerebral cortex. Antecubital venous blood samples were obtained at rest and at V̇O2 max to determine oxidative (ascorbate radical by electron paramagnetic resonance spectroscopy), nitrosative (nitric oxide metabolites by ozone-based chemiluminescence and 3-nitrotyrosine by enzyme-linked immunosorbent assay) and inflammatory stress biomarkers (soluble intercellular/vascular cell adhesion 1 molecules by enzyme-linked immunosorbent assay). Hypoxia was associated with increased cerebral and muscle tissue deoxygenation and lower V̇O2 max (P exercise-induced increase in oxidative-nitrosative-inflammatory stress, hypoxia per se did not have an additive effect (P > 0.05 versus normoxia). Consequently, we failed to observe correlations between any metabolic, haemodynamic and cardiorespiratory parameters (P > 0.05). Collectively, these findings suggest that altered free radical metabolism cannot explain the elevated microvascular deoxygenation and corresponding lower V̇O2 max in hypoxia. Further research is required to determine whether free radicals when present in excess do indeed contribute to the premature termination of exercise in hypoxia. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

  11. Agmatine Protects against Zymosan-Induced Acute Lung Injury in Mice by Inhibiting NF-κB-Mediated Inflammatory Response

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    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.

  12. Agmatine protects against zymosan-induced acute lung injury in mice by inhibiting NF-κB-mediated inflammatory response.

    Science.gov (United States)

    Li, Xuanfei; Liu, Zheng; Jin, He; Fan, Xia; Yang, Xue; Tang, Wanqi; Yan, Jun; Liang, Huaping

    2014-01-01

    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.

  13. The cholinergic pathway alleviates acute oxygen and glucose deprivation induced renal tubular cell injury by reducing the secretion of inflammatory medium of macrophages

    Directory of Open Access Journals (Sweden)

    Ming WU

    2017-10-01

    Full Text Available Objective To investigate the effects of cholinergic pathway on acute renal tubular cell injury induced by acute oxygen and glucose deprivation. Methods Rat kidney macrophages were isolated and cultured for constructing macrophages and renal epithelial cells co-cultivating model of oxygen-glucose deprivation (OGD, and the model cells were divided into three groups: OGD alone group, acetylcholine (ACh 100μmol/L+OGD group and ACh + galantamine (Gal 10μmol/L+OGD group. The cells underwent OGD treatment for 1 hour, and normally cultured for 24 hours. The expressions of TNF alpha, IL-1 beta, and IL-10 in supernatant fluid were detected by ELISA, the renal tubular cell viability was determined by MTT assay, the expression of acetylcholine esterase (AChE mRNA and protein were determined by RT-qPCR and Western blotting. The activity of AChE was determined by colorimetric method. Results The expressions of TNF alpha (pg/ml in OGD, Ach+OGD group, Ach+Gal+OGD groups were 140.2±44.81, 119.46±4.42 and 103.31±1.62 respectively (P0.05; The values of renal tubular cell proliferation were 55.02%±6.28%, 66.65%±6.47%, and 79.75%±4.22% respectively (P0.05; those of AchE protein were 0.66±0.07, 0.74±0.04 and 0.67±0.06 respectively (P>0.05; The activity of AChE (kU/L was 0.51±0.02, 0.35±0.05 and 0.32±0.04 respectively (P=0.001, 0.001 and 0.368. Conclusions ACh and Gal could inhibit the secretion of inflammatory mediators and cholinesterase activity and can reduce the acute hypoxic renal tubular cell injury. The modulation of the cholinergic pathway in macrophages may be the important treatment method for acute renal injury in the future. DOI: 10.11855/j.issn.0577-7402.2017.08.01

  14. PROTEOSE INTOXICATIONS AND INJURY OF BODY PROTEIN : V. THE INCREASE IN NON-PROTEIN NITROGEN OF THE BLOOD IN ACUTE INFLAMMATORY PROCESSES AND ACUTE INTOXICATIONS.

    Science.gov (United States)

    Cooke, J V; Whipple, G H

    1918-08-01

    Sterile abscess formation in the dog is accompanied by a large increase in output of urinary nitrogen and also by a small but definite increase in the blood non-protein nitrogen. All this nitrogenous material of course is derived from body protein injury and autolysis. Septic inflammation in the dog (pleurisy, pneumonia, peritonitis, etc.) likewise shows a distinct rise in the blood non-protein nitrogen. This rise is not often so great as that frequently observed in the intoxication of intestinal obstruction. Many acute infections in man (septicemia, peritonitis, pneumonia, etc.) show a definite rise in the non-protein nitrogen and urea nitrogen of the blood; some cases show a very great rise above normal (over 100 mg. of non-protein nitrogen per 100 cc. of blood). There may be no anatomical change in the kidney beyond the familiar picture of cloudy swelling. This does not exclude the possibility of some transient functional derangement of the kidney epithelium. Certain obscure intoxications in man may show a considerable rise in the non-protein nitrogen of the blood, indicating a large amount of protein disintegration. These findings must be taken into account in any clinical analysis and interpretation of high non-protein nitrogen of the blood in pathological conditions.

  15. Plant derived aporphinic alkaloid S-(+-dicentrine induces antinociceptive effect in both acute and chronic inflammatory pain models: evidence for a role of TRPA1 channels.

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    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.

  16. Value of electroneurography as a prognostic indicator for recovery in acute severe inflammatory facial paralysis: a prospective study of Bell's palsy and Ramsay Hunt syndrome.

    Science.gov (United States)

    Byun, Hayoung; Cho, Yang-Sun; Jang, Jeon Yeob; Chung, Kyu Whan; Hwang, Soojin; Chung, Won-Ho; Hong, Sung Hwa

    2013-10-01

    To evaluate the prognostic and predictive value of electroneuronography (ENoG) in acute severe inflammatory facial paralysis, including Bell's palsy and Ramsay Hunt syndrome (RHS). Prospective observational study. Patients with acute severe facial paralysis of House-Brackmann (H-B) grade IV or worse and diagnosed with Bell's palsy or RHS were enrolled from August 2007 to July 2011. After treatment with oral corticosteroid, antiviral agent, and protective eye care, patients were followed up until recovery or 12 months from onset. Sixty-six patients with Bell's palsy and 22 with RHS were included. Multiple logistic regression analysis showed significant effect of ENoG value on recovery in both Bell's palsy and RHS. Values of ENoG were significantly worse in RHS than Bell's palsy. Chance of early recovery within 6 weeks after correction of ENoG effect was still significantly worse in RHS. Logistic regression analysis showed 90% chance of recovery within 6 months, expected with ENoG values of 69.2% degeneration (Bell's palsy) and 59.3% (RHS). The receiver operating characteristics (ROC) curves showed ENoG values of 82.5% (Bell's palsy) and 78.0% (RHS) as a critical cutoff value of nonrecovery until 1 year, with the best sensitivity and specificity. A higher chance of recovery was expected with better ENoG in Bell's palsy and RHS. Based on our data, nonrecovery is predicted in patients with ENoG value greater than 82.5% in Bell's palsy, and 78% in RHS. 4. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  17. 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.

  18. 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

    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......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...... (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...

  19. Inflammatory early events associated to the role of P2X7 receptor in acute murine toxoplasmosis.

    Science.gov (United States)

    Corrêa, Gladys; Almeida Lindenberg, Carolina de; Moreira-Souza, Aline Cristina de Abreu; Savio, Luiz Eduardo Baggio; Takiya, Christina Maeda; Marques-da-Silva, Camila; Vommaro, Rossiane Claudia; Coutinho-Silva, Robson

    2017-04-01

    Activation of the purinergic P2X7 receptor by extracellular ATP (eATP) potentiates proinflammatory responses during infections by intracellular pathogens. Extracellular ATP triggers an antimicrobial response in macrophages infected with Toxoplasma gondii in vitro, suggesting that purinergic signaling may stimulate host defense mechanisms against toxoplasmosis. Here, we provide in vivo evidence in support of this hypothesis, by showing that P2X7 -/- mice are more susceptible than P2X7 +/+ mice to acute infection by the RH strain of T. gondii, and that this phenomenon is associated with a deficient proinflammatory response. Four days post-infection, peritoneal washes from infected P2X7 -/- mice had no or little increase in the levels of the proinflammatory cytokines IL-12, IL-1β, IFN-γ, and TNF-α, whose levels increased markedly in samples from infected P2X7 +/+ mice. Infected P2X7 -/- mice displayed an increase in organ weight and histological alterations in some of the 'shock organs' in toxoplasmosis - the liver, spleen and mesenteric lymph nodes. The liver of infected P2X7 -/- mice had smaller granulomas, but increased parasite load/granuloma. Our results confirm that the P2X7 receptor is involved in containing T. gondii spread in vivo, by stimulating inflammation. Copyright © 2016 Elsevier GmbH. All rights reserved.

  20. 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. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Anti-inflammatory effect of Helichrysum oligocephalum DC extract on acetic acid - Induced acute colitis in rats

    Directory of Open Access Journals (Sweden)

    Mohsen Minaiyan

    2014-01-01

    Full Text Available Background: Helichrysum oligocephalum DC. from Asteraceae family is an endemic plant growing wild in Iran. This study was carried out to investigate the effect of H. oligocephalum hydroalcoholic extract (HOHE on ulcerative colitis (UC induced by acetic acid (AA in rats. Materials and Methods: Rats were grouped (n = 6 and fasted for 24 h before colitis induction. Treatments were started 2 h before the induction of colitis and continued for two consecutive days with different doses of HOHE (100, 200, and 400 mg/kg orally (p.o. and intraperitoneally (i.p.. The colon tissue was removed and tissue damages were scored after macroscopic and histopathologic assessments. Results: Among the examined doses of HOHE, 100 mg/kg was the most effective dose that reduced the extent of UC lesions and resulted in significant alleviation. Weight/length ratio as an index of tissue inflammation and extravasation was also diminished in the treatment group administered HOHE at a dose of 100 mg/kg, and the results showed correlation with macroscopic and histopathologic evaluations. These data suggest that HOHE (100 mg/kg administered either p.o. or i.p. was effective in diminishing inflammation and ulcer indices in this murine model of acute colitis in a non-dose-related manner. Conclusions: H. oligocephalum could be considered as a suitable anticolitis alternative; however, further studies are needed to support this hypothesis for clinical setting.

  2. Anti-inflammatory effect of Helichrysum oligocephalum DC extract on acetic acid — Induced acute colitis in rats

    Science.gov (United States)

    Minaiyan, Mohsen; Ghassemi-Dehkordi, Nasrollah; Mahzouni, Parvin; Ahmadi, Najme-Sadat

    2014-01-01

    Background: Helichrysum oligocephalum DC. from Asteraceae family is an endemic plant growing wild in Iran. This study was carried out to investigate the effect of H. oligocephalum hydroalcoholic extract (HOHE) on ulcerative colitis (UC) induced by acetic acid (AA) in rats. Materials and Methods: Rats were grouped (n = 6) and fasted for 24 h before colitis induction. Treatments were started 2 h before the induction of colitis and continued for two consecutive days with different doses of HOHE (100, 200, and 400 mg/kg) orally (p.o.) and intraperitoneally (i.p.). The colon tissue was removed and tissue damages were scored after macroscopic and histopathologic assessments. Results: Among the examined doses of HOHE, 100 mg/kg was the most effective dose that reduced the extent of UC lesions and resulted in significant alleviation. Weight/length ratio as an index of tissue inflammation and extravasation was also diminished in the treatment group administered HOHE at a dose of 100 mg/kg, and the results showed correlation with macroscopic and histopathologic evaluations. These data suggest that HOHE (100 mg/kg) administered either p.o. or i.p. was effective in diminishing inflammation and ulcer indices in this murine model of acute colitis in a non–dose-related manner. Conclusions: H. oligocephalum could be considered as a suitable anticolitis alternative; however, further studies are needed to support this hypothesis for clinical setting. PMID:24761395

  3. Impact of a cardiac rehabilitation program and inflammatory state on endothelial progenitor cells in acute coronary syndrome patients.

    Science.gov (United States)

    Cesari, Francesca; Marcucci, Rossella; Gori, Anna Maria; Burgisser, Costanza; Francini, Sara; Sofi, Francesco; Gensini, Gian Franco; Abbate, Rosanna; Fattirolli, Francesco

    2013-09-01

    Among the benefits of a cardiac rehabilitation (CR) program for patients after an acute coronary syndrome (ACS) is the mobilization of endothelial progenitor cells (EPCs). However not all patients respond to CR with an increase of EPC. We performed this study to identify the characteristics of patients who will not benefit from an increase of EPCs at the end of a CR program. 112 ACS patients were admitted to a four-week CR program. EPCs, high sensitivity C-reactive protein (hsCRP) and NT-ProBNP levels were determined at the beginning (T1) and at the end (T2) of the CR program. All patients performed a cardiopulmonary exercise test at T1 and at T2. EPCs were defined as CD34+KDR+, CD133+KDR+ and CD34+CD133+KDR+. hsCRP and NT-ProBNP were measured by nephelometric and immunometric method, respectively. At T2, we observed a significant increase of EPCs (p=0.001), VO2 peak, Watt max HDL-cholesterol (pprogram. A CR program determines an increase of EPCs with a decrease of CRP and NT-ProBNP. A different trend for EPCs can be detected among patients correlated to CRP levels and exercise tolerance. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. Endogenous PGI2 signaling through IP inhibits neutrophilic lung inflammation in LPS-induced acute lung injury mice model.

    Science.gov (United States)

    Toki, Shinji; Zhou, Weisong; Goleniewska, Kasia; Reiss, Sara; Dulek, Daniel E; Newcomb, Dawn C; Lawson, William E; Peebles, R Stokes

    2018-04-13

    Endogenous prostaglandin I 2 (PGI 2 ) has inhibitory effects on immune responses against pathogens or allergens; however, the immunomodulatory activity of endogenous PGI 2 signaling in endotoxin-induced inflammation is unknown. To test the hypothesis that endogenous PGI 2 down-regulates endotoxin-induced lung inflammation, C57BL/6 wild type (WT) and PGI 2 receptor (IP) KO mice were challenged intranasally with LPS. Urine 6-keto-PGF 1α , a stable metabolite of PGI 2, was significantly increased following the LPS-challenge, suggesting that endogenous PGI 2 signaling modulates the host response to LPS-challenge. IPKO mice had a significant increase in neutrophils in the BAL fluid as well as increased proteins of KC, LIX, and TNF-α in lung homogenates compared with WT mice. In contrast, IL-10 was decreased in LPS-challenged IPKO mice compared with WT mice. The PGI 2 analog cicaprost significantly decreased LPS-induced KC, and TNF-α, but increased IL-10 and AREG in bone marrow-derived dendritic cells (BMDCs) and bone marrow-derived macrophages (BMMs) compared with vehicle-treatment. These results indicated that endogenous PGI 2 signaling attenuated neutrophilic lung inflammation through the reduced inflammatory cytokine and chemokine and enhanced IL-10. Copyright © 2018. Published by Elsevier Inc.

  5. 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.

  6. 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.

  7. A modified inflammatory bowel disease questionnaire and the Vaizey Incontinence questionnaire are more sensitive measures of acute gastrointestinal toxicity during pelvic radiotherapy than RTOG grading

    International Nuclear Information System (INIS)

    Khalid, Usman; McGough, Camilla; Hackett, Claire; Blake, Peter; Harrington, Kevin J.; Khoo, Vincent S.; Tait, Diana; Norman, Andrew R.; Andreyev, H. Jervoise N.

    2006-01-01

    Purpose: Simple scales with greater sensitivity than Radiation Therapy Oncology Group (RTOG) grading to detect acute gastrointestinal toxicity during pelvic radiotherapy, could be clinically useful. Methods and Materials: Do questionnaires used in benign gastrointestinal diseases detect toxicity in patients undergoing radiotherapy? The patient-completed Inflammatory Bowel Disease (IBDQ) and Vaizey Incontinence questionnaires were compared prospectively at baseline and at Week 5 to physician-completed RTOG grading. Results: A total of 107 patients, median age 63 years, were recruited. After 5 weeks of treatment, patients with gynecologic and gastrointestinal cancer were more symptomatic than urologic patients (p 0.012; p = 0.014). Overall, 94% had altered bowel habits, 80% loose stool, 74% frequency, 65% difficult gas, 60% pain, >48% distress, 44% tenesmus, >40% restrictions in daily activity, 39% urgency, 37% fecal incontinence, and 40% required antidiarrheal medication. The median RTOG score was 1 (range, 0-2), median IBDQ score 204.5 (range, 74-224), and median Vaizey score 5 (range, 0-20). Chemotherapy preceding radiotherapy increased fecal incontinence (p 0.002). RTOG scores stabilized after 3 weeks, IBDQ scores peaked at Week 4, and Vaizey scores worsened throughout treatment. IBDQ and Vaizey scores distinguished between groups with different RTOG scores. Conclusion: The IBDQ and Vaizey questionnaires are reliable and sensitive, offering greater insight into the severity and range of symptoms compared with RTOG grading

  8. Epigallocatechin-3-gallate Ameliorates Seawater Aspiration-Induced Acute Lung Injury via Regulating Inflammatory Cytokines and Inhibiting JAK/STAT1 Pathway in Rats

    Science.gov (United States)

    Liu, Wei; Dong, Mingqing; Bo, Liyan; Li, Congcong; Liu, Qingqing; Li, Yanyan; Ma, Lijie; Xie, Yonghong; Fu, Enqing; Mu, Deguang; Pan, Lei; Jin, Faguang; Li, Zhichao

    2014-01-01

    Signal transducers and activators of transcriptions 1 (STAT1) play an important role in the inflammation process of acute lung injury (ALI). Epigallocatechin-3-gallate (EGCG) exhibits a specific and strong anti-STAT1 activity. Therefore, our study is to explore whether EGCG pretreatment can ameliorate seawater aspiration-induced ALI and its possible mechanisms. We detected the arterial partial pressure of oxygen, lung wet/dry weight ratios, protein content in bronchoalveolar lavage fluid, and the histopathologic and ultrastructure staining of the lung. The levels of IL-1, TNF-α, and IL-10 and the total and the phosphorylated protein level of STAT1, JAK1, and JAK2 were assessed in vitro and in vivo. The results showed that EGCG pretreatment significantly improved hypoxemia and histopathologic changes, alleviated pulmonary edema and lung vascular leak, reduced the production of TNF-α and IL-1, and increased the production of IL-10 in seawater aspiration-induced ALI rats. EGCG also prevented the seawater aspiration-induced increase of TNF-α and IL-1 and decrease of IL-10 in NR8383 cell line. Moreover, EGCG pretreatment reduced the total and the phosphorylated protein level of STAT1 in vivo and in vitro and reduced the phosphorylated protein level of JAK1 and JAK2. The present study demonstrates that EGCG ameliorates seawater aspiration-induced ALI via regulating inflammatory cytokines and inhibiting JAK/STAT1 pathway in rats. PMID:24692852

  9. The role of osteopontin in children with systemic inflammatory ...

    African Journals Online (AJOL)

    involvement in the acute inflammatory diseases and its possible role as a marker differentiating ... or nonsteroidal anti-inflammatory drugs. Sample collection .... interactions with several integrins, also it mediates .... inflammatory bowel disease.

  10. Gene expression profiling in brain of mice exposed to the marine neurotoxin ciguatoxin reveals an acute anti-inflammatory, neuroprotective response

    Directory of Open Access Journals (Sweden)

    Ryan James C

    2010-08-01

    Full Text Available Abstract Background Ciguatoxins (CTXs are polyether marine neurotoxins and potent activators of voltage-gated sodium channels. This toxin is carried by multiple reef-fish species and human consumption of ciguatoxins can result in an explosive gastrointestinal/neurologic illness. This study characterizes the global transcriptional response in mouse brain to a symptomatic dose of the highly toxic Pacific ciguatoxin P-CTX-1 and additionally compares this data to transcriptional profiles from liver and whole blood examined previously. Adult male C57/BL6 mice were injected with 0.26 ng/g P-CTX-1 while controls received only vehicle. Animals were sacrificed at 1, 4 and 24 hrs and transcriptional profiling was performed on brain RNA with Agilent whole genome microarrays. RT-PCR was used to independently validate gene expression and the web tool DAVID was used to analyze gene ontology (GO and molecular pathway enrichment of the gene expression data. Results A pronounced 4°C hypothermic response was recorded in these mice, reaching a minimum at 1 hr and lasting for 8 hrs post toxin exposure. Ratio expression data were filtered by intensity, fold change and p-value, with the resulting data used for time course analysis, K-means clustering, ontology classification and KEGG pathway enrichment. Top GO hits for this gene set included acute phase response and mono-oxygenase activity. Molecular pathway analysis showed enrichment for complement/coagulation cascades and metabolism of xenobiotics. Many immediate early genes such as Fos, Jun and Early Growth Response isoforms were down-regulated although others associated with stress such as glucocorticoid responsive genes were up-regulated. Real time PCR confirmation was performed on 22 differentially expressed genes with a correlation of 0.9 (Spearman's Rho, p Conclusions Many of the genes differentially expressed in this study, in parallel with the hypothermia, figure prominently in protection against

  11. Gene expression profiling in brain of mice exposed to the marine neurotoxin ciguatoxin reveals an acute anti-inflammatory, neuroprotective response.

    Science.gov (United States)

    Ryan, James C; Morey, Jeanine S; Bottein, Marie-Yasmine Dechraoui; Ramsdell, John S; Van Dolah, Frances M

    2010-08-26

    Ciguatoxins (CTXs) are polyether marine neurotoxins and potent activators of voltage-gated sodium channels. This toxin is carried by multiple reef-fish species and human consumption of ciguatoxins can result in an explosive gastrointestinal/neurologic illness. This study characterizes the global transcriptional response in mouse brain to a symptomatic dose of the highly toxic Pacific ciguatoxin P-CTX-1 and additionally compares this data to transcriptional profiles from liver and whole blood examined previously. Adult male C57/BL6 mice were injected with 0.26 ng/g P-CTX-1 while controls received only vehicle. Animals were sacrificed at 1, 4 and 24 hrs and transcriptional profiling was performed on brain RNA with Agilent whole genome microarrays. RT-PCR was used to independently validate gene expression and the web tool DAVID was used to analyze gene ontology (GO) and molecular pathway enrichment of the gene expression data. A pronounced 4°C hypothermic response was recorded in these mice, reaching a minimum at 1 hr and lasting for 8 hrs post toxin exposure. Ratio expression data were filtered by intensity, fold change and p-value, with the resulting data used for time course analysis, K-means clustering, ontology classification and KEGG pathway enrichment. Top GO hits for this gene set included acute phase response and mono-oxygenase activity. Molecular pathway analysis showed enrichment for complement/coagulation cascades and metabolism of xenobiotics. Many immediate early genes such as Fos, Jun and Early Growth Response isoforms were down-regulated although others associated with stress such as glucocorticoid responsive genes were up-regulated. Real time PCR confirmation was performed on 22 differentially expressed genes with a correlation of 0.9 (Spearman's Rho, p < 0.0001) with microarray results. Many of the genes differentially expressed in this study, in parallel with the hypothermia, figure prominently in protection against neuroinflammation. Pathologic

  12. Combined use of nonsteroidal anti-inflammatory drugs with diuretics and/or renin-angiotensin system inhibitors in the community increases the risk of acute kidney injury.

    Science.gov (United States)

    Dreischulte, Tobias; Morales, Daniel R; Bell, Samira; Guthrie, Bruce

    2015-08-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI) when used in triple combination with renin-angiotensin system inhibitors and diuretics, but previous research reported that NSAIDs in dual combinations with either renin-angiotensin system inhibitors or diuretics alone were not. However, earlier studies relied on hospital coding to define AKI, which may underestimate true risk. This nested case-control study characterized the risk of community-acquired AKI associated with NSAID use among 78,379 users of renin-angiotensin system inhibitors and/or diuretics, where AKI was defined as a 50% or greater increase in creatinine from baseline. The AKI incidence was 68/10,000 person-years. The relative increase in AKI risk was similar for NSAID use in both triple (adjusted rate ratio 1.64 (95% CI 1.25-2.14)) and dual combinations with either renin-angiotensin system inhibitors (1.60 (1.18-2.17)) or diuretics (1.64 (1.17-2.29)). However, the absolute increase in AKI risk was higher for NSAIDs used in triple versus dual combinations with renin-angiotensin system inhibitors or diuretics alone (numbers needed to harm for 1 year treatment with NSAID of 158 vs. over 300). AKI risk was highest among users of loop diuretic/aldosterone antagonist combinations, in those over 75 years of age, and in those with renal impairment. Thus, the nephrotoxic potential of both dual and triple combinations of NSAIDs with renin-angiotensin system inhibitors and/or diuretics yields a higher incidence of AKI than previously thought.

  13. Anti-inflammatory effect of Heliotropium indicum Linn on lipopolysaccharide-induced uveitis in New Zealand white rabbits.

    Science.gov (United States)

    Kyei, Samuel; Koffuor, George Asumeng; Ramkissoon, Paul; Ameyaw, Elvis Ofori; Asiamah, Emmanuel Akomanin

    2016-01-01

    To investigate the anti-inflammatory effect of an aqueous whole plant extract of Heliotropium indicum (HIE) on endotoxin-induced uveitis in New Zealand white rabbits. Clinical signs of uveitis including flares, iris hyperemia and miosis, were sought for and scored in 1.0 mg/kg lipopolysaccharide (LPS) -induced uveitic rabbits treated orally with HIE (30-300 mg/kg), prednisolone (30 mg/kg), or normal saline (10 mL/kg). The number of polymorphonuclear neutrophils infiltrating, the protein concentration, as well as levels of tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), and monocyte chemmoattrant protein-1 (MCP-1) in the aqueous humor after the various treatments were also determined. A histopathological study of the anterior uveal was performed. The extract and prednisolone-treatment significantly reduced (P≤0.001) both the clinical scores of inflammation (1.0-1.8 compared to 4.40±0.40 in the normal saline-treated rabbits) and inflammatory cells infiltration. The level of protein, and the concentrations of TNF-α, PGE2 and MCP-1 in the aqueous humor were also significantly reduced (P≤0.001). Histopathological studies showed normal uveal morphology in the HIE and prednisolone-treated rabbits while normal saline-treated rabbits showed marked infiltration of inflammatory cells. The HIE exhibits anti-inflammatory effect on LPS-induced uveitis possibly by reducing the production of pro-inflammatory mediators.

  14. Immunomodulatory and Anti-Inflammatory Activities of Chicken Cathelicidin-2 Derived Peptides

    Science.gov (United States)

    van Dijk, Albert; van Eldik, Mandy; Veldhuizen, Edwin J. A.; Tjeerdsma-van Bokhoven, Hanne L. M.; de Zoete, Marcel R.; Bikker, Floris J.; Haagsman, Henk P.

    2016-01-01

    Host Defence Peptides and derived peptides are promising classes of antimicrobial and immunomodulatory lead compounds. For this purpose we examined whether chicken cathelicidin-2 (CATH-2)-derived peptides modulate the function and inflammatory response of avian immune cells. Using a chicken macrophage cell line (HD11) we found that full-length CATH-2 dose-dependently induced transcription of chemokines CXCLi2/IL-8, MCP-3 and CCLi4/RANTES, but not of pro-inflammatory cytokine IL-1β. In addition, CATH-2 efficiently inhibited IL-1β and nitric oxide production by HD11 cells induced by different sources of lipopolysaccharides (LPS). N-terminal truncated CATH-2 derived peptides maintained the capacity to selectively induce chemokine transcription, but despite their high LPS affinity several analogs lacked LPS-neutralizing capacity. Substitution of phenylalanine residues by tryptophan introduced endotoxin neutralization capacity in inactive truncated CATH-2 derived peptides. In contrast, amino acid substitution of phenylalanine by tyrosine abrogated endotoxin neutralization activity of CATH-2 analogs. These findings support a pivotal role for aromatic residues in peptide-mediated endotoxin neutralization by CATH-2 analogs and were shown to be independent of LPS affinity. The capacity to modulate chemokine production and dampen endotoxin-induced pro-inflammatory responses in chicken immune cells implicates that small CATH-2 based peptides could serve as leads for the design of CATH-2 based immunomodulatory anti-infectives. PMID:26848845

  15. Immunomodulatory and Anti-Inflammatory Activities of Chicken Cathelicidin-2 Derived Peptides.

    Directory of Open Access Journals (Sweden)

    Albert van Dijk

    Full Text Available Host Defence Peptides and derived peptides are promising classes of antimicrobial and immunomodulatory lead compounds. For this purpose we examined whether chicken cathelicidin-2 (CATH-2-derived peptides modulate the function and inflammatory response of avian immune cells. Using a chicken macrophage cell line (HD11 we found that full-length CATH-2 dose-dependently induced transcription of chemokines CXCLi2/IL-8, MCP-3 and CCLi4/RANTES, but not of pro-inflammatory cytokine IL-1β. In addition, CATH-2 efficiently inhibited IL-1β and nitric oxide production by HD11 cells induced by different sources of lipopolysaccharides (LPS. N-terminal truncated CATH-2 derived peptides maintained the capacity to selectively induce chemokine transcription, but despite their high LPS affinity several analogs lacked LPS-neutralizing capacity. Substitution of phenylalanine residues by tryptophan introduced endotoxin neutralization capacity in inactive truncated CATH-2 derived peptides. In contrast, amino acid substitution of phenylalanine by tyrosine abrogated endotoxin neutralization activity of CATH-2 analogs. These findings support a pivotal role for aromatic residues in peptide-mediated endotoxin neutralization by CATH-2 analogs and were shown to be independent of LPS affinity. The capacity to modulate chemokine production and dampen endotoxin-induced pro-inflammatory responses in chicken immune cells implicates that small CATH-2 based peptides could serve as leads for the design of CATH-2 based immunomodulatory anti-infectives.

  16. Metalloproteinase inhibition prevents acute respiratory distress syndrome.

    Science.gov (United States)

    Carney, D E; McCann, U G; Schiller, H J; Gatto, L A; Steinberg, J; Picone, A L; Nieman, G F

    2001-08-01

    The acute respiratory distress syndrome (ARDS) occurs in patients with clearly identifiable risk factors, and its treatment remains merely supportive. We postulated that patients at risk for ARDS can be protected against lung injury by a prophylactic treatment strategy that targets neutrophil-derived proteases. We hypothesized that a chemically modified tetracycline 3 (COL-3), a potent inhibitor of neutrophil matrix metalloproteinases (MMPs) and neutrophil elastase (NE) with minimal toxicity, would prevent ARDS in our porcine endotoxin-induced ARDS model. Yorkshire pigs were anesthetized, intubated, surgically instrumented for hemodynamic monitoring, and randomized into three groups: (1) control (n = 4), surgical instrumentation only; (2) lipopolysaccharide (LPS) (n = 4), infusion of Escherichia coli lipopolysaccharide at 100 microg/kg; and (3) COL-3 + LPS (n = 5), ingestion of COL-3 (100 mg/kg) 12 h before LPS infusion. All animals were monitored for 6 h following LPS or sham LPS infusion. Serial bronchoalveolar lavage (BAL) samples were analyzed for MMP concentration by gelatin zymography. Lung tissue was fixed for morphometric assessment at necropsy. LPS infusion was marked by significant (P decrement in arterial oxygen partial pressure (P(a)O(2)) (LPS = 66 +/- 15 mm Hg, Control = 263 +/- 25 mm Hg) 6 h following LPS or sham LPS infusion, respectively. Pretreatment with COL-3 reduced the above pathophysiological changes 6 h following LPS infusion (P(plat) = 18.5 +/- 1.7 mm Hg, P(a)O(2) = 199 +/- 35 mm Hg; P = NS vs control). MMP-9 and MMP-2 concentration in BAL fluid was significantly increased between 2 and 4 h post-LPS infusion; COL-3 reduced the increase in MMP-9 and MMP-2 concentration at all time periods. Morphometrically LPS caused a significant sequestration of neutrophils and monocytes into pulmonary tissue. Pretreatment with COL-3 ameliorated this response. The wet/dry lung weight ratio was significantly greater (P single prophylactic treatment with COL

  17. Curcumin in inflammatory diseases.

    Science.gov (United States)

    Shehzad, Adeeb; Rehman, Gauhar; Lee, Young Sup

    2013-01-01

    Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

  18. A matrix of cholesterol crystals, but not cholesterol alone, primes human monocytes/macrophages for excessive endotoxin-induced production of tumor necrosis factor-alpha. Role in atherosclerotic inflammation?

    DEFF Research Database (Denmark)

    Bendtzen, Klaus; Christensen, Ole; Nielsen, Claus Henrik

    2014-01-01

    When exposed to small amounts of bacterial endotoxin, matrices of cholesterol crystals, but not cholesterol itself, primed human monocytes/macrophages to a highly augmented (>10-fold) production of inflammatory tumor necrosis factor-α. Priming also sensitized the cells, as 10- to 100-fold lower...

  19. ISSLS PRIZE IN CLINICAL SCIENCE 2018: longitudinal analysis of inflammatory, psychological, and sleep-related factors following an acute low back pain episode-the good, the bad, and the ugly.

    Science.gov (United States)

    Klyne, David M; Barbe, Mary F; van den Hoorn, Wolbert; Hodges, Paul W

    2018-04-01

    Prospective longitudinal study. To determine whether systemic cytokines and C-reactive protein (CRP) during an acute episode of low back pain (LBP) differ between individuals who did and did not recover by 6 months and to identify sub-groups based on patterns of inflammatory, psychological, and sleep features associated with recovery/non-recovery. Systemic inflammation is observed in chronic LBP and may contribute to the transition from acute to persistent LBP. Longitudinal studies are required to determine whether changes present early or develop over time. Psychological and/or sleep-related factors may be related. Individuals within 2 weeks of onset of acute LBP (N = 109) and pain-free controls (N = 55) provided blood for assessment of CRP, tumor necrosis factor (TNF), interleukin-6 (IL-6) and interleukin-1β, and completed questionnaires related to pain, disability, sleep, and psychological status. LBP participants repeated measurements at 6 months. Biomarkers were compared between LBP and control participants at baseline, and in longitudinal (baseline/6 months) analysis, between unrecovered (≥pain and disability), partially recovered (reduced pain and/or disability) and recovered (no pain and disability) participants at 6 months. We assessed baseline patterns of inflammatory, psychological, sleep, and pain data using hierarchical clustering and related the clusters to recovery (% change in pain) at 6 months. CRP was higher in acute LBP than controls at baseline. In LBP, baseline CRP was higher in the recovered than non-recovered groups. Conversely, TNF was higher at both time-points in the non-recovered than recovered groups. Two sub-groups were identified that associated with more ("inflammatory/poor sleep") or less ("high TNF/depression") recovery. This is the first evidence of a relationship between an "acute-phase" systemic inflammatory response and recovery at 6 months. High inflammation (CRP/IL-6) was associated with good recovery, but specific

  20. Body temperature measurement in mice during acute illness: implantable temperature transponder versus surface infrared thermometry.

    Science.gov (United States)

    Mei, Jie; Riedel, Nico; Grittner, Ulrike; Endres, Matthias; Banneke, Stefanie; Emmrich, Julius Valentin

    2018-02-23

    Body temperature is a valuable parameter in determining the wellbeing of laboratory animals. However, using body temperature to refine humane endpoints during acute illness generally lacks comprehensiveness and exposes to inter-observer bias. Here we compared two methods to assess body temperature in mice, namely implanted radio frequency identification (RFID) temperature transponders (method 1) to non-contact infrared thermometry (method 2) in 435 mice for up to 7 days during normothermia and lipopolysaccharide (LPS) endotoxin-induced hypothermia. There was excellent agreement between core and surface temperature as determined by method 1 and 2, respectively, whereas the intra- and inter-subject variation was higher for method 2. Nevertheless, using machine learning algorithms to determine temperature-based endpoints both methods had excellent accuracy in predicting death as an outcome event. Therefore, less expensive and cumbersome non-contact infrared thermometry can serve as a reliable alternative for implantable transponder-based systems for hypothermic responses, although requiring standardization between experimenters.

  1. Non-Steroidal Anti-Inflammatory Drug Use and the Risk of Acute Myocardial Infarction in the General German Population: A Nested Case-Control Study.

    Science.gov (United States)

    Thöne, Kathrin; Kollhorst, Bianca; Schink, Tania

    2017-09-01

    Use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with an increased relative risk of acute myocardial infarction (AMI), but the label warnings refer particularly to patients with cardiovascular risk factors. The magnitude of relative AMI risk for patients with and without cardiovascular risk factors varies between studies depending on the drugs and doses studied. The aim of our study was to estimate population-based relative AMI risks for individual and widely used NSAIDs, for a cumulative amount of NSAID use, and for patients with and without a prior history of cardiovascular risk factors. Based on data from the German Pharmacoepidemiological Research Database (GePaRD) of about 17 million insurance members from four statutory health insurance providers, for the years 2004-2009, a nested case-control study was conducted within a cohort of 3,476,931 new NSAID users classified into current, recent, or past users. Up to 100 controls were matched to each case by age, sex, and length of follow-up using risk set sampling. Multivariable conditional logistic regression was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Duration of NSAID use was calculated by the cumulative amount of dispensed defined daily doses (DDDs), and stratified analyses were conducted for potential effect modifiers. Overall, 17,236 AMI cases were matched to 1,714,006 controls. Elevated relative AMI risks were seen for current users of fixed combinations of diclofenac with misoprostol (OR 1.76, 95% CI 1.26-2.45), indometacin (1.69, 1.22-2.35), ibuprofen (1.54, 1.43-1.65), etoricoxib (1.52, 1.24-1.87), and diclofenac (1.43, 1.34-1.52) compared with past use. A low cumulative NSAID amount was associated with a higher relative AMI risk for ibuprofen, diclofenac, and indometacin. The relative risk associated with current use of diclofenac, fixed combinations of diclofenac with misoprostol, etoricoxib, and ibuprofen was highest in the younger age group

  2. Synthesis and optimization of novel allylated mono-carbonyl analogs of curcumin (MACs) act as potent anti-inflammatory agents against LPS-induced acute lung injury (ALI) in rats.

    Science.gov (United States)

    Zhu, Heping; Xu, Tingting; Qiu, Chenyu; Wu, Beibei; Zhang, Yali; Chen, Lingfeng; Xia, Qinqin; Li, Chenglong; Zhou, Bin; Liu, Zhiguo; Liang, Guang

    2016-10-04

    A series of novel symmetric and asymmetric allylated mono-carbonyl analogs of curcumin (MACs) were synthesized using an appropriate synthetic route and evaluated experimentally thru the LPS-induced expression of TNF-α and IL-6. Most of the obtained compounds exhibited improved water solubility as a hydrochloride salt compared to lead molecule 8f. The most active compound 7a was effective in reducing the Wet/Dry ratio in the lungs and protein concentration in bronchoalveolar lavage fluid. Meanwhile, 7a also inhibited mRNA expression of several inflammatory cytokines, including TNF-α, IL-6, IL-1β, and VCAM-1, in Beas-2B cells after Lipopolysaccharide (LPS) challenge. These results suggest that 7a could be therapeutically beneficial for use as an anti-inflammatory agent in the clinical treatment of acute lung injury (ALI). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. What is the best treatment to decrease pro-inflammatory cytokine release in acute skeletal muscle injury induced by trauma in rats: low-level laser therapy, diclofenac, or cryotherapy?

    Science.gov (United States)

    de Almeida, Patrícia; Tomazoni, Shaiane Silva; Frigo, Lucio; de Carvalho, Paulo de Tarso Camillo; Vanin, Adriane Aver; Santos, Larissa Aline; Albuquerque-Pontes, Gianna Móes; De Marchi, Thiago; Tairova, Olga; Marcos, Rodrigo Labat; Lopes-Martins, Rodrigo Álvaro Brandão; Leal-Junior, Ernesto Cesar Pinto

    2014-03-01

    Currently, treatment of muscle injuries represents a challenge in clinical practice. In acute phase, the most employed therapies are cryotherapy and nonsteroidal anti-inflammatory drugs. In the last years, low-level laser therapy (LLLT) has becoming a promising therapeutic agent; however, its effects are not fully known. The aim of this study was to analyze the effects of sodium diclofenac (topical application), cryotherapy, and LLLT on pro-inflammatory cytokine levels after a controlled model of muscle injury. For such, we performed a single trauma in tibialis anterior muscle of rats. After 1 h, animals were treated with sodium diclofenac (11.6 mg/g of solution), cryotherapy (20 min), or LLLT (904 nm; superpulsed; 700 Hz; 60 mW mean output power; 1.67 W/cm(2); 1, 3, 6 or 9 J; 17, 50, 100 or 150 s). Assessment of interleukin-1β and interleukin-6 (IL-1β and IL-6) and tumor necrosis factor-alpha (TNF-α) levels was performed at 6 h after trauma employing enzyme-linked immunosorbent assay method. LLLT with 1 J dose significantly decreased (p cryotherapy groups. On the other hand, treatment with diclofenac and cryotherapy does not decrease pro-inflammatory cytokine levels compared to the non-treated injured group. Therefore, we can conclude that 904 nm LLLT with 1 J dose has better effects than topical application of diclofenac or cryotherapy in acute inflammatory phase after muscle trauma.

  4. [Risk of fatal/non-fatal events in patients with previous coronary heart disease/acute myocardial infarction and treatment with non-steroidal anti-inflammatory drugs].

    Science.gov (United States)

    Muñoz Olmo, L; Juan Armas, J; Gomariz García, J J

    2017-09-04

    Primary Care is the fundamental axis of our health system and obliges us to be consistent with our prescriptions. The non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with increased cardiovascular risk and increased risk of all causes of death, as well as acute myocardial infarction (AMI) in patients with a previous myocardial infarction. Pain and cardiac patient management are 2 basic pillars in our daily activity, and we must know the limitations of NSAIDs in patients with established cardiovascular risk. We present a review of the scientific literature with primary interest in the role of NSAIDs and cardiovascular risk. The objective is to determine the relationship between the consumption of different NSAIDs and the fatal and non-fatal events among patients with known coronary disease. This is a review of the scientific literature with primary interest in the role of NSAIDs and cardiovascular risk. The literature review was conducted in PubMed search engines like Tripdatabase and with certain keywords. Of the 15 original papers found, 9 did not correspond completely to the central focus, so the approach was decided from 6 original articles from the past 5 years, which address the central focus of increased cardiovascular risk found (fatal and non-fatal events) in patients with prior cardiovascular disease or AMI being prescribed NSAIDs for any reason. The risk of fatal/non-fatal events in each of the studies is expressed by the odds ratio (OR)/hazard ratio (HR), defined as the probability of an event occurring. A moderate risk was observed for ibuprofen. It increases the risk of acute coronary syndrome after 5 years of cardiovascular event, especially in the 2nd year (OR 1.63; 95% CI 1.42-1.87). It also increases the risk of stroke (HR 1.23; 95% IC 1.10-1.38). Cyclo-oxygenase-2 inhibitors were the third risk group, after nabumetone and diclofenac. Celecoxib increases risk from the 14th day of treatment (HR 2.3; 95% CI 1.79-3.02), having an OR

  5. Sex differences in the pro-inflammatory cytokine response to endotoxin unfold in vivo but not ex vivo in healthy humans.

    Science.gov (United States)

    Wegner, Alexander; Benson, Sven; Rebernik, Laura; Spreitzer, Ingo; Jäger, Marcus; Schedlowski, Manfred; Elsenbruch, Sigrid; Engler, Harald

    2017-07-01

    Clinical data indicate that inflammatory responses differ across sexes, but the mechanisms remain elusive. Herein, we assessed in vivo and ex vivo cytokine responses to bacterial endotoxin in healthy men and women to elucidate the role of systemic and cellular factors underlying sex differences in inflammatory responses. Participants received an i.v. injection of low-dose endotoxin (0.4 ng/kg body mass), and plasma TNF-α and IL-6 responses were analyzed over a period of 6 h. In parallel, ex vivo cytokine production was measured in endotoxin-stimulated blood samples obtained immediately before in vivo endotoxin administration. As glucocorticoids (GCs) play an important role in the negative feedback regulation of the inflammatory response, we additionally analyzed plasma cortisol concentrations and ex vivo GC sensitivity of cytokine production. Results revealed greater in vivo pro-inflammatory responses in women compared with men, with significantly higher increases in plasma TNF-α and IL-6 concentrations. In addition, the endotoxin-induced rise in plasma cortisol was more pronounced in women. In contrast, no sex differences in ex vivo cytokine production and GC sensitivity were observed. Together, these findings demonstrate major differences in in vivo and ex vivo responses to endotoxin and underscore the importance of systemic factors underlying sex differences in the inflammatory response.

  6. Pandemic H1N1 influenza A directly induces a robust and acute inflammatory gene signature in primary human bronchial epithelial cells downstream of membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Paquette, Stéphane G. [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario (Canada); Banner, David [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); Chi, Le Thi Bao [Department of Microbiology, Hue University of Medicine and Pharmacy, Thua Thien Hue (Viet Nam); Carlo Urbani Centre, Hue University of Medicine and Pharmacy, Thua Thien Hue (Viet Nam); Leon, Alberto J. [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); International Institute of Infection and Immunity, Shantou University Medical College, Shantou, Guangdong (China); Xu, Luoling; Ran, Longsi [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); Huang, Stephen S.H. [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario (Canada); Farooqui, Amber [Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario (Canada); International Institute of Infection and Immunity, Shantou University Medical College, Shantou, Guangdong (China); and others

    2014-01-05

    Pandemic H1N1 influenza A (H1N1pdm) elicits stronger pulmonary inflammation than previously circulating seasonal H1N1 influenza A (sH1N1), yet mechanisms of inflammatory activation in respiratory epithelial cells during H1N1pdm infection are unclear. We investigated host responses to H1N1pdm/sH1N1 infection and virus entry mechanisms in primary human bronchial epithelial cells in vitro. H1N1pdm infection rapidly initiated a robust inflammatory gene signature (3 h post-infection) not elicited by sH1N1 infection. Protein secretion inhibition had no effect on gene induction. Infection with membrane fusion deficient H1N1pdm failed to induce robust inflammatory gene expression which was rescued with restoration of fusion ability, suggesting H1N1pdm directly triggered the inflammatory signature downstream of membrane fusion. Investigation of intra-virion components revealed H1N1pdm viral RNA (vRNA) triggered a stronger inflammatory phenotype than sH1N1 vRNA. Thus, our study is first to report H1N1pdm induces greater inflammatory gene expression than sH1N1 in vitro due to direct virus–epithelial cell interaction. - Highlights: • We investigated H1N1pdm/sH1N1 infection in primary epithelial cells. • H1N1pdm directly initiated a robust inflammatory gene signature, sH1N1 did not. • H1N1pdm viral RNA triggered a stronger response than sH1N1. • H1N1pdm induces greater response due to direct virus–cell interaction. • These results have potential to impact vaccine and therapeutic development.

  7. Pandemic H1N1 influenza A directly induces a robust and acute inflammatory gene signature in primary human bronchial epithelial cells downstream of membrane fusion

    International Nuclear Information System (INIS)

    Paquette, Stéphane G.; Banner, David; Chi, Le Thi Bao; Leon, Alberto J.; Xu, Luoling; Ran, Longsi; Huang, Stephen S.H.; Farooqui, Amber

    2014-01-01

    Pandemic H1N1 influenza A (H1N1pdm) elicits stronger pulmonary inflammation than previously circulating seasonal H1N1 influenza A (sH1N1), yet mechanisms of inflammatory activation in respiratory epithelial cells during H1N1pdm infection are unclear. We investigated host responses to H1N1pdm/sH1N1 infection and virus entry mechanisms in primary human bronchial epithelial cells in vitro. H1N1pdm infection rapidly initiated a robust inflammatory gene signature (3 h post-infection) not elicited by sH1N1 infection. Protein secretion inhibition had no effect on gene induction. Infection with membrane fusion deficient H1N1pdm failed to induce robust inflammatory gene expression which was rescued with restoration of fusion ability, suggesting H1N1pdm directly triggered the inflammatory signature downstream of membrane fusion. Investigation of intra-virion components revealed H1N1pdm viral RNA (vRNA) triggered a stronger inflammatory phenotype than sH1N1 vRNA. Thus, our study is first to report H1N1pdm induces greater inflammatory gene expression than sH1N1 in vitro due to direct virus–epithelial cell interaction. - Highlights: • We investigated H1N1pdm/sH1N1 infection in primary epithelial cells. • H1N1pdm directly initiated a robust inflammatory gene signature, sH1N1 did not. • H1N1pdm viral RNA triggered a stronger response than sH1N1. • H1N1pdm induces greater response due to direct virus–cell interaction. • These results have potential to impact vaccine and therapeutic development

  8. Inflammatory Mediators and Pain in the First Year After Acute Episode of Low-Back Pain in Elderly Women: Longitudinal Data from Back Complaints in the Elders-Brazil.

    Science.gov (United States)

    Queiroz, Bárbara Zille; Pereira, Daniele Sirineu; Rosa, Nayza Maciel de Britto; Lopes, Renata Antunes; Andrade, André Gustavo Pereira; Felício, Diogo Carvalho; Jardim, Renata Muniz Freire Vinhal Siqueira; Leopoldino, Amanda Aparecida Oliveira; Silva, Juscélio Pereira; Pereira, Leani Souza Máximo

    2017-08-01

    The aims of this study were to determine the course of plasma levels of inflammatory mediators (interleukin 6 [IL-6], tumor necrosis factor α [TNF-α], soluble TNF receptor 1 [sTNF-R1]) and the severity of low-back pain (LBP) over 6 to 12 months after an acute episode of LBP in elderly women and to establish an association between inflammatory mediators and LBP recovery. This was a longitudinal study of a subsample (155 elderly women with acute LBP, aged ≥65 years) of the international Back Complaints in the Elders cohort study. Plasma levels of IL-6, TNF-α, and sTNF-R1 were measured using enzyme-linked immunosorbent assays and pain severity using the numerical pain scale. There was a decrease in the severity of LBP (P = 0.033) and in the levels of IL-6 and TNF-α (P relief at the 12-month follow-up was 2.22 times higher in elderly women who had low levels of IL-6 (<1.58 pg/mL) at baseline. Our findings showed a relationship between inflammation and LBP by establishing that low IL-6 plasma levels preceded outcome (LBP recovery), supporting the concept that proinflammatory cytokines promote pain.

  9. Effect of inflammatory attacks in the classical type hyper-IgD syndrome on immunoglobulin D, cholesterol and parameters of the acute phase response.

    NARCIS (Netherlands)

    Simon, A.; Bijzet, J.; Voorbij, H.A.; Mantovani, A.; Meer, J.W.M. van der; Drenth, J.P.H.

    2004-01-01

    BACKGROUND: Classical type hyper-immunoglobulin D (IgD) syndrome (HIDS) is an hereditary auto-inflammatory disorder, characterized by recurrent episodes of fever, lymphadenopathy, abdominal distress and a high serum concentration of IgD. It is caused by mevalonate kinase deficiency. OBJECTIVE: To

  10. Hashimoto's Thyroiditis Presenting as Acute Painful Thyroiditis and as a Manifestation of an Immune Reconstitution Inflammatory Syndrome in a Human Immunodeficiency Virus-Seropositive Patient.

    NARCIS (Netherlands)

    Visser, R.; Mast, Q. de; Netea-Maier, R.T.; Ven, A.J.A.M. van der

    2012-01-01

    Background: An immune reconstitution inflammatory syndrome (IRIS) may complicate immune restoration following start of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected patients. The occurrence of Graves' disease in the setting of an IRIS is well recognized. We hereby

  11. Paracetamol (acetaminophen) or non-steroidal anti-inflammatory drugs, alone or combined, for pain relief in acute otitis media in children.

    Science.gov (United States)

    Sjoukes, Alies; Venekamp, Roderick P; van de Pol, Alma C; Hay, Alastair D; Little, Paul; Schilder, Anne Gm; Damoiseaux, Roger Amj

    2016-12-15

    Acute otitis media (AOM) is one of the most common childhood infectious diseases and a significant reason for antibiotic prescriptions in children worldwide. Pain from middle ear infection and pressure behind the eardrum is the key symptom of AOM. Ear pain is central to children's and parents' experience of the illness. Because antibiotics provide only marginal benefits, analgesic treatment including paracetamol (acetaminophen) and non-steroidal anti-inflammatory drugs (NSAIDs) is regarded as the cornerstone of AOM management in children. Our primary objective was to assess the effectiveness of paracetamol (acetaminophen) or NSAIDs, alone or combined, compared with placebo or no treatment in relieving pain in children with AOM. Our secondary objective was to assess the effectiveness of NSAIDs compared with paracetamol in children with AOM. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 7, July 2016; MEDLINE (Ovid, from 1946 to August 2016), Embase (from 1947 to August 2016), CINAHL (from 1981 to August 2016), LILACS (from 1982 to August 2016) and Web of Science (from 1955 to August 2016) for published trials. We screened reference lists of included studies and relevant systematic reviews for additional trials. We searched WHO ICTRP, ClinicalTrials.gov, and the Netherlands Trial Registry (NTR) for completed and ongoing trials (search date 19 August 2016). We included randomised controlled trials (RCTs) comparing the effectiveness of paracetamol or NSAIDs, alone or combined, for pain relief in children with AOM. We also included trials of paracetamol or NSAIDs, alone or combined, for children with fever or upper respiratory tract infections (URTIs) if we were able to extract subgroup data on pain relief in children with AOM either directly or after obtaining additional data from study authors. Two review authors independently assessed methodological quality of the included trials and extracted data. We used the GRADE approach to rate

  12. The relationship between acute changes in the systemic inflammatory response and plasma ascorbic acid, alpha-tocopherol and lipid peroxidation after elective hip arthroplasty.

    Science.gov (United States)

    Conway, F J S; Talwar, D; McMillan, D C

    2015-08-01

    Vitamin C (ascorbic acid, AA) is a water soluble vitamin with many functions including antioxidative properties, haemostasis, hormone synthesis, collagen synthesis, carnitine synthesis, bile salt production and enhancing iron absorption. There is some evidence that there is a negative inverse relationship between plasma vitamin C concentration and the systemic inflammatory response as measured by C-reactive protein (CRP). The aim of the present study was to examine, in the context of a longitudinal study, the change in plasma concentrations of ascorbic acid (AA) and Vitamin E (α-tocopherol, AT) and their relationship to free radical damage during the evolution of the systemic inflammatory response. Venous blood samples were obtained pre-operatively and at 1, 2, 3 and 90 days post-operatively from 11 patients undergoing elective hip arthroplasty at Glasgow Royal Infirmary. AA, AT, cholesterol, MDA (marker of free radical damage), CRP and albumin were measured in plasma. Plasma AA fell significantly by 74% (P < 0.01), AT fell by 36% (P < 0.01), cholesterol by 40% (P < 0.01), MDA by 38% (P < 0.01), albumin by 29% (P < 0.01) and CRP increased significantly by 160 fold (P < 0.01) during the systemic inflammatory response. The fall in plasma AA remained significant when adjusted for albumin (P < 0.01). Plasma AT adjusted for cholesterol did not change significantly during the study period. The fall in plasma MDA remained significant when adjusted for albumin (P 0.01). At 3 months post-operatively, all measurements (including AA) except albumin had returned to baseline values. Plasma AA levels are unlikely to be a reliable measurement of Vitamin C where there is evidence of a systemic inflammatory response. The decrease in plasma AA concentration is likely to be secondary to increased consumption, increased usage neutralising free radicals, increased utilisation in supporting AT regeneration and increased urinary excretion. Copyright © 2014 Elsevier Ltd and European

  13. Surfen is a broad-spectrum calcium channel inhibitor with analgesic properties in mouse models of acute and chronic inflammatory pain

    Czech Academy of Sciences Publication Activity Database

    Rivas-Ramirez, Paula; Gadotti, V. M.; Zamponi, G. W.; Weiss, Norbert

    2017-01-01

    Roč. 469, č. 10 (2017), s. 1325-1334 ISSN 0031-6768 R&D Projects: GA ČR GA15-13556S; GA MŠk 7AMB15FR015 Institutional support: RVO:61388963 Keywords : calcium channel * pain * inflammatory pain * calcium channel blocker * surfen * DRG neuron Subject RIV: ED - Physiology OBOR OECD: Physiology (including cytology) Impact factor: 3.156, year: 2016

  14. Antioxidant and anti-inflammatory effects of virgin coconut oil supplementation abrogate acute chemotherapy oxidative nephrotoxicity induced by anticancer drug methotrexate in rats.

    Science.gov (United States)

    Famurewa, Ademola C; Aja, Patrick M; Maduagwuna, Ekenechukwu K; Ekeleme-Egedigwe, Chima A; Ufebe, Odomero G; Azubuike-Osu, Sharon O

    2017-12-01

    Methotrexate (MTX) is an efficacious anticancer agent constrained in clinical use due to its toxicity on non-targeted tissue, a considerable source of worry to clinicians. Because the toxicity is associated with oxidative stress and inflammation, the study explored antioxidant and anti-inflammatory effect of virgin coconut oil (VCO) supplementation in nephrotoxicity induced by MTX in rats. Rats were randomized into 4 groups (n=6) as follows: Control group; MTX group injected with single dose of MTX (20mg/kg, ip) on day 14; VCO (5%)+MTX and VCO (15%)+MTX groups were pre-treated with VCO diet and injected with single dose of MTX (20mg/kg, ip) on day 14. After 3 days of MTX injection, serum kidney markers, renal activities of antioxidant enzymes and glutathione (GSH) content were determined. Lipid peroxidation level and inflammatory markers- interleukin-6 (IL-6), nitric oxide (NO) and C-reactive protein (CRP) were estimated in kidney. Histopathological alterations were examined for kidney damage. MTX nephrotoxicity was evidenced by markedly elevated serum renal markers along with significant decreases in renal GSH and activities of antioxidant enzymes confirmed by histopathology. Lipid peroxidation level, IL-6, NO and CRP markedly increased compared to control. VCO supplementation prior to MTX injection attenuated MTX-induced oxidative nephrotoxicity via prominent increases in GSH and antioxidant enzyme activities in a dose-dependent manner. The renal inflammatory markers and MDA depleted considerably compared to MTX control group. Histopathological alterations were mitigated to confirm the biochemical indices. VCO supplementation demonstrates nephroprotective activity by attenuating MTX oxidative nephrotoxicity via antioxidant and anti-inflammatory activities in kidney. Our results suggested that VCO may benefit cancer patients on MTX chemotherapy against kidney injury. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Paracetamol (acetaminophen) or non-steroidal anti-inflammatory drugs, alone or combined, for pain relief in acute otitis media in children

    NARCIS (Netherlands)

    Sjoukes, Alies; Venekamp, Roderick P; van de Pol, Alma C; Hay, Alastair D; Little, Paul; Schilder, Anne GM; Damoiseaux, Roger Amj

    2016-01-01

    BACKGROUND: Acute otitis media (AOM) is one of the most common childhood infectious diseases and a significant reason for antibiotic prescriptions in children worldwide. Pain from middle ear infection and pressure behind the eardrum is the key symptom of AOM. Ear pain is central to children's and

  16. Men and women differ in inflammatory and neuroendocrine responses to endotoxin but not in the severity of sickness symptoms.

    Science.gov (United States)

    Engler, Harald; Benson, Sven; Wegner, Alexander; Spreitzer, Ingo; Schedlowski, Manfred; Elsenbruch, Sigrid

    2016-02-01

    Impaired mood and increased anxiety represent core symptoms of sickness behavior that are thought to be mediated by pro-inflammatory cytokines. Moreover, excessive inflammation seems to be implicated in the development of mood/affective disorders. Although women are known to mount stronger pro-inflammatory responses during infections and are at higher risk to develop depressive and anxiety disorders compared to men, experimental studies on sex differences in sickness symptoms are scarce. Thus, the present study aimed at comparing physiological and psychological responses to endotoxin administration between men and women. Twenty-eight healthy volunteers (14 men, 14 women) were intravenously injected with a low dose (0.4 ng/kg) of lipopolysaccharide (LPS) and plasma concentrations of cytokines and neuroendocrine factors as well as negative state emotions were measured before and until six hours after LPS administration. Women exhibited a more profound pro-inflammatory response with significantly higher increases in tumor necrosis factor (TNF)-α and interleukin (IL)-6. In contrast, the LPS-induced increase in anti-inflammatory IL-10 was significantly higher in men. The cytokine alterations were accompanied by changes in neuroendocrine factors known to be involved in inflammation regulation. Endotoxin injection induced a significant increase in noradrenaline, without evidence for sex differences. The LPS-induced increase in cortisol was significantly higher in woman, whereas changes in dehydroepiandrosterone were largely comparable. LPS administration also increased secretion of prolactin, but only in women. Despite these profound sex differences in inflammatory and neuroendocrine responses, men and women did not differ in endotoxin-induced alterations in mood and state anxiety or non-specific sickness symptoms. This suggests that compensatory mechanisms exist that counteract the more pronounced inflammatory response in women, preventing an exaggerated sickness

  17. The protective effect of lidocaine on lipopolysaccharide-induced acute lung injury in rats through NF-κB and p38 MAPK signaling pathway and excessive inflammatory responses.

    Science.gov (United States)

    Chen, L-J; Ding, Y-B; Ma, P-L; Jiang, S-H; Li, K-Z; Li, A-Z; Li, M-C; Shi, C-X; Du, J; Zhou, H-D

    2018-04-01

    Acute lung injury is a severe disease with a high rate of mortality, leading to more important illness. We aimed at exploring the protective role and potential mechanisms of lidocaine on lipopolysaccharide (LPS)-induced acute lung injury (ALI). Sprague Dawley (SD) rats were randomly assigned to control group receiving 0.9% saline solution, LPS group treated with 4 mg/kg LPS i.p., LPS + lidocaine(treated with 4 mg/kg LPS i.p. followed by giving 1 mg/kg, 3 mg/kg, 5 mg/kg of lidocaine i.v.). Lung specimens and the bronchoalveolar lavage fluid (BALF) were collected for histopathological examination and biochemical analyze 12 h after LPS induction. The cytokines expression of TNF-α, IL-6 and MCP-1 was measured by ELISA. In addition, the malondialdehyde (MDA) content, the activities of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) in lung tissues were also detected using ELISA. The protein expressions of p38, p-p38, p65, p-p65 and IκB were analyzed by Western blot. The results indicated that after lidocaine treatment was able to decrease significantly wet-to-dry (W/D) ratio and ameliorate the histopathologic damage. Additionally, total protein content and the number of leukocytes in BALF significantly decreased. ELISA result indicated that the levels of TNF-α, IL-6 and MCP-1 in BALF were markedly suppressed. Meanwhile, the activities of T-AOC and SOD in lung tissues significantly increased, while the content of MDA significantly decreased after treatment with lidocaine. Moreover, Western blot suggested that lidocaine inhibited phosphorylation of NF-κB p65 and p38 MAPK. Therefore, lidocaine could ameliorate the LPS-induced lung injury via NF-κB/p38 MAPK signaling and excessive inflammatory responses, providing a potential for becoming the anti-inflammatory agent against lung injury.

  18. Heat stress upregulation of Toll-like receptors 2/4 and acute inflammatory cytokines in peripheral blood mononuclear cell (PBMC) of Bama miniature pigs: an in vivo and in vitro study.

    Science.gov (United States)

    Ju, X-H; Xu, H-J; Yong, Y-H; An, L-L; Jiao, P-R; Liao, M

    2014-09-01

    Global warming is a challenge to animal health, because of increased heat stress, with subsequent induction of immunosuppression and increased susceptibility to disease. Toll-like receptors (TLR) are pattern recognition receptors that act as sentinels of pathogen invasion and tissue damage. Ligation of TLRs results in a signaling cascade and production of inflammatory cytokines, which eradicate pathogens and maintain the health of the host. We hypothesized that the TLR signaling pathway plays a role in immunosuppression in heat-stressed pigs. We explored the changes in the expression of TLR2, TLR4 and the concentration of acute inflammatory cytokines, such as IL-2, IL-8, IL-12 and IFN-γ in Bama miniature pigs subjected to 21 consecutive days of heat stress, both in vitro and in vivo models. The results showed that heat stress induced the upregulation of cortisol in the plasma of pigs (Pblood mononuclear cells (PBMC, Pblood cell count and the percentage of granulocytes (eosinophilic+basophilic) decreased significantly in heat-stressed pigs (Pheat shocked for 1 h followed by a 9 h recovery period), TLR2 and TLR4 mRNA expression also increased, as did the concentration of IL-12 in supernatants. However, IFN-γ was significantly reduced in PBMC culture supernatants (Pheat stress period elevated the expression of TLR2 and TLR4 in PBMC and increased the plasma levels of inflammatory cytokines. These data indicate that TLR activation and dysregulation of cytokine expression in response to prolonged heat stress may be associated with immunosuppression and increased susceptibility to antigenic challenge in Bama miniature pigs.

  19. The cell-type specific uptake of polymer-coated or micelle-embedded QDs and SPIOs does not provoke an acute pro-inflammatory response in the liver

    Directory of Open Access Journals (Sweden)

    Markus Heine

    2014-09-01

    Full Text Available Semiconductor quantum dots (QD and superparamagnetic iron oxide nanocrystals (SPIO have exceptional physical properties that are well suited for biomedical applications in vitro and in vivo. For future applications, the direct injection of nanocrystals for imaging and therapy represents an important entry route into the human body. Therefore, it is crucial to investigate biological responses of the body to nanocrystals to avoid harmful side effects. In recent years, we established a system to embed nanocrystals with a hydrophobic oleic acid shell either by lipid micelles or by the amphiphilic polymer poly(maleic anhydride-alt-1-octadecene (PMAOD. The goal of the current study is to investigate the uptake processes as well as pro-inflammatory responses in the liver after the injection of these encapsulated nanocrystals. By immunofluorescence and electron microscopy studies using wild type mice, we show that 30 min after injection polymer-coated nanocrystals are primarily taken up by liver sinusoidal endothelial cells. In contrast, by using wild type, Ldlr-/- as well as Apoe-/- mice we show that nanocrystals embedded within lipid micelles are internalized by Kupffer cells and, in a process that is dependent on the LDL receptor and apolipoprotein E, by hepatocytes. Gene expression analysis of pro-inflammatory markers such as tumor necrosis factor alpha (TNFα or chemokine (C-X-C motif ligand 10 (Cxcl10 indicated that 48 h after injection internalized nanocrystals did not provoke pro-inflammatory pathways. In conclusion, internalized nanocrystals at least in mouse liver cells, namely endothelial cells, Kupffer cells and hepatocytes are at least not acutely associated with potential adverse side effects, underlining their potential for biomedical applications.

  20. Epigenetic regulation of pro-inflammatory cytokine secretion by sphingosine 1-phosphate (S1P) in acute lung injury: Role of S1P lyase.

    Science.gov (United States)

    Ebenezer, David L; Fu, Panfeng; Suryadevara, Vidyani; Zhao, Yutong; Natarajan, Viswanathan

    2017-01-01

    Cellular level of sphingosine-1-phosphate (S1P), the simplest bioactive sphingolipid, is tightly regulated by its synthesis catalyzed by sphingosine kinases (SphKs) 1 & 2 and degradation mediated by S1P phosphatases, lipid phosphate phosphatases, and S1P lyase. The pleotropic actions of S1P are attributed to its unique inside-out (extracellular) signaling via G-protein-coupled S1P1-5 receptors, and intracellular receptor independent signaling. Additionally, S1P generated in the nucleus by nuclear SphK2 modulates HDAC1/2 activity, regulates histone acetylation, and transcription of pro-inflammatory genes. Here, we present data on the role of S1P lyase mediated S1P signaling in regulating LPS-induced inflammation in lung endothelium. Blocking S1P lyase expression or activity attenuated LPS-induced histone acetylation and secretion of pro-inflammatory cytokines. Degradation of S1P by S1P lyase generates Δ2-hexadecenal and ethanolamine phosphate and the long-chain fatty aldehyde produced in the cytoplasmic compartment of the endothelial cell seems to modulate histone acetylation pattern, which is different from the nuclear SphK2/S1P signaling and inhibition of HDAC1/2. These in vitro studies suggest that S1P derived long-chain fatty aldehyde may be an epigenetic regulator of pro-inflammatory genes in sepsis-induced lung inflammation. Trapping fatty aldehydes and other short chain aldehydes such as 4-hydroxynonenal derived from S1P degradation and lipid peroxidation, respectively by cell permeable agents such as phloretin or other aldehyde trapping agents may be useful in treating sepsis-induced lung inflammation via modulation of histone acetylation. . Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Pulmonary response to surface‐coated nanotitanium dioxide particles includes induction of acute phase response genes, inflammatory cascades, and changes in microRNAs: A toxicogenomic study

    DEFF Research Database (Denmark)

    Halappanavar, Sabina; Jackson, Petra; Williams, Andrew

    2011-01-01

    with acute phase, inflammation and immune response 5 days post exposure with concomitant changes in several miRNAs. The role of these miRNAs in pulmonary response to inhaled particles is unknown and warrants further research. Environ. Mol. Mutagen., 2011. © 2011 Wiley‐Liss, Inc....... in increased levels of mRNA for acute phase markers serum amyloid A‐1 (Saa1) and serum amyloid A‐3 (Saa3), several C‐X‐C and C‐C motif chemokines, and cytokine tumor necrosis factor genes. Protein analysis of Saa1 and 3 showed selective upregulation of Saa3 in lung tissues. Sixteen miRNAs were induced by more...... than 1.2‐fold (adjusted P‐value changes in the expression of genes associated...

  2. MyD88 mediates in vivo effector functions of alveolar macrophages in acute lung inflammatory responses to carbon nanotube exposure

    Energy Technology Data Exchange (ETDEWEB)

    Frank, Evan A. [Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH 45267 (United States); Birch, M. Eileen [National Institute for Occupational Safety and Health, Cincinnati, OH 45213 (United States); Yadav, Jagjit S., E-mail: Jagjit.Yadav@uc.edu [Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH 45267 (United States)

    2015-11-01

    Carbon nanotubes (CNTs) are rapidly emerging as high-priority occupational toxicants. CNT powders contain fibrous particles that aerosolize readily in places of manufacture and handling, posing an inhalation risk for workers. Studies using animal models indicate that lung exposure to CNTs causes prolonged inflammatory responses and diffuse alveolar injury. The mechanisms governing CNT-induced lung inflammation are not fully understood but have been suggested to involve alveolar macrophages (AMs). In the current study, we sought to systematically assess the effector role of AMs in vivo in the induction of lung inflammatory responses to CNT exposures and investigate their cell type-specific mechanisms. Multi-wall CNTs characterized for various physicochemical attributes were used as the CNT type. Using an AM-specific depletion and repopulation approach in a mouse model, we unambiguously demonstrated that AMs are major effector cells necessary for the in vivo elaboration of CNT-induced lung inflammation. We further investigated in vitro AM responses and identified molecular targets which proved critical to pro-inflammatory responses in this model, namely MyD88 as well as MAPKs and Ca{sup 2} {sup +}/CamKII. We further demonstrated that MyD88 inhibition in donor AMs abrogated their capacity to reconstitute CNT-induced inflammation when adoptively transferred into AM-depleted mice. Taken together, this is the first in vivo demonstration that AMs act as critical effector cell types in CNT-induced lung inflammation and that MyD88 is required for this in vivo effector function. AMs and their cell type-specific mechanisms may therefore represent potential targets for future therapeutic intervention of CNT-related lung injury. - Highlights: • Demonstrated in vivo effector role of alveolar macrophages (AMs) in CNT toxicity • MyD88, MAPKs, and Ca{sup 2} {sup +}/CamKII are required for AM inflammatory responses in vitro. • MyD88 signaling is required for in vivo effector

  3. Acute inflammatory response to a foreign body in Calomys callosus Perfil de migração celular agudo induzido pela presença de corpo estranho em Calomys callosus

    Directory of Open Access Journals (Sweden)

    André Kipnis

    2008-07-01

    Full Text Available

    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 C. callosus and thirty B10A mice received implant and were comparatively analyzed during 144 hours. Circular cover slides implanted in C. callosus showed predominance of macrophages and eosinophils whereas in the mice, the neutrophils followed by the macrophages were the migratory dominant cells (p <0.05. It was concluded that C. callosus present inflammatory mechanisms for the removal of foreign body different from the ones found in the other rodents as well as in the human beings.

     

    KEY WORDS: Acute inflammation, cover slip, granuloma, histology, wild rodents.

    Calomys callosus são roedores silvestres presentes no cerrado brasileiro, que foram adaptados às condições laboratoriais. Trata-se de animais que apresentam resistência às infecções que induzem respostas inflamatórias crônicas (Trypanosoma cruzi e Paracoccidioides brasiliensis. O objetivo deste trabalho foi caracterizar a reação inflamatória, na fase aguda, induzida pela implantação subcutânea de um corpo estranho. Vinte e sete C. callosus e trinta camundongos (B10A foram implantados e analisados comparativamente durante 144 horas. Lamínulas implantadas em C. callosus mostraram predomínio de macrófagos e eosinófilos, enquanto que, nos camundongos, os neutrófilos seguidos pelos macrófagos foram as células migratórias dominantes (p< 0,05. Conclui-se que os C. callosus

  4. Increased extracellular heat shock protein 90α in severe sepsis and SIRS associated with multiple organ failure and related to acute inflammatory-metabolic stress response in children.

    Science.gov (United States)

    Fitrolaki, Michaela-Diana; Dimitriou, Helen; Venihaki, Maria; Katrinaki, Marianna; Ilia, Stavroula; Briassoulis, George

    2016-08-01

    Mammalian heat-shock-protein (HSP) 90α rapidly responses to environmental insults. We examined the hypothesis that not only serum HSP72 but also HSP90α is increased in the systemic inflammatory response syndrome (SIRS), severe-sepsis (SS), and/or sepsis (S) compared to healthy children (H); we assessed HSP90α relation to (a) multiple organ system failure (MOSF) and (b) inflammatory-metabolic response and severity of illness.A total of 65 children with S, SS, or SIRS and 25 H were included. ELISA was used to evaluate extracellular HSP90α and HSP72, chemiluminescence interleukins (ILs), flow-cytometry neutrophil-CD64 (nCD64)-expression.HSP90α, along with HSP72, were dramatically increased among MOSF patients. Patients in septic groups and SIRS had elevated HSP90α compared to H (P stress, fever, outcome endpoints, and predicted mortality and inversely related to the low-LDL/low-HDL stress metabolic pattern.

  5. Anti-inflammatory effect of Heliotropium indicum Linn on lipopolysaccharide-induced uveitis in New Zealand white rabbits

    Directory of Open Access Journals (Sweden)

    Samuel Kyei

    2016-04-01

    Full Text Available AIM: To investigate the anti-inflammatory effect of an aqueous whole plant extract of Heliotropium indicum (HIE on endotoxin-induced uveitis in New Zealand white rabbits. METHODS: Clinical signs of uveitis including flares, iris hyperemia and miosis, were sought for and scored in 1.0 mg/kg lipopolysaccharide (LPS -induced uveitic rabbits treated orally with HIE (30-300 mg/kg, prednisolone (30 mg/kg, or normal saline (10 mL/kg. The number of polymorphonuclear neutrophils infiltrating, the protein concentration, as well as levels of tumor necrosis factor-α (TNF-α, prostaglandin E2 (PGE2, and monocyte chemmoattrant protein-1 (MCP-1 in the aqueous humor after the various treatments were also determined. A histopathological study of the anterior uveal was performed. RESULTS: The extract and prednisolone-treatment significantly reduced (P≤0.001 both the clinical scores of inflammation (1.0-1.8 compared to 4.40±0.40 in the normal saline-treated rabbits and inflammatory cells infiltration. The level of protein, and the concentrations of TNF-α, PGE2 and MCP-1 in the aqueous humor were also significantly reduced (P≤0.001. Histopathological studies showed normal uveal morphology in the HIE and prednisolone-treated rabbits while normal saline-treated rabbits showed marked infiltration of inflammatory cells. CONCLUSION: The HIE exhibits anti-inflammatory effect on LPS-induced uveitis possibly by reducing the production of pro-inflammatory mediators.

  6. Drug-induced acute pancreatitis

    NARCIS (Netherlands)

    I.A. Eland (Ingo)

    2003-01-01

    textabstractAcute pancreatitis is an inflammatory disease of the pancreas with sudden onset. The severity of acute pancreatitis may vary from mild to life threatening. There are many risk factors for acute pancreatitis, among which gallstones and alcohol abuse are most widely known. Drugs are

  7. Bojesodok-eum, a Herbal Prescription, Ameliorates Acute Inflammation in Association with the Inhibition of NF-κB-Mediated Nitric Oxide and ProInflammatory Cytokine Production

    Directory of Open Access Journals (Sweden)

    Kook Ho Sohn

    2012-01-01

    Full Text Available Bojesodok-eum (BSE is a herbal prescription consisting of Coptidis Rhizoma and Scutellariae Radix as main components. This paper investigated the effects of BSE on the induction of nitric oxide (NO, prostaglandin E2 (PGE2, and proinflammatory cytokines that are caused by lipopolysaccharide (LPS in murine macrophage cell line and on the paw edema formation in animals. Administration of BSE (0.3 g/kg and 1 g/kg in rats significantly inhibited carrageenan-induced paw edema formation, as did dexamethasone, an anti-inflammatory positive control drug. In cell model, treatment of BSE decreased the production of NO and PGE2 in RAW264.7 cells stimulated by LPS. BSE also inhibited the expression of iNOS and COX-2 protein as well as COX activity in a concentration-dependent manner. Consistently, BSE suppressed the ability of LPS to produce TNF-α, interleukin-1β, and interleukin-6. LPS treatment induced nuclear NF-κB level and I-κBα phosphorylation, which were inhibited subsequent treatment of BSE, suggesting its repression of LPS-inducible NF-κB activation. BSE abrogated the induction of NO, PGE2, and proinflammatory cytokines, as well as iNOS and COX-2 protein expression in RAW264.7 cells stimulated by LPS as mediated with NF-κB inhibition.

  8. Changes of nitric oxide system and lipid peroxidation parameters in the digestive system of rats under conditions of acute stress, and use of nonsteroidal anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Fomenko Iryna

    2015-03-01

    Full Text Available The use of nonsteroidal anti-inflammatory drugs (NSAIDs in combination with being physiologically stressed often occurs in in the course of different pathologies. This situation may result in the alteration of digestive system functioning. The effect of stress brings about changes in the activity of nitric oxide synthase (NOS, arginase, cyclooxygenase (COX and lipid peroxidation, whereas the use of NSAIDs interrupts the multiple functions of the cell via the inhibition of prostaglandins (PGs synthesis. Taking into account that NOS and COX-systems are connected in their regulation, the aim of the study was to determine the role played by NOS and lipid peroxidation under conditions of the combined action of NSAIDs and stress. In our study, male rats were used. The NSAIDs (naproxen - a non-selective COX inhibitor, celecoxib - a selective COX-2 blocker, and the compound 2A5DHT (which is the active substance of dual COX, and the lipoxygenase (LOX inhibitor, darbufelone were all administered at a dose 10 mg/kg, prior to water restraint stress (WRS. WRS brought about an increase of inducible NOS (iNOS activity in the intestinal mucosal and muscular membranes, as well as in the pancreas. Because of this, constitutive NOS izoform (cNOS and arginase activities decreased. Moreover, the MDA concentration increased, indicating the development of oxidative stress. In our work, pretreatment with naproxen, as in the WRS model, engendered a decrease in iNOS activity. What is more, administration of Celecoxib did not change iNOS activity, as compared to WRS alone, and it showed a tendency to reduce lipid peroxidation. In addition, 2A5DHT prior WRS brought about a decrease of iNOS activity, with the subsequent rise of cNOS activity. Of note, MDA concentration decreased in all studied organs, indicating the reduction of lipid peroxidation under the action of the darbufelone active substance.

  9. Infusion of Trx-1-overexpressing hucMSC prolongs the survival of acutely irradiated NOD/SCID mice by decreasing excessive inflammatory injury.

    Science.gov (United States)

    Hu, JiangWei; Yang, ZaiLiang; Wang, Jun; Tang, YongYong; Liu, Hao; Zhang, Bin; Chen, Hu

    2013-01-01

    A protective reagent for ARI should have the ability to repair injured tissue caused by radiation and prevent continuous damage from secondary risk factors. Trx-1 was explored as a candidate therapy for ARI, as it scavenges reactive oxygen species, regulates cell growth and differentiation, participates in immune reactions, and inhibits apoptosis by acting inside and/or outside cells. Trx-1 can also decrease excessive inflammation in ARI by regulating the creation of inflamed media, by inhibiting the activation of complement, and by reducing the chemotaxis, adhesion, and migration of inflammatory cells. As effectively and stably expressing exogenous genes in the long term and regulating immune inflammation and tissue repair, MSC are a good choice for Trx-1 gene therapy. In this study, Trx-1-overexpressing hucMSC-Trx-1 were obtained by adenoviral vector-mediated infection. We first measured the redox capacity of hucMSC-Trx-1 with an antioxidant capacity (T-AOC) assay, a hydrogen peroxide (H2O2) content determination assay in vivo, a H2O2-induced oxidation hemolysis assay, and a lipid peroxidation assay in vitro. Then, we measured survival time, the protection of the hematopoietic system, and the regulation of inflammation in important organs in three treatment groups of NOD/SCID mice (treated with hucMSC-Trx-1, with hucMSC, and with saline) that were exposed to 4.5 Gy (60)Co-γ-ray radiation. The hucMSC-Trx-1 group achieved superior antioxidation results, protecting bone marrow hematopoietic stem cells (Lin(-)CD117(+): hucMSC-Trx-1 vs. hucMSC, PTrx-1 vs. NS, PTrx-1 vs. hucMSC or NS, PTrx-1 vs. NS, PTrx-1 vs. hucMSC, PTrx-1 vs. NS, PTrx-1 vs. hucMSC, PTrx-1 vs. hucMSC or NS, PTrx-1 combines the merits of gene and cell therapy as a multifunctional radioprotector for ARI.

  10. Association of peripheral arterial disease with periodontal disease: analysis of inflammatory cytokines and an acute phase protein in gingival crevicular fluid and serum.

    Science.gov (United States)

    Çalapkorur, M Unlu; Alkan, B A; Tasdemir, Z; Akcali, Y; Saatçi, E

    2017-06-01

    Inflammation is a common feature of both peripheral arterial disease (PAD) and periodontal disease. The aim of this study was to evaluate the relationship between PAD and periodontal disease by examining the levels of inflammatory cytokines (pentraxin 3 and interleukin 1β) and high sensitive C-reactive protein from gingival crevicular fluid and serum. A total of 60 patients were included in this cross-sectional study. Patients were divided into two groups based on ankle-brachial index values: with PAD (test group) and non-PAD (control group). Demographic evaluations, clinical periodontal examinations and biochemical analysis for pentraxin 3, interleukin 1β and high sensitive C-reactive protein were performed to compare the two groups. There were no significant differences with respect to gender, age, body mass index, or smoking history (duration, amount) between the two groups (p > 0.05). There were no significant differences between the two groups in terms of clinical periodontal parameters (p > 0.05). Neither gingival crevicular fluid nor serum levels of the cytokines showed differences between the two groups. Logistic regression analysis revealed that, after adjusting for confounding factors (age, gender, diabetes, hypertension and body mass index), periodontitis raised the odds ratio for having PAD to 5.842 (95% confidence interval: 1.558-21.909). Although there were no significant differences with respect to clinical periodontal parameters and biochemical analyses between the study group and control, periodontitis did raise the odds ratio for having PAD. To clarify this possible relationship, future prospective studies are needed. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Infusion of Trx-1-overexpressing hucMSC prolongs the survival of acutely irradiated NOD/SCID mice by decreasing excessive inflammatory injury.

    Directory of Open Access Journals (Sweden)

    JiangWei Hu

    Full Text Available A protective reagent for ARI should have the ability to repair injured tissue caused by radiation and prevent continuous damage from secondary risk factors. Trx-1 was explored as a candidate therapy for ARI, as it scavenges reactive oxygen species, regulates cell growth and differentiation, participates in immune reactions, and inhibits apoptosis by acting inside and/or outside cells. Trx-1 can also decrease excessive inflammation in ARI by regulating the creation of inflamed media, by inhibiting the activation of complement, and by reducing the chemotaxis, adhesion, and migration of inflammatory cells. As effectively and stably expressing exogenous genes in the long term and regulating immune inflammation and tissue repair, MSC are a good choice for Trx-1 gene therapy. In this study, Trx-1-overexpressing hucMSC-Trx-1 were obtained by adenoviral vector-mediated infection. We first measured the redox capacity of hucMSC-Trx-1 with an antioxidant capacity (T-AOC assay, a hydrogen peroxide (H2O2 content determination assay in vivo, a H2O2-induced oxidation hemolysis assay, and a lipid peroxidation assay in vitro. Then, we measured survival time, the protection of the hematopoietic system, and the regulation of inflammation in important organs in three treatment groups of NOD/SCID mice (treated with hucMSC-Trx-1, with hucMSC, and with saline that were exposed to 4.5 Gy (60Co-γ-ray radiation. The hucMSC-Trx-1 group achieved superior antioxidation results, protecting bone marrow hematopoietic stem cells (Lin(-CD117(+: hucMSC-Trx-1 vs. hucMSC, P<0.05; hucMSC-Trx-1 vs. NS, P<0.01, promoting the formation of red blood cells and hemoglobin (hucMSC-Trx-1 vs. hucMSC or NS, P<0.05, reducing inflammation and damage in important organs (Bone marrow and lung: hucMSC-Trx-1 vs. NS, P<0.01; hucMSC-Trx-1 vs. hucMSC, P<0.05. Liver and intestine: hucMSC-Trx-1 vs. NS, P<0.05; hucMSC-Trx-1 vs. hucMSC, P<0.05, and prolonging survival (hucMSC-Trx-1 vs. hucMSC or NS, P<0

  12. Inflammatory cascades driven by tumor necrosis factor-alpha play a major role in the progression of acute liver failure and its neurological complications.

    Directory of Open Access Journals (Sweden)

    Anne Chastre

    Full Text Available Acute liver failure (ALF due to ischemic or toxic liver injury is a clinical condition that results from massive loss of hepatocytes and may lead to hepatic encephalopathy (HE, a serious neuropsychiatric complication. Although increased expression of tumor necrosis factor-alpha (TNF-α in liver, plasma and brain has been observed, conflicting results exist concerning its roles in drug-induced liver injury and on the progression of HE. The present study aimed to investigate the therapeutic value of etanercept, a TNF-α neutralizing molecule, on the progression of liver injury and HE in mice with ALF resulting from azoxymethane (AOM hepatotoxicity.Mice were administered saline or etanercept (10 mg/kg; i.p. 30 minutes prior to, or up to 6 h after AOM. Etanercept-treated ALF mice were sacrificed in parallel with vehicle-treated comatose ALF mice and controls. AOM induced severe hepatic necrosis, leading to HE, and etanercept administered prior or up to 3 h after AOM significantly delayed the onset of coma stages of HE. Etanercept pretreatment attenuated AOM-induced liver injury, as assessed by histological examination, plasma ammonia and transaminase levels, and by hepatic glutathione content. Peripheral inflammation was significantly reduced by etanercept as shown by decreased plasma IL-6 (4.1-fold; p<0.001 and CD40L levels (3.7-fold; p<0.001 compared to saline-treated ALF mice. Etanercept also decreased IL-6 levels in brain (1.2-fold; p<0.05, attenuated microglial activation (assessed by OX-42 immunoreactivity, and increased brain glutathione concentrations.These results indicate that systemic sequestration of TNF-α attenuates both peripheral and cerebral inflammation leading to delayed progression of liver disease and HE in mice with ALF due to toxic liver injury. These results suggest that etanercept may provide a novel therapeutic approach for the management of ALF patients awaiting liver transplantation.

  13. [Effect of compound danshen dripping pill combined with intravenous transplantation of human umbilical cord blood mononuclear cells on local inflammatory response in the myocardium of rabbits with acute myocardial infarction].

    Science.gov (United States)

    Deng, Liu-xia; Yu, Guo-long; Al, Qi; Yuan, Chun-ju

    2013-11-01

    To investigate effect of Compound Danshen Dripping Pill (CDDP) on the inflammatory response of the myocardium of acute myocardial infarction (AMI) rabbits, to observe the therapeutic effect of CDDP combined intravenous transplantation of human umbilical cord blood mononuclear cells (HUCBMCs) on inflammatory response, pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) , and heart function in the myocardium of AMI rabbits, and to explore the possible protective mechanisms of the combined therapy. The AMI model was successfully established by ligation of the left anterior coronary artery (LAD) in 40 healthy rabbits.Then they were randomly divided into four groups, i.e., the control group, the CDDP group, the transplantation group, and the combined group, 10 in each group. Rabbits in the control group received intravenous injection of 0.5 mL normal saline via ear vein within 24 h after AMI and then intragastric infusion of normal saline at 5 mL per day. Rabbits in the CDDP group received intravenous injection of 0.5 mL normal saline via ear vein within 24 h after AMI and then intragastric infusion of solution obtained by solving 270 mg CDDP in 5 mL normal saline per day. Rabbits in the transplantation group received intravenous injection of 0.5 mL normal saline labeled with green fluorescent protein (GFP) containing 3 x 10(7) of HUCBMCs via ear vein within 24 h after AMI and then intragastric infusion of normal saline at 5 mL per day. Rabbits in the combined group received intravenous injection of 0.5 mL normal saline labeled with GFP containing 3 x 10(7) of HUCBMCs via ear vein within 24 h after AMI and then intragastric infusion of solution obtained by solving 270 mg CDDP in 5 mL normal saline per day. At week 1 and 4 after treatment, cardiac function indices such as left ventricular fractional shorting (LVFS) and left ventricular ejection fraction (LVEF) were performed by echocardiography; the number of transplanted cells in the myocardium was found

  14. Timing matters: the interval between acute stressors within chronic mild stress modifies behavioral and physiologic stress responses in male rats.

    Science.gov (United States)

    Cavigelli, Sonia A; Bao, Alexander D; Bourne, Rebecca A; Caruso, Michael J; Caulfield, Jasmine I; Chen, Mary; Smyth, Joshua M

    2018-04-12

    Chronic mild stress can lead to negative health outcomes. Frequency, duration, and intensity of acute stressors can affect health-related processes. We tested whether the temporal pattern of daily acute stressors (clustered or dispersed across the day) affects depression-related physiology. We used a rodent model to keep stressor frequency, duration, and intensity constant, and experimentally manipulated the temporal pattern of acute stressors delivered during the active phase of the day. Adult male Sprague-Dawley rats were exposed to one of three chronic mild stress groups: Clustered: stressors that occurred within 1 hour of each other (n = 21), Dispersed: stressors that were spread out across the active phase (n = 21), and Control: no stressors presented (n = 21). Acute mild stressors included noise, strobe lights, novel cage, cage tilt, wet bedding, and water immersion. Depression-related outcomes included: sucrose preference, body weight, circulating glucocorticoid (corticosterone) concentration after a novel acute stressor and during basal morning and evening times, and endotoxin-induced circulating interleukin-6 concentrations. Compared to control rats, those in the Clustered group gained less weight, consumed less sucrose, had a blunted acute corticosterone response, and an accentuated acute interleukin-6 response. Rats in the Dispersed group had an attenuated corticosterone decline during the active period and after an acute stressor compared to the Control group. During a chronic mild stress experience, the temporal distribution of daily acute stressors affected health-related physiologic processes. Regular exposure to daily stressors in rapid succession may predict more depression-related symptoms, whereas exposure to stressors dispersed throughout the day may predict diminished glucocorticoid negative feedback.

  15. Inflammatory mechanisms in the lung

    Directory of Open Access Journals (Sweden)

    B Moldoveanu

    2008-12-01

    Full Text Available B Moldoveanu1, P Otmishi1, P Jani1, J Walker1,2, X Sarmiento3, J Guardiola1, M Saad1, Jerry Yu11Department of Medicine, University of Louisville, Louisville, KY, USA, 40292; 2Department of Respiratory Therapy, Bellarmine University, Louisville, KY, USA, 40205; 3Intensive Care Medicine Service, University Hospital Germans Trias i Pujol, Badalona, Spain 08916Abstract: Inflammation is the body’s response to insults, which include infection, trauma, and hypersensitivity. The inflammatory response is complex and involves a variety of mechanisms to defend against pathogens and repair tissue. In the lung, inflammation is usually caused by pathogens or by exposure to toxins, pollutants, irritants, and allergens. During inflammation, numerous types of inflammatory cells are activated. Each releases cytokines and mediators to modify activities of other inflammatory cells. Orchestration of these cells and molecules leads to progression of inflammation. Clinically, acute inflammation is seen in pneumonia and acute respiratory distress syndrome (ARDS, whereas chronic inflammation is represented by asthma and chronic obstructive pulmonary disease (COPD. Because the lung is a vital organ for gas exchange, excessive inflammation can be life threatening. Because the lung is constantly exposed to harmful pathogens, an immediate and intense defense action (mainly inflammation is required to eliminate the invaders as early as possible. A delicate balance between inflammation and anti-inflammation is essential for lung homeostasis. A full understanding of the underlying mechanisms is vital in the treatment of patients with lung inflammation. This review focuses on cellular and molecular aspects of lung inflammation during acute and chronic inflammatory states.Keywords: inflammation, lung, inflammatory mediators, cytokines

  16. Involvement of AMPA receptor GluR2 and GluR3 trafficking in trigeminal spinal subnucleus caudalis and C1/C2 neurons in acute-facial inflammatory pain.

    Directory of Open Access Journals (Sweden)

    Makiko Miyamoto

    Full Text Available To evaluate the involvement of trafficking of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR GluR2 and GluR3 subunits in an acute inflammatory orofacial pain, we analyzed nocifensive behavior, phosphorylated extracellular signal-regulated kinase (pERK and Fos expression in Vi/Vc, Vc and C1/C2 in GluR2 delta7 knock-in (KI, GluR3 delta7 KI mice and wild-type mice. We also studied Vc neuronal activity to address the hypothesis that trafficking of GluR2 and GluR3 subunits plays an important role in Vi/Vc, Vc and C1/C2 neuronal activity associated with orofacial inflammation in these mice. Late nocifensive behavior was significantly depressed in GluR2 delta7 KI and GluR3 delta7 KI mice. In addition, the number of pERK-immunoreactive (IR cells was significantly decreased bilaterally in the Vi/Vc, Vc and C1/C2 in GluR2 delta7 KI and GluR3 delta7 KI mice compared to wild-type mice at 40 min after formalin injection, and was also significantly smaller in GluR3 delta7 KI compared to GluR2 delta7 KI mice. The number of Fos protein-IR cells in the ipsilateral Vi/Vc, Vc and C1/C2 was also significantly smaller in GluR2 delta7 KI and GluR3 delta7 KI mice compared to wild-type mice 40 min after formalin injection. Nociceptive neurons functionally identified as wide dynamic range neurons in the Vc, where pERK- and Fos protein-IR cell expression was prominent, showed significantly lower spontaneous activity in GluR2 delta7 KI and GluR3 delta7 KI mice than wild-type mice following formalin injection. These findings suggest that GluR2 and GluR3 trafficking is involved in the enhancement of Vi/Vc, Vc and C1/C2 nociceptive neuronal excitabilities at 16-60 min following formalin injection, resulting in orofacial inflammatory pain.

  17. CD1d-restricted IFN-γ-secreting NKT cells promote immune complex-induced acute lung injury by regulating macrophage-inflammatory protein-1α production and activation of macrophages and dendritic cells.

    Science.gov (United States)

    Kim, Ji Hyung; Chung, Doo Hyun

    2011-02-01

    Immune complex-induced acute lung injury (IC-ALI) has been implicated in various pulmonary disease states. However, the role of NKT cells in IC-ALI remains unknown. Therefore, we explored NKT cell functions in IC-ALI using chicken egg albumin and anti-chicken egg albumin IgG. The bronchoalveolar lavage fluid of CD1d(-/-) and Jα18(-/-) mice contained few Ly6G(+)CD11b(+) granulocytes, whereas levels in B6 mice were greater and were increased further by α-galactosyl ceramide. IFN-γ and MIP-1α production in the lungs was greater in B6 than CD1d(-/-) mice. Adoptive transfer of wild type (WT) but not IFN-γ-, MIP-1α-, or FcγR-deficient NKT cells into CD1d(-/-) mice caused recruitment of inflammatory cells to the lungs. Moreover, adoptive transfer of IFN-γR-deficient NKT cells enhanced MIP-1α production and cell recruitment in the lungs of CD1d(-/-) or CD1d(-/-)IFN-γ(-/-) mice, but to a lesser extent than WT NKT cells. This suggests that IFN-γ-producing NKT cells enhance MIP-1α production in both an autocrine and a paracrine manner. IFN-γ-deficient NKT cells induced less IL-1β and TNF-α production by alveolar macrophages and dendritic cells in CD1d(-/-) mice than did WT NKT cells. Taken together, these data suggest that CD1d-restricted IFN-γ-producing NKT cells promote IC-ALI by producing MIP-1α and enhancing proinflammatory cytokine production by alveolar macrophages and dendritic cells.

  18. The Concomitant Use of Diuretics, Non-Steroidal Anti-Inflammatory Drugs, and Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers (Triple Whammy), Extreme Heat, and In-Hospital Acute Kidney Injury in Older Medical Patients.

    Science.gov (United States)

    Mangoni, Arduino A; Kholmurodova, Feruza; Mayner, Lidia; Hakendorf, Paul; Woodman, Richard J

    2017-11-01

    We investigated whether the concomitant use of diuretics, non-steroidal anti-inflammatory drugs, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (triple whammy, TW) predicts in-hospital acute kidney injury (AKI) and whether admission during recorded periods of extreme heat influences this association. We retrospectively collected data on patient characteristics and use of TW/non-TW drugs on admission, AKI (increase in serum creatinine ≥ 27 µmol/l either within the first 48 h of admission or throughout hospitalization, primary outcome), length of stay (LOS), and mortality (secondary outcomes) in medical patients ≥65 years admitted (1) during five consecutive heat waves (HWs) between 2007 and 2009 (n = 382) or (2) either before or after each HW, matched for HW period, age, and admission day of the week (non-HW, controls, n = 1339). Number of TW and non-TW drugs, co-morbidities, number of daily admissions, incidence of in-hospital AKI, LOS, and mortality were similar in the HW and non-HW groups. After adjusting for clinical and demographic confounders, logistic regression showed that TW use did not predict AKI within 48 h of admission either during non-HW periods (OR 0.79, 95% CI 0.34-1.83, P = 0.58) or during HWs (OR 1.02, 95% CI 0.21-2.97, P = 0.97). Similar results were observed when AKI was captured throughout hospitalization. TW use did not predict LOS or mortality irrespective of environmental temperature on admission. TW use on admission did not predict in-hospital AKI, LOS, or mortality in older medical patients admitted either during periods of normal environmental temperature or during HWs.

  19. 18F-fluoro-2-deoxyglucose PET informs neutrophil accumulation and activation in lipopolysaccharide-induced acute lung injury.

    Science.gov (United States)

    Rodrigues, Rosana S; Bozza, Fernando A; Hanrahan, Christopher J; Wang, Li-Ming; Wu, Qi; Hoffman, John M; Zimmerman, Guy A; Morton, Kathryn A

    2017-05-01

    Molecular imaging of the earliest events related to the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) could facilitate therapeutic development and patient management. We previously reported that 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) PET identifies ALI/ARDS prior to radiographic abnormalities. The purpose of this study was to establish the time courses of 18 F-FDG uptake, edema and neutrophil recruitment in an endotoxin-induced acute lung injury model and to examine molecular events required for 14 C-2DG uptake in activated neutrophils. Lung uptake of 18 F-FDG was measured by PET in control male Sprague Dawley rats and at 2, 6 and 24h following the intraperitoneal injection of 10mg/kg LPS. Lung edema (attenuation) was measured by microCT. Neutrophil influx into the lungs was measured by myeloperoxidase assay. Control and activated human donor neutrophils were compared for uptake of 14 C-2DG, transcription and content of hexokinase and GLUT isoforms and for hexokinase (HK) activity. Significant uptake of 18 F-FDG occurred by 2h following LPS, and progressively increased to 24h. Lung uptake of 18 F-FDG preceded increased CT attenuation (lung edema). Myeloperoxidase activity in the lungs, supporting neutrophil influx, paralleled 18 F-FDG uptake. Activation of isolated human neutrophils resulted in increased uptake of 14 C-2DG, expression of GLUT 3 and GLUT 4 and expression and increased HK1 activity. Systemic endotoxin-induced ALI results in very early and progressive uptake of 18 F-FDG, parallels neutrophil accumulation and occurs earlier than lung injury edema. Activated neutrophils show increased uptake of 14 C-2DG, expression of specific GLUT3, GLUT4 and HK1 protein and HK activity. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: 18 F-FDG pulmonary uptake is an early biomarker of neutrophil recruitment in ALI and is associated with specific molecular events that mediate 14 C-2DG uptake in activated neutrophils. 18 F

  20. Postpartum Inflammatory Sacroiliitis-A Case Report

    Directory of Open Access Journals (Sweden)

    Seniz Akcay Yalbuzdag

    2013-08-01

    Full Text Available During the pregnancy several changes occur in sacroiliac joint and pelvis which may predispose for sacroiliac joint strain and septic sacroiliitis. We describe a case of acute inflammatory sacroiliitis in a patient with HLA B27 positivity during postpartum period, and diagnosed psoriatic arthritis during the follow up period. We aimed to emphasize that inflammatory sacroiliitis should take place whithin differantial diagnose of postpartum low back pain.

  1. Acute dental pain II

    DEFF Research Database (Denmark)

    Jonasson, Peter; Kirkevang, Lise-Lotte; Rosen, Annika

    2016-01-01

    Acute dental pain most often occurs in relation to inflammatory conditions in the dental pulp or in the periradicular tissues surrounding a tooth, but it is not always easy to reach a diagnose and determine what treatment to perform. The anamnesis and the clinical examination provide valuable...

  2. Autophagy Limits Endotoxemic Acute Kidney Injury and Alters Renal Tubular Epithelial Cell Cytokine Expression.

    Directory of Open Access Journals (Sweden)

    Jeremy S Leventhal

    Full Text Available Sepsis related acute kidney injury (AKI is a common in-hospital complication with a dismal prognosis. Our incomplete understanding of disease pathogenesis has prevented the identification of hypothesis-driven preventive or therapeutic interventions. Increasing evidence in ischemia-reperfusion and nephrotoxic mouse models of AKI support the theory that autophagy protects renal tubular epithelial cells (RTEC from injury. However, the role of RTEC autophagy in septic AKI remains unclear. We observed that lipopolysaccharide (LPS, a mediator of gram-negative bacterial sepsis, induces RTEC autophagy in vivo and in vitro through TLR4-initiated signaling. We modeled septic AKI through intraperitoneal LPS injection in mice in which autophagy-related protein 7 was specifically knocked out in the renal proximal tubules (ATG7KO. Compared to control littermates, ATG7KO mice developed more severe renal dysfunction (24hr BUN 100.1mg/dl +/- 14.8 vs 54.6mg/dl +/- 11.3 and parenchymal injury. After injection with LPS, analysis of kidney lysates identified higher IL-6 expression and increased STAT3 activation in kidney lysates from ATG7KO mice compared to controls. In vitro experiments confirmed an altered response to LPS in RTEC with genetic or pharmacological impairment of autophagy. In conclusion, RTEC autophagy protects against endotoxin induced injury and regulates downstream effects of RTEC TLR4 signaling.

  3. Assessment of anti-inflammatory potential of Sesbania bispinosa ...

    African Journals Online (AJOL)

    Aim and objectives: Leaf extracts and fractions of S. bispinosa were evaluated for anti-inflammatory activity in mice using acute and chronic anti-inflammatory models with aspirin as a reference drug. Materials and methods: Methanol, chloroform and hexane were used to prepare leaf extracts by soxhlet extraction method, ...

  4. Bioassay guided isolation and identification of anti-inflammatory and ...

    African Journals Online (AJOL)

    The present study describes the anti-inflammatory, anti-microbial activity and lipophilic profile with acute toxicological studies of Urtica dioica. Successive extraction of the leaves with organic solvents of increasing polarity and their screening for anti-inflammatory and anti-microbial activity was assessed. Hexane extract ...

  5. Importancia de algunos medios auxiliares de diagnóstico en la enfermedad inflamatoria pélvica aguda Importance of some diagnostic aids in the acute pelvic inflammatory disease

    Directory of Open Access Journals (Sweden)

    Pastor Villavicencio Crespo

    2008-03-01

    en comparación con la laparoscopia es el ultrasonido (77 %, al cual siguió el tacto vaginal (70 %INTRODUCTION. At present, the acute pelvic inflammatory disease is considered a syndrome clinically attributed to the ascending passage of microorganisms from the vagina to the cervix, the endometrium and the Fallopian's tubes. It is also capable of disseminating to the neighbouring structures. The objective of this paper was to know the behaviour of the disease, the efficiency of some diagnostic aids and procedures, the performance of the haematological tests, and to identify the most common germs to define the further conduct. METHODS. The study group consisted of 108 females seen at "Julio Trigo López" Hospital due to an acute inflammatory pelvic disease. The sample was selected at random and variables such as general and health data and data from the gynecoobstetric history were registered. Vaginal manipulation, with anaesthesia or without it, puncture of Douglas' pouch, ultrasound, laparoscopy, red-blood cell count, white-blood cell count, and erythrosedimentation were used to make the diagnosis. Laparoscopy was used in all cases as a confirmatory test. RESULTS. Most of the patients were aged 20-25. Abdominal pain (98.1 % and leucorrhoea (30.6 % predominated as clinical symptomatology. A high incidence of this disease was observed in females at reproductive age, with 2 or more pregnancies and abortions and history of implanted intrauterine device. Moreover, there was a diagnostic concordance between the results of the vaginal manipulation and ultrasound, on comparing them with laparoscopy. The least specific test was vaginal manipulation (20.5 % and the predictive values of the lowest positive test were obtained with the same procedure (64.6 %, as well as with erythrosedimentation (70 %. Therefore, ultrasound proved to be the most effective diagnostic aid (87,5 % after laparoscopy. CONCLUSIONS. It was concluded that ultrasound (77 % is the most effective test

  6. A Role for the Inflammasome in Spontaneous Labor at Term with Acute Histologic Chorioamnionitis.

    Science.gov (United States)

    Gomez-Lopez, Nardhy; Romero, Roberto; Xu, Yi; Plazyo, Olesya; Unkel, Ronald; Than, Nandor Gabor; Chaemsaithong, Piya; Chaiworapongsa, Tinnakorn; Dong, Zhong; Tarca, Adi L; Abrahams, Vikki M; Yeo, Lami; Hassan, Sonia S

    2017-06-01

    Inflammasomes are cytosolic signaling platforms that regulate the activation of caspase (CASP)-1, which induces the maturation of interleukin (IL)-1β and IL-18. Herein, we determined whether the chorioamniotic membranes from women in spontaneous labor at term with acute histologic chorioamnionitis express major inflammasome components and whether these changes are associated with the activation of CASP-1 and CASP-4 and the release of mature IL-1β and IL-18. When comparing the chorioamniotic membranes from women in spontaneous labor at term with acute histologic chorioamnionitis to those without this placental lesion, we found that (1) the messenger RNA (mRNA) abundance of NLR family pyrin domain containing 3 ( NLRP3), NLR family CARD domain containing 4 ( NLRC4), absent in melanoma 2 ( AIM2), and nucleotide binding oligomerization domain 2 ( NOD2) was higher; (2) the NLRP3 and NLRC4 protein quantities were increased; (3) the mRNA and protein expressions of CASP-1 and its active forms were greater; (4) CASP-4 was increased at the mRNA level only; (5) the mRNA and protein expressions of IL-1β and its mature form were higher; and (6) a modest increase in the total protein concentration and abundance of the mature form of IL-18 was observed. In vitro incubation of the chorioamniotic membranes with the CASP-1 inhibitor, VX765, decreased the release of endotoxin-induced IL-1β and IL-18 (2-fold) but not IL-6 or tumor necrosis factor α. In conclusion, spontaneous labor at term with acute histologic chorioamnionitis is characterized by an upregulation of inflammasome components which, in turn, may participate in the activation of CASP-1 and lead to the release of mature IL-1β by the chorioamniotic membranes. These results support a role for the inflammasome in the mechanisms responsible for spontaneous labor at term with acute histologic chorioamnionitis.

  7. The effect of glutamine infusion on the inflammatory response and HSP70 during human experimental endotoxaemia

    DEFF Research Database (Denmark)

    Andreasen, Anne Sofie; Pedersen-Skovsgaard, Theis; Mortensen, Ole Hartvig

    2009-01-01

    was associated with alterations in white blood cell and differential counts, tumour necrosis factor-alpha, IL-6, temperature and heart rate, but glutamine affected neither the endotoxin-induced change in these variables nor the expression of HSP70 in BMNCs. CONCLUSIONS: Endotoxin reduced plasma glutamine...

  8. 18F-fluoro-2-deoxyglucose PET informs neutrophil accumulation and activation in lipopolysaccharide-induced acute lung injury genetic algorithm

    International Nuclear Information System (INIS)

    Rodrigues, Rosana S.; Bozza, Fernando A.; Hanrahan, Christopher J.; Wang, Li-Ming; Wu, Qi; Hoffman, John M.; Zimmerman, Guy A.; Morton, Kathryn A.

    2017-01-01

    Introduction: Molecular imaging of the earliest events related to the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) could facilitate therapeutic development and patient management. We previously reported that 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) PET identifies ALI/ARDS prior to radiographic abnormalities. The purpose of this study was to establish the time courses of 18 F-FDG uptake, edema and neutrophil recruitment in an endotoxin-induced acute lung injury model and to examine molecular events required for 14 C-2DG uptake in activated neutrophils. Methods: Lung uptake of 18 F-FDG was measured by PET in control male Sprague Dawley rats and at 2, 6 and 24 h following the intraperitoneal injection of 10 mg/kg LPS. Lung edema (attenuation) was measured by microCT. Neutrophil influx into the lungs was measured by myeloperoxidase assay. Control and activated human donor neutrophils were compared for uptake of 14 C-2DG, transcription and content of hexokinase and GLUT isoforms and for hexokinase (HK) activity. Results: Significant uptake of 18 F-FDG occurred by 2 h following LPS, and progressively increased to 24 h. Lung uptake of 18 F-FDG preceded increased CT attenuation (lung edema). Myeloperoxidase activity in the lungs, supporting neutrophil influx, paralleled 18 F-FDG uptake. Activation of isolated human neutrophils resulted in increased uptake of 14 C-2DG, expression of GLUT 3 and GLUT 4 and expression and increased HK1 activity. Conclusion: Systemic endotoxin-induced ALI results in very early and progressive uptake of 18 F-FDG, parallels neutrophil accumulation and occurs earlier than lung injury edema. Activated neutrophils show increased uptake of 14 C-2DG, expression of specific GLUT3, GLUT4 and HK1 protein and HK activity. Advances in knowledge and implications for patient care: 18 F-FDG pulmonary uptake is an early biomarker of neutrophil recruitment in ALI and is associated with specific molecular events that mediate 14

  9. Redox signaling in acute pancreatitis

    Science.gov (United States)

    Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

    2015-01-01

    Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF–VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis. PMID:25778551

  10. Redox signaling in acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Salvador Pérez

    2015-08-01

    Full Text Available Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF–VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis.

  11. Anti-inflammatory and analgesic activity of r.a.p . ( Radix Angelicae ...

    African Journals Online (AJOL)

    The objective of this paper was to study the anti-inflammatory and analgesic effects of Radix Angelicae Pubescentis (R.A.P) ethanol extracts. Three classic anti-inflammatory models and two analgesic models were used in this research. In anti-inflammatory tests, all the extracts have a certain inhibition on the acute ...

  12. Systemic corticosteroid therapy for acute sinusitis

    NARCIS (Netherlands)

    Venekamp, Roderick P.; Thompson, Matthew J.; Rovers, Maroeska M.

    2015-01-01

    CLINICAL QUESTION: Are oral or parenteral corticosteroids associated with improved clinical outcomes in patients with acute sinusitis compared with placebo or nonsteroidal anti-inflammatory drugs (NSAIDs)? BOTTOM LINE: Oral corticosteroids combined with antibioticsmay be associated with modest

  13. Systemic corticosteroid therapy for acute sinusitis

    NARCIS (Netherlands)

    Venekamp, R.P.; Thompson, M.J.; Rovers, M.M.

    2015-01-01

    CLINICAL QUESTION: Are oral or parenteral corticosteroids associated with improved clinical outcomes in patients with acute sinusitis compared with placebo or nonsteroidal anti-inflammatory drugs (NSAIDs)? BOTTOM LINE: Oral corticosteroids combined with antibiotics may be associated with modest

  14. The α-MSH analogue AP214 attenuates rise in pulmonary pressure and fall in ejection fraction in lipopolysaccharide-induced systemic inflammatory response syndrome in pigs.

    Science.gov (United States)

    Kristensen, Jens; Jonassen, Thomas E N; Rehling, Michael; Tønnesen, Else; Sloth, Erik; Nielsen, Søren; Frøkiaer, Jørgen

    2011-01-01

    The effect of an α-melanocyte stimulating hormone (α-MSH) analogue (AP214) on experimentally endotoxin-induced systemic inflammatory response syndrome (SIRS) was studied, because α-MSH in rodent models has shown promise in attenuating inflammatory response markers and associated organ damage in SIRS. SIRS is associated with considerable morbidity and mortality. Consequently, new treatment modalities are still warranted to address the different aspects of the pathophysiological process. SIRS was induced by lipopolysaccharide (LPS) (Escherichia coli endotoxin) infusion in anaesthetized Danish Landrace pigs (20-25 kg). The pigs received an α-MSH analogue (AP214) or saline as a bolus at the initiation of the LPS infusion. The hemodynamic response was registered as well as echocardiographic indices of left ventricular function. The cardiovascular response was recorded together with echocardiographic indices of left ventricular function in control and in intervention animals. AP214 reduced the early peak in pulmonary pressure and pulmonary vascular resistance by approximately 33%. Furthermore, AP214 prevented the decline in left ventricular fractional shortening as observed in the control group. Mean change and standard deviation in fractional shortening (ΔFS) in control group: - 7·3 (4·7), AP214 (low dose): 0·9 (8·2) and AP214 (high dose) 4·1 (6·0), P < 0·05 for both intervention groups versus control. In the porcine model, the peak increase in pulmonary pressure was attenuated, and the LPS-induced decline in left ventricular function was prevented. © 2010 The Authors. Clinical Physiology and Functional Imaging © 2010 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

  15. Acute leukaemoid reaction following cardiac surgery

    Directory of Open Access Journals (Sweden)

    Webb Stephen T

    2007-01-01

    Full Text Available Abstract Chronic myelomonocytic leukaemia is an atypical myeloproliferative disorder with a natural history of progression to acute myeloid leukaemia, a complex and poorly understood response by the bone marrow to stress. Cardiac surgery activates many inflammatory cascades and may precipitate a systemic inflammatory response syndrome. We present a case of undiagnosed chronic myelomonocytic leukaemia who developed rapidly fatal multi-organ dysfunction following cardiac surgery due to an acute leukaemoid reaction.

  16. Inflammatory myofibroblastic tumor

    Directory of Open Access Journals (Sweden)

    Sangeeta Palaskar

    2011-01-01

    Full Text Available Inflammatory myofibroblastic tumor is an uncommon lesion of unknown cause. It encompasses a spectrum of myofibroblastic proliferation along with varying amount of inflammatory infiltrate. A number of terms have been applied to the lesion, namely, inflammatory pseudotumor, fibrous xanthoma, plasma cell granuloma, pseudosarcoma, lymphoid hamartoma, myxoid hamartoma, inflammatory myofibrohistiocytic proliferation, benign myofibroblatoma, and most recently, inflammatory myofibroblastic tumor. The diverse nomenclature is mostly descriptive and reflects the uncertainty regarding true biologic nature of these lesions. Recently, the concept of this lesion being reactive has been challenged based on the clinical demonstration of recurrences and metastasis and cytogenetic evidence of acquired clonal chromosomal abnormalities. We hereby report a case of inflammatory pseudotumor and review its inflammatory versus neoplastic behavior.

  17. Anti-Inflammatory Iridoids of Botanical Origin

    Science.gov (United States)

    Viljoen, A; Mncwangi, N; Vermaak, I

    2012-01-01

    Inflammation is a manifestation of a wide range of disorders which include; arthritis, atherosclerosis, Alzheimer’s disease, inflammatory bowel syndrome, physical injury and infection amongst many others. Common treatment modalities are usually non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, paracetamol, indomethacin and ibuprofen as well as corticosteroids such as prednisone. These however, may be associated with a host of side effects due to non-selectivity for cyclooxygenase (COX) enzymes involved in inflammation and those with selectivity may be highly priced. Thus, there is a continuing search for safe and effective anti-inflammatory molecules from natural sources. Research has confirmed that iridoids exhibit promising anti-inflammatory activity which may be beneficial in the treatment of inflammation. Iridoids are secondary metabolites present in various plants, especially in species belonging to the Apocynaceae, Lamiaceae, Loganiaceae, Rubiaceae, Scrophulariaceae and Verbenaceae families. Many of these ethnobotanicals have an illustrious history of traditional use alluding to their use to treat inflammation. Although iridoids exhibit a wide range of pharmacological activities such as cardiovascular, hepatoprotection, hypoglycaemic, antimutagenic, antispasmodic, anti-tumour, antiviral, immunomodulation and purgative effects this review will acutely focus on their anti-inflammatory properties. The paper aims to present a summary for the most prominent iridoid-containing plants for which anti-inflammatory activity has been demonstrated in vitro and / or in vivo. PMID:22414102

  18. Hypertonic saline reduces inflammation and enhances the resolution of oleic acid induced acute lung injury

    Directory of Open Access Journals (Sweden)

    Costello Joseph F

    2008-07-01

    Full Text Available Abstract Background Hypertonic saline (HTS reduces the severity of lung injury in ischemia-reperfusion, endotoxin-induced and ventilation-induced lung injury. However, the potential for HTS to modulate the resolution of lung injury is not known. We investigated the potential for hypertonic saline to modulate the evolution and resolution of oleic acid induced lung injury. Methods Adult male Sprague Dawley rats were used in all experiments. Series 1 examined the potential for HTS to reduce the severity of evolving oleic acid (OA induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 12 or hypertonic saline (HTS, n = 12, and the extent of lung injury assessed after 6 hours. Series 2 examined the potential for HTS to enhance the resolution of oleic acid (OA induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 6 or hypertonic saline (HTS, n = 6, and the extent of lung injury assessed after 6 hours. Results In Series I, HTS significantly reduced bronchoalveolar lavage (BAL neutrophil count compared to Control [61.5 ± 9.08 versus 102.6 ± 11.89 × 103 cells.ml-1]. However, there were no between group differences with regard to: A-a O2 gradient [11.9 ± 0.5 vs. 12.0 ± 0.5 KPa]; arterial PO2; static lung compliance, or histologic injury. In contrast, in Series 2, hypertonic saline significantly reduced histologic injury and reduced BAL neutrophil count [24.5 ± 5.9 versus 46.8 ± 4.4 × 103 cells.ml-1], and interleukin-6 levels [681.9 ± 190.4 versus 1365.7 ± 246.8 pg.ml-1]. Conclusion These findings demonstrate, for the first time, the potential for HTS to reduce pulmonary inflammation and enhance the resolution of oleic acid induced lung injury.

  19. Influência da resposta inflamatória de fase aguda nos níveis séricos de retinol e da proteína de ligação do retinol em pacientes com AIDS Influence of acute-phase inflammatory response on serum levels of retinol and retinol binding protein in HIV/AIDS patients

    Directory of Open Access Journals (Sweden)

    Fábio Fernandes Neves

    2010-02-01

    Full Text Available INTRODUÇÃO: a hiporretinolemia constitui fator prognóstico independente em pacientes com AIDS, e a atividade inflamatória causa redução dos níveis séricos deste nutriente na população em geral. Entretanto, faltam estudos que avaliem o impacto da atividade inflamatória sobre o nível sérico do retinol em pacientes com AIDS. MÉTODOS: foram avaliados transversalmente 41 pacientes internados por complicações da AIDS, que tiveram quantificados alguns marcadores de inflamação (proteína C reativa e fator de necrose tumoral alfa e concentrações séricas de retinol e da proteína de ligação do retinol. RESULTADOS: apesar da baixa (14,6% prevalência de hiporretinolemia evidenciou-se correlação negativa dos marcadores de inflamação com os níveis séricos de retinol e de sua proteína de ligação nos pacientes com AIDS. CONCLUSÕES: a atividade inflamatória de fase aguda está associada a baixos níveis séricos de retinol em indivíduos com AIDS.INTRODUCTION: Hyporetinolemia is an independent prognostic factor in AIDS patients. Inflammatory activity causes a reduction in the serum levels of this nutrient in the general population. However, there are no studies assessing the impact of inflammatory activity on the serum retinol level in AIDS patients. METHODS: A cross-sectional assessment was conducted on 41 patients hospitalized due to AIDS complications. Inflammatory markers (C-reactive protein and tumor necrosis factor-alpha and serum retinol and retinol binding protein concentrations were quantified. RESULTS: Despite the low (14.6% prevalence of hyporetinolemia, a significant negative correlation was observed between the inflammatory markers and the serum retinol and retinol binding protein levels in AIDS patients. CONCLUSIONS: Acute-phase inflammatory activity is associated with low serum retinol levels in individuals with AIDS.

  20. Translation Control: A Multifaceted Regulator of Inflammatory Response

    Science.gov (United States)

    Mazumder, Barsanjit; Li, Xiaoxia; Barik, Sailen

    2010-01-01

    A robust innate immune response is essential to the protection of all vertebrates from infection, but it often comes with the price tag of acute inflammation. If unchecked, a runaway inflammatory response can cause significant tissue damage, resulting in myriad disorders, such as dermatitis, toxicshock, cardiovascular disease, acute pelvic and arthritic inflammatory diseases, and various infections. To prevent such pathologies, cells have evolved mechanisms to rapidly and specifically shut off these beneficial inflammatory activities before they become detrimental. Our review of recent literature, including our own work, reveals that the most dominant and common mechanism is translational silencing, in which specific regulatory proteins or complexes are recruited to cis-acting RNA structures in the untranslated regions of single or multiple mRNAs that code for the inflammatory protein(s). Enhancement of the silencing function may constitute a novel pharmacological approach to prevent immunity-related inflammation. PMID:20304832

  1. Inflammatory diseases of the myelon

    International Nuclear Information System (INIS)

    Spitzer, C.; Krings, T.; Block, F.; Universitaetsklinikum Aachen

    2001-01-01

    Myelitis is defined as inflammatory disease of the spinal cord irrespective of the underlying aetiology or pathologic-anatomic alterations. It can be caused by direct infections, postinfectious or postvaccinal immunological processes or other (auto)immunological diseases such as multiple sclerosis or systemic vasculitis. The clinical presentation is diverse and varies from temporary sensory deficits to persistent tetraplegia with respiratory insufficiency. Diagnostic work-up must include a thorough anamnesis, clinical-neurological examination, neurophysiological studies, analysis of blood and cerebospinal fluid and neuroradiological investigations. Most important is the spinal MRI: small lesions as well as large lesions throughout the extent of the cord with accompanying edema can be identified reliably. Furthermore, neuroradiological examination can proof or rule out important differential diagnoses. In particular in acute transverse myelitis a quick diagnostic work-up with a spinal MRI is indispensible in order to start an appropriate therapy as soon as possible. (orig.) [de

  2. Systemic corticosteroids for acute gout.

    NARCIS (Netherlands)

    Janssens, H.; Lucassen, P.L.B.J.; Laar, F.A. van de; Janssen, M.; Lisdonk, E.H. van de

    2008-01-01

    BACKGROUND: Gout is one of the most frequently occurring rheumatic diseases, worldwide. Given the well-known drawbacks of the regular treatments for acute gout (non-steroidal anti-inflammatory drugs (NSAIDs), colchicine), systemic corticosteroids might be safe alternatives. OBJECTIVES: To assess the

  3. Oral fungal immunomodulatory protein-Flammulina velutipes has influence on pulmonary inflammatory process and potential treatment for allergic airway disease: A mouse model

    Directory of Open Access Journals (Sweden)

    Po-Yu Chu

    2017-06-01

    Conclusion: Oral FIP-fve had an anti-inflammatory effect on the acute phase of the airway inflammatory process induced by HDM in the mouse model and might have a potentially therapeutic role for allergic airway diseases.

  4. Anti-inflammatory effects of insulin.

    Science.gov (United States)

    Dandona, Paresh; Chaudhuri, Ajay; Mohanty, Priya; Ghanim, Husam

    2007-07-01

    This review deals with the recent observations on the pro-inflammatory effects of glucose and the anti-inflammatory actions of insulin. Apart from being novel, they are central to our understanding of why hyperglycemia is a prognosticator of bad clinical outcomes including patients with acute coronary syndromes, stroke and in patients in the intensive care unit. The pro-inflammatory effect of glucose as well as that of other macronutrients including fast food meals provides the basis of chronic oxidative stress and inflammation in the obese and their propensity to atherosclerotic disease. The anti-inflammatory action of insulin provides a neutralizing effect to balance macronutrient induced inflammation on the one hand and the possibility of using insulin as an anti-inflammatory drug on the other. The actions of macronutrients and insulin described above explain why insulin resistant states like obesity and type 2 diabetes are associated with oxidative stress, inflammation and atherosclerosis. They also suggest that insulin may be antiatherogenic.

  5. Changes in ion transport in inflammatory disease

    Directory of Open Access Journals (Sweden)

    Eisenhut Michael

    2006-03-01

    Full Text Available Abstract Ion transport is essential for maintenance of transmembranous and transcellular electric potential, fluid transport and cellular volume. Disturbance of ion transport has been associated with cellular dysfunction, intra and extracellular edema and abnormalities of epithelial surface liquid volume. There is increasing evidence that conditions characterized by an intense local or systemic inflammatory response are associated with abnormal ion transport. This abnormal ion transport has been involved in the pathogenesis of conditions like hypovolemia due to fluid losses, hyponatremia and hypokalemia in diarrhoeal diseases, electrolyte abnormalites in pyelonephritis of early infancy, septicemia induced pulmonary edema, and in hypersecretion and edema induced by inflammatory reactions of the mucosa of the upper respiratory tract. Components of membranous ion transport systems, which have been shown to undergo a change in function during an inflammatory response include the sodium potassium ATPase, the epithelial sodium channel, the Cystic Fibrosis Transmembrane Conductance Regulator and calcium activated chloride channels and the sodium potassium chloride co-transporter. Inflammatory mediators, which influence ion transport are tumor necrosis factor, gamma interferon, interleukins, transforming growth factor, leukotrienes and bradykinin. They trigger the release of specific messengers like prostaglandins, nitric oxide and histamine which alter ion transport system function through specific receptors, intracellular second messengers and protein kinases. This review summarizes data on in vivo measurements of changes in ion transport in acute inflammatory conditions and in vitro studies, which have explored the underlying mechanisms. Potential interventions directed at a correction of the observed abnormalities are discussed.

  6. Vaginal toxic shock reaction triggering desquamative inflammatory vaginitis.

    Science.gov (United States)

    Pereira, Nigel; Edlind, Thomas D; Schlievert, Patrick M; Nyirjesy, Paul

    2013-01-01

    The study aimed to report 2 cases of desquamative inflammatory vaginitis associated with toxic shock syndrome toxin 1 (TSST-1)-producing Staphylococcus aureus strains. Case report of 2 patients, 1 with an acute and 1 with a chronic presentation, diagnosed with desquamative inflammatory vaginitis on the basis of clinical findings and wet mount microscopy. Pretreatment and posttreatment vaginal bacterial and yeast cultures were obtained. Pretreatment vaginal bacterial cultures from both patients grew TSST-1-producing S. aureus. Subsequent vaginal bacterial culture results after oral antibiotic therapy were negative. Desquamative inflammatory vaginitis may be triggered through TSST-1-mediated vaginal toxic shock reaction.

  7. Physical exercise, inflammatory process and adaptive condition: an overview

    OpenAIRE

    Silva, Fernando Oliveira Catanho da; Macedo, Denise Vaz

    2011-01-01

    Physical exercise induces inflammation, a physiological response that is part of immune system activity and promotes tissue remodeling after exercise overload. The activation of the inflammatory process is local and systemic and is mediated by different cells and secreted compounds. The objective is to reestablish organ homeostasis after a single bout of exercise or after several exercise sessions. The acute-phase response involves the combined actions of activated leukocytes, cytokines, acut...

  8. Inflammatory Drug (NSAID)

    African Journals Online (AJOL)

    Inflammatory Drug (NSAID)-Induced Seizures in a Patient with HIV Infection ... interaction not supported by existing literature, and it is possible that the background HIV infection may have a role to .... Foods and Drug Administration and Control.

  9. Inflammatory Breast Cancer

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... white women. Inflammatory breast tumors are frequently hormone receptor negative, which means they cannot be treated with ...

  10. Chronic inflammatory demyelinative polyneuropathy

    DEFF Research Database (Denmark)

    Said, Gérard; Krarup, Christian

    2013-01-01

    Chronic inflammatory demyelinative polyneuropathy (CIDP) is an acquired polyneuropathy presumably of immunological origin. It is characterized by a progressive or a relapsing course with predominant motor deficit. The diagnosis rests on the association of non-length-dependent predominantly motor...

  11. Modeling human gastrointestinal inflammatory diseases using microphysiological culture systems.

    Science.gov (United States)

    Hartman, Kira G; Bortner, James D; Falk, Gary W; Ginsberg, Gregory G; Jhala, Nirag; Yu, Jian; Martín, Martín G; Rustgi, Anil K; Lynch, John P

    2014-09-01

    Gastrointestinal illnesses are a significant health burden for the US population, with 40 million office visits each year for gastrointestinal complaints and nearly 250,000 deaths. Acute and chronic inflammations are a common element of many gastrointestinal diseases. Inflammatory processes may be initiated by a chemical injury (acid reflux in the esophagus), an infectious agent (Helicobacter pylori infection in the stomach), autoimmune processes (graft versus host disease after bone marrow transplantation), or idiopathic (as in the case of inflammatory bowel diseases). Inflammation in these settings can contribute to acute complaints (pain, bleeding, obstruction, and diarrhea) as well as chronic sequelae including strictures and cancer. Research into the pathophysiology of these conditions has been limited by the availability of primary human tissues or appropriate animal models that attempt to physiologically model the human disease. With the many recent advances in tissue engineering and primary human cell culture systems, it is conceivable that these approaches can be adapted to develop novel human ex vivo systems that incorporate many human cell types to recapitulate in vivo growth and differentiation in inflammatory microphysiological environments. Such an advance in technology would improve our understanding of human disease progression and enhance our ability to test for disease prevention strategies and novel therapeutics. We will review current models for the inflammatory and immunological aspects of Barrett's esophagus, acute graft versus host disease, and inflammatory bowel disease and explore recent advances in culture methodologies that make these novel microphysiological research systems possible. © 2014 by the Society for Experimental Biology and Medicine.

  12. Antioxidant, anti-inflammatory and antinociceptive activities of ...

    African Journals Online (AJOL)

    Background of study: Plants used for traditional medicine contain a wide range of substances which can be used to treat various infectious diseases. Aim: The study evaluated the in vitro antioxidant, antinociceptive, and anti-inflammatory activities of the methanolic extract of Justicia secunda Vahl leaf. Methods: The acute ...

  13. Diagnostic value of inflammatory markers (complete blood count ...

    African Journals Online (AJOL)

    Objective The aim of the study was to evaluate the diagnostic value of inflammatory markers [complete blood cell count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)] for the differentiation of acute appendicitis from nonspecific abdominal pain in children. Patients and methods In this prospective ...

  14. Antinociceptive and anti-inflammatory properties of methanol fruit ...

    African Journals Online (AJOL)

    Purpose: To investigate the anti-inflammatory and antinociceptive properties of crude methanol fruit extract of Quercus incana (QI), as well as its acute toxicity and phytochemical profile. Methods: Two animal models were used: Wistar rats for carrageenan-induced paw inflammation and Swiss albino mice for acetic ...

  15. Diagnostic value of inflammatory markers (complete blood count ...

    African Journals Online (AJOL)

    Objective The aim of the study was to evaluate the diagnostic value of inflammatory markers [complete blood cell count (CBC), erythrocyte sedimentation rate (ESR),. C-reactive protein (CRP)] for the differentiation of acute appendicitis from nonspecific abdominal pain in children. Patients and methods In this prospective ...

  16. Investigations into the antioxidant and anti-inflammatory potentials of ...

    African Journals Online (AJOL)

    This study was designed to investigate the antioxidant and anti-inflammatory potentials of the ethanolic extract and fractions of Citrus sinensis stem-bark, investigate and to evaluate the hepatoprotective potential of the most active fraction (EAF) of the ethanolic extract against acetaminophen-induced acute hepatic injury.

  17. Inflammatory Process in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    MARCO ANTONIO eMERAZ RIOS

    2013-08-01

    Full Text Available Alzheimer Disease (AD is a neurodegenerative disorder and the most common form of dementia. Histopathologically is characterized by the presence of two major hallmarks, the intracellular neurofibrillary tangles (NFTs and extracellular neuritic plaques (NPs surrounded by activated astrocytes and microglia. NFTs consist of paired helical filaments of truncated tau protein that is abnormally hyperphosphorylated. The main component in the NP is the amyloid-β peptide (Aβ, a small fragment of 40-42 amino acids with a molecular weight of 4kD. It has been proposed that the amyloid aggregates and microglia activation are able to favor the neurodegenerative process observed in AD patients. However, the role of inflammation in AD is controversial, because in early stages the inflammation could have a beneficial role in the pathology, since it has been thought that the microglia and astrocytes activated could be involved in Aβ clearance. Nevertheless the chronic activation of the microglia has been related with an increase of Aβ and possibly with tau phosphorylation. Studies in AD brains have shown an upregulation of complement molecules, pro-inflammatory cytokines, acute phase reactants and other inflammatory mediators that could contribute with the neurodegenerative process. Clinical trials and animal models with nonsteroidal anti-inflammatory drugs (NSAIDs indicate that these drugs may decrease the risk of developing AD and apparently reduce Aβ deposition. Finally, further studies are needed to determine whether treatment with anti-inflammatory strategies, may decrease the neurodegenerative process that affects these patients.

  18. Blocking NF-κB: an inflammatory issue.

    Science.gov (United States)

    Rahman, Arshad; Fazal, Fabeha

    2011-11-01

    The nuclear factor (NF)-κB is considered the master regulator of inflammatory responses. Studies in mouse models have established this transcription factor as an important mediator of many inflammatory disease states, including pulmonary diseases such as acute lung injury and acute respiratory distress syndrome. Endothelial cells provide the first barrier for leukocytes migrating to the inflamed sites and hence offer an attractive cellular context for targeting NF-κB for treatment of these diseases. However, recent studies showing that NF-κB also plays an important role in resolution phase of inflammation and in tissue repair and homeostasis have challenged the view of therapeutic inhibition of NF-κB. This article reviews the regulation of NF-κB in the context of endothelial cell signaling and provides a perspective on why "dampening" rather than "abolishing" NF-κB activation may be a safe and effective treatment strategy for inflammation-associated pulmonary and other inflammatory diseases.

  19. C-Phycocyanin protects against acute tributyltin chloride neurotoxicity by modulating glial cell activity along with its anti-oxidant and anti-inflammatory property: A comparative efficacy evaluation with N-acetyl cysteine in adult rat brain.

    Science.gov (United States)

    Mitra, Sumonto; Siddiqui, Waseem A; Khandelwal, Shashi

    2015-08-05

    Spirulina is a widely used health supplement and is a dietary source of C-Phycocyanin (CPC), a potent anti-oxidant. We have previously reported the neurotoxic potential of tributyltin chloride (TBTC), an environmental pollutant and potent biocide. In this study, we have evaluated the protective efficacy of CPC against TBTC induced neurotoxicity. To evaluate the extent of neuroprotection offered by CPC, its efficacy was compared with the degree of protection offered by N-acetylcysteine (NAC) (a well known neuroprotective drug, taken as a positive control). Male Wistar rats (28 day old) were administered with 20mg/kg TBTC (oral) and 50mg/kg CPC or 50mg/kg NAC (i.p.), alone or in combination, and various parameters were evaluated. These include blood-brain barrier (BBB) damage; redox parameters (ROS, GSH, redox pathway associated enzymes, oxidative stress markers); inflammatory, cellular, and stress markers; apoptotic proteins and in situ cell death assay (TUNEL). We observed increased CPC availability in cortical tissue following its administration. Although BBB associated proteins like claudin-5, p-glycoprotein and ZO-1 were restored, CPC/NAC failed to protect against TBTC induced overall BBB permeability (Evans blue extravasation). Both CPC and NAC remarkably reduced oxidative stress and inflammation. NAC effectively modulated redox pathway associated enzymes whereas CPC countered ROS levels efficiently. Interestingly, CPC and NAC were equivalently capable of reducing apoptotic markers, astroglial activation and cell death. This study illustrates the various pathways involved in CPC mediated neuroprotection against this environmental neurotoxicant and highlights its capability to modulate glial cell activity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Mechanisms of permanent loss of olfactory receptor neurons induced by the herbicide 2,6-dichlorobenzonitrile: Effects on stem cells and noninvolvement of acute induction of the inflammatory cytokine IL-6

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Fang; Fang, Cheng [Laboratory of Molecular Toxicology, Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); School of Public Health, State University of New York at Albany, NY 12201 (United States); Schnittke, Nikolai [Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111 (United States); Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111 (United States); Schwob, James E. [Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111 (United States); Ding, Xinxin, E-mail: xding@wadsworth.org [Laboratory of Molecular Toxicology, Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); School of Public Health, State University of New York at Albany, NY 12201 (United States)

    2013-11-01

    We explored the mechanisms underlying the differential effects of two olfactory toxicants, the herbicide 2,6-dichlorobenzonitrile (DCBN) and the anti-thyroid drug methimazole (MMZ), on olfactory receptor neuron (ORN) regeneration in mouse olfactory epithelium (OE). DCBN, but not MMZ, induced inflammation-like pathological changes in OE, and DCBN increased interleukin IL-6 levels in nasal-wash fluid to much greater magnitude and duration than did MMZ. At 24 h after DCBN injection, the population of horizontal basal cells (HBCs; reserve, normally quiescent OE stem cells) lining the DMM became severely depleted as some of them detached from the basal lamina, and sloughed into the nasal cavity along with the globose basal cells (GBCs; heterogeneous population of stem and progenitor cells), neurons, and sustentacular cells of the neuroepithelium. In contrast, the layer of HBCs remained intact in MMZ-treated mice, as only the mature elements of the neuroepithelium were shed. Despite the respiratory metaplasia accompanying the greater severity of the DCBN lesion, residual HBCs that survived intoxication were activated by the injury and contributed to the metaplastic respiratory epithelium, as shown by tracing their descendants in a K5CreEr{sup T2}::fl(stop)TdTomato strain of mice in which recombination causes HBCs to express TdTomato in advance of the lesion. But, contrary to published observations with MMZ, the HBCs failed to form ORNs. A role for IL-6 in suppressing ORN regeneration in DCBN-treated mice was rejected by the failure of the anti-inflammatory drug dexamethasone to prevent the subsequent respiratory metaplasia in the DMM, suggesting that other factors lead to HBC neuro-incompetence. - Highlights: • The herbicide dichlobenil (DCBN) can damage olfactory epithelium stem cells. • Another olfactory toxicant, methimazole, leaves the olfactory stem cells intact. • DCBN, but not methimazole, induces a prolonged increase in nasal IL-6 levels. • Dexamethasone

  1. Short communication: Camel milk ameliorates inflammatory responses and oxidative stress and downregulates mitogen-activated protein kinase signaling pathways in lipopolysaccharide-induced acute respiratory distress syndrome in rats.

    Science.gov (United States)

    Zhu, Wei-Wei; Kong, Gui-Qing; Ma, Ming-Ming; Li, Yan; Huang, Xiao; Wang, Li-Peng; Peng, Zhen-Yi; Zhang, Xiao-Hua; Liu, Xiang-Yong; Wang, Xiao-Zhi

    2016-01-01

    Acute respiratory distress syndrome (ARDS) is a complex syndrome disorder with high mortality rate. Camel milk (CM) contains antiinflammatory and antioxidant properties and protects against numerous diseases. This study aimed to demonstrate the function of CM in lipopolysaccharide (LPS)-induced ARDS in rats. Camel milk reduced the lung wet:dry weight ratio and significantly reduced LPS-induced increases in neutrophil infiltration, interstitial and intra-alveolar edema, thickness of the alveolar wall, and lung injury scores of lung tissues. It also had antiinflammatory and antioxidant effects on LPS-induced ARDS. After LPS stimulation, the levels of proinflammatory cytokines (tumor necrosis factor-α, IL-10, and IL-1β) in serum and oxidative stress markers (malondialdehyde, myeloperoxidase, and total antioxidant capacity) in lung tissue were notably attenuated by CM. Camel milk also downregulated mitogen-activated protein kinase signaling pathways. Given these results, CM is a potential complementary food for ARDS treatment. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  2. Inflammatory reaction in chondroblastoma

    International Nuclear Information System (INIS)

    Yamamura, Sigeki; Sato, Keiji; Sugiura, Hideshi; Iwata, Hisashi

    1996-01-01

    The objective of this study was to evaluate the inflammatory reaction accompanying chondroblastoma and to define the value of the finding in clinical practice. We reviewed the clinical, radiographic, and magnetic resonance (MR) findings in six patients with histologically proven chondroblastoma. In all cases, MR imaging showered marrow and soft tissue edema. In four of six cases, periosteal reaction related to intra-osseous edema was more clearly demonstrated on MR imaging than on radiographs. Follow-up MR studies after surgery were available in three patients and all showed disappearance of inflammatory responses such as marrow and soft tissue edema, and reactive synovitis. We propose that these inflammatory reactions of chondroblastomas are inportant signs for detecting residual tumor in recurrences after surgery, as well as for making a precise diagnosis. The MR changes may also be valuable in demonstrating eradication of the tumor. (orig./MG)

  3. Lung inflammatory pseudo tumor

    International Nuclear Information System (INIS)

    Veliz, Elizabeth; Leone, Gaetano; Cano, Fernando; Sanchez, Jaime

    2005-01-01

    The inflammatory pseudo tumor is a non neoplastic process characterized by an irregular growth of inflammatory cells. We described the case of a 38 year-old patient, she went to our institute for a in situ cervix cancer and left lung nodule without breathing symptoms; valued by neumology who did bronchoscopy with biopsy whose result was negative for malignancy. She went to surgery in where we find intraparenquima nodule in felt lingula of approximately 4 cms, we remove it; the result was: Inflammatory pseudotumor. This pathology is a not very frequent, it can develop in diverse regions of the organism, it is frequent in lung. The image tests are not specific for the diagnose, which it is possible only with the biopsy. The treatment is the complete resection. (The author)

  4. Inflammatory reaction in chondroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Yamamura, Sigeki [Dept. of Orthopedic Surgery, Nagoya Univ. School of Medicine (Japan); Sato, Keiji [Dept. of Orthopedic Surgery, Nagoya Univ. School of Medicine (Japan); Sugiura, Hideshi [Dept. of Orthopedic Surgery, Nagoya Univ. School of Medicine (Japan); Iwata, Hisashi [Dept. of Orthopedic Surgery, Nagoya Univ. School of Medicine (Japan)

    1996-05-01

    The objective of this study was to evaluate the inflammatory reaction accompanying chondroblastoma and to define the value of the finding in clinical practice. We reviewed the clinical, radiographic, and magnetic resonance (MR) findings in six patients with histologically proven chondroblastoma. In all cases, MR imaging showered marrow and soft tissue edema. In four of six cases, periosteal reaction related to intra-osseous edema was more clearly demonstrated on MR imaging than on radiographs. Follow-up MR studies after surgery were available in three patients and all showed disappearance of inflammatory responses such as marrow and soft tissue edema, and reactive synovitis. We propose that these inflammatory reactions of chondroblastomas are inportant signs for detecting residual tumor in recurrences after surgery, as well as for making a precise diagnosis. The MR changes may also be valuable in demonstrating eradication of the tumor. (orig./MG)

  5. Vasculitis and inflammatory arthritis.

    Science.gov (United States)

    Watts, Richard A; Scott, David G I

    2016-10-01

    Vasculitis has been described in most types of inflammatory arthritis. The best described and most widely recognised form is rheumatoid vasculitis. The incidence of systemic rheumatoid vasculitis has declined significantly following the general early use of methotrexate in the 1990s, and it is now a rare form of vasculitis. Treatment of rheumatoid vasculitis is conventionally with glucocorticoids and cyclophosphamide, but there is an increasing role for rituximab similar to that in other types of vasculitis. Despite these developments the mortality of rheumatoid vasculitis remains high. Vasculitis in other types of inflammatory arthritis is less well described and the treatment remains empirical. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Recombinant human brain natriuretic peptide attenuates trauma-/haemorrhagic shock-induced acute lung injury through inhibiting oxidative stress and the NF-κB-dependent inflammatory/MMP-9 pathway.

    Science.gov (United States)

    Song, Zhi; Zhao, Xiu; Liu, Martin; Jin, Hongxu; Wang, Ling; Hou, Mingxiao; Gao, Yan

    2015-12-01

    Acute lung injury (ALI) is one of the most serious complications in traumatic patients and is an important part of multiple organ dysfunction syndrome (MODS). Recombinant human brain natriuretic peptide (rhBNP) is a peptide with a wide range of biological activity. In this study, we investigated local changes in oxidative stress and the NF-κB-dependent matrix metalloproteinase-9 (MMP-9) pathway in rats with trauma/haemorrhagic shock (TH/S)-induced ALI and evaluated the effects of pretreatment with rhBNP. Forty-eight rats were randomly divided into four groups: sham operation group, model group, low-dosage rhBNP group and high-dosage rhBNP group (n = 12 for each group). Oxidative stress and MPO activity were measured by ELISA kits. MMP-9 activity was detected by zymography analysis. NF-κB activity was determined using Western blot assay. With rhBNP pretreatment, TH/S-induced protein leakage, increased MPO activity, lipid peroxidation and metalloproteinase (MMP)-9 activity were inhibited. Activation of antioxidative enzymes was reversed. The phosphorylation of NF-κB and the degradation of its inhibitor IκB were suppressed. The results suggested that the protection mechanism of rhBNP is possibly mediated through upregulation of anti-oxidative enzymes and inhibition of NF-κB activation. More studies are needed to further evaluate whether rhBNP is a suitable candidate as an effective inhaling drug to reduce the incidence of TH/S-induced ALI. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

  7. Inflammation: a trigger for acute coronary syndrome

    International Nuclear Information System (INIS)

    SAGER, Hendrik B.; NAHRENDORF, Matthias

    2016-01-01

    Atherosclerosis is a chronic inflammatory disease of the vessel wall and a major cause of death worldwide. One of atherosclerosis’ most dreadful complications are acute coronary syndromes that comprise ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina. We now understand that inflammation substantially contributes to the initiation, progression, and destabilization of atherosclerosis. In this review, we will focus on the role of inflammatory leukocytes, which are the cellular protagonists of vascular inflammation, in triggering disease progression and, ultimately, the destabilization that causes acute coronary syndromes.

  8. Inflammatory manifestations of experimental lymphatic insufficiency.

    Directory of Open Access Journals (Sweden)

    Raymond Tabibiazar

    2006-07-01

    Full Text Available BACKGROUND: Sustained lymph stagnation engenders a pathological response that is complex and not well characterized. Tissue inflammation in lymphedema may reflect either an active or passive consequence of impaired immune traffic. METHODS AND FINDINGS: We studied an experimental model of acute post-surgical lymphedema in the tails of female hairless, immunocompetent SKH-1 mice. We performed in vivo imaging of impaired immune traffic in experimental, murine acquired lymphatic insufficiency. We demonstrated impaired mobilization of immunocompetent cells from the lymphedematous region. These findings correlated with histopathological alterations and large-scale transcriptional profiling results. We found intense inflammatory changes in the dermis and the subdermis. The molecular pattern in the RNA extracted from the whole tissue was dominated by the upregulation of genes related to acute inflammation, immune response, complement activation, wound healing, fibrosis, and oxidative stress response. CONCLUSIONS: We have characterized a mouse model of acute, acquired lymphedema using in vivo functional imaging and histopathological correlation. The model closely simulates the volume response, histopathology, and lymphoscintigraphic characteristics of human acquired lymphedema, and the response is accompanied by an increase in the number and size of microlymphatic structures in the lymphedematous cutaneous tissues. Molecular characterization through clustering of genes with known functions provides insights into processes and signaling pathways that compose the acute tissue response to lymph stagnation. Further study of genes identified through this effort will continue to elucidate the molecular mechanisms and lead to potential therapeutic strategies for lymphatic vascular insufficiency.

  9. Antibiotics and inflammatory bowel diseases.

    Science.gov (United States)

    Scribano, Maria Lia; Prantera, Cosimo

    2013-01-01

    Inflammatory bowel diseases are characterized by an altered composition of gut microbiota (dysbiosis) that may contribute to their development. Antibiotics can alter the bacterial flora, and a link between antibiotic use and onset of Crohn's disease (CD), but not ulcerative colitis, has been reported. The hypothesis that Mycobacterium avium subspecies paratuberculosis (MAP) could be an etiologic agent of CD has not been confirmed by a large study on patients treated by an association of antibiotics active against MAP. The observations supporting a role of intestinal microbiota in CD pathogenesis provide the rationale for a therapeutic manipulation of the intestinal flora through the employment of antibiotics. However, current data do not strongly support a therapeutic benefit from antibiotics, and there is still controversy regarding their use as primary therapy for treatment of acute flares of CD, and for postoperative recurrence prevention. Nevertheless, clinical practice and some studies suggest that a subgroup of patients with colonic involvement, early disease, and abnormal laboratory test of inflammation may respond better to antibiotic treatment. Since their long-term use is frequently complicated by a high rate of side effects, the use of antibiotics that work locally appears to be promising.

  10. Renal inflammatory myofibroblastic tumor

    DEFF Research Database (Denmark)

    Heerwagen, S T; Jensen, C; Bagi, P

    2007-01-01

    Renal inflammatory myofibroblastic tumor (IMT) is a rare soft-tissue tumor of controversial etiology with a potential for local recurrence after incomplete surgical resection. The radiological findings in renal IMT are not well described. We report two cases in adults with a renal mass treated...

  11. Pelvic Inflammatory Disease (PID)

    Science.gov (United States)

    ... a serious condition, in women. 1 in 8 women with a history of PID experience difficulties getting pregnant. You can prevent PID if you know how to protect yourself. What is PID? Pelvic inflammatory disease is an infection of a woman’s reproductive organs. It is a complication often caused ...

  12. Inflammatory bowel disease epidemiology

    DEFF Research Database (Denmark)

    Burisch, Johan; Munkholm, Pia

    2013-01-01

    The occurrence of inflammatory bowel disease (IBD) is increasing worldwide, yet the reasons remain unknown. New therapeutic approaches have been introduced in medical IBD therapy, but their impact on the natural history of IBD remains uncertain. This review will summarize the recent findings...

  13. Histological study on acute inflammatory reaction to polyurethane-coated silicone implants in rats Estudo histológico da reação inflamatória aguda ao implante de silicone revestido com poliuretano em ratos

    Directory of Open Access Journals (Sweden)

    Paulo Roberto da Silva Mendes

    2008-02-01

    Full Text Available PURPOSE: Evaluating histologically the silicone peri-implant coated by polyurethane inflammation associated to the use of anti-microbial and bacterial contamination. METHODS: It was used 35 Wistar rats. The animals were divided in seven groups: I - Control; II - implant cavity contamination with10 bacteria/ml; III - implant cavity contamination with 10 bacteria/ml; IV - implant cavity contamination with 10 bacteria/ml; V - identical contamination to group II and implant immersions in anti-microbial solution; VI - identical contamination in group III and implant immersions in the anti-microbial solution; VII - identical contamination of group IV and implant immersions in anti-microbial solution. It was evaluated morphometrically the peri-implant capsules after 30 days of introduction. RESULTS: The factors with more discriminating power were the giants cells of a strange body and the mononuclear. There was no correlation between the bacterial concentrations and the histological alterations. CONCLUSION: 1 The histological standard of the inflammatory reaction around the silicone implant coated with polyurethan is chronic granulomatosis type of a strange body; 2 There isn´t correlation between concentration of Staphylococcus epidermidis and histological changes; 3 The use of anti-microbial solution decreased the mononuclear cell reactions, with the increase of giant cells in a strange body.OBJETIVO: Avaliar, histologicamente, a reação inflamatória aos implantes de silicone revestidos por poliuretano, com contaminação bacteriana, associada ou não ao uso de antimicrobianos. MÉTODOS: Utilizou-se 35 ratos Wistar. Os animais foram divididos em 7 grupos: I- Controle, II- contaminação da cavidade do implante com 10¹ bactérias/ml, III- contaminação da cavidade do implante com 10³ bactérias/ml, IV- contaminação da cavidade do implante com 10(5 bactérias/ml, V- contaminação idêntica ao grupo II e imersão dos implantes em solu

  14. Anti-inflammatory management for tendon injuries - friends or foes?

    Directory of Open Access Journals (Sweden)

    Chan Kai-Ming

    2009-10-01

    Full Text Available Abstract Acute and chronic tendon injuries are very common among athletes and in sedentary population. Most physicians prescribe anti-inflammatory managements to relieve the worst symptoms of swelling and pain, including non-steroidal anti-inflammatory drugs, corticosteroids and physical therapies. However, experimental research shows that pro-inflammatory mediators such as prostaglandins may play important regulatory roles in tendon healing. Noticeably nearly all cases of chronic tendon injuries we treat as specialists have received non-steroidal anti-inflammatory drugs by their physician, suggesting that there might be a potential interaction in some of these cases turning a mild inflammatory tendon injury into chronic tendinopathy in predisposed individuals. We are aware of the fact that non-steroidal anti-inflammatory drugs and corticosteroids may well have a positive effect on the pain control in the clinical situation whilst negatively affect the structural healing. It follows that a comprehensive evaluation of anti-inflammatory management for tendon injuries is needed and any such data would have profound clinical and health economic importance.

  15. Acute nephritic syndrome

    Science.gov (United States)

    Glomerulonephritis - acute; Acute glomerulonephritis; Nephritis syndrome - acute ... Acute nephritic syndrome is often caused by an immune response triggered by an infection or other disease. Common causes in children ...

  16. Enteral nutrition in inflammatory bowel disease.

    Science.gov (United States)

    Gassull, M A; Abad, A; Cabré, E; González-Huix, F; Giné, J J; Dolz, C

    1986-01-01

    To assess the effect of the addition of enteral tube feeding with polymeric diets to the standard treatment of acute attacks of inflammatory bowel disease a total of 43 patients admitted to hospital (23 with Crohn's disease and 20 with ulcerative colitis) were studied retrospectively. Total enteral nutrition was given to 26 as the sole nutritional supply and to 17 in conjunction with a normal ward diet, when appropriate, according to the severity of attack (control group). Nutritional state was assessed and classified in all patients at admission and at the end of the study, by measuring the triceps skinfold thickness, mid arm muscle circumference, and serum albumin concentration as representative of body fat, muscle protein, and visceral protein, respectively. At admission the three nutritional variables were not statistically different between the groups. There was a significantly positive effect on mid arm muscle circumference in patients on total enteral nutrition compared with the control group, but there was no effect on either triceps skinfold thickness or serum albumin concentration. The percentage of subjects requiring intravenous albumin infusion, however, was significantly less in the group fed enterally than in the control group. In addition, fewer patients in the group fed enterally required surgical treatment compared with the control group, despite the fact that one of the criteria for starting enteral nutritional support was the expectancy that surgery would be needed. Total enteral nutrition was well tolerated and no major side effects arose during its use in patients with acute exacerbations of inflammatory bowel disease. PMID:3098646

  17. Chagas disease: modulation of the inflammatory response by acetylcholinesterase in hematological cells and brain tissue.

    Science.gov (United States)

    Silva, Aniélen D; Bottari, Nathieli B; do Carmo, Guilherme M; Baldissera, Matheus D; Souza, Carine F; Machado, Vanessa S; Morsch, Vera M; Schetinger, Maria Rosa C; Mendes, Ricardo E; Monteiro, Silvia G; Da Silva, Aleksandro S

    2018-01-01

    Chagas disease is an acute or chronic illness that causes severe inflammatory response, and consequently, it may activate the inflammatory cholinergic pathway, which is regulated by cholinesterases, including the acetylcholinesterase. This enzyme is responsible for the regulation of acetylcholine levels, an anti-inflammatory molecule linked to the inflammatory response during parasitic diseases. Thus, the aim of this study was to investigate whether Trypanosoma cruzi infection can alter the activity of acetylcholinesterase and acetylcholine levels in mice, and whether these alterations are linked to the inflammatory cholinergic signaling pathway. Twenty-four mice were divided into two groups: uninfected (control group, n = 12) and infected by T. cruzi, Y strain (n = 12). The animals developed acute disease with a peak of parasitemia on day 7 post-infection (PI). Blood, lymphocytes, and brain were analyzed on days 6 and 12 post-infection. In the brain, acetylcholine and nitric oxide levels, myeloperoxidase activity, and histopathology were analyzed. In total blood and brain, acetylcholinesterase activity decreased at both times. On the other hand, acetylcholinesterase activity in lymphocytes increased on day 6 PI compared with the control group. Infection by T. cruzi increased acetylcholine and nitric oxide levels and histopathological damage in the brain of mice associated to increased myeloperoxidase activity. Therefore, an intense inflammatory response in mice with acute Chagas disease in the central nervous system caused an anti-inflammatory response by the activation of the cholinergic inflammatory pathway.

  18. Pathogen- and host-directed anti-inflammatory activities of macrolide antibiotics.

    Science.gov (United States)

    Steel, Helen C; Theron, Annette J; Cockeran, Riana; Anderson, Ronald; Feldman, Charles

    2012-01-01

    Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In addition to high levels of tissue penetration, which may counteract seemingly macrolide-resistant bacterial pathogens, these agents also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. Macrolides target cells of both the innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful inflammatory responses during acute and chronic bacterial infection. These secondary anti-inflammatory activities of macrolides appear to be particularly effective in attenuating neutrophil-mediated inflammation. This, in turn, may contribute to the usefulness of these agents in the treatment of acute and chronic inflammatory disorders of both microbial and nonmicrobial origin, predominantly of the airways. This paper is focused on the various mechanisms of macrolide-mediated anti-inflammatory activity which target both microbial pathogens and the cells of the innate and adaptive immune systems, with emphasis on their clinical relevance.

  19. Bilateral acute iris transillumination (BAIT initially misdiagnosed as acute iridocyclitis

    Directory of Open Access Journals (Sweden)

    Saban Gonul

    2015-04-01

    Full Text Available Bilateral acute iris transillumination (BAIT is a relatively new clinical entity characterized by bilateral acute loss of iris pigment epithelium, iris transillumination, pigment dispersion in the anterior chamber, and sphincter paralysis. We report the case of a 30-year-old male who was initially diagnosed with acute iridocyclitis in a different clinic and treated with topical and systemic corticosteroids. He was referred to our clinic to seek another opinion because his symptoms did not improve. An ocular examination revealed bilateral pigment dispersion into the anterior chamber, diffuse iris transillumination, pigment dusting on the anterior lens capsule, atonic and distorted pupils, and increased intraocular pressure, suggesting a diagnosis of BAIT rather than iridocyclitis. Clinicians should be aware of the differential diagnosis of syndromes associated with pigment dispersion from iridocyclitis to avoid aggressive anti-inflammatory therapy and detailed investigation for uveitis.

  20. The systemic inflammatory response syndrome.

    Science.gov (United States)

    Robertson, Charles M; Coopersmith, Craig M

    2006-04-01

    The systemic inflammatory response syndrome (SIRS) is the body's response to an infectious or noninfectious insult. Although the definition of SIRS refers to it as an "inflammatory" response, it actually has pro- and anti-inflammatory components. This review outlines the pathophysiology of SIRS and highlights potential targets for future therapeutic intervention in patients with this complex entity.

  1. Perioperative acute renal failure.

    LENUS (Irish Health Repository)

    Mahon, Padraig

    2012-02-03

    PURPOSE OF REVIEW: Recent biochemical evidence increasingly implicates inflammatory mechanisms as precipitants of acute renal failure. In this review, we detail some of these pathways together with potential new therapeutic targets. RECENT FINDINGS: Neutrophil gelatinase-associated lipocalin appears to be a sensitive, specific and reliable biomarker of renal injury, which may be predictive of renal outcome in the perioperative setting. For estimation of glomerular filtration rate, cystatin C is superior to creatinine. No drug is definitively effective at preventing postoperative renal failure. Clinical trials of fenoldopam and atrial natriuretic peptide are, at best, equivocal. As with pharmacological preconditioning of the heart, volatile anaesthetic agents appear to offer a protective effect to the subsequently ischaemic kidney. SUMMARY: Although a greatly improved understanding of the pathophysiology of acute renal failure has offered even more therapeutic targets, the maintenance of intravascular euvolaemia and perfusion pressure is most effective at preventing new postoperative acute renal failure. In the future, strategies targeting renal regeneration after injury will use bone marrow-derived stem cells and growth factors such as insulin-like growth factor-1.

  2. Challenges in uncomplicated acute appendicitis

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    Fernando Resende

    2016-03-01

    Full Text Available Acute appendicitis is one of the most common abdominal emergencies requiring surgery. It still represents, however, a challenging diagnosis. In order to facilitate this process, several scoring systems were developed, namely, the Alvarado score, acute inflammatory response and Raja Isteri Pengiran Anak Saleha Appendicitis scores, which are the most used in clinical practice. This clinical condition encompasses a wide spectrum of clinical presentations, from the uncomplicated form to the one with diffuse peritonitis. Treatment of uncomplicated acute appendicitis remains a matter of discussion. Although appendectomy has been regarded as the gold-standard, conservative management with antibiotics is gaining more and more acceptance. The approach to appendectomy constitutes another controversial issue, namely, its performance through an open or a laparoscopic approach, which seems to be establishing itself, in some centers, as the standard of care. With this paper, we intend to give some insight on the aforementioned topics, through a review of the available literature on uncomplicated appendicitis.

  3. Immunohistochemical localization of inflammatory cells and cell cycle proteins in the gills of Loma salmonae infected rainbow trout (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Powell, M. D.; Yousaf, M. N.; Rasmussen, Karina Juhl

    2014-01-01

    Microsporidial gill diseases particularly those caused by Loma salmonae incur significant economic losses to the salmonid aquaculture industry. The gill responses to infection include the formation of xenomas and the acute hyperplastic inflammatory responses once the xenomas rupture releasing inf...

  4. DOI: 10.4025/actascibiolsci.v33i3.8011 Acta Scientiarum. Biological Sciences Maringá, v. 33, n. 3, p. 239-246, 2011 Acute inflammatory response in Nile tilapia fed probiotic Lactobacillus plantarum in the diet = Resposta inflamatória aguda em tilápia do Nilo alimentada com probiótico, Lactobacillus plantarum na dieta

    Directory of Open Access Journals (Sweden)

    Geovana Dotta

    2011-07-01

    Full Text Available The present study evaluated the acute inflammatory response induced bycarrageenin (500 £gg injected in the swim bladder of Nile tilapia, after fed or not probiotic supplemented diet. Fifty four fish were distributed in six treatments and three replicates: Group A: Fish fed unsupplemented diet: 0.5 mL saline-injected fish; fish injected with 500 £gg carrageenin diluted in 0.5 mL saline; Non-injected. Group B: Fish fed probiotic supplemented diet: saline-injected fish; carrageenin-injected fish; Non-injected. Fifteen days after feeding the fish were injected with carrageenin or saline. After six hours, inflammatory exudate was collected, as well as the blood for hematocrit, red blood cell (RBC and white blood cell (WBC counts, differential count of leucocytes and phagocytic activity in the blood. Supplementation with probiotic did not influence the RBC, hematocrit and the numbers of lymphocytes and basophils in the blood. The number of neutrophils was significantly higher in supplemented fish injected with carrageenin. Glucose concentration in supplemented and non-injected fish was higher than that observed in the saline injected ones. Probiotic potentialized the migration of cells to the inflammatory focus in the animals injected with the carrageenin irritant. In fish injected with saline and carrageenin occurred the greatest phagocytic activity in the blood in relation to those treatments.Este trabalho avaliou a resposta inflamatoria aguda induzida por injecao de carragenina (500 ƒÝg na bexiga natatoria de tilapia do Nilo suplementada ou nao com probiotico na racao. Cinquenta e quatro animais foram distribuidos em seis tratamentos com tres repeticoes: Grupo A: peixes alimentados com racao naosuplementada: Controle (injecao de 0,5 mL de solucao salina esteril; Carragenina (injecao de500 £gg de carragenina; Nao-injetada. Grupo B: peixes alimentados com racao suplementada com probiotico: Controle; Carragenina; Nao-injetada. Apos 15 dias de

  5. Modeling and Hemofiltration Treatment of Acute Inflammation

    Directory of Open Access Journals (Sweden)

    Robert S. Parker

    2016-10-01

    Full Text Available The body responds to endotoxins by triggering the acute inflammatory response system to eliminate the threat posed by gram-negative bacteria (endotoxin and restore health. However, an uncontrolled inflammatory response can lead to tissue damage, organ failure, and ultimately death; this is clinically known as sepsis. Mathematical models of acute inflammatory disease have the potential to guide treatment decisions in critically ill patients. In this work, an 8-state (8-D differential equation model of the acute inflammatory response system to endotoxin challenge was developed. Endotoxin challenges at 3 and 12 mg/kg were administered to rats, and dynamic cytokine data for interleukin (IL-6, tumor necrosis factor (TNF, and IL-10 were obtained and used to calibrate the model. Evaluation of competing model structures was performed by analyzing model predictions at 3, 6, and 12 mg/kg endotoxin challenges with respect to experimental data from rats. Subsequently, a model predictive control (MPC algorithm was synthesized to control a hemoadsorption (HA device, a blood purification treatment for acute inflammation. A particle filter (PF algorithm was implemented to estimate the full state vector of the endotoxemic rat based on time series cytokine measurements. Treatment simulations show that: (i the apparent primary mechanism of HA efficacy is white blood cell (WBC capture, with cytokine capture a secondary benefit; and (ii differential filtering of cytokines and WBC does not provide substantial improvement in treatment outcomes vs. existing HA devices.

  6. Systemic inflammatory response in erderly patients following hernioplastical operation

    Directory of Open Access Journals (Sweden)

    Grimaldi Maria

    2006-03-01

    Full Text Available Abstract The number of old and oldest old patients undergoing surgery of varying severity is increasing. Ageing is a process that changes the performances of most physiological systems and increases susceptibility to diseases and death; accordingly, host responses to surgical stress are altered with ageing and the occurrence of age-related increase in susceptibility to post-operative complications has been claimed. Twenty-four male patients undergoing Lichtenstein (LH hernioplasty for unilateral inguinal hernia were included in this study and divided in two groups (Young and Old respectively, according to their age. As expression of the acute phase response, we measured changes in concentration of pro-inflammatory cytokines Tumor necrosis factor-α and Interleukin-1β, leukocytes, acute phase proteins C-reactive protein and α 1-antitrypsin. Elderly humans showed prolonged and strong inflammatory activity compared to younger subjects in response to surgical stress, indicating that the acute-phase response to surgical stress of elderly humans varies from that of the young, showing initial hyperactivity and a delayed termination of the response. Thus, the acute phase response to surgical stress is higher in old subjects, but the clinical significance of this remains unclear. It is not known whether a causal relationship exists between this stronger acute phase response and the increases in susceptibility to post-operative complications observed in aged patients.

  7. Acute Pancreatitis and Pregnancy

    Science.gov (United States)

    ... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

  8. Serum cardiac troponin I in acute stroke is related to serum cortisol and TNF-alpha

    DEFF Research Database (Denmark)

    Christensen, Hanne Krarup; Johannesen, Helle Hjorth; Christensen, Anders Fogh

    2004-01-01

    Serum cardiac troponin I (cTnI) is a specific marker of myocardial injury related to in-patient fatality and cardiac injury in acute stroke. We investigated whether cTnI in acute stroke is related to serum cortisol, acute inflammatory response, and insular damage. We also investigated whether c...

  9. Analgesic and Anti-Inflammatory Activity of Pinus roxburghii Sarg.

    Directory of Open Access Journals (Sweden)

    Dhirender Kaushik

    2012-01-01

    Full Text Available The Chir Pine, Pinus roxburghii, named after William Roxburgh, is a pine native to the Himalaya. Pinus roxburghii Sarg. (Pinaceae is traditionally used for several medicinal purposes in India. As the oil of the plant is extensively used in number of herbal preparation for curing inflammatory disorders, the present study was undertaken to assess analgesic and anti-inflammatory activities of its bark extract. Dried and crushed leaves of Pinus roxburghii Sarg. were defatted with petroleum ether and then extracted with alcohol. The alcoholic extract at the doses of 100 mg/kg, 300 mg/kg, and 500 mg/kg body weight was subjected to evaluation of analgesic and anti-inflammatory activities in experimental animal models. Analgesic activity was evaluated by acetic acid-induced writhing and tail immersion tests in Swiss albino mice; acute and chronic anti-inflammatory activity was evaluated by carrageenan-induced paw oedema and cotton pellet granuloma in Wistar albino rats. Diclofenac sodium and indomethacin were employed as reference drugs for analgesic and anti-inflammatory studies, respectively. In the present study, the alcoholic bark extract of Pinus roxburghii Sarg. demonstrated significant analgesic and anti-inflammatory activities in the tested models.

  10. Immune-modulating therapy in acute pancreatitis: Fact or fiction

    Science.gov (United States)

    Akinosoglou, Karolina; Gogos, Charalambos

    2014-01-01

    Acute pancreatitis (AP) is one of the most common diseases of the gastrointestinal tract, bearing significant morbidity and mortality worldwide. Current treatment of AP remains unspecific and supportive and is mainly targeted to aggressively prevent systemic complications and organ failure by intensive care. As acute pancreatitis shares an indistinguishable profile of inflammation with sepsis, therapeutic approaches have turned towards modulating the systemic inflammatory response. Targets, among others, have included pro- and anti-inflammatory modulators, cytokines, chemokines, immune cells, adhesive molecules and platelets. Even though, initial results in experimental models have been encouraging, clinical implementation of immune-regulating therapies in acute pancreatitis has had a slow progress. Main reasons include difficulty in clinical translation of experimental data, poor understanding of inflammatory response time-course, flaws in experimental designs, need for multimodal approaches and commercial drawbacks. Whether immune-modulation in acute pancreatitis remains a fact or just fiction remains to be seen in the future. PMID:25386069

  11. Maternal endotoxin-induced fetal growth restriction in rats: Fetal responses in toll-like receptor

    Directory of Open Access Journals (Sweden)

    Banun Kusumawardani

    2012-09-01

    Full Text Available Background: Porphyromonas gingivalis as a major etiology of periodontal disease can produce virulence factor, lipopolysaccharide/LPS, which is expected to play a role in the intrauterine fetal growth. Trophoblast at the maternal-fetal interface actively participates in response to infection through the expression of a family of natural immune receptors, toll-like receptor (TLR. Purpose: the aims of study were to identify endotoxin concentration in maternal blood serum of Porphyromonas gingivalis-infected pregnant rats, to characterize the TLR-4 expression in trophoblast cells, and to determine its effect on fetal growth. Methods: Female rats were infected with live-Porphyromonas gingivalis at concentration of 2 x 109 cells/ml into subgingival sulcus area of the maxillary first molar before and/or during pregnancy. They were sacrified on 14th and 20th gestational day. Fetuses were evaluated for weight and length. Endotoxin was detected by limulus amebocyte lysate assay in the maternal blood serum. The TLR-4 expression in trophoblast cells was detected by immunohistochemistry. Digital Imaging Analysis for the Study of Endotoxin-Induced Mitochondrial Ultrastructure Injury

    Directory of Open Access Journals (Sweden)

    Mandar S. Joshi

    2000-01-01

    Full Text Available Primary defects in mitochondrial function have been implicated in over 100 diverse diseases. In situ, mitochondria possess unique and well-defined morphology in normal healthy cells, but diseases linked to defective mitochondrial function are characterized by the presence of morphologically abnormal and swollen mitochondria with distorted cristae. In situ study of mitochondrial morphology is established as an indicator of mitochondrial health but thus far assessments have been via subjective evaluations by trained observers using discontinuous scoring systems. Here we investigated the value of digital imaging analysis to provide for unbiased, reproducible, and convenient evaluations of mitochondrial ultrastructure. Electron photomicrographs of ileal mucosal mitochondria were investigated using a scoring system previously described by us, and also analyzed digitally by using six digital parameters which define size, shape, and electron density characteristics of over 700 individual mitochondria. Statistically significant changes in mitochondrial morphology were detected in LPS treated animals relative to vehicle control using both the subjective scoring system and digital imaging parameters (p < 0:05. However, the imaging approach provided convenient and high throughput capabilities and was easily automated to remove investigator influences. These results illustrate significant changes in ileal mucosal mitochondrial ultrastructure during sepsis and demonstrate the value of digital imaging technology for routine assessments in this setting.

  12. Blockade by fenspiride of endotoxin-induced neutrophil migration in the rat.

    Science.gov (United States)

    Cunha, F Q; Boukili, M A; da Motta, J I; Vargaftig, B B; Ferreira, S H

    1993-07-06

    Fenspiride, an antiinflammatory drug with low anti-cyclooxygenase activity, administered orally at 60-200 mg/kg inhibited neutrophil migration into peritoneal and air pouches cavities as well as exudation into peritoneal cavities induced by endotoxin but not induced by carrageenin. Up to 100 microM, fenspiride failed to inhibit the in vitro release of a neutrophil chemotactic activity by endotoxin-stimulated macrophages and the in vivo migration into the peritoneal cavities induced by the supernatant of those macrophages. The release of tumour necrosis factor by stimulated macrophages was inhibited by fenspiride in a dose-dependent manner. These results suggest that the antiinflammatory effects of fenspiride are associated with the inhibition of the tumour necrosis factor release by resident macrophages.

  13. Edaravone protects endotoxin-induced liver injury by inhibiting apoptosis and reducing proinflammatory cytokines.

    Science.gov (United States)

    Zong, L; Yu, Q H; Du, Y X; Deng, X M

    2014-02-01

    Studies have shown that edaravone may prevent liver injury. This study aimed to investigate the effects of edaravone on the liver injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS) in female BALB/c mice. Edaravone was injected into mice 30 min before and 4 h after GalN/LPS injection. The survival rate was determined within the first 24 h. Animals were killed 8 h after GalN/LPS injection, and liver injury was biochemically and histologically assessed. Hepatocyte apoptosis was measured by TUNEL staining; proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in the liver were assayed by ELISA; expression of caspase-8 and caspase-3 proteins was detected by Western blot assay; and caspase-3 activity was also determined. Results showed that GalN/LPS induced marked elevations in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Edaravone significantly inhibited elevation of serum AST and ALT, accompanied by an improvement in histological findings. Edaravone lowered the levels of TNF-α and IL-6 and reduced the number of TUNEL-positive cells. In addition, 24 h after edaravone treatment, caspase-3 activity and mortality were reduced. Edaravone may effectively ameliorate GalN/LPS-induced liver injury in mice by reducing proinflammatory cytokines and inhibiting apoptosis.

  14. Edaravone protects endotoxin-induced liver injury by inhibiting apoptosis and reducing proinflammatory cytokines

    Energy Technology Data Exchange (ETDEWEB)

    Zong, L. [Second Military Medical University, Changhai Hospital, Department of Anesthesiology, Shanghai, China, Department of Anesthesiology, Changhai Hospital, Second Military Medical University, Shanghai (China); No. 82 Hospital of People' s Liberation Army, Department of Anesthesiology, Jiangsu, China, Department of Anesthesiology, No. 82 Hospital of People' s Liberation Army, Jiangsu (China); Yu, Q. H. [Second Military Medical University, Changhai Hospital, Department of Gastroenterology, Shanghai, China, Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai (China); Du, Y. X. [No. 82 Hospital of People' s Liberation Army, Department of Anesthesiology, Jiangsu, China, Department of Anesthesiology, No. 82 Hospital of People' s Liberation Army, Jiangsu (China); Deng, X. M. [Second Military Medical University, Changhai Hospital, Department of Anesthesiology, Shanghai, China, Department of Anesthesiology, Changhai Hospital, Second Military Medical University, Shanghai (China)

    2014-03-03

    Studies have shown that edaravone may prevent liver injury. This study aimed to investigate the effects of edaravone on the liver injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS) in female BALB/c mice. Edaravone was injected into mice 30 min before and 4 h after GalN/LPS injection. The survival rate was determined within the first 24 h. Animals were killed 8 h after GalN/LPS injection, and liver injury was biochemically and histologically assessed. Hepatocyte apoptosis was measured by TUNEL staining; proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in the liver were assayed by ELISA; expression of caspase-8 and caspase-3 proteins was detected by Western blot assay; and caspase-3 activity was also determined. Results showed that GalN/LPS induced marked elevations in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Edaravone significantly inhibited elevation of serum AST and ALT, accompanied by an improvement in histological findings. Edaravone lowered the levels of TNF-α and IL-6 and reduced the number of TUNEL-positive cells. In addition, 24 h after edaravone treatment, caspase-3 activity and mortality were reduced. Edaravone may effectively ameliorate GalN/LPS-induced liver injury in mice by reducing proinflammatory cytokines and inhibiting apoptosis.

  15. Edaravone protects endotoxin-induced liver injury by inhibiting apoptosis and reducing proinflammatory cytokines

    Directory of Open Access Journals (Sweden)

    L. Zong

    2014-03-01

    Full Text Available Studies have shown that edaravone may prevent liver injury. This study aimed to investigate the effects of edaravone on the liver injury induced by D-galactosamine (GalN and lipopolysaccharide (LPS in female BALB/c mice. Edaravone was injected into mice 30 min before and 4 h after GalN/LPS injection. The survival rate was determined within the first 24 h. Animals were killed 8 h after GalN/LPS injection, and liver injury was biochemically and histologically assessed. Hepatocyte apoptosis was measured by TUNEL staining; proinflammatory cytokines [tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6] in the liver were assayed by ELISA; expression of caspase-8 and caspase-3 proteins was detected by Western blot assay; and caspase-3 activity was also determined. Results showed that GalN/LPS induced marked elevations in serum aspartate aminotransferase (AST and alanine aminotransferase (ALT. Edaravone significantly inhibited elevation of serum AST and ALT, accompanied by an improvement in histological findings. Edaravone lowered the levels of TNF-α and IL-6 and reduced the number of TUNEL-positive cells. In addition, 24 h after edaravone treatment, caspase-3 activity and mortality were reduced. Edaravone may effectively ameliorate GalN/LPS-induced liver injury in mice by reducing proinflammatory cytokines and inhibiting apoptosis.

  16. Edaravone protects endotoxin-induced liver injury by inhibiting apoptosis and reducing proinflammatory cytokines

    International Nuclear Information System (INIS)

    Zong, L.; Yu, Q.H.; Du, Y.X.; Deng, X.M.

    2014-01-01

    Studies have shown that edaravone may prevent liver injury. This study aimed to investigate the effects of edaravone on the liver injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS) in female BALB/c mice. Edaravone was injected into mice 30 min before and 4 h after GalN/LPS injection. The survival rate was determined within the first 24 h. Animals were killed 8 h after GalN/LPS injection, and liver injury was biochemically and histologically assessed. Hepatocyte apoptosis was measured by TUNEL staining; proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in the liver were assayed by ELISA; expression of caspase-8 and caspase-3 proteins was detected by Western blot assay; and caspase-3 activity was also determined. Results showed that GalN/LPS induced marked elevations in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Edaravone significantly inhibited elevation of serum AST and ALT, accompanied by an improvement in histological findings. Edaravone lowered the levels of TNF-α and IL-6 and reduced the number of TUNEL-positive cells. In addition, 24 h after edaravone treatment, caspase-3 activity and mortality were reduced. Edaravone may effectively ameliorate GalN/LPS-induced liver injury in mice by reducing proinflammatory cytokines and inhibiting apoptosis

  17. Lipocalin 2 deficiency dysregulates iron homeostasis and exacerbates endotoxin-induced sepsis

    DEFF Research Database (Denmark)

    Srinivasan, Gayathri; Aitken, Jesse D; Zhang, Benyue

    2012-01-01

    Various states of inflammation, including sepsis, are associated with hypoferremia, which limits iron availability to pathogens and reduces iron-mediated oxidative stress. Lipocalin 2 (Lcn2; siderocalin, 24p3) plays a central role in iron transport. Accordingly, Lcn2-deficient (Lcn2KO) mice exhib...

  18. Fingolimod against endotoxin-induced fetal brain injury in a rat model.

    Science.gov (United States)

    Yavuz, And; Sezik, Mekin; Ozmen, Ozlem; Asci, Halil

    2017-11-01

    Fingolimod is a sphingosine-1-phosphate receptor modulator used for multiple sclerosis treatment and acts on cellular processes such as apoptosis, endothelial permeability, and inflammation. We hypothesized that fingolimod has a positive effect on alleviating preterm fetal brain injury. Sixteen pregnant rats were divided into four groups of four rats each. On gestational day 17, i.p. endotoxin was injected to induce fetal brain injury, followed by i.p. fingolimod (4 mg/kg maternal weight). Hysterotomy for preterm delivery was performed 6 h after fingolimod. The study groups included (i) vehicle controls (i.p. normal saline only); (ii) positive controls (endotoxin plus saline); (iii) saline plus fingolimod; and (iv) endotoxin plus fingolimod treatment. Brain tissues of the pups were dissected for evaluation of interleukin (IL)-6, caspase-3, and S100β on immunohistochemistry. Maternal fingolimod treatment attenuated endotoxin-related fetal brain injury and led to lower immunoreactions for IL-6, caspase-3, and S100β compared with endotoxin controls (P < 0.0001 for all comparisons). Antenatal maternal fingolimod therapy had fetal neuroprotective effects by alleviating preterm birth-related fetal brain injury with inhibitory effects on inflammation and apoptosis. © 2017 Japan Society of Obstetrics and Gynecology.

  19. Acute pancreatitis.

    Science.gov (United States)

    Talukdar, Rupjyoti; Vege, Santhi S

    2015-09-01

    To summarize recent data on classification systems, cause, risk factors, severity prediction, nutrition, and drug treatment of acute pancreatitis. Comparison of the Revised Atlanta Classification and Determinant Based Classification has shown heterogeneous results. Simvastatin has a protective effect against acute pancreatitis. Young black male, alcohol, smoldering symptoms, and subsequent diagnosis of chronic pancreatitis are risk factors associated with readmissions after acute pancreatitis. A reliable clinical or laboratory marker or a scoring system to predict severity is lacking. The PYTHON trial has shown that oral feeding with on demand nasoenteric tube feeding after 72 h is as good as nasoenteric tube feeding within 24 h in preventing infections in predicted severe acute pancreatitis. Male sex, multiple organ failure, extent of pancreatic necrosis, and heterogeneous collection are factors associated with failure of percutaneous drainage of pancreatic collections. The newly proposed classification systems of acute pancreatitis need to be evaluated more critically. New biomarkers are needed for severity prediction. Further well designed studies are required to assess the type of enteral nutritional formulations for acute pancreatitis. The optimal minimally invasive method or combination to debride the necrotic collections is evolving. There is a great need for a drug to treat the disease early on to prevent morbidity and mortality.

  1. Toll-like receptors in cerebral ischemic inflammatory injury

    OpenAIRE

    Wang, Yan-Chun; Lin, Sen; Yang, Qing-Wu

    2011-01-01

    Abstract Cerebral ischemia triggers acute inflammation, which has been associated with an increase in brain damage. The mechanisms that regulate the inflammatory response after cerebral ischemia are multifaceted. An important component of this response is the activation of the innate immune system. However, details of the role of the innate immune system within the complex array of mechanisms in cerebral ischemia remain unclear. There have been recent great strides in our understanding of the...

  2. Inflammatory bowel disease.

    Science.gov (United States)

    Gibson, Peter R; Iser, John

    2005-04-01

    Inflammatory bowel disease (IBD) is increasing in frequency in Australia. General practitioners play an important role in early diagnosis and in a multidisciplinary approach to managing such patients. Keeping abreast of evolving concepts, particularly in treatment, is challenging. This article aims to address key issues in diagnosis and management to better equip general practitioners for their role in multidisciplinary management of patients with IBD. Making the diagnosis can be difficult, but is facilitated by appropriate clinical suspicion and sensible judgment as to who undergoes diagnostic tests such as colonoscopy. Treatment of ulcerative colitis has changed little in recent years, except for our improved ability to deliver mesalazine to the large bowel via the recent availability of several oral and rectal preparations. Prevention of relapse using these is an important strategy in the majority of patients. Treatment of Crohn disease is changing due to more realistic concepts of the natural history of the disease and the development of new, powerful anti-inflammatory therapies. Attention to issues other than intestinal inflammation such as nutrition, education and counselling, remain important in achieving optimal management.

  3. Inflammatory breast cancer

    International Nuclear Information System (INIS)

    Wagnerova, M.

    2012-01-01

    Inflammatory breast cancer (IBC) is an extremely aggressive disease that progresses rapidly and carries a very grim prognosis. It is characterized by erythema, rapid enlargement of the breast, skin ridging, and a characteristics peau d´orange appearance of the skin secondary to dermal lymphatic tumor involvement. Although a palpable tumor may not by present, about 55% to 85% of patient will present with metastases to the axillary or supraclavicular lymph nodes. Diagnosis of IBC is made on the basis of these clinical characteristics, as well as histologic verification of carcinoma. Accurate diagnosis is critically important, as multimodal therapy can significantly improve outcome if instituted early enough. Primary systemic treatment (neoadjuvant, induction, initials) is standard treatment for inflammatory breast cancer. If treatment response is not satisfactory it is necessary to look for new treatment regimens with different concept of dose intensity, density and sequence of treatment. In the neoadjuvant setting it is possible to employ all targeted and non-targeted therapies as was shown in a number of clinical trials. (author)

  4. Anti-inflammatory and antinociceptive activities of azadirachtin in mice.

    Science.gov (United States)

    Soares, Darly G; Godin, Adriana M; Menezes, Raquel R; Nogueira, Rafaela D; Brito, Ana Mercy S; Melo, Ivo S F; Coura, Giovanna Maria E; Souza, Danielle G; Amaral, Flávio A; Paulino, Tony P; Coelho, Márcio M; Machado, Renes R

    2014-06-01

    Azadirachta indica (Meliaceae) extracts have been reported to exhibit anti-inflammatory and antinociceptive properties. However, the activities of azadirachtin, a limonoid and the major bioactive compound found in the extracts, have been poorly investigated in animal models. In the present study, we investigated the effects induced by azadirachtin in experimental models of pain and inflammation in mice. Carrageenan-induced paw edema and fibrovascular tissue growth induced by subcutaneous cotton pellet implantation were used to investigate the anti-inflammatory activity of azadirachtin in mice. Zymosan-induced writhing and hot plate tests were employed to evaluate the antinociceptive activity. To explore putative mechanisms of action, the level of tumor necrosis factor-α in inflammatory tissue was measured and the effect induced by opioidergic and serotonergic antagonists was evaluated. Previous per os (p. o.) administration of azadirachtin (120 mg/kg) significantly reduced the acute paw edema induced by carrageenan. However, the concomitant increase of the paw concentration of tumor necrosis factor-α induced by this inflammatory stimulus was not reduced by azadirachtin. In addition to inhibiting the acute paw edema induced by carrageenan, azadirachtin (6, 60, and 120 mg/kg) inhibited the proliferative phase of the inflammatory response, as demonstrated by the reduced formation of fibrovascular tissue growth. Azadirachtin (120 mg/kg) also inhibited the nociceptive response in models of nociceptive (hot plate) and inflammatory (writhing induced by zymosan) pain. The activity of azadirachtin (120 mg/kg) in the model of nociceptive pain was attenuated by a nonselective opioid antagonist, naltrexone (10 mg/kg, i. p.), but not by a nonselective serotonergic antagonist, cyproheptadine. In conclusion, this study demonstrates the activity of azadirachtin in experimental models of nociceptive and inflammatory pain, and also in models of acute and chronic inflammation

  5. inflammatory drugs fail to enhance healing of acute hamstring

    African Journals Online (AJOL)

    r pylori e in. J 1993; n of. 96. ive as educing. 28-31. 85. cillin to ation of . MA. SAMJ ... Treatment produced a significant improvement in ..... Dry mouth .... McLatchie GA, Allister C, MacEwen C, Hamilton G, MacGregor H. Variable schedules.

  6. Acute Pelvic Inflammatory Disease in Cameroon: A Cross Sectional ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    Saharan countries, the incidence is not well known and might be ... infertility has not, due to the fact that the majority of ... calculated using the following formula for ... Cervical motion tenderness. 66 (94.3). Fever (≥38.3°C). 58 (82.9). Fatigue.

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

    DEFF Research Database (Denmark)

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

    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...... 19 healthy control horses. SAA and haptoglobin were measured in both serum and PF. Colic cases were classified according to diagnosis, treatment and outcome based on the clinical records. Protein concentrations were compared between groups with student´s t-test and ANOVA. Results Colic horses had...... significantly higher mean concentrations of serum SAA, PF SAA and PF haptoglobin compared to controls. PF SAA was significantly higher in horses with infectious conditions compared to both simple and strangulating obstructions, where as PF haptoglobin was higher in both strangulating and infectious conditions...

  8. Effects of gabapentin in acute inflammatory pain in humans

    DEFF Research Database (Denmark)

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

    2001-01-01

    ,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...

  9. The Acute Inflammatory Response in Trauma / Hemorrhage and ...

    African Journals Online (AJOL)

    Inflammation describes a coordinated series of molecular, cellular, tissue, organ, and ... for immune surveillance, optimal post-injury tissue repair, and regeneration. ... Hemorrhagic Shock, Traumatic Brain Injury, Inflammation, Systems Biology ...

  10. Treatment of inflammatory diseases with mesenchymal stem cells.

    Science.gov (United States)

    Newman, Robert E; Yoo, Dana; LeRoux, Michelle A; Danilkovitch-Miagkova, Alla

    2009-06-01

    Human mesenchymal stem cells (hMSCs) are rare progenitor cells present in adult bone marrow that have the capacity to differentiate into a variety of tissue types, including bone, cartilage, tendon, fat, and muscle. In addition to multilineage differentiation capacity, MSCs regulate immune and inflammatory responses, providing therapeutic potential for treating diseases characterized by the presence of an inflammatory component. The availability of bone marrow and the ability to isolate and expand hMSCs ex vivo make these cells an attractive candidate for drug development. The low immunogenicity of these cells suggests that hMSCs can be transplanted universally without matching between donors and recipients. MSCs universality, along with the ability to manufacture and store these cells long-term, present a unique opportunity to produce an "off-the-shelf" cellular drug ready for treatment of diseases in acute settings. Accumulated animal and human data support MSC therapeutic potential for inflammatory diseases. Several phase III clinical trials for treatment of acute Graft Versus Host Disease (GVHD) and Crohn's disease are currently in progress. The current understanding of cellular and molecular targets underlying the mechanisms of MSCs action in inflammatory settings as well as clinical experience with hMSCs is summarized in this review.

  11. Neuroimmune regulation of inflammatory responses in inflammatory bowel disease

    NARCIS (Netherlands)

    Rijnierse, Anneke

    2006-01-01

    The term inflammatory bowel disease (IBD) is used to describe chronic inflammatory conditions of the gastro-intestinal tract. Patients suffer from abdominal pain, diarrhea, rectal bleeding and a substantial personal burden. The etiology of IBD is gradually being unraveled but remains a complex

  12. Synthesis and Anti-inflammatory Evaluation of Novel Benzimidazole and Imidazopyridine Derivatives.

    Science.gov (United States)

    Chen, Gaozhi; Liu, Zhiguo; Zhang, Yali; Shan, Xiaoou; Jiang, Lili; Zhao, Yunjie; He, Wenfei; Feng, Zhiguo; Yang, Shulin; Liang, Guang

    2013-01-10

    Sepsis, an acute inflammatory disease, remains the most common cause of death in intensive care units. A series of benzimidazole and imidazopyridine derivatives were synthesized and screened for anti-inflammatory activities, and the imidazopyridine series showed excellent inhibition of the expression of inflammatory cytokines in LPS-stimulated macrophages. Compounds X10, X12, X13, X14, and X15 inhibited TNF-α and IL-6 release in a dose-dependent manner, and X12 showed no cytotoxicity in hepatic cells. Furthermore, X12 exhibited a significant protection against LPS-induced septic death in mouse models. Together, these data present a series of new imidazopyridines with potential therapeutic effects in acute inflammatory diseases.

  13. Flavonoids in Inflammatory Bowel Disease: A Review

    Science.gov (United States)

    Vezza, Teresa; Rodríguez-Nogales, Alba; Algieri, Francesca; Utrilla, Maria Pilar; Rodriguez-Cabezas, Maria Elena; Galvez, Julio

    2016-01-01

    Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the intestine that compromises the patients’ life quality and requires sustained pharmacological and surgical treatments. Since their etiology is not completely understood, non-fully-efficient drugs have been developed and those that have shown effectiveness are not devoid of quite important adverse effects that impair their long-term use. In this regard, a growing body of evidence confirms the health benefits of flavonoids. Flavonoids are compounds with low molecular weight that are widely distributed throughout the vegetable kingdom, including in edible plants. They may be of great utility in conditions of acute or chronic intestinal inflammation through different mechanisms including protection against oxidative stress, and preservation of epithelial barrier function and immunomodulatory properties in the gut. In this review we have revised the main flavonoid classes that have been assessed in different experimental models of colitis as well as the proposed mechanisms that support their beneficial effects. PMID:27070642

  14. Flavonoids in Inflammatory Bowel Disease: A Review

    Directory of Open Access Journals (Sweden)

    Teresa Vezza

    2016-04-01

    Full Text Available Inflammatory bowel disease (IBD is characterized by chronic inflammation of the intestine that compromises the patients’ life quality and requires sustained pharmacological and surgical treatments. Since their etiology is not completely understood, non-fully-efficient drugs have been developed and those that have shown effectiveness are not devoid of quite important adverse effects that impair their long-term use. In this regard, a growing body of evidence confirms the health benefits of flavonoids. Flavonoids are compounds with low molecular weight that are widely distributed throughout the vegetable kingdom, including in edible plants. They may be of great utility in conditions of acute or chronic intestinal inflammation through different mechanisms including protection against oxidative stress, and preservation of epithelial barrier function and immunomodulatory properties in the gut. In this review we have revised the main flavonoid classes that have been assessed in different experimental models of colitis as well as the proposed mechanisms that support their beneficial effects.

  15. Pediatric Inflammatory Bowel Diseases

    DEFF Research Database (Denmark)

    Lauritzen, Didde; Andreassen, Bente Utoft; Heegaard, Niels Henrik H

    2018-01-01

    Background: Kidney disease has been reported in adults with inflammatory bowel disease (IBD) and is regarded an extraintestinal manifestation or more rarely a side effect of the medical treatment. Methods: In this cross-sectional study we describe the extent of kidney pathology in a cohort of 56...... children with IBD. Blood and urine samples were analyzed for markers of kidney disease and ultrasonography was performed to evaluate pole-to-pole kidney length. Results: We found that 25% of the patients had either previously reported kidney disease or ultrasonographic signs of chronic kidney disease...... are at risk of chronic kidney disease, and the risk seems to be increased with the severity of the disease....

  16. Inflammatory biomarkers and cancer

    DEFF Research Database (Denmark)

    Rasmussen, Line Jee Hartmann; Schultz, Martin; Gaardsting, Anne

    2017-01-01

    and previous cancer diagnoses compared to patients who were not diagnosed with cancer. Previous cancer, C-reactive protein (CRP) and suPAR were significantly associated with newly diagnosed cancer during follow-up in multiple logistic regression analyses adjusted for age, sex and CRP. Neither any of the PRRs......In Denmark, patients with serious nonspecific symptoms and signs of cancer (NSSC) are referred to the diagnostic outpatient clinics (DOCs) where an accelerated cancer diagnostic program is initiated. Various immunological and inflammatory biomarkers have been associated with cancer, including...... soluble urokinase plasminogen activator receptor (suPAR) and the pattern recognition receptors (PRRs) pentraxin-3, mannose-binding lectin, ficolin-1, ficolin-2 and ficolin-3. We aimed to evaluate these biomarkers and compare their diagnostic ability to classical biomarkers for diagnosing cancer...

  17. Spontaneous Transient Lateral Thoracic Lung Herniation Resulting in Systemic Inflammatory Response Syndrome (SIRS and Subsequent Contralateral Lung Injury

    Directory of Open Access Journals (Sweden)

    Antony Kaliyadan

    2011-01-01

    Full Text Available Lung herniation is a relatively rare clinical entity that is most commonly either congenital or acquired traumatically. We describe a case of spontaneous lung herniation secondary to acute cough in an obese male smoker complicated by contralateral acute lung injury and systemic inflammatory response syndrome (SIRS. Mechanisms of lung herniation, classification, diagnosis, and management will be discussed.

  18. Acute Pancreatitis

    DEFF Research Database (Denmark)

    Bertilsson, Sara; Håkansson, Anders; Kalaitzakis, Evangelos

    2017-01-01

    Aims: We aimed to evaluate the potential relation between the incidence of (alcoholic and non-alcoholic) acute pancreatitis (AP) and alcohol consumption in the general population, and whether the occurrence of AP shows any seasonal variation, particularly in relation to periods with expected...... consumption in the general population do not appear to be related to changes in the incidence of AP and there are no significant seasonal differences in the occurrence of AP in Sweden. Short summary: The incidence of acute pancreatitis (AP) is increasing, and alcohol is still recognized as one of the most...

  19. Perfil inflamatório, metabólico e lipídico na síndrome isquêmica aguda: relação com eventos intra e pós-hospitalares Inflammatory, lipid, and metabolic profile in acute ischemic syndrome: correlation with hospital and posthospital events

    Directory of Open Access Journals (Sweden)

    Elizabeth da Rosa Duarte

    2005-02-01

    Full Text Available OBJETIVO: Associar o perfil lipídico, inflamatório (proteína C reativa ultra sensível - PCR us - e fibrinogênio e metabólico (glicose com eventos intra e pós-hospitalares de pacientes com síndrome isquêmica aguda (SIA e descrever preditores de mortalidade nesta população. MÉTODOS: Estudo de coorte com 199 pacientes com SIA (angina instável, infarto agudo do miocárdio com ou sem supradesnivelamento de ST internados na unidade de terapia intensiva (UTI de uma instituição de referência cardiológica, no período de março a novembro de 2002. Foram registrados as doenças prévias, as medicações em uso e os fatores de risco coronarianos. Os eventos clínicos intra-hospitalares considerados foram Re-IAM, angina, insuficiência cardíaca (IC, fibrilação ventricular e óbito e os pós-hospitalares (30 dias após a alta foram Re-IAM, angina, IC, óbito e re-internação para procedimentos percutâneos (ACTP ou de revascularização (CRM. RESULTADOS: A PCR us e a glicemia alterada associaram-se, significativamente, com os eventos intra-hospitalares (p=0,03 e pOBJECTIVE: To associate the markers lipid profile, inflammatory profile (high-sensitivity C-reactive protein HSCRP and fibrinogen, and metabolic profile (glucose determination with hospital and posthospital events in patients with acute ischemic syndrome (AIS and to describe the predictors of mortality in this population. METHODS: A cohort study with 199 patients with AIS (unstable angina, acute myocardial infarction (AMI with or without ST segment elevation admitted to the intensive care unit (ICU of a university cardiology Hospital, from March to November 2002. The previous diseases, the medication in use, and the coronary risk factors were recorded. The clinical events considered in the hospital were reinfarction, angina, heart failure (HF, ventricular fibrillation, and death; the posthospital events considered (30 days after hospital discharge were reinfarction, angina, HF

  20. Acute exacerbation of COPD.

    Science.gov (United States)

    Ko, Fanny W; Chan, Ka Pang; Hui, David S; Goddard, John R; Shaw, Janet G; Reid, David W; Yang, Ian A

    2016-10-01

    The literature of acute exacerbation of chronic obstructive pulmonary disease (COPD) is fast expanding. This review focuses on several aspects of acute exacerbation of COPD (AECOPD) including epidemiology, diagnosis and management. COPD poses a major health and economic burden in the Asia-Pacific region, as it does worldwide. Triggering factors of AECOPD include infectious (bacteria and viruses) and environmental (air pollution and meteorological effect) factors. Disruption in the dynamic balance between the 'pathogens' (viral and bacterial) and the normal bacterial communities that constitute the lung microbiome likely contributes to the risk of exacerbations. The diagnostic approach to AECOPD varies based on the clinical setting and severity of the exacerbation. After history and examination, a number of investigations may be useful, including oximetry, sputum culture, chest X-ray and blood tests for inflammatory markers. Arterial blood gases should be considered in severe exacerbations, to characterize respiratory failure. Depending on the severity, the acute management of AECOPD involves use of bronchodilators, steroids, antibiotics, oxygen and noninvasive ventilation. Hospitalization may be required, for severe exacerbations. Nonpharmacological interventions including disease-specific self-management, pulmonary rehabilitation, early medical follow-up, home visits by respiratory health workers, integrated programmes and telehealth-assisted hospital at home have been studied during hospitalization and shortly after discharge in patients who have had a recent AECOPD. Pharmacological approaches to reducing risk of future exacerbations include long-acting bronchodilators, inhaled steroids, mucolytics, vaccinations and long-term macrolides. Further studies are needed to assess the cost-effectiveness of these interventions in preventing COPD exacerbations. © 2016 Asian Pacific Society of Respirology.

  1. Macrophage elastase (MMP-12: a pro-inflammatory mediator?

    Directory of Open Access Journals (Sweden)

    Soazig Nénan

    2005-03-01

    Full Text Available As many metalloproteinases (MMPs, macrophage elastase (MMP-12 is able to degrade extracellular matrix components such as elastin and is involved in tissue remodeling processes. Studies using animal models of acute and chronic pulmonary inflammatory diseases, such as pulmonary fibrosis and chronic obstrutive pulmonary disease (COPD, have given evidences that MMP-12 is an important mediator of the pathogenesis of these diseases. However, as very few data regarding the direct involvement of MMP-12 in inflammatory process in the airways were available, we have instilled a recombinant form of human MMP-12 (rhMMP-12 in mouse airways. Hence, we have demonstrated that this instillation induced a severe inflammatory cell recruitment characterized by an early accumulation of neutrophils correlated with an increase in proinflammatory cytokines and in gelatinases and then by a relatively stable recruitment of macrophages in the lungs over a period of ten days. Another recent study suggests that resident alveolar macrophages and recruited neutrophils are not involved in the delayed macrophage recruitment. However, epithelial cells could be one of the main targets of rhMMP-12 in our model. We have also reported that a corticoid, dexamethasone, phosphodiesterase 4 inhibitor, rolipram and a non-selective MMP inhibitor, marimastat could reverse some of these inflammatory events. These data indicate that our rhMMP-12 model could mimic some of the inflammatory features observed in COPD patients and could be used for the pharmacological evaluation of new anti-inflammatory treatment. In this review, data demonstrating the involvement of MMP-12 in the pathogenesis of pulmonary fibrosis and COPD as well as our data showing a pro-inflammatory role for MMP-12 in mouse airways will be summarized.

  2. [Acid-base imbalance in acute obstructive uropathies].

    Science.gov (United States)

    Belyĭ, L E

    2007-01-01

    The aim of this study was to evaluate impairment of acid-base balance (ABB) in acute obstructive uropathies. Evaluation of acid-base balance was performed by pH, partial carbon dioxide pressure, plasma bicarbonate concentration, buffer bases, basis excess, hydrogen ion concentration. An automatic gas analyzer was used, plasma anion gap was calculated. Characteristic ABB alterations in different acute obstructive uropathies were detected. Acidotic shifts in acute obstruction of the upper urinary tracts and its inflammatory complications were assessed pathophysiologically. A comparative study of pathological acid-base disorders in acute supra- and infravesical obstructive uropathies was performed.

  3. [S1 Herpes zoster localization: acute urinary retention in woman].

    Science.gov (United States)

    Vella, Marco; Mastrocinque, Giuseppe; Romeo, Salvatore; Giammanco, Giovanni; Melloni, Darwin

    2011-01-01

    Acute urinary retention in women is rare. The varicella-zoster virus causes inflammatory lesions of the sensory-root ganglions, meninges and, less frequently, spinal cord. Herpes zoster has been reported to affect, although rarely, lower urinary tract innervations, and acute urinary retention can be thought to occur in the presence of sacral dermatome involvement. Usually it is located in S2-4 dermatome and the prognosis for acute urinary retention is benign resolving in about 20 days. We present a case in which the S1 dermatome was involved and acute urinary retention developed. After 10 days of specific therapy and self-catheterization the problem resolved.

  4. Inflammatory pathways of importance for management of inflammatory bowel disease

    DEFF Research Database (Denmark)

    Pedersen, Jannie; Coskun, Mehmet; Soendergaard, Christoffer

    2014-01-01

    Inflammatory bowel disease (IBD) is a group of chronic disorders of the gastrointestinal tract comprising Crohn's disease (CD) and ulcerative colitis (UC). Their etiologies are unknown, but they are characterised by an imbalanced production of pro-inflammatory mediators, e.g., tumor necrosis factor......-inflammatory cytokines, antibodies targeting integrins, and small anti-adhesion molecules that block adhesion between leukocytes and the intestinal vascular endothelium, reducing their infiltration into the inflamed mucosa. In this review we have elucidated the major signaling pathways of clinical importance for IBD...

  5. Idiopathic inflammatory myositis.

    Science.gov (United States)

    Tieu, Joanna; Lundberg, Ingrid E; Limaye, Vidya

    2016-02-01

    Knowledge on idiopathic inflammatory myopathy (IIM) has evolved with the identification of myositis-associated and myositis-specific antibodies, development of histopathological classification and the recognition of how these correlate with clinical phenotype and response to therapy. In this paper, we outline key advances in diagnosis and histopathology, including the more recent identification of antibodies associated with immune-mediated necrotising myopathy (IMNM) and inclusion body myositis (IBM). Ongoing longitudinal observational cohorts allow further classification of these patients with IIM, their predicted clinical course and response to specific therapies. Registries have been developed worldwide for this purpose. A challenging aspect in IIM, a multisystem disease with multiple clinical subtypes, has been defining disease status and clinically relevant improvement. Tools for assessing activity and damage are now recognised to be important in determining disease activity and guiding therapeutic decision-making. The International Myositis Assessment and Clinical Studies (IMACS) group has developed such tools for use in research and clinical settings. There is limited evidence for specific treatment strategies in IIM. With significant development in the understanding of IIM and improved classification, longitudinal observational cohorts and trials using validated outcome measures are necessary, to provide important information for evidence-based care in the clinical setting. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  6. Cardiac inflammatory myofibroblastic tumor: does it recur after complete surgical resection in an adult?

    Directory of Open Access Journals (Sweden)

    Yang Xuedong

    2012-05-01

    Full Text Available Abstract Inflammatory myofibroblastic tumor is currently considered to be a low-grade neoplasm, and it rarely involves the heart. We reported a rare case of a 59-year-old female who received cardiac surgery for complete resection of inflammatory myofibroblastic tumor in the left atrium. Five months after surgery, the patient presented with acute cardiogenic pulmonary edema and subsequent sudden death due to a left atrial tumor which protruded into the left ventricle through mitral annulus during diastole. The recurrence of inflammatory myofibroblastic tumor in the left atrium was strongly suggested clinically.

  7. Phenolic excipients of insulin formulations induce cell death, pro-inflammatory signaling and MCP-1 release

    Directory of Open Access Journals (Sweden)

    Claudia Weber

    2015-01-01

    Insulin solutions displayed cytotoxic and pro-inflammatory potential caused by phenol or m-cresol. We speculate that during insulin pump therapy phenol and m-cresol might induce cell death and inflammatory reactions at the infusion site in vivo. Inflammation is perpetuated by release of MCP-1 by activated monocytic cells leading to enhanced recruitment of inflammatory cells. To minimize acute skin complications caused by phenol/m-cresol accumulation, a frequent change of infusion sets and rotation of the infusion site is recommended.

  8. Citocinas e proteínas de fase aguda do soro como marcadores de regressão da resposta inflamatória ao tratamento da tuberculose pulmonar Cytokines and acute phase serum proteins as markers of inflammatory regression during the treatment of pulmonary tuberculosis

    Directory of Open Access Journals (Sweden)

    Eliana Peresi

    2008-11-01

    Full Text Available OBJETIVO: Analisar o padrão de citocinas pró- e antiinflamatórias e da resposta de fase aguda (RFA como marcadores de resposta ao tratamento da tuberculose pulmonar. MÉTODOS: Determinação dos níveis de interferon-gama (IFN-γ, tumor necrosis factor-alpha (TNF-α, fator de necrose tumoral-alfa, interleucina-10 (IL-10 e transforming growth factor-beta (TGF-β, fator transformador de crescimento-beta, pelo método ELISA, em sobrenadante de cultura de células mononucleares do sangue periférico e monócitos, assim como dos níveis de proteínas totais, albumina, globulinas, alfa-1-glicoproteína ácida (AGA, proteína C reativa (PCR e velocidade de hemossedimentação (VHS em 28 doentes com tuberculose pulmonar, em três tempos: antes (T0, aos três meses (T3 e aos seis meses (T6 de tratamento, em relação aos controles saudáveis, em um único tempo. RESULTADOS: Os pacientes apresentaram valores maiores de citocinas e RFA que os controles em T0, com diminuição em T3 e diminuição (TNF-α, IL-10, TGF-β, AGA e VHS ou normalização (IFN-γ e PCR em T6. CONCLUSÕES: PCR, AGA e VHS são possíveis marcadores para auxiliar no diagnóstico de tuberculose pulmonar e na indicação de tratamento de indivíduos com baciloscopia negativa; PCR (T0 > T3 > T6 = referência pode também ser marcador de resposta ao tratamento. Antes do tratamento, o perfil Th0 (IFN-γ, IL-10, TNF-α e TGF-β, indutor de e protetor contra inflamação, prevaleceu nos pacientes; em T6, prevaleceu o perfil Th2 (IL-10, TNF-α e TGF-β, protetor contra efeito nocivo pró-inflamatório do TNF-α ainda presente. O comportamento do IFN-γ (T0 > T3 > T6 = controle sugere sua utilização como marcador de resposta ao tratamento.OBJECTIVE: To evaluate the pattern of pro-inflammatory cytokines, anti-inflammatory cytokines and the acute phase response (APR as markers of the response to treatment of pulmonary tuberculosis. METHODS: Twenty-eight patients with pulmonary tuberculosis

  9. The axonal guidance receptor neogenin promotes acute inflammation.

    Directory of Open Access Journals (Sweden)

    Klemens König

    Full Text Available Neuronal guidance proteins (NGP were originally described in the context of axonal growth and migration. Yet recent work has demonstrated that NGPs also serve as guidance cues for immune competent cells. A crucial target receptor for NGPs during embryonic development is the neogenin receptor, however its role during acute inflammation is unknown. We report here that neogenin is abundantly expressed outside the nervous system and that animals with endogenous repression of neogenin (Neo1(-/- demonstrate attenuated changes of acute inflammation. Studies using functional inhibition of neogenin resulted in a significant attenuation of inflammatory peritonitis. In studies employing bone marrow chimeric animals we found the hematopoietic presence of Neo1(-/- to be responsible for the attenuated inflammatory response. Taken together our studies suggest that the guidance receptor neogenin holds crucial importance for the propagation of an acute inflammatory response and further define mechanisms shared between the nervous and the immune system.

  10. Pharmacologic therapy for acute pancreatitis

    Science.gov (United States)

    Kambhampati, Swetha; Park, Walter; Habtezion, Aida

    2014-01-01

    While conservative management such as fluid, bowel rest, and antibiotics is the mainstay of current acute pancreatitis management, there is a lot of promise in pharmacologic therapies that target various aspects of the pathogenesis of pancreatitis. Extensive review of preclinical studies, which include assessment of therapies such as anti-secretory agents, protease inhibitors, anti-inflammatory agents, and anti-oxidants are discussed. Many of these studies have shown therapeutic benefit and improved survival in experimental models. Based on available preclinical studies, we discuss potential novel targeted pharmacologic approaches that may offer promise in the treatment of acute pancreatitis. To date a variety of clinical studies have assessed the translational potential of animal model effective experimental therapies and have shown either failure or mixed results in human studies. Despite these discouraging clinical studies, there is a great clinical need and there exist several preclinical effective therapies that await investigation in patients. Better understanding of acute pancreatitis pathophysiology and lessons learned from past clinical studies are likely to offer a great foundation upon which to expand future therapies in acute pancreatitis. PMID:25493000

  11. Integrated Inflammatory Stress (ITIS) Model

    DEFF Research Database (Denmark)

    Bangsgaard, Elisabeth O.; Hjorth, Poul G.; Olufsen, Mette S.

    2017-01-01

    maintains a long-term level of the stress hormone cortisol which is also anti-inflammatory. A new integrated model of the interaction between these two subsystems of the inflammatory system is proposed and coined the integrated inflammatory stress (ITIS) model. The coupling mechanisms describing....... A constant activation results in elevated levels of the variables in the model while a prolonged change of the oscillations in ACTH and cortisol concentrations is the most pronounced result of different LPS doses predicted by the model....

  12. Acute pancreatitis: staging with CT

    International Nuclear Information System (INIS)

    Gialeli, E.; Petrocheilou, G.; Georgaki, S.; Tzemailas, I.; Adraktas, A.; Charilas, G.; Patsiogiannis, V.

    2012-01-01

    Full text: Introduction: Computed Tomography (CT) is the imaging modality of choice for the diagnosis and staging of acute pancreatitis and its complications. Objectives and tasks: The purpose of this presentation is to demonstrate the findings in CT images which are useful for staging acute pancreatitis according to Balthazar, their significance and restrictions. Materials and methods: CT images from patients who were referred to our Department for an abdominal CT scan for the diagnosis or/and staging of acute pancreatitis were retrospectively studied. Results: In acute pancreatitis, CT helps to stage the severity of inflammatory process, to detect pancreatic necrosis and to depict local complications. CT severity index (CTSI), which was proposed by Balthazar et al, combines the grade of pancreatitis with the extent of pancreatic necrosis assigning points to the patients in order to find the severity index which scales from 0-10. More points are given for a higher grade of pancreatitis and for more extensive necrosis. Types of pancreatitis according to CTSI are: interstitial (Balthazar grade A-C), exudative (Balthazar grade D or E), necrotising (Balthazar grade E, CTSI:10) and central gland necrotising. Patients with pancreatitis but no collections or necrosis have an interstitial (mild) pancreatitis. In exudative pancreatitis there is normal enhancement of the entire pancreas associated with extensive peripancreatic collections. Necrotizing (severe) pancreatitis is characterized by protacted clinical course, high incidence of local complications and high mortality rate. Central gland necrosis is a subtype of necrotizing pancreatitis. Conclusions: The combination of CT imaging and clinical and laboratory evaluation allows the early diagnosis of acute pancreatitis. Acute pancreatitis may vary from a mild uneventful disease to a severe life-threatening illness with multisystemic organ failure. Thus, it is crucial to identify patients who are at high risk of severe

  13. Macrolide therapy is associated with reduced mortality in acute respiratory distress syndrome (ARDS) patients

    NARCIS (Netherlands)

    Simonis, Fabienne D.; de Iudicibus, Gianfranco; Cremer, Olaf L.; Ong, David S.Y.; van der Poll, Tom; Bos, Lieuwe D.; Schultz, Marcus J.

    Background: Macrolides have been associated with favorable immunological effects in various inflammatory disease states. We investigated the association between macrolide therapy and mortality in patients with the acute respiratory distress syndrome (ARDS). Methods: This was an unplanned secondary

  14. Transfusion related acute lung injury presenting with acute dyspnoea: a case report

    Directory of Open Access Journals (Sweden)

    Haji Altaf

    2008-10-01

    Full Text Available Abstract Introduction Transfusion-related acute lung injury is emerging as a common cause of transfusion-related adverse events. However, awareness about this entity in the medical fraternity is low and it, consequently, remains a very under-reported and often an under-diagnosed complication of transfusion therapy. Case presentation We report a case of a 46-year old woman who developed acute respiratory and hemodynamic instability following a single unit blood transfusion in the postoperative period. Investigation results were non-specific and a diagnosis of transfusion-related acute lung injury was made after excluding other possible causes of acute lung injury. She responded to symptomatic management with ventilatory and vasopressor support and recovered completely over the next 72 hours. Conclusion The diagnosis of transfusion-related acute lung injury relies on excluding other causes of acute pulmonary edema following transfusion, such as sepsis, volume overload, and cardiogenic pulmonary edema. All plasma containing blood products have been implicated in transfusion-related acute lung injury, with the majority being linked to whole blood, packed red blood cells, platelets, and fresh-frozen plasma. The pathogenesis of transfusion-related acute lung injury may be explained by a "two-hit" hypothesis, involving priming of the inflammatory machinery and then activation of this primed mechanism. Treatment is supportive, with prognosis being substantially better than for most other causes of acute lung injury.

  15. Acute rhabdomyolysis

    Directory of Open Access Journals (Sweden)

    Pascale de Lonlay

    2015-01-01

    Full Text Available Rhabdomyolysis results from the rapid breakdown of skeletal muscle fibers, which leads to leakage of potentially toxic cellular contents into the systemic circulation. Acquired causes by direct injury to the sarcolemma are the most frequent. The inherited causes are: metabolic with failure of energy production, including mitochondrial fatty acid ß-oxidation defects, LPIN1 mutations, inborn errors of glycogenolysis and glycolysis, more rarely mitochondrial respiratory chain deficiency, purine defects and peroxysomalα-Methylacyl-CoA-racemase defect (AMACR; dystrophinopathies and myopathies; calcic causes with RYR1 mutations; inflammatory with myositis. Irrespective of the cause of rhabdomyolysis, the pathophysiologic events follow a common pathway, the ATP depletion leading to an increased intracellular calcium concentration and necrosis. Most episodes of rhabdomyolysis are triggered by an environmental stress, mostly fever. This condition is associated with two events, elevated temperature and high circulating levels of pro-inflammatory mediators such as cytokines and chemokines. We describe here an example of rhabdomyolysis related to high temperature, aldolase deficiency, in 3 siblings with episodic rhabdomyolysis without hemolytic anemia. Myoglobinuria was always triggered by febrile illnesses. We show that the underlying mechanism involves an exacerbation of aldolase A deficiency at high temperatures that affected myoblasts but not erythrocytes. Thermolability was enhanced in patient myoblasts compared to control. The aldolase A deficiency was rescued by arginine supplementation in vitro. Lipid droplets accumulated in patient myoblasts relative to control and this was increased by cytokines. Lipotoxicity may participate to myolysis. Our results expand the clinical spectrum of aldolase A deficiency to isolated temperature-dependent rhabdomyolysis, and suggest that thermolability may be tissue specific. We also propose a

  16. Acute abdomen

    Directory of Open Access Journals (Sweden)

    Wig J

    1978-01-01

    Full Text Available 550 cases of acute abdomen have been analysed in detail includ-ing their clinical presentation and operative findings. Males are more frequently affected than females in a ratio of 3: 1. More than 45% of patients presented after 48 hours of onset of symptoms. Intestinal obstruction was the commonest cause of acute abdomen (47.6%. External hernia was responsible for 26% of cases of intestinal obstruction. Perforated peptic ulcer was the commonest cause of peritonitis in the present series (31.7% while incidence of biliary peritonitis was only 2.4%.. The clinical accuracy rate was 87%. The mortality in operated cases was high (10% while the over-all mortality rate was 7.5%.

  17. Acute Blindness.

    Science.gov (United States)

    Meekins, Jessica M

    2015-09-01

    Sudden loss of vision is an ophthalmic emergency with numerous possible causes. Abnormalities may occur at any point within the complex vision pathway, from retina to optic nerve to the visual center in the occipital lobe. This article reviews specific prechiasm (retina and optic nerve) and cerebral cortical diseases that lead to acute blindness. Information regarding specific etiologies, pathophysiology, diagnosis, treatment, and prognosis for vision is discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Acute Necrotizing Esophagitis Followed by Duodenal Necrosis

    Science.gov (United States)

    del Hierro, Piedad Magdalena

    2011-01-01

    Acute Necrotizing Esophagitis is an uncommon pathology, characterized by endoscopic finding of diffuse black coloration in esophageal mucosa and histological presence of necrosis in patients with upper gastrointestinal bleeding. The first case of acute necrotizing esophagitis followed by duodenal necrosis, in 81 years old woman with a positive history of Type 2 Diabetes Mellitus, Hypertension, and usual intake of Nonsteroidal Anti-inflammatory drugs, is reported. Although its etiology remains unknown, the duodenal necrosis suggests that ischemia could be the main cause given that the branches off the celiac axis provide common blood supply to the distal esophageal and duodenal tissue. The massive gastroesophagic reflux and NSAID intake could be involved. PMID:27957030

  19. Imaging findings in acute calcific prevertebral tendinitis

    International Nuclear Information System (INIS)

    Grassi, Caio Giometti; Diniz, Fabio de Vilhena; Garcia, Marcio Ricardo Taveira; Gomes, Regina Lucia Elia; Daniel, Mauro Miguel; Funari, Marcelo Buarque de Gusmao

    2011-01-01

    Acute calcific prevertebral tendinitis is a benign and rare condition that presents calcification of the superior oblique fibers of longus colli muscle with local inflammatory reaction. Such condition is one of the less common presentations of calcium hydroxyapatite deposition disease. Clinical signs are usually acute neck pain and odynophagia, and it may be misdiagnosed as retropharyngeal abscess, spondylodiscitis or traumatic injury. The imaging findings in calcific prevertebral tendinitis are pathognomonic. The knowledge of such findings is extremely important to avoid unnecessary interventions in a patient presenting a condition with a good response to conservative treatment. (author)

  20. Imaging findings in acute calcific prevertebral tendinitis

    Energy Technology Data Exchange (ETDEWEB)

    Grassi, Caio Giometti; Diniz, Fabio de Vilhena; Garcia, Marcio Ricardo Taveira; Gomes, Regina Lucia Elia; Daniel, Mauro Miguel; Funari, Marcelo Buarque de Gusmao [Hospital Israelita Albert Einstein (HIAE), Sao Paulo, SP (Brazil). Imaging Dept.

    2011-09-15

    Acute calcific prevertebral tendinitis is a benign and rare condition that presents calcification of the superior oblique fibers of longus colli muscle with local inflammatory reaction. Such condition is one of the less common presentations of calcium hydroxyapatite deposition disease. Clinical signs are usually acute neck pain and odynophagia, and it may be misdiagnosed as retropharyngeal abscess, spondylodiscitis or traumatic injury. The imaging findings in calcific prevertebral tendinitis are pathognomonic. The knowledge of such findings is extremely important to avoid unnecessary interventions in a patient presenting a condition with a good response to conservative treatment. (author)

  1. Cogan's syndrome mimicking acute Lyme arthritis.

    Science.gov (United States)

    Schwegmann, J P; Enzenauer, R J

    1995-05-01

    A pediatric case of Cogan's syndrome mimicking acute Lyme arthritis is described. A 12-year-old black boy was admitted to the pediatric service for presumed right knee septic arthritis. Symptoms included acute pain and swelling with decreased range-of-motion. Although the patient's right knee symptoms and positive Lyme serology were consistent with a diagnosis of Lyme arthritis, the presence of sensorineural hearing loss and interstitial keratitis with inflammatory arthritis suggested a diagnosis of Cogan's syndrome. Subsequent Western blot analysis was negative for Borrelia burgdorferi antigens. The patient had dramatic clinical improvement of musculoskeletal and ophthalmologic complaints shortly after receiving high-dose corticosteroids, although residual sensorineural hearing loss persisted.

  2. Radiotherapy of brain inflammatory diseases

    International Nuclear Information System (INIS)

    Pil', B.N.

    1982-01-01

    An experience of radiation treatment of brain inflammatory diseases is described. Radiation treatment goes with antiinflammatory, anticonvulsive agents, with resorbing and dehydrating measures and some times with surgical treatment. The methods of radiation treatment of convexital and optochiasmic arachnoiditis

  3. Atypical idiopathic inflammatory demyelinating lesions

    DEFF Research Database (Denmark)

    Wallner-Blazek, Mirja; Rovira, Alex; Fillipp, Massimo

    2013-01-01

    Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can be class......Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can...... be classified according to previously suggested radiologic characteristics and how this classification relates to prognosis. Searching the databases of eight tertiary referral centres we identified 90 adult patients (61 women, 29 men; mean age 34 years) with ≥1 AIIDL. We collected their demographic, clinical...

  4. Anti-inflammatory activity of Ambrosia artemisiaefolia and Rhoeo spathacea.

    Science.gov (United States)

    Pérez G, R M

    1996-09-01

    Alcoholic extracts of the leaves of Ambrosia artemisiaefolia and Rhoeo spathacea have been investigated for anti-inflammatory activity using various experimental models of inflammation (croton oil ear oedema, carrageenan-induced edema, cotton pellet granuloma and formaldehyde induced arthritis) and the results compared with phenylbutazone and bethamethasone, standard anti-inflammatory drugs. These extracts at doses of 50, 100 and 150mg/kg of A. artemisiaefolia and R. spathacea, showed significant inhibition of acute oedema in rats and mice induced by the phlogistic agents, carrageenan and croton oil, in a dose-dependant manner. The ethanol extracts reduced cotton pellet granuloma and caused a statistically significant inhibitory effect on edema in the chronic model of formaldehyde arthritis in rats. Since Ambrosia artemisiaefolia and Rhoeo spathacea were found to be effective in both acute and chronic phases of inflammation they can be considered as general anti-inflammatory agents. Copyright © 1996 Gustav Fischer Verlag · Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.

  5. Comparison of two models of inflammatory bowel disease in rats.

    Science.gov (United States)

    Catana, Cristina Sorina; Magdas, Cristian; Tabaran, Flaviu Alexandru; Crăciun, Elena Cristina; Deak, Georgiana; Magdaş, Virginia Ana; Cozma, Vasile; Gherman, Călin Mircea; Berindan-Neagoe, Ioana; Dumitraşcu, Dan Lucian

    2018-03-26

    There is a need for experimental animal models for inflammatory bowel diseases (IBD), but no proposed model has been unanimously accepted. The aim of this study was to develop 2 affordable models of IBD in rats and to compare them. We produced IBD in rats using either dextran sodium sulfate (DSS) or 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). The requirements for experimental models were: a predictable clinical course, histopathology and inflammation similar to human ulcerative colitis (UC) and Crohn's disease (CD). The effect of acute administration of DSS and TNBS on oxidative stress (as measured by the assessment of glutathione peroxidase - GPx) was verified. The activity of whole blood GPx was measured using a commercially available Randox kit (Crumlin, UK). The administration of DSS increased GPx activity compared to the control and TNBS-treated groups, but not to a statistically significant degree. Histological examination of the colonic mucosa following the administration of DSS showed multifocal erosions with minimal to mild inflammatory infiltrate, mainly by polymorphonuclear cells (PMN), lymphocytes and plasma cells. For TNBS-induced colitis, the histological changes manifested as multifocal areas of ulcerative colitis with mild to severe inflammatory infiltrate. Whole blood GPx values displayed a direct dependence on the chemical agent used. Our results show a correlation between histopathology, proinflammatory state and oxidative stress. The experimental DSSor TNBS-induced bowel inflammation used in this study corresponds to human IBD and is reproducible with characteristics indicative of acute inflammation in the case of the protocols mentioned.

  6. Update on Inflammatory Biomarkers and Treatments in Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Aldo Bonaventura

    2016-11-01

    Full Text Available After an acute ischemic stroke (AIS, inflammatory processes are able to concomitantly induce both beneficial and detrimental effects. In this narrative review, we updated evidence on the inflammatory pathways and mediators that are investigated as promising therapeutic targets. We searched for papers on PubMed and MEDLINE up to August 2016. The terms searched alone or in combination were: ischemic stroke, inflammation, oxidative stress, ischemia reperfusion, innate immunity, adaptive immunity, autoimmunity. Inflammation in AIS is characterized by a storm of cytokines, chemokines, and Damage-Associated Molecular Patterns (DAMPs released by several cells contributing to exacerbate the tissue injury both in the acute and reparative phases. Interestingly, many biomarkers have been studied, but none of these reflected the complexity of systemic immune response. Reperfusion therapies showed a good efficacy in the recovery after an AIS. New therapies appear promising both in pre-clinical and clinical studies, but still need more detailed studies to be translated in the ordinary clinical practice. In spite of clinical progresses, no beneficial long-term interventions targeting inflammation are currently available. Our knowledge about cells, biomarkers, and inflammatory markers is growing and is hoped to better evaluate the impact of new treatments, such as monoclonal antibodies and cell-based therapies.

  7. Clinical pathology of acute necrotising pancreatitis.

    OpenAIRE

    Nordback, I; Lauslahti, K

    1986-01-01

    Seventy nine pancreatic specimens were obtained from patients treated with pancreatic resection for acute necrotising pancreatitis. The necrotising process had started in the periphery of the gland, so that eight of seventy nine cases contained peripancreatic (mainly fat) necrosis only without any parenchymal necrosis. Peripheral parenchymal necrosis was characterised by a severe inflammatory reaction, with multinucleated leucocytes and microabscess. In the deep parts of the pancreas coagulat...

  8. Acute irradiation syndrome : radiation disease

    International Nuclear Information System (INIS)

    Mestries, J.C.; Multon, E.

    1995-01-01

    It is classically assumed that the symptomatology of the acute radiation syndrome is mainly due to stem and progenitor cells death in compartimentalized tissues, particularly in bone marrow and intestine. Our observations on baboons, irradiated with a mixed neutron/gamma or a gamma radiation, showed that the whole organism response plays a major role. There is an inflammatory syndrome, not only during the prodromal phase, but also a second one, that precedes and accompanies the manifest-illness phase. This inflammatory syndrome was associated with coagulation disorders which are largely responsible for bleeding. This syndrome makes the therapeutic approach more complicated since some cytokines, which could be able to improve the hematopoietic cells recovery (e.g. IL-6), exhibit pro-inflammatory activities as well. Regarding radiobiological triage, no biological marker has a prognosis value during the first days following a radiation exposure, for those individuals exposed to around a LD50. On the contrary, some inflammation markers allow to anticipate a fatal issue, without any treatment, as early as the beginning of the manifest-illness phase. (authors). 10 refs., 11 figs

  9. Functional imaging of interleukin 1 beta expression in inflammatory process using bioluminescence imaging in transgenic mice

    Directory of Open Access Journals (Sweden)

    Liu Zhihui

    2008-08-01

    Full Text Available Abstract Background Interleukin 1 beta (IL-1β plays an important role in a number of chronic and acute inflammatory diseases. To understand the role of IL-1β in disease processes and develop an in vivo screening system for anti-inflammatory drugs, a transgenic mouse line was generated which incorporated the transgene firefly luciferase gene driven by a 4.5-kb fragment of the human IL-1β gene promoter. Luciferase gene expression was monitored in live mice under anesthesia using bioluminescence imaging in a number of inflammatory disease models. Results In a LPS-induced sepsis model, dramatic increase in luciferase activity was observed in the mice. This transgene induction was time dependent and correlated with an increase of endogenous IL-1β mRNA and pro-IL-1β protein levels in the mice. In a zymosan-induced arthritis model and an oxazolone-induced skin hypersensitivity reaction model, luciferase expression was locally induced in the zymosan injected knee joint and in the ear with oxazolone application, respectively. Dexamethasone suppressed the expression of luciferase gene both in the acute sepsis model and in the acute arthritis model. Conclusion Our data suggest that the transgenic mice model could be used to study transcriptional regulation of the IL-1β gene expression in the inflammatory process and evaluation the effect of anti-inflammatory drug in vivo.

  10. Inflammatory bowel disease: the role of inflammatory cytokine gene polymorphisms

    Directory of Open Access Journals (Sweden)

    Joanna Balding

    2004-01-01

    Full Text Available THE mechanisms responsible for development of inflammatory bowel disease (IBD have not been fully elucidated, although the main cause of disease pathology is attributed to up-regulated inflammatory processes. The aim of this study was to investigate frequencies of polymorphisms in genes encoding pro-inflammatory and anti-inflammatory markers in IBD patients and controls. We determined genotypes of patients with IBD (n=172 and healthy controls (n=389 for polymorphisms in genes encoding various cytokines (interleukin (IL-1β, IL-6, tumour necrosis factor (TNF, IL-10, IL-1 receptor antagonist. Association of these genotypes to disease incidence and pathophysiology was investigated. No strong association was found with occurrence of IBD. Variation was observed between the ulcerative colitis study group and the control population for the TNF-α-308 polymorphism (p=0.0135. There was also variation in the frequency of IL-6-174 and TNF-α-308 genotypes in the ulcerative colitis group compared with the Crohn's disease group (p=0.01. We concluded that polymorphisms in inflammatory genes are associated with variations in IBD phenotype and disease susceptibility. Whether the polymorphisms are directly involved in regulating cytokine production, and consequently pathophysiology of IBD, or serve merely as markers in linkage disequilibrium with susceptibility genes remains unclear.

  11. Anti-inflammatory and analgesic effects of Careya arborea stem bark ...

    African Journals Online (AJOL)

    The present study was carried out to evaluate the anti-inflammatory and analgesic activities of methanol extract of Careya arborea (MECA). The effects of MECA on the acute and chronic phases of inflammation were studied in carrageenan, dextran and mediators (histamine and serotonin) induced paw oedema and cotton ...

  12. Inflammatory status in patients with rheumatic mitral stenosis: Guilty before and after balloon mitral valvuloplasty

    Directory of Open Access Journals (Sweden)

    Mohamed Ahmed Abdel Rahman

    2016-06-01

    Conclusion: Inflammatory pathogenesis of rheumatic fever, suggested by hsCRP, seems fixed both before, and after BMV. A basal increase in hsCRP before BMV is related to BMV success and an acute increase immediately after BMV seems related to trauma of balloon dilatations.

  13. Non-steroidal anti-inflammatory drugs for chronic low back pain