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Sample records for acute inflammatory reactions

  1. A proinflammatory factor in lymphocytes. Its role in the development of acute, non-immunological inflammatory reactions.

    PubMed Central

    Leme, J. C.; Bechara, G. H.; Dos Santos, R. R.

    1976-01-01

    Drug-induced leucopenia renders rats hyporeactive to various inflammatory stimuli. Administration to leucopenic rats of suspensions of lymphocytes, sufficient to apparently correct the induced lymphocytopenia, led to a partial but marked reversal of the inhibited responses. Similar results were observed when lysates of lymphocytes or filtrates of the disintegrated cells were injected. Suspensions of polymorphonuclear granulocytes, on the contrary, were ineffective in producing a reversal of inhibited inflammatory reactions in leucopenic rats. The presence of a proinflammatory factor (LpIF) in lymphocytes, which might be involved in the modulation of acute inflammatory responses is suggested. PMID:971405

  2. Apigenin attenuates acute myocardial infarction of rats via the inhibitions of matrix metalloprotease-9 and inflammatory reactions

    PubMed Central

    Du, Hong; Hao, Jie; Liu, Fan; Lu, Jingchao; Yang, Xiuchun

    2015-01-01

    Acute myocardial infarction (AMI) is the myocardial necrosis caused by coronary artery acute and persistent ischemia and hypoxia. Matrix metalloprotease-9 (MMP-9) plays an important role in a series of process of occurrence and development of AMI. Inflammatory reaction plays the key role in all kinds of damage factors in AMI. Apigenin (API) has effectively restrained the activity of MMP-9, anti-inflammatory and hepatic fat oxidizing properties. API significantly improved AMI of rats through inhibiting MMP-9 and inflammatory reactions in a few recent studies. Our investigation detected the infarct size of AMI rats, casein kinase (CK), the MB isoenzyme of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) activities in AMI rats were also analyzed with commercial kits. Additionally, Nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) levels of whole bloods of AMI rats were also detected using commercial kits. Next, MMP-9 protein of cardiac in AMI rats was measured with gelatin zymography assays. Finally, caspase-3 and caspase-9 activities in AMI rats were analyzed with commercial kits. In the present study, our work indicated API might significantly reduce the infarction size of AMI rat. It was shown that the treatment of API could decrease the expression of MMP-9 level and reduce the activities of NF-κB, TNF-α, IL-1β and IL-6 in AMI rats. Next, API treatment could reduce caspase-3 and caspase-9 activities and decrease cellular apoptosis of AMI rats. Our findings concluded that API ameliorates acute myocardial infarction of rats via inhibiting MMP-9 and inflammatory reactions. PMID:26309539

  3. [Investigations on the acute, carrageenan-induced inflammatory reaction and pharmacology of orally administered sodium salicylate in turkeys].

    PubMed

    Cramer, Kerstin; Schmidt, Volker; Richter, Andreas; Fuhrmann, Herbert; Abraham, Getu; Krautwald-Junghanns, Maria-Elisabeth

    2015-01-01

    The complex mechanisms of acute inflammation have been subject to veterinary investigations since a long time. However, knowledge on the role of specific inflammatory mediators, as well as pharmacokinetics (PK) and -dynamics (PD) of non-steroidal anti-inflammatory drugs (NSAID) in birds is limited. The objective of this work therefore was to establish a modified tissue cage-model to investigate the acute, carrageenan-mediated inflammatory response, as well as plasma and exudate-kinetics and the antiphlogistic effect of orally administered sodium salicylate on the elicited inflammatory reaction in turkeys. Within the class Aves, comparable studies have so far only been published in chicken. Following bilateral subcutaneous implantation of carrageenan-treated synthetic sponges in the lateral thoracic region, sodium salicylate was administered orally at a dose of 50 mg/kg body weight (BW; therapy group) twice daily on three consecutive days, while a control group received drinking water as a placebo (n = 24 per group). Combined PK and PD of sodium salicylate were evaluated on the basis of salicylate- and prostaglandin (PG) E2-plasma- and -exudate-concentrations, exudate volumes, as well as leukocyte exudate counts. Sodium salicylate was readily absorbed from the gastrointestinal tract and accumulated in the inflammatory exudate. At 4, 6, and 10 h after first application, sodium salicylate significantly reduced PG E2-concentrations in the inflammatory exudate when compared to the control group, whereas leukocyte exudate counts increased over time in both study groups, unaffected by sodium salicylate The described modified tissue cage-model can be beneficial for further research on the pathophysiology of avian inflammatory processes and the investigation of the combined pharmacodynamics and -kinetics of drugs in birds of adequate size. PMID:26054231

  4. Inflammatory sequences in acute pulmonary radiation injury.

    PubMed Central

    Slauson, D. O.; Hahn, F. F.; Benjamin, S. A.; Chiffelle, T. L.; Jones, R. K.

    1976-01-01

    The histopathologic events in the developing acute pulmonary inflammatory reaction to inhaled particles of Yttrium 90 are detailed. In animals that died or were sacrificed during the first year after inhalation exposure, microscopic findings of acute inflammation predominated and included vascular congestion; stasis, focal hemorrhage; edema; various inflammatory cell infiltrates; cytolysis and desquamation of bronchiolar and alveolar epithelium followed by regeneration; vascular injury and repair; and the eventual development of pulmonary fibrosis. Accumulation of alveolar fibrin deposits was an additional characteristic, though not a constant feature of the early stages of radiation pneumonitis. In addition to the direct effects of radiation on pulmonary cell populations, the histopathologic findings were suggestive of diverse activation of various cellular and humoral mediation systems in their pathogenesis. The potential interrelationships of systems responsible for increased vascular permeability, coagulation and fibrinolysis, chemotaxis, and direct cellular injury were discussed and related to the pathogenesis of the microscopic findings characteristic of early pulmonary radiation injury. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:1258976

  5. Inflammatory reaction - communication of cells.

    PubMed

    Terheyden, Hendrik; Stadlinger, Bernd; Sanz, Mariano; Garbe, Annette I; Meyle, Jörg

    2014-04-01

    This article presents scientific background information on the animated 3D film "Inflammatory Reactions - Communication of Cells" (Quintessence Publications, ISBN 978-1-85097-231-0). Gingivitis and periodontitis are understood as the result of a coordinated action of a few clearly identified cellular players who communicate with each other via cytokines. For didactic reasons, the course of a periodontal infection is described here in four phases: (1) bacterial biofilm formation and development of a host response in the marginal periodontium, (2) innate immune response leading to gingivitis, (3) role of the adaptive immune system in attachment loss and pocket formation, and (4) down-regulation of inflammation and periodontal regeneration and repair following biofilm removal. The control of the cells is discussed as a cytokine network, which can be modulated in pro- or anti-inflammatory direction depending on the control of the bacterial infection. Degradation of soft tissue structural proteins like collagen and proteoglycans by matrix metalloproteinases and degradation of hard tissue matrix by osteoclasts are explained as an interference of the immune system with the natural equilibrium of tissue remodeling. Five mechanisms of promotion of bone loss through the influence of the immune system are described. One example is bone resorption as a consequence of the shift of the RANKL/osteoprotegerin balance by soluble RANKL synthesized by CD4(+) Th 1 cells as well as the interference with the coupling of osteoclasts and osteoblasts through dedifferentiation of osteoblasts by TNFα. Finally, the signaling required for down-regulation of inflammatory reactions and the reasons for the incomplete regeneration after periodontal bone loss are discussed. PMID:23600659

  6. Acute phase reaction and acute phase proteins*

    PubMed Central

    Gruys, E.; Toussaint, M.J.M.; Niewold, T.A.; Koopmans, S.J.

    2005-01-01

    A review of the systemic acute phase reaction with major cytokines involved, and the hepatic metabolic changes, negative and positive acute phase proteins (APPs) with function and associated pathology is given. It appears that APPs represent appropriate analytes for assessment of animal health. Whereas they represent non-specific markers as biological effect reactants, they can be used for assessing nutritional deficits and reactive processes, especially when positive and negative acute phase variables are combined in an index. When such acute phase index is applied to separate healthy animals from animals with some disease, much better results are obtained than with single analytes and statistically acceptable results for culling individual animals may be reached. Unfortunately at present no cheap, comprehensive and easy to use system is available for assessing various acute phase proteins in serum or blood samples at the same time. Protein microarray or fluid phase microchip technology may satisfy this need; and permit simultaneous analysis of numerous analytes in the same small volume sample and enable integration of information derived from systemic reactivity and nutrition with disease specific variables. Applying such technology may help to solve health problems in various countries not only in animal husbandry but also in human populations. PMID:16252337

  7. Acute pain transfusion reaction.

    PubMed

    Hardwick, Jody; Osswald, Michael; Walker, Daniel

    2013-11-01

    A 34-year-old woman with a diagnosis of hemophagocytic lymphohistocytosis (HLH) received a double umbilical cord blood transplantation following a myeloablative chemotherapy preparative regimen with busulfan and cyclophosphamide. HLH is a rare, potentially fatal hematologic disorder characterized by the overactivation of histocytes and T lymphocytes, leading to organ infiltration and acute illness. On day 25 post-transplantation, the patient required a platelet transfusion for a platelet count of 6,000 per ml (normal range = 150,000-450,000 per ml). The patient's blood type prior to the cord blood transplantation was B positive and, although both umbilical cord blood donors were O positive, the patient was still B positive per blood bank testing on that day. Although the recipient of an allogenic stem cell transplantation will eventually become the blood type of the donor, the time for this process to occur varies for each person. That process must be monitored by the blood bank for the purpose of cross-matching blood products to decrease hemolysis as much as possible. The patient was premedicated with the facility's standard for platelet transfusions: acetaminophen 650 mg and diphenhydramine 25 mg about 30 minutes prior to the platelet transfusion. PMID:24161631

  8. [Progressive Multifocal Leukoencephalopathy with Inflammatory Reactions].

    PubMed

    Shishido-Hara, Yukiko; Uchihara, Toshiki; Sanjo, Nobuo

    2016-04-01

    Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder caused by reactivation of the JC virus associated with impaired host immunity. However, PML may occur even without an evident cause of immunosuppression. In such cases, JC virus DNA in cerebrospinal fluid (CSF) may not be detectable with polymerase chain reactions (PCR), and a brain biopsy may be performed. Pathology may exhibit marked inflammatory reactions around the JC virus-infected cells, although typical intranuclear viral inclusions would rarely be seen. Atypical inflammation in patients with PML likely an indication of the host's immune-response against the virus. this is usually observed in those with relatively-mild immunosuppression with favorable prognosis. Here, we describe cases of PML that exhibited inflammatory reactions; a recent topic, PML with immune reconstruction inflammatory syndrome (IRIS), will also be discussed. PMID:27056866

  9. Acute Painful Stress and Inflammatory Mediator Production

    PubMed Central

    Griffis, Charles A.; Breen, Elizabeth Crabb; Compton, Peggy; Goldberg, Alyssa; Witarama, Tuff; Kotlerman, Jenny; Irwin, Michael R.

    2014-01-01

    Pro-inflammatory pathways may be activated under conditions of painful stress, which is hypothesized to worsen the pain experience and place medically-vulnerable populations at risk for increased morbidity. Objectives To evaluate the effects of pain and subjective pain-related stress on pro-inflammatory activity. Methods A total of 19 healthy control subjects underwent a single standard cold-pressor pain test (CPT) and a no-pain control condition. Indicators of pain and stress were measured and related to inflammatory immune responses (CD811a, IL-1RA, and IL-6) immediately following the painful stimulus, and compared to responses under non-pain conditions. Heart rate and mean arterial pressure were measured as indicators of sympathetic stimulation. Results CPT was clearly painful and generated an activation of the sympathetic nervous system. CD811a increased in both conditions, but with no statistically significant greater increase following CPT (p < .06). IL-1RA demonstrated a non-statistically significant increase following CPT (p < .07). The change in IL-6 following CPT differed significantly from the response seen in the control condition (p < .02). Conclusions These findings suggest that CP acute pain may affect proinflammatory pathways, possibly through mechanisms related to adrenergic activation. PMID:23407214

  10. Acute dystonic reaction due to dexketoprofen trometamol.

    PubMed

    Kayipmaz, Afsin Emre; Giray, Tufan Akin; Tasci, Suleyman Serdar; Tasci, Suleyman Serdar; Kavalci, Cemil; Kocalar, Ummu Gulsum

    2015-11-01

    Dexketoprofentrometamol (DKP), is a tromethamine salt of the water-soluble S-enantiomer of ketoprofen. As with all other non-steroidal anti-inflammatory agents, the most common side effect of DKP is gastric complications. In this paper, we report a case of dystonic reaction after intravenous DKP use. A 24-year-old man was admitted to our hospital after suffering a leg burn from boiling oil. He had no drug hypersensitivity. An intravenous preparation containing the active ingredient DKP was injected for analgesia, after which the patient experienced an involuntary flexion response in both upper extremities. With a suspected diagnosis of dystonia, biperiden lactate 5 mg/ml was administered via the intramuscular route and the contractions abated within 30 seconds of the injection.As non-steroidal anti-inflammatory agents are commonly used and prescribed in emergency departments, it should be kept in mind that an acute dystonic reaction can develop against one of these agents, DKP. PMID:26564300

  11. Acute transfusion reactions: an update.

    PubMed

    Scorer, T; Doughty, H

    2014-01-01

    Over the last decade the use of blood products by the United Kingdom (UK) military has increased significantly; with the increase in transfusion comes an increased incidence of transfusion-related incidents. Acute transfusion reactions (ATRs) are a common consequence of transfusion, which vary widely in their severity and are likely to be under-reported, although reporting is a regulatory requirement. This paper discusses the importance of identifying ATRs and managing them appropriately. It introduces a flowchart (due to be incorporated in the next version of Joint Service Publication (JSP) 999, Clinical Guidelines for Operations (CGOs)), which is designed to assist the military multi-disciplinary team caring for patients in the operational environment. PMID:25895413

  12. Bothrops jararaca venom (BjV) induces differential leukocyte accumulation in mice genetically selected for acute inflammatory reaction: the role of host genetic background on expression of adhesion molecules and release of endogenous mediators.

    PubMed

    Carneiro, Adriana S; Ribeiro, Orlando G; Cabrera, Wafa H K; Vorraro, Francisca; De Franco, Marcelo; Ibañez, Olga M; Starobinas, Nancy

    2008-10-01

    The dynamics of the local inflammatory events induced by Bothrops jararaca venom (BjV) inoculation in footpad of mice genetically selected for maximal (AIRmax) and minimal (AIRmin) acute inflammatory reactivity (AIR) was investigated. The BjV injection induced a marked inflammatory cell infiltrate with predominance of neutrophils, with increased blood cell numbers before its accumulation, suggesting a stimulatory action of BjV on mechanisms of cell mobilization from bone marrow. The process of cell migration is regulated by different cell-adhesion molecules (CAM). Our results showed that neutrophil cells from both lines had the same pattern of response concerning CAMs expression, presenting the involvement of l-selectin, Mac-1 and PECAM-1 adhesion molecules in BjV-induced neutrophil accumulation. The effect of BjV on the release of pro-inflammatory cytokines and chemokines related with cellular migration was also studied and IL-1beta, IL-6, TNF-alpha and MIP-2 levels could be detected after venom injection. The AIRmax mice were shown to be more responsive than AIRmin with respect to leukocyte influx, expression of MIP-2 and release of IL-1beta and IL-6. These results demonstrate the importance of host genetic background in the local response and the involvement of alleles accumulated in AIRmax mice in the inflammatory events induced by BjV. PMID:18723041

  13. Inflammatory markers in ST-elevation acute myocardial infarction.

    PubMed

    Seropian, Ignacio M; Sonnino, Chiara; Van Tassell, Benjamin W; Biasucci, Luigi M; Abbate, Antonio

    2016-08-01

    After acute myocardial infarction, ventricular remodeling is characterized by changes at the molecular, structural, geometrical and functional level that determine progression to heart failure. Inflammation plays a key role in wound healing and scar formation, affecting ventricular remodeling. Several, rather different, components of the inflammatory response were studied as biomarkers in ST-elevation acute myocardial infarction. Widely available and inexpensive tests, such as leukocyte count at admission, as well as more sophisticated immunoassays provide powerful predictors of adverse outcome in patients with ST-elevation acute myocardial infarction. We review the value of inflammatory markers in ST-elevation acute myocardial infarction and their association with ventricular remodeling, heart failure and sudden death. In conclusion, the use of these biomarkers may identify subjects at greater risk of adverse events and perhaps provide an insight into the mechanisms of disease progression. PMID:25681486

  14. Nefazadone-induced acute dystonic reaction.

    PubMed

    Burda, A; Webster, K; Leikin, J B; Chan, S B; Stokes, K A

    1999-10-01

    A 53-y-o patient presented approximately 2 h after taking her first dose of nefazadone. Chief complaint was lip smacking with hand and arm gesturing. The patient also took 25 mg meclizine which she had used before with no adverse effects. Diphenhydramine followed by benztropine led to resolution of symptoms within 1 h. Patient subsequently used meclizine with no untoward reactions. Nefazadone should be added to the list of agents that cause acute dystonic reactions. PMID:10509438

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

    PubMed Central

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

    2015-01-01

    AIM To evaluate the therapeutic effect of netrin-4 on the early acute phase of inflammation in the alkali-burned eye. METHODS Eye drops containing netrin-4 or phosphate buffered saline (PBS) were administered to a alkali-burn-induced corneal acute inflammatory model four times daily. The clinical evaluations, including fluorescein staining and inflammatory index, were performed on day 1, 4 and 7 using slit lamp microscopy. Global specimens were collected on day 7 and processed for immunofluorescent staining. The levels of inflammatory mediators in the corneas were determined by real-time polymerase chain reaction (PCR). RESULTS Exogenous netrin-4 administered on rat ocular surfaces showed more improvements in decreasing fluorescein staining on day 4 and 7, and resolved alkali burn-induced corneal inflammation index on day 7 (P<0.01). The levels of IL-1β, IL-6, intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1) in corneas were decreased in netrin-4-treated groups (P<0.05). In addition, netrin-4 significantly reduced the expression of leukocyte common antigen 45 (CD45) in the alkali-burn cornea (P<0.001). CONCLUSION Topical netrin-4 accelerated wound healing and reduced the inflammation on alkali-burn rat model, suggesting a potential as an anti-inflammatory agent in the clinical to treat the acute inflammation. PMID:25938032

  16. Mast cells mediate acute inflammatory responses to implanted biomaterials

    PubMed Central

    Tang, Liping; Jennings, Timothy A.; Eaton, John W.

    1998-01-01

    Implanted biomaterials trigger acute and chronic inflammatory responses. The mechanisms involved in such acute inflammatory responses can be arbitrarily divided into phagocyte transmigration, chemotaxis, and adhesion to implant surfaces. We earlier observed that two chemokines—macrophage inflammatory protein 1α/monocyte chemoattractant protein 1—and the phagocyte integrin Mac-1 (CD11b/CD18)/surface fibrinogen interaction are, respectively, required for phagocyte chemotaxis and adherence to biomaterial surfaces. However, it is still not clear how the initial transmigration of phagocytes through the endothelial barrier into the area of the implant is triggered. Because implanted biomaterials elicit histaminic responses in the surrounding tissue, and histamine release is known to promote rapid diapedesis of inflammatory cells, we evaluated the possible role of histamine and mast cells in the recruitment of phagocytes to biomaterial implants. Using i.p. and s.c. implantation of polyethylene terephthalate disks in mice we find: (i) Extensive degranulation of mast cells, accompanied by histamine release, occurs adjacent to short-term i.p. implants. (ii) Simultaneous administration of H1 and H2 histamine receptor antagonists (pyrilamine and famotidine, respectively) greatly diminishes recruitment and adhesion of both neutrophils (<20% of control) and monocytes/macrophages (<30% of control) to implants. (iii) Congenitally mast cell-deficient mice also exhibit markedly reduced accumulation of phagocytes on both i.p. and s.c implants. (iv) Finally, mast cell reconstitution of mast cell-deficient mice restores “normal” inflammatory responses to biomaterial implants. We conclude that mast cells and their granular products, especially histamine, are important in recruitment of inflammatory cells to biomaterial implants. Improved knowledge of such responses may permit purposeful modulation of both acute and chronic inflammation affecting implanted biomaterials. PMID

  17. Acute Exercise-Induced Mitochondrial Stress Triggers an Inflammatory Response in the Myocardium via NLRP3 Inflammasome Activation with Mitophagy

    PubMed Central

    Li, Haiying; Miao, Weiguo; Ma, Jingfen; Xv, Zhen; Li, Jianyu; Zhang, Yong; Ji, Li Li

    2016-01-01

    Increasing evidence has indicated that acute strenuous exercise can induce a range of adverse reactions including oxidative stress and tissue inflammation. However, little is currently known regarding the mechanisms that underlie the regulation of the inflammatory response in the myocardium during acute heavy exercise. This study evaluated the mitochondrial function, NLRP3 inflammasome activation, and mitochondrial autophagy-related proteins to investigate the regulation and mechanism of mitochondrial stress regarding the inflammatory response of the rat myocardium during acute heavy exercise. The results indicated that the mitochondrial function of the myocardium was adaptively regulated to meet the challenge of stress during acute exercise. The exercise-induced mitochondrial stress also enhanced ROS generation and triggered an inflammatory reaction via the NLRP3 inflammasome activation. Moreover, the mitochondrial autophagy-related proteins including Beclin1, LC3, and Bnip3 were all significantly upregulated during acute exercise, which suggests that mitophagy was stimulated in response to the oxidative stress and inflammatory response in the myocardium. Taken together, our data suggest that, during acute exercise, mitochondrial stress triggers the rat myocardial inflammatory response via NLRP3 inflammasome activation and activates mitophagy to minimize myocardial injury. PMID:26770647

  18. Inflammatory stimuli acutely modulate peripheral taste function.

    PubMed

    Kumarhia, Devaki; He, Lianying; McCluskey, Lynnette Phillips

    2016-06-01

    Inflammation-mediated changes in taste perception can affect health outcomes in patients, but little is known about the underlying mechanisms. In the present work, we hypothesized that proinflammatory cytokines directly modulate Na(+) transport in taste buds. To test this, we measured acute changes in Na(+) flux in polarized fungiform taste buds loaded with a Na(+) indicator dye. IL-1β elicited an amiloride-sensitive increase in Na(+) transport in taste buds. In contrast, TNF-α dramatically and reversibly decreased Na(+) flux in polarized taste buds via amiloride-sensitive and amiloride-insensitive Na(+) transport systems. The speed and partial amiloride sensitivity of these changes in Na(+) flux indicate that IL-1β and TNF-α modulate epithelial Na(+) channel (ENaC) function. A portion of the TNF-mediated decrease in Na(+) flux is also blocked by the TRPV1 antagonist capsazepine, although TNF-α further reduced Na(+) transport independently of both amiloride and capsazepine. We also assessed taste function in vivo in a model of infection and inflammation that elevates these and additional cytokines. In rats administered systemic lipopolysaccharide (LPS), CT responses to Na(+) were significantly elevated between 1 and 2 h after LPS treatment. Low, normally preferred concentrations of NaCl and sodium acetate elicited high response magnitudes. Consistent with this outcome, codelivery of IL-1β and TNF-α enhanced Na(+) flux in polarized taste buds. These results demonstrate that inflammation elicits swift changes in Na(+) taste function, which may limit salt consumption during illness. PMID:27009163

  19. Reduced Acute Inflammatory Responses to Microgel Conformal Coatings

    PubMed Central

    Bridges, Amanda W.; Singh, Neetu; Burns, Kellie L.; Babensee, Julia E.; Lyon, L. Andrew; García, Andrés J.

    2008-01-01

    Implantation of synthetic materials into the body elicits inflammatory host responses that limit medical device integration and biological performance. This inflammatory cascade involves protein adsorption, leukocyte recruitment and activation, cytokine release, and fibrous encapsulation of the implant. We present a coating strategy based on thin films of poly(N-isopropylacrylamide) hydrogel microparticles (i.e. microgels) cross-linked with poly(ethylene glycol) diacrylate. These particles were grafted onto a clinically relevant polymeric material to generate conformal coatings that significantly reduced in vitro fibrinogen adsorption and primary human monocytes/macrophage adhesion and spreading. These microgel coatings also reduced leukocyte adhesion and expression of pro-inflammatory cytokines (TNF-α, IL-1β, MCP-1) in response to materials implanted acutely in the murine intraperitoneal space. These microgel coatings can be applied to biomedical implants as a protective coating to attenuate biofouling, leukocyte adhesion and activation, and adverse host responses for biomedical and biotechnological applications. PMID:18804859

  20. Repeated, but Not Acute, Stress Suppresses Inflammatory Plasma Extravasation

    NASA Astrophysics Data System (ADS)

    Strausbaugh, Holly J.; Dallman, Mary F.; Levine, Jon D.

    1999-12-01

    Clinical findings suggest that inflammatory disease symptoms are aggravated by ongoing, repeated stress, but not by acute stress. We hypothesized that, compared with single acute stressors, chronic repeated stress may engage different physiological mechanisms that exert qualitatively different effects on the inflammatory response. Because inhibition of plasma extravasation, a critical component of the inflammatory response, has been associated with increased disease severity in experimental arthritis, we tested for a potential repeated stress-induced inhibition of plasma extravasation. Repeated, but not single, exposures to restraint stress produced a profound inhibition of bradykinin-induced synovial plasma extravasation in the rat. Experiments examining the mechanism of inhibition showed that the effect of repeated stress was blocked by adrenalectomy, but not by adrenal medullae denervation, suggesting that the adrenal cortex mediates this effect. Consistent with known effects of stress and with mediation by the adrenal cortex, restraint stress evoked repeated transient elevations of plasma corticosterone levels. This elevated corticosterone was necessary and sufficient to produce inhibition of plasma extravasation because the stress-induced inhibition was blocked by preventing corticosterone synthesis and, conversely, induction of repeated transient elevations in plasma corticosterone levels mimicked the effects of repeated stress. These data suggest that repetition of a mild stressor can induce changes in the physiological state of the animal that enable a previously innocuous stressor to inhibit the inflammatory response. These findings provide a potential explanation for the clinical association between repeated stress and aggravation of inflammatory disease symptoms and provide a model for study of the biological mechanisms underlying the stress-induced aggravation of chronic inflammatory diseases.

  1. [Treatment of acute pelvic inflammatory diseases with a new antibiotic compound preparation (author's transl)].

    PubMed

    Burmucic, R

    1980-11-30

    48 patients with acute pelvic inflammatory diseases (35 cases of acute adnexitis and 13 cases of inflammatory adnexal tumours) were treated with an antibiotic combination of Ampicillin/Oxacillin and Sisomicin. As initial parenteral therapy Ampicillin/Oxacillin 3.0 g was given intravenously twice daily and additionally Sisomicin 75 or 100 mg according to the body-weight was administered intramuscular twice daily. If required a further oral treatment with 500 mg Ampicillin/Dicloxacillin capsules four times a day was carried out. The average duration of parenteral treatment was 6.3 days; together with the oral treatment the duration of antibiotic treatment was 18.5 days. In 43 patients (89.6%) the disease could be cured completely or a distinct improvement could be achieved. Only in 5 cases (10.4%) the results were unsatisfactory. As side-effects allergic reactions were observed in three cases and gastro-enteritis in one case. PMID:7467388

  2. Berberine inhibits inflammatory mediators and attenuates acute pancreatitis through deactivation of JNK signaling pathways.

    PubMed

    Choi, Sun-Bok; Bae, Gi-Sang; Jo, Il-Joo; Wang, Shaofan; Song, Ho-Joon; Park, Sung-Joo

    2016-06-01

    Acute pancreatitis (AP) is a life-threatening disease. Berberine (BBR), a well-known plant alkaloid, is reported to have anti-inflammatory activity in many diseases. However, the effects of BBR on AP have not been clearly elucidated. Therefore, the present study aimed to investigate the effects of BBR on cerulein-induced AP in mice. AP was induced by either cerulein or l-arginine. In the BBR treated group, BBR was administered intraperitoneally 1h before the first cerulein or l-arginine injection. Blood samples were obtained to determine serum amylase and lipase activities and nitric oxide production. The pancreas and lung were rapidly removed for examination of histologic changes, myeloperoxidase (MPO) activity, and real-time reverse transcription-polymerase chain reaction. Furthermore, the regulating mechanisms of BBR were evaluated. Treatment of mice with BBR reduced pancreatic injury and activities of amylase, lipase, and pancreatitis-associated lung injury, as well as inhibited several inflammatory parameters such as the expression of pro-inflammatory cytokines and inducible nitric oxide synthesis (iNOS). Furthermore, BBR administration significantly inhibited c-Jun N-terminal kinase (JNK) activation in the cerulein-induced AP. Deactivation of JNK resulted in amelioration of pancreatitis and the inhibition of inflammatory mediators. These results suggest that BBR exerts anti-inflammatory effects on AP via JNK deactivation on mild and severe acute pancreatitis model, and could be a beneficial target in the management of AP. PMID:27148818

  3. Diagnostic approaches to acute transfusion reactions.

    PubMed

    Leo, A; Pedal, I

    2010-06-01

    The erroneous transfusion of ABO-incompatible red cells may lead to life-threatening hemolysis and complement-induced shock, resulting in death in less than 10% of cases (acute hemolytic transfusion reaction, AHTR). Identification of the cause of an erroneous transfusion is accomplished in nearly all incidents merely by checking the identity of the patient, blood sample and blood bag. The erroneous transfusion is confirmed by serological and--in the case of a fatality- immunohistochemical methods. The differential diagnosis should rule out transfusion-related acute lung injury (TRALI), other immunologically triggered causes such as febrile nonhemolytic transfusion reaction (FNHTR) or allergic reactions, but also nonimmunological causes such as bacterial contamination of the blood components, transfusion-associated circulatory overload (TACO) and other rare events such as citrate overload or embolism (by air or debris). In the case of a fatality, evaluation of a patient's medical records, serological and microbiological analyses, autopsy and histology, taken together, clarify questions of causality. PMID:20140541

  4. Laparoscopic surgery for inflammatory complications of acute sigmoid diverticulitis.

    PubMed

    Fine, A P

    2001-01-01

    From March 1995 through March 2000, we treated patients with the laparoscopic approach who had emergent and urgent indications for surgery. We report a series of 17 procedures in 16 patients in the acute category excluding those with active bleeding. One case of morbidity (DVT) but no moralities occurred, with 3 of 17 patients converted to an open approach. The postoperative course and subsequent recoveries compare favorably with the open approach to this disease process. Three other series are discussed for comparison, all showing similar favorable results. We concluded that given sufficient experience in minimally invasive colon surgery, surgeons can manage acute inflammatory complications of sigmoid diverticulitis laparoscopically with potential benefit to the patient. PMID:11548828

  5. Laparoscopic Surgery for Inflammatory Complications of Acute Sigmoid Diverticulitis

    PubMed Central

    2001-01-01

    From March 1995 through March 2000, we treated patients with the laparoscopic approach who had emergent and urgent indications for surgery. We report a series of 17 procedures in 16 patients in the acute category excluding those with active bleeding. One case of morbidity (DVT) but no moralities occurred, with 3 of 17 patients converted to an open approach. The postoperative course and subsequent recoveries compare favorably with the open approach to this disease process. Three other series are discussed for comparison, all showing similar favorable results. We concluded that given sufficient experience in minimally invasive colon surgery, surgeons can manage acute inflammatory complications of sigmoid diverticulitis laparoscopically with potential benefit to the patient. PMID:11548828

  6. Acute Pelvic Inflammatory Disease and Clinical Response to Parenteral Doxycycline

    PubMed Central

    Chow, Anthony W.; Malkasian, Kay L.; Marshall, John R.; Guze, Lucien B.

    1975-01-01

    The bacteriology of acute pelvic inflammatory disease (PID) and clinical response to parenteral doxycycline were evaluated in 30 patients. Only 3 of 21 cul-de-sac cultures from PID patients were sterile, whereas all 8 normal control subjects yielded negative results (P< 0.005). Poor correlation was observed between cervical and cul-de-sac cultures. Neisseria gonorrhoeae, isolated from the cervix in 17 patients (57%), was recovered from the cul-de-sac only once. Streptococcus, Peptococcus, Peptostreptococcus, coliforms, and other organisms normally present in the vagina were the predominant isolates recovered from the cul-de-sac. Parenteral doxycycline resulted in rapid resolution of signs and symptoms (within 48 h) in 20 of 27 evaluable patients (74%). In five others, signs and symptoms of infection abated within 4 days. The remaining two patients failed to respond; in both cases, adnexal masses developed during doxycycline therapy. Gonococci were eradicated from the cervix in all but one patient who, nevertheless, had a rapid defervescence of symptoms. There was no clear-cut correlation between the clinical response and in vitro susceptibility of cul-de-sac isolates to doxycycline. These data confirm the usefulness of broad-spectrum antibiotics in acute PID. Culdocentesis is a reliable means of obtaining material for the bacteriological diagnosis of acute PID; however, the pathogenetic role and relative importance of gonococci and various other bacteria in acute PID need to be clarified further. PMID:1169908

  7. Pathophysiological role of the acute inflammatory response during acetaminophen hepatotoxicity

    SciTech Connect

    Cover, Cathleen; Liu Jie; Farhood, Anwar; Malle, Ernst; Waalkes, Michael P.; Bajt, Mary Lynn; Jaeschke, Hartmut . E-mail: jaeschke@email.arizona.edu

    2006-10-01

    Neutrophils are recruited into the liver after acetaminophen (AAP) overdose but the pathophysiological relevance of this acute inflammatory response remains unclear. To address this question, we compared the time course of liver injury, hepatic neutrophil accumulation and inflammatory gene mRNA expression for up to 24 h after treatment with 300 mg/kg AAP in C3Heb/FeJ and C57BL/6 mice. Although there was no relevant difference in liver injury (assessed by the increase of plasma alanine aminotransferase activities and the areas of necrosis), the number of neutrophils and the expression of several pro-inflammatory genes (e.g., tumor necrosis factor-{alpha}, interleukin-1{beta} and macrophage inflammatory protein-2) was higher in C3Heb/FeJ than in C57BL/6 mice. In contrast, the expression of the anti-inflammatory genes interleukin-10 and heme oxygenase-1 was higher in C57BL/6 mice. Despite substantial hepatic neutrophil accumulation, none of the liver sections from both strains stained positive for hypochlorite-modified proteins, a specific marker for a neutrophil-induced oxidant stress. In addition, treatment with the NADPH oxidase inhibitors diphenyleneiodonium chloride or apocynin or the anti-neutrophil antibody Gr-1 did not protect against AAP hepatotoxicity. Furthermore, although intercellular adhesion molecule-1 (ICAM-1) was previously shown to be important for neutrophil extravasation and tissue injury in several models, ICAM-1-deficient mice were not protected against AAP-mediated liver injury. Together, these data do not support the hypothesis that neutrophils aggravate liver injury induced by AAP overdose.

  8. Pathophysiological role of the acute inflammatory response during acetaminophen hepatotoxicity.

    PubMed

    Cover, Cathleen; Liu, Jie; Farhood, Anwar; Malle, Ernst; Waalkes, Michael P; Bajt, Mary Lynn; Jaeschke, Hartmut

    2006-10-01

    Neutrophils are recruited into the liver after acetaminophen (AAP) overdose but the pathophysiological relevance of this acute inflammatory response remains unclear. To address this question, we compared the time course of liver injury, hepatic neutrophil accumulation and inflammatory gene mRNA expression for up to 24 h after treatment with 300 mg/kg AAP in C3Heb/FeJ and C57BL/6 mice. Although there was no relevant difference in liver injury (assessed by the increase of plasma alanine aminotransferase activities and the areas of necrosis), the number of neutrophils and the expression of several pro-inflammatory genes (e.g., tumor necrosis factor-alpha, interleukin-1beta and macrophage inflammatory protein-2) was higher in C3Heb/FeJ than in C57BL/6 mice. In contrast, the expression of the anti-inflammatory genes interleukin-10 and heme oxygenase-1 was higher in C57BL/6 mice. Despite substantial hepatic neutrophil accumulation, none of the liver sections from both strains stained positive for hypochlorite-modified proteins, a specific marker for a neutrophil-induced oxidant stress. In addition, treatment with the NADPH oxidase inhibitors diphenyleneiodonium chloride or apocynin or the anti-neutrophil antibody Gr-1 did not protect against AAP hepatotoxicity. Furthermore, although intercellular adhesion molecule-1 (ICAM-1) was previously shown to be important for neutrophil extravasation and tissue injury in several models, ICAM-1-deficient mice were not protected against AAP-mediated liver injury. Together, these data do not support the hypothesis that neutrophils aggravate liver injury induced by AAP overdose. PMID:16781746

  9. Innate immune inflammatory response in the acutely ischemic myocardium.

    PubMed

    Deftereos, Spyridon; Angelidis, Christos; Bouras, Georgios; Raisakis, Konstantinos; Gerckens, Ulrich; Cleman, Michael W; Giannopoulos, Georgios

    2014-01-01

    The "holy grail" of modern interventional cardiology is the salvage of viable myocardial tissue in the distribution of an acutely occluded coronary artery. Thrombolysis and percutaneous coronary interventions, provided they can be delivered on time, can interrupt the occlusion and save tissue. At the same time restoring the patency of the coronary vessels and providing the ischemic myocardium with blood can cause additional tissue damage. A key element of ischemic and reperfusion injury and major determinant of the evolution of damage in the injured myocardium is the inflammatory response. The innate immune system initiates and directs this response which is a prerequisite for subsequent healing. The complement cascade is set in motion following the release of subcellular membrane constituents. Endogenous 'danger' signals known as danger-associated molecular patterns (DAMPs) released from ischemic and dying cells alert the innate immune system and activate several signal transduction pathways through interactions with the highly conserved Toll like receptors (TLRs). Reactive oxygen species (ROS) generation directly induces pro-inflammatory cascades and triggers formation of the inflammasome. The challenge lies into designing strategies that specifically block the inflammatory cascades responsible for tissue damage without affecting those concerned with tissue healing. PMID:25102201

  10. Role of anaerobes in acute pelvic inflammatory disease.

    PubMed

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

    2003-01-01

    Pouch of Douglas aspirates were collected from 50 women with history and examination suggestive of acute pelvic inflammatory disease (PID) and 20 healthy women admitted for tubal ligation served as control. A total of 57 microorganisms were isolated from 37 patients out of 50 in study group. Of 37 positive cultures 21(56.7%) were monomicrobial and 16(43.2%) were polymicrobial. Most common symptom in study group was lower abdominal pain (90%), vaginal discharge (70%) and irregular bleeding (40%) and 30% patients had history of intrauterine contraceptive device (IUCD) implantation. The predominant aerobic isolates were Escherichia coli, Coagulase Negative Staphylococcus (CONS), Staphylococcus aureus, Klebsiella pneumoniae while common anaerobes were Bacteroides fragilis, Prevotella melaninogenica, Fusobacterium nucleatum and Peptostreptococcus spp. Our study shows that cefotaxime, cefuroxime and gentamicin may be used for gram negative aerobic bacilli; cloxacillin, cephaloridine and erythromycin for aerobic gram positive cocci and amikacin and ceftazidime for Pseudomonas aeruginosa. Thus for optimum therapy of acute PID it is beneficial to keep in mind major conceptual changes and therapeutic realities that have influenced current understanding of acute PID and have affected the choice of therapy. PMID:17643017

  11. Local and systemic inflammatory and immunologic reactions to cyathostomin larvicidal therapy in horses.

    PubMed

    Nielsen, M K; Loynachan, A T; Jacobsen, S; Stewart, J C; Reinemeyer, C R; Horohov, D W

    2015-12-15

    Encysted cyathostomin larvae are ubiquitous in grazing horses. Arrested development occurs in this population and can lead to an accumulation of encysted larvae. Large numbers of tissue larvae place the horse at risk for developing larval cyathostominosis. This disease complex is caused by mass emergence of these larvae and is characterized by a generalized acute typhlocolitis and manifests itself as a profuse protein-losing watery diarrhea with a reported case-fatality rate of about 50%. Two anthelmintic formulations have a label claim for larvicidal therapy of these encysted stages; moxidectin and a five-day regimen of fenbendazole. There is limited knowledge about inflammatory and immunologic reactions to larvicidal therapy. This study was designed to evaluate blood acute phase reactants as well as gene expression of pro-inflammatory cytokines, both locally in the large intestinal walls and systemically. Further, mucosal tissue samples were evaluated histopathologically as well as analyzed for gene expression of pro- and anti-inflammatory cytokines, cluster of differentiation (CD) cell surface proteins, and select transcription factors. Eighteen juvenile horses with naturally acquired cyathostomin infections were randomly assigned to three treatment groups; one group served as untreated controls (Group 1), one received a five-day regimen of fenbendazole (10mg/kg) (Group 2), and one group received moxidectin (0.4mg/kg) (Group 3). Horses were treated on day 0 and euthanatized on days 18-20. Serum and whole blood samples were collected on days 0, 5, and 18. All horses underwent necropsy with collection of tissue samples from the ventral colon and cecum. Acute phase reactants measured included serum amyloid A, iron and fibrinogen, and the cytokines evaluated included interferon γ, tumor necrosis factor α, transforming growth factor (TGF)-β, and interleukins 1β, 4, 5, 6, and 10. Transcription factors evaluated were FoxP3, GATA3 and tBet, and CD markers included

  12. Acute hypoxemia in humans enhances the neutrophil inflammatory response.

    PubMed

    Tamura, Douglas Y; Moore, Ernest E; Partrick, David A; Johnson, Jeffrey L; Offner, Patrick J; Silliman, Christopher C

    2002-04-01

    The neutrophil (PMN) is regarded as a key component in the hyperinflammatory response known as the systemic inflammatory response syndrome. Acute respiratory distress syndrome (ARDS) and subsequent multiple organ failure (MOF) are related to the severity of this hyperinflammation. ICU patients who are at highest risk of developing MOF may have acute hypoxic events that complicate their hospital course. This study was undertaken to evaluate the effects of acute hypoxia and subsequent hypoxemia on circulating PMNs in human volunteers. Healthy subjects were exposed to a changing O2/N2 mixture until their O2 saturation (SaO2) reached a level of 68% saturation. These subjects were then exposed to room air and then returned to their baseline SaO2. PMNs were isolated from pre- and post-hypoxemic arterial blood samples and were then either stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) or PMA alone, or they were primed with L-alpha-phosphatidylcholine, beta-acetyl-gamma-O-alkyl (PAF) followed by fMLP activation. Reactive oxygen species generation as measured by superoxide anion production was enhanced in primed PMNs after hypoxemia. Protease degranulation as measured by elastase release was enhanced in both quiescent PMNs and primed PMNs after fMLP activation following the hypoxemic event. Adhesion molecule upregulation as measured by CD11b/CD18, however, was not significantly changed after hypoxemia. Apoptosis of quiescent PMNs was delayed after the hypoxemic event. TNFalpha, IL-1, IL-6, and IL-8 cytokine levels were unchanged following hypoxemia. These results indicate that relevant acute hypoxemic events observed in the clinical setting enhance several PMN cytotoxic functions and suggest that a transient hypoxemic insult may promote hyperinflammation. PMID:11954825

  13. Histamine release and fibrinogen adsorption mediate acute inflammatory responses to biomaterial implants in humans

    PubMed Central

    Zdolsek, Johann; Eaton, John W; Tang, Liping

    2007-01-01

    Background Medical implants often fail as a result of so-called foreign body reactions during which inflammatory cells are recruited to implant surfaces. Despite the clinical importance of this phenomenon, the mechanisms involved in these reactions to biomedical implants in humans are not well understood. The results from animal studies suggest that both fibrinogen adsorption to the implant surface and histamine release by local mast cells are involved in biomaterial-mediated acute inflammatory responses. The purpose of this study was to test this hypothesis in humans. Methods Thirteen male medical student volunteers (Caucasian, 21–30 years of age) were employed for this study. To assess the importance of fibrinogen adsorption, six volunteers were implanted with polyethylene teraphthalate disks pre-coated with their own (fibrinogen-containing) plasma or (fibrinogen-free) serum. To evaluate the importance of histamine, seven volunteers were implanted with uncoated disks with or without prior oral administration of histamine receptor antagonists. The acute inflammatory response was estimated 24 hours later by measuring the activities of implant-associated phagocyte-specific enzymes. Results Plasma coated implants accumulated significantly more phagocytes than did serum coated implants and the recruited cells were predominantly macrophage/monocytes. Administration of both H1 and H2 histamine receptor antagonists greatly reduced the recruitment of macrophages/monocytes and neutrophils on implant surfaces. Conclusion In humans – as in rodents – biomaterial-mediated inflammatory responses involve at least two crucial events: histamine-mediated phagocyte recruitment and phagocyte accumulation on implant surfaces engendered by spontaneously adsorbed host fibrinogen. Based on these results, we conclude that reducing fibrinogen:surface interactions should enhance biocompatibility and that administration of histamine receptor antagonists prior to, and shortly after

  14. Defining and Regulating Acute Inflammatory Lesion Formation during the Pathogenesis of Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis.

    PubMed

    Bolton, Christopher; Smith, Paul

    2015-01-01

    The primary pathology of the human central nervous system disease multiple sclerosis (MS) and the animal counterpart experimental autoimmune encephalomyelitis (EAE) includes immunological and inflammatory events. Immune system involvement in MS has been widely debated but the role of inflammation has received less attention. Classic acute inflammation features vasculitis, resident tissue macrophage and mast cell participation plus the involvement of circulatory-derived neutrophils and platelets. Pre-lesion development in MS incorporates cerebral vasculitis, activated resident microglia in normal appearing white matter together with infiltrating cell types and factors indicative of an acute inflammatory reaction. Similarly, the formation of perivascular lesions during early EAE includes characteristic neurovasculitis, the participation of central nervous system microglial phenotypes plus haemopoietic cells and mediators, signifying an ongoing acute inflammatory response. EAE has been extensively used as a screen to select drugs for MS treatment but has been criticised as unrepresentative of the human condition due to fundamental differences in disease induction and pathogenesis. The review provides compelling evidence for a distinct acute inflammatory phase in MS lesion formation that is convincingly reproduced in early EAE pathology. Moreover, consideration of drug efficacy studies undertaken during initial EAE validates the occurrence of an acute inflammatory phase in disease pathogenesis. Critical appraisal, recognition and acceptance of the mutual acute inflammatory components inherent in the primary pathology of MS and EAE reveals new targets and encourages confident and reliable employment of the animal model in the assessment of novel compounds for the control of key primary pathological events in human demyelinating disease. PMID:26177741

  15. [Persistent inflammatory reaction at the injection site of Il-2 with lymphoma-like inflammatory infiltrates].

    PubMed

    Assmann, K; Nashan, D; Grabbe, S; Luger, T A; Metze, D

    2002-08-01

    Interleukin-2 (Il-2) is widely used for treatment of carcinomas, leukemia, and melanoma. Adverse drug effects of Il-2 include various systemic and generalized cutaneous drug reactions. In the following we report on a persistent inflammatory reaction at the injection site of Il-2. A patient received chemoimmuno-therapy for treatment of metastasizing melanoma, including subcutaneous application of recombinant interleukin-2 (Proleukin((R))). Within a few days reddish nodules developed at the injection sites that persisted after cessation of Il-2 injections for two years until final lethal outcome. Histologic examination revealed a lobular panniculitis expressing atypical lymphocytes and multinucleated histiocytes. PMID:12221472

  16. Comparative studies on the tolerance to photoinduced cutaneous inflammatory reactions by psoralen and rose bengal.

    PubMed

    Kumar, J R; Haberman, H F; Ranadive, N S

    1997-02-01

    The photochemotherapeutic value of topical 8-methoxypsoralen (8-MOP) plus UVA irradiation has been well recognized. The phototoxicity associated with psoralen plus UVA (PUVA) therapy is hallmarked by an increase in vascular permeability (iVP), the accumulation of polymorphonuclear leukocytes (aPMN) and erythema formation in situ. Rose bengal (RB) plus UVA-VIS light (320-700 nm) produces a similar acute inflammatory response, but without immediate or delayed erythema and perceptible edema. This study describes some of the parameters involved in inflammatory reactions evoked by PUVA and the results are compared with RB-induced phototoxic reactions. The rates of iVP and aPMN with a 3 h pulse were quantified using 125I-albumin and 51Cr-labelled PMNs respectively. The erythemal response was graded visually. 8-MOP cream was applied topically, while RB was injected intradermally in rabbit skin before UVA-VIS (9.4 J cm-2) irradiation. The data show that there is no significant difference in the rates of iVP, aPMN and erythema formation between normal skin sites and mast cell-depleted skin sites when challenged with 8-MOP plus light. These results suggest that in situ mast cells do not play a significant role in 8-MOP-photoinduced acute cutaneous inflammatory reactions, in contrast with RB-photoinduced reactions. The iVP and aPMN responses are minimal or absent in sites subjected to repeated exposure to 8-MOP plus light for three or more consecutive days, suggesting the establishment of a desensitized/unresponsive state. Moreover, 8-MOP-photo-desensitized sites do not produce iVP and aPMN of the same magnitude as the normal (naive) skin sites when challenged with RB plus light. Similarly, RB-photo-desensitized sites do not produce iVP and aPMN of the same magnitude as the native skin sites when challenged with 8-MOP plus light. The desensitization and cross-desensitization of skin sites to 8-MOP- or RB-photoinduced reactions suggest that there is either direct attack on the

  17. Temporal profile of serum anti-inflammatory and pro-inflammatory interleukins in acute ischemic stroke patients.

    PubMed

    Perini, F; Morra, M; Alecci, M; Galloni, E; Marchi, M; Toso, V

    2001-08-01

    The presence of an inflammatory response in the pathophysiology of acute brain ischemia is relatively well established, but less is known about the anti-inflammatory mechanisms. The aim of the present study was to evaluate part of the immune response in acute stroke patients and to analyze a possible correlation with other hematological parameters, clinical outcome, size of infarct and subtypes of strokes. We prospectively studied 42 stroke patients, without signs of infections or inflammatory diseases, at days 0, 1, 3, 7 and 14, and 39 healthy control subjects. We measured serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) and the pro-inflammatory cytokine interleukin-6 (IL-6) by ELISA method. We observed a highly inverse correlation between these two molecules in control subjects (r=-0.78, p=0.0000001), and this correlation was lost in stroke patients. Patients had significantly lowered IL-10 serum levels soon after the acute event (p=0.00005), with a slight increase at the seventh day. On the other hand, patients had increased IL-6 serum levels compared with controls after day one until day 14 (p<0.04), with a maximum increase at day 3. Interleukin-6 correlated with clinical outcome whereas interleukin-10 did not. Low levels of interleukin-10 indicate that the antiinflammatory response is down-regulated in acute stroke patients. The pro-inflammatory response begins 24 hours after the onset of acute cerebral ischemia, as indicated by the increased serum levels of interleukin-6. The physiological balance between these two molecules is altered in acute stroke patients. PMID:11808851

  18. Colchicine Acutely Suppresses Local Cardiac Production of Inflammatory Cytokines in Patients With an Acute Coronary Syndrome

    PubMed Central

    Martínez, Gonzalo J; Robertson, Stacy; Barraclough, Jennifer; Xia, Qiong; Mallat, Ziad; Bursill, Christina; Celermajer, David S; Patel, Sanjay

    2015-01-01

    Background Interleukin (IL)-1β, IL-18, and downstream IL-6 are key inflammatory cytokines in the pathogenesis of coronary artery disease. Colchicine is believed to block the NLRP3 inflammasome, a cytosolic complex responsible for the production of IL-1β and IL-18. In vivo effects of colchicine on cardiac cytokine release have not been previously studied. This study aimed to (1) assess the local cardiac production of inflammatory cytokines in patients with acute coronary syndromes (ACS), stable coronary artery disease and in controls; and (2) determine whether acute administration of colchicine inhibits their production. Methods and Results Forty ACS patients, 33 with stable coronary artery disease, and 10 controls, were included. ACS and stable coronary artery disease patients were randomized to oral colchicine treatment (1 mg followed by 0.5 mg 1 hour later) or no colchicine, 6 to 24 hours prior to cardiac catheterization. Blood samples from the coronary sinus, aortic root (arterial), and lower right atrium (venous) were collected and tested for IL-1β, IL-18, and IL-6 using ELISA. In ACS patients, coronary sinus levels of IL-1β, IL-18, and IL-6 were significantly higher than arterial and venous levels (P=0.017, <0.001 and <0.001, respectively). Transcoronary (coronary sinus-arterial) gradients for IL-1β, IL-18, and IL-6 were highest in ACS patients and lowest in controls (P=0.077, 0.033, and 0.014, respectively). Colchicine administration significantly reduced transcoronary gradients of all 3 cytokines in ACS patients by 40% to 88% (P=0.028, 0.032, and 0.032, for IL-1β, IL-18, and IL-6, respectively). Conclusions ACS patients exhibit increased local cardiac production of inflammatory cytokines. Short-term colchicine administration rapidly and significantly reduces levels of these cytokines. PMID:26304941

  19. Paradoxical reactions and immune reconstitution inflammatory syndrome in tuberculosis.

    PubMed

    Bell, Lucy C K; Breen, Ronan; Miller, Robert F; Noursadeghi, Mahdad; Lipman, Marc

    2015-03-01

    The coalescence of the HIV-1 and tuberculosis (TB) epidemics in Sub-Saharan Africa has had a significant and negative impact on global health. The availability of effective antimicrobial treatment for both HIV-1 (in the form of highly active antiretroviral therapy (HAART)) and TB (with antimycobacterial agents) has the potential to mitigate the associated morbidity and mortality. However, the use of both HAART and antimycobacterial therapy is associated with the development of inflammatory paradoxical syndromes after commencement of therapy. These include paradoxical reactions (PR) and immune reconstitution inflammatory syndromes (IRIS), conditions that complicate mycobacterial disease in HIV seronegative and seropositive individuals. Here, we discuss case definitions for PR and IRIS, and explore how advances in identifying the risk factors and immunopathogenesis of these conditions informs our understanding of their shared underlying pathogenesis. We propose that both PR and IRIS are characterized by the triggering of exaggerated inflammation in a setting of immunocompromise and antigen loading, via the reversal of immunosuppression by HAART and/or antimycobacterials. Further understanding of the molecular basis of this pathogenesis may pave the way for effective immunotherapies for the treatment of PR and IRIS. PMID:25809754

  20. Perivascular Inflammatory Reaction After Percutaneous Placement of Covered Stents

    SciTech Connect

    Link, Johann; Mueller-Huelsbeck, Stefan; Brossmann, Joachim; Steffens, Johann C.; Heller, Martin

    1996-09-15

    A 52-year-old woman with an extensive superficial femoral artery occlusion was treated with percutaneous transluminal angioplasty. Because of extensive dissections, two covered stents were placed percutaneously. The intervention was successful with respect to vessel patency, but local pain and fever developed 5 hr after the intervention. Swelling of the thigh occurred, but deep venous thrombosis was excluded. MRI revealed pronounced soft-tissue edema in the adductor canal that persisted for 4 weeks. The fever responded to antiinflammatory medication, but the pain remained for 4 weeks. The vessel was patent at the last follow-up, 8 weeks after graft placement. Soft-tissue edema after percutaneous placement of covered stents has been reported previously. The cause of the inflammatory reaction is unclear.

  1. Parthenolide ameliorates Concanavalin A-induced acute hepatitis in mice and modulates the macrophages to an anti-inflammatory state.

    PubMed

    Wang, Dan; Wang, Huafeng; Fu, Shuyu; Cheng, Xixi; Yang, Fengrui; Zhang, Qi; Li, Yan; Xue, Zhenyi; Zhang, Lijuan; Huang, Wenjing; Yang, Luhong; Na, Dongchen; Da, Yurong; Kong, Ying; Zhang, Rongxin

    2016-09-01

    Parthenolide, the principal sesquiterpene lactone present in medicinal plants such as feverfew, has anti-microbial, anti-inflammatory and anticancer activities. In the present study, we investigated the protective role of parthenolide against acute hepatitis in mice. Mice acute hepatitis were induced by Concanavalin A and treated by parthenolide in vivo. Results shown that parthenolide remarkably reduced the congestion and necroinflammation of the mice livers with Concanavalin A-induced acute hepatitis. Meanwhile, parthenolide treatment recover the liver function which indicated by decreased the serum alanine transaminase and alkaline phosphatase activities and promoted the expression of Ki67 in the livers of these mice. In addition, parthenolide administration suppressed the Concanavalin A-induced immune reaction, as indicated by the number of F4/80, CD49b and CD4 cells present in the liver. Furthermore, parthenolide also significantly reduced the expression of pro-inflammatory cytokines such as IFN-γ, TNF-α, IL-17A, IL-1β and IL-6 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells in vitro. Moreover, parthenolide exposure decreased the phosphorylation of STAT3 and p38, and promoted the phosphorylation of p53 in RAW264.7 cells in vitro. In conclusion, parthenolide represents a drug candidate to protect the liver against Concanavalin A-induced acute hepatitis. The possible molecular mechanism involves the anti-inflammatory effects of parthenolide may by suppressing the STAT3/p38 signals and enhanced the p53 signals. PMID:27270078

  2. C-reactive protein and the acute phase reaction in geriatric patients.

    PubMed

    Bertsch, Thomas; Triebel, Jakob; Bollheimer, Cornelius; Christ, Michael; Sieber, Cornel; Fassbender, Klaus; Heppner, Hans Jürgen

    2015-10-01

    The C-reactive protein (CRP), first described as a serum component capable of precipitating the C-polysaccharide of pneumococci, is one of the most important proteins because the serum concentration rises in the acute phase reaction. The acute phase reaction is the nonspecific reaction of the body to noxious stimuli of the most varied kinds, such as infections, burns, neoplasms and tissue trauma. The CRP is synthesized in liver parenchymal cells by cytokines which are derived from stimulated leucocytes and released into the circulation. Because of its molecular structure and in synergy with the complement system, it is able to precipitate and/or lyse microorganisms, thereby rendering them harmless. Measurement of the serum CRP concentration can provide important information with respect to the diagnosis and monitoring of treatment. Due to immunosenescence in geriatric patients the synthesis of CRP appears to be limited to inflammatory stimuli; however, this phenomenon does not appear to be of major clinical relevance. Despite the introduction of new parameters of the acute phase reaction, sometimes with better performance, such as interleukin-6, procalcitonin and the soluble endotoxin receptor sCD14, measurement of CRP for diagnosis and treatment monitoring is still justified even in geriatric patients as testing is rapid, economic and nearly ubiquitously available round the clock. Biochemical markers of the acute phase reaction should always be interpreted together with the clinical picture and their specific limitations. PMID:26334841

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

    PubMed

    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. PMID:25917334

  4. Acute Cryptococcal Immune Reconstitution Inflammatory Syndrome in a Patient on Natalizumab

    PubMed Central

    Gundacker, Nathan D.; Jordan, Stephen J.; Jones, Benjamin A.; Drwiega, Joseph C.; Pappas, Peter G.

    2016-01-01

    Presented is the first case of acute immune reconstitution inflammatory syndrome (IRIS)-associated cryptococcal meningoencephalitis in a patient on natalizumab for multiple sclerosis. The patient developed acute cerebral edema after initiation of amphotericin B. We propose several mechanisms that explain the acuity of IRIS in this specific patient population and suggest possible therapies. PMID:27006962

  5. Blood transfusion for the treatment of acute anaemia in inflammatory bowel disease and other digestive diseases

    PubMed Central

    García-Erce, José Antonio; Gomollón, Fernando; Muñoz, Manuel

    2009-01-01

    Allogeneic blood transfusion (ABT) is frequently used as the first therapeutic option for the treatment of acute anaemia in patients with inflammatory bowel disease (IBD), especially when it developed due to gastrointestinal or perioperative blood loss, but is not risk-free. Adverse effects of ABT include, but are not limited to, acute hemolytic reaction (wrong blood or wrong patient), febrile non-hemolytic transfusional reaction, bacterial contamination, transfusion-related acute lung injury, transfusion associated circulatory overload, transfusion-related immuno-modulation, and transmission of almost all infectious diseases (bacteria, virus, protozoa and prion), which might result in increased risk of morbidity and mortality. Unfortunately, the main physiological goal of ABT, i.e. to increase oxygen consumption by the hypoxic tissues, has not been well documented. In contrast, the ABT is usually misused only to increase the haemoglobin level within a fixed protocol [mostly two by two packed red blood cell (PRC) units] independently of the patient’s tolerance to normovolemic anaemia or his clinical response to the transfusion of PRC units according to a “one-by-one” administration schedule. Evidence-based clinical guidelines may promote best transfusion practices by implementing restrictive transfusion protocols, thus reducing variability and minimizing the avoidable risks of transfusion, and the use of autologous blood and pharmacologic alternatives. In this regard, preoperative autologous blood donation (PABD) consistently diminished the frequency of ABT, although its contribution to ABT avoidance is reduced when performed under a transfusion protocol. In addition, interpretation of utility of PABD in surgical IBD patients is hampered by scarcity of published data. However, the role of autologous red blood cells as drug carriers is promising. Finally, it must be stressed that a combination of methods used within well-constructed protocols will offer better

  6. Blood transfusion for the treatment of acute anaemia in inflammatory bowel disease and other digestive diseases.

    PubMed

    García-Erce, José Antonio; Gomollón, Fernando; Muñoz, Manuel

    2009-10-01

    Allogeneic blood transfusion (ABT) is frequently used as the first therapeutic option for the treatment of acute anaemia in patients with inflammatory bowel disease (IBD), especially when it developed due to gastrointestinal or perioperative blood loss, but is not risk-free. Adverse effects of ABT include, but are not limited to, acute hemolytic reaction (wrong blood or wrong patient), febrile non-hemolytic transfusional reaction, bacterial contamination, transfusion-related acute lung injury, transfusion associated circulatory overload, transfusion-related immuno-modulation, and transmission of almost all infectious diseases (bacteria, virus, protozoa and prion), which might result in increased risk of morbidity and mortality. Unfortunately, the main physiological goal of ABT, i.e. to increase oxygen consumption by the hypoxic tissues, has not been well documented. In contrast, the ABT is usually misused only to increase the haemoglobin level within a fixed protocol [mostly two by two packed red blood cell (PRC) units] independently of the patient's tolerance to normovolemic anaemia or his clinical response to the transfusion of PRC units according to a "one-by-one" administration schedule. Evidence-based clinical guidelines may promote best transfusion practices by implementing restrictive transfusion protocols, thus reducing variability and minimizing the avoidable risks of transfusion, and the use of autologous blood and pharmacologic alternatives. In this regard, preoperative autologous blood donation (PABD) consistently diminished the frequency of ABT, although its contribution to ABT avoidance is reduced when performed under a transfusion protocol. In addition, interpretation of utility of PABD in surgical IBD patients is hampered by scarcity of published data. However, the role of autologous red blood cells as drug carriers is promising. Finally, it must be stressed that a combination of methods used within well-constructed protocols will offer better

  7. Acute and Chronic Cutaneous Reactions to Ionizing Radiation Therapy.

    PubMed

    Bray, Fleta N; Simmons, Brian J; Wolfson, Aaron H; Nouri, Keyvan

    2016-06-01

    Ionizing radiation is an important treatment modality for a variety of malignant conditions. However, development of radiation-induced skin changes is a significant adverse effect of radiation therapy (RT). Cutaneous repercussions of RT vary considerably in severity, course, and prognosis. When they do occur, cutaneous changes to RT are commonly graded as acute, consequential-late, or chronic. Acute reactions can have severe sequelae that impact quality of life as well as cancer treatment. Thus, dermatologists should be informed about these adverse reactions, know how to assess their severity and be able to determine course of management. The majority of measures currently available to prevent these acute reactions are proper skin hygiene and topical steroids, which limit the severity and decrease symptoms. Once acute cutaneous reactions develop, they are treated according to their severity. Treatments are similar to those used in prevention, but incorporate wound care management that maintains a moist environment to hasten recovery. Chronic changes are a unique subset of adverse reactions to RT that may develop months to years following treatment. Chronic radiation dermatitis is often permanent, progressive, and potentially irreversible with substantial impact on quality of life. Here, we also review the etiology, clinical manifestations, pathogenesis, prevention, and management of late-stage cutaneous reactions to radiotherapy, including chronic radiation dermatitis and radiation-induced fibrosis. PMID:27250839

  8. Kinsenoside isolated from Anoectochilus formosanus suppresses LPS-stimulated inflammatory reactions in macrophages and endotoxin shock in mice.

    PubMed

    Hsiao, Hung-Bo; Wu, Jin-Bin; Lin, Ho; Lin, Wen-Chuan

    2011-02-01

    In the present study, we reported that kinsenoside, a major component of Anoectochilus formosanus, inhibited inflammatory reactions in mouse peritoneal lavage macrophages and protects mice from endotoxin shock. In LPS-stimulated mouse peritoneal lavage macrophages, kinsenoside inhibited the inflammatory mediators, such as nitric oxide, TNF-[alpha], IL-1[beta], monocyte chemoattractant protein 1, and macrophage migration inhibitory factor production. Furthermore, kinsenoside decreased the formation of a nuclear factor [kappa]B-DNA complex and nuclear p65 and p50 protein levels. Kinsenoside inhibited nuclear factor [kappa]B translocation through both I[kappa]B[alpha]-dependent and -independent pathway. In contrast, it stimulated anti-inflammatory cytokine IL-10 generation and enhanced the mRNA expression of IL-10 and suppressor of cytokine signaling 3 in the same cells induced by LPS. In an animal model, both pretreatment and posttreatment of kinsenoside increased the survival rate of ICR mice challenged by LPS (80 mg/kg, i.p.). Pretreatment with kinsenoside decreased serum levels of TNF-[alpha], IL-1[beta], IL-10, monocyte chemoattractant protein 1, and migration inhibitory factor at 1 h after sublethal dose of LPS (40 mg/kg, i.p.) in mice. In contrast, kinsenoside enhanced serum IL-10 level at 24 h after LPS injection in mice. In conclusion, kinsenoside inhibited the production of inflammatory mediators and enhanced anti-inflammatory cytokine generation. Therefore, kinsenoside can alleviate acute inflammatory hazards. PMID:20661184

  9. Modulation of Inflammatory and Profibrotic Signaling in a Rabbit Model of Acute Phonotrauma Using Triamcinolone

    PubMed Central

    Hall, Joseph E.; Suehiro, Atsushi; Branski, Ryan C.; Garrett, C. Gaelyn; Rousseau, Bernard

    2015-01-01

    Objective To investigate the hypothesis that prophylactic triamcinolone modulates acute vocal fold inflammatory and profibrotic signaling during acute phonotrauma. Study Design In vivo rabbit phonation model. Setting Academic medical center. Subjects and Methods Forty New Zealand white breeder rabbits were randomly assigned to 1 of 4 groups: control (no intervention), no treatment (30 minutes of raised intensity phonation), sham treatment (bilateral intralaryngeal triamcinolone acetonide injection at 0 μg/25 μL followed by 30 minutes of raised intensity phonation), or steroid treatment (bilateral intralaryngeal triamcinolone acetonide injection at 400 μg/25 μL followed by 30 minutes of raised intensity phonation). Quantitative polymerase chain reaction (qPCR) was used to investigate gene expression levels of cyclooxygenase-2 (COX-2), interleukin (IL)–1β, and transforming growth factor (TGF)–β1. Results Results revealed a significant main effect for COX-2 (P = .002). Post hoc testing revealed that rabbits receiving no treatment (15.10) had higher COX-2 gene expression than control (5.90; P <.001). There were no significant differences in COX-2 expression between treatment groups. Results revealed a significant main effect for IL-1β (P < .001). Post hoc testing revealed that rabbits receiving no treatment (14.70) had higher IL-1β gene expression than control (6.30) (P = .001). There were no significant differences in IL-1β gene expression between treatment groups. There were no significant differences in TGF-β1 gene expression (P = .525) between treatment and control groups. Conclusion Given conflicting evidence, further studies are necessary to investigate vocal fold steroid injections prior to and following the induction of phonotrauma. Prophylactic administration of triamcinolone immediately prior to acute phonotrauma resulted in no significant changes in COX-2, IL-1β, and TGF-β1 gene transcript levels. PMID:22399283

  10. Hypersensitivity Reactions to Nonsteroidal Anti-inflammatory Drugs in Children and Adolescents: Selective Reactions.

    PubMed

    Blanca-López, N; Cornejo-García, J A; Pérez-Alzate, D; Pérez-Sánchez, N; Plaza-Serón, M C; Doña, I; Torres, M J; Canto, G; Kidon, M; Perkins, J R; Blanca, M

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are used throughout the world to treat pain and inflammation; however, they can trigger several types of drug hypersensitivity reactions (DHRs) in all age groups. Although most such reactions occur through activation of the leukotriene pathway without specific immunological recognition (cross-intolerance), a significant number of DHRs to NSAIDs are due to immunological mechanisms (selective reactions [SRs]). SRs are thought to be induced by specific IgE antibodies or by T cells. In this manuscript, we focus on SRs, which are of great concern in children and adolescents and comprise a heterogeneous set of clinical pictures ranging from mild entities such as urticaria/angioedema to potentially life-threatening conditions such as Stevens-Johnson syndrome/toxic epidermal necrolysis. Paracetamol and ibuprofen are the most frequent elicitors of IgE-mediated SRs, although pyrazolones have also been implicated. T cell-mediated reactions are infrequent in children but have been associated with ibuprofen, naproxen, and dipyrone. In this review, we analyze the available literature on SRs in children and adolescents, with emphasis on epidemiological data, mechanisms, and drugs involved, as well as on diagnostic procedures. PMID:26817135

  11. Management of acute adverse reactions to contrast media.

    PubMed

    Thomsen, Henrik S; Morcos, Sameh K

    2004-03-01

    When anaphylactoid and other severe adverse reactions to contrast media occur, prompt recognition and immediate treatment are essential. Simple guidelines for treatment have been requested by many radiologists, and therefore the Contrast Media Safety Committee has produced guidelines for treatment of acute adverse reactions to contrast media. The committee made an extensive review of the literature on treatment of adverse reactions to contrast media. Based on this, a report and guidelines were prepared. The resulting report was discussed at the 10th European Symposium on Urogenital Radiology in Uppsala. Sweden, September 2003. Guidelines for treatment of acute adverse reactions and a list of first-line drugs and equipment that should be available in the room where contrast medium is given are provided. PMID:14740165

  12. The patterns of toxicity and management of acute nonsteroidal anti-inflammatory drug (NSAID) overdose

    PubMed Central

    Hunter, Laura J; Wood, David M; Dargan, Paul I

    2011-01-01

    The nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their analgesic, anti-inflammatory and antipyretic actions. They are commonly taken in overdose in many areas of the world. The majority of patients with acute NSAID overdose will remain asymptomatic or develop minor self-limiting gastrointestinal symptoms. However, serious clinical sequelae have been reported in patients with acute NSAID overdose and these include convulsions, metabolic acidosis, coma and acute renal failure. There appear to be some differences between the NSAIDs in terms of the relative risk of these complications; in particular mefenamic acid is most commonly associated with convulsions. The management of these serious clinical features is largely supportive and there are no specific antidotes for acute NSAID toxicity. PMID:27147851

  13. Contribution of endothelial selectins and alpha 4 integrins to eosinophil trafficking in allergic and nonallergic inflammatory reactions in skin.

    PubMed

    Teixeira, M M; Hellewell, P G

    1998-09-01

    The role of endothelial selectins in mediating eosinophil recruitment was assessed using the trafficking of 111In-labeled blood eosinophils in mouse skin. An intradermal injection of chemoattractants (leukotriene B4, macrophage inflammatory protein-l alpha, and eotaxin) resulted in a rapid accumulation of 111In eosinophils that was reduced 49 to 91% by anti-P-selectin mAb. An anti-E-selectin mAb was ineffective, although a combined E- and P-selectin blockade resulted in >95% inhibition of all responses. The accumulation of a pulse of 111In eosinophils at sites of active cutaneous anaphylaxis (ACA) at 4 to 8 h and at 20 to 24 h after Ag challenge was completely dependent upon E- and P-selectin in combination, but not in isolation. In contrast, at 20 to 24 h after Ag challenge in a delayed-type hypersensitivity (DTH) reaction in skin, 111In eosinophil accumulation was largely independent of endothelial selectins, even when L-selectin was also blocked. An anti-alpha 4 integrin mAb significantly reduced 111In eosinophil trafficking in both allergic reactions but was slightly more effective in the DTH reaction compared with the ACA reaction. These results show that P-selectin and to a lesser extent E-selectin mediate eosinophil recruitment in skin in acute inflammatory reactions. In allergic, late-onset inflammatory reactions, neither P- nor E-selectin alone are sufficient to mediate eosinophil accumulation; when combined, they are essential for trafficking in ACA but are less important in the DTH reaction. Whether alpha 4 integrin-based strategies will be more effective than selectin-based strategies at inhibiting eosinophil recruitment in human disease remains to be determined. PMID:9725251

  14. Inflammatory Mediators of Leprosy Reactional Episodes and Dental Infections: A Systematic Review

    PubMed Central

    Cortela, D. C. B.; de Souza Junior, A. L.; Virmond, M. C. L.; Ignotti, E.

    2015-01-01

    Reactional episodes in leprosy are a result of complex interactions between the immune system, Mycobacterium leprae, and predisposing factors, including dental infections. To determine the main inflammatory mediators in the immunopathological process of dental infections and leprosy reactions, we conducted a systematic review of primary literature published between 1996 and 2013. A three-stage literature search was performed (Stage I, “leprosy reactions” and “inflammatory mediators”; Stage II, “dental infections” and “inflammatory mediators”; and Stage III, “leprosy reactions,” “dental infections,” and “inflammatory mediators”). Of the 911 eligible publications, 10 were selected in Stage I, 68 in Stage II, and 1 in Stage III. Of the 27 studied inflammatory mediators, the main proinflammatory mediators were IL-6, IFN-γ, TNF-α, IL-1β, and IL-17; the main anti-inflammatory mediators were IL-10 and IL-4. Serum IL-6 and TNF-α concentrations were significant during periodontal and reactional lesion evolution; IFN-γ and IL-1β were associated with types 1 and 2 reactions and chronic periodontal disease. The proinflammatory mediators in dental infections and leprosy reactions, especially IL-6 and TNF-α, were similar across studies, regardless of the laboratory technique and sample type. IFN-γ and IL-1β were significant for leprosy reactions and periodontal diseases. This pattern was maintained in serum. PMID:26339136

  15. Human milk anti-inflammatory component contents during acute mastitis.

    PubMed

    Buescher, E S; Hair, P S

    2001-06-15

    Mastitis is a common complication of human lactation. We examined milk specimens from eight women with clinical mastitis to determine their content of anti-inflammatory components. Antioxidant activity (spontaneous cytochrome c reducing activity), selected pro-inflammatory cytokines (IL-6, IL-1beta), selected endogenous cytokine control molecules (sIL-6R, sIL-1RII, and sTNFRI), lactoferrin, Na(+):K(+) ratios, and milk bioactivities that cause shedding of sIL-1RII from human polymorphonuclear leukocytes (PMN), suppress PMN aggregation, and suppress PMN adherence responses were not increased compared to normal milks. Neither the bioactivities that deplete PMN intracellular Ca(2+) stores nor those that block Ca(2+) influx into fMLP-stimulated PMN were significantly increased in mastitis milks. In contrast, levels of TNFalpha, sTNFRII, and IL-1RA and bioactivities that cause shedding of sTNFRI from human PMN were significantly increased compared to normal milks. Mastitis milk has the same anti-inflammatory components and characteristics of normal milk, with elevations in selected components/activities that may help protect the nursing infant from developing clinical illness due to feeding on mastitis milk. PMID:11520075

  16. Dexmedetomidine attenuates inflammatory reaction in the lung tissues of septic mice by activating cholinergic anti-inflammatory pathway.

    PubMed

    Liu, Zhaoguo; Wang, Yueping; Wang, Yaoqi; Ning, Qiaoqing; Zhang, Yong; Gong, Chunzhi; Zhao, Wenxiang; Jing, Guangjian; Wang, Qianqian

    2016-06-01

    Dexmedetomidine (Dex) is a highly selective α2-adrenergic receptor agonist that is widely used for sedation in intensive care units and in clinical anesthesia. Dex has also been shown to possess anti-inflammatory benefits. However, the underlying mechanism by which Dex relieves the inflammatory reaction in the lung tissues of septic mice has not been fully elucidated. In this study, we aimed to evaluate the protective effects and possible mechanism of Dex on the sepsis-induced lung inflammatory response in mice. Sepsis was induced in mice models through the intraperitoneal injection of lipopolysaccharide (LPS). The preemptive administration of Dex substantially abated sepsis-induced pulmonary edema, pulmonary histopathological changes, and NF-κB p65 activity. The production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) at both the mRNA and protein levels was also reduced. Moreover, these effects were significantly blocked by the α7 nicotinic acetylcholine receptor (α7nAChR) antagonist α-bungarotoxin (α-Bgt). α-Bgt aggravated pulmonary edema and pulmonary histopathological changes, as well as increased NF-κB p65 activity and TNF-α and IL-6 expression at both the mRNA and protein levels. The overall results demonstrate that Dex inhibits the LPS-induced inflammatory reaction in the lung tissues of septic mice partly through the α7nAChR-dependent cholinergic anti-inflammatory pathway. PMID:27074053

  17. Anti-Inflammatory Property of Plantago major Leaf Extract Reduces the Inflammatory Reaction in Experimental Acetaminophen-Induced Liver Injury.

    PubMed

    Hussan, Farida; Mansor, Adila Sofea; Hassan, Siti Nazihahasma; Tengku Nor Effendy Kamaruddin, Tg Nurul Tasnim; Budin, Siti Balkis; Othman, Faizah

    2015-01-01

    Hepatic injury induces inflammatory process and cell necrosis. Plantago major is traditionally used for various diseases. This study aimed to determine the anti-inflammatory property of P. major leaf extracts on inflammatory reaction following acetaminophen (APAP) hepatotoxicity. Thirty male Sprague-Dawley rats were divided into 5 groups, namely, normal control (C), APAP, aqueous (APAP + AQ), methanol (APAP + MT), and ethanol (APAP + ET) extract treated groups. All APAP groups received oral APAP (2 g/kg) at day 0. Then, 1000 mg/kg dose of P. major extracts was given for six days. The levels of liver transaminases were measured at day 1 and day 7 after APAP induction. At day 7, the blood and liver tissue were collected to determine plasma cytokines and tissue 11β-HSD type 1 enzyme. The in vitro anti-inflammatory activities of methanol, ethanol, and aqueous extracts were 26.74 ± 1.6%, 21.69 ± 2.81%, and 12.23 ± 3.15%, respectively. The ALT and AST levels were significantly higher in the APAP groups at day 1 whereas the enzyme levels of all groups showed no significant difference at day 7. The extracts treatment significantly reduced the proinflammatory cytokine levels and significantly increased the 11β-HSD type 1 enzyme activity (p < 0.05). In conclusion, the P. major extracts attenuate the inflammatory reaction following APAP-induced liver injury. PMID:26300946

  18. Recognition, Investigation and Management of Acute Transfusion Reactions

    PubMed Central

    Al-Riyami, Arwa Z.; Al-Hashmi, Sabria; Al-Arimi, Zainab; Wadsworth, Louis D.; Al-Rawas, Abdulhakim; Al-Khabori, Murtadha; Daar, Shahina

    2014-01-01

    The recognition and management of transfusion reactions (TRs) are critical to ensure patient safety during and after a blood transfusion. Transfusion reactions are classified into acute transfusion reactions (ATRs) or delayed transfusion reactions, and each category includes different subtypes. Different ATRs share common signs and symptoms which can make categorisation difficult at the beginning of the reaction. Moreover, TRs are often under-recognised and under-reported. To ensure uniform practice and safety, it is necessary to implement a national haemovigilance system and a set of national guidelines establishing policies for blood transfusion and for the detection and management of TRs. In Oman, there are currently no local TR guidelines to guide physicians and hospital blood banks. This paper summarises the available literature and provides consensus guidelines to be used in the recognition, management and reporting of ATRs. PMID:25097764

  19. Administration of Reconstituted Polyphenol Oil Bodies Efficiently Suppresses Dendritic Cell Inflammatory Pathways and Acute Intestinal Inflammation

    PubMed Central

    Cavalcanti, Elisabetta; Vadrucci, Elisa; Delvecchio, Francesca Romana; Addabbo, Francesco; Bettini, Simona; Liou, Rachel; Monsurrò, Vladia; Huang, Alex Yee-Chen; Pizarro, Theresa Torres

    2014-01-01

    Polyphenols are natural compounds capable of interfering with the inflammatory pathways of several in vitro model systems. In this study, we developed a stable and effective strategy to administer polyphenols to treat in vivo models of acute intestinal inflammation. The in vitro suppressive properties of several polyphenols were first tested and compared for dendritic cells (DCs) production of inflammatory cytokines. A combination of the polyphenols, quercetin and piperine, were then encapsulated into reconstituted oil bodies (OBs) in order to increase their stability. Our results showed that administration of low dose reconstituted polyphenol OBs inhibited LPS-mediated inflammatory cytokine secretion, including IL-6, IL-23, and IL-12, while increasing IL-10 and IL-1Rα production. Mice treated with the polyphenol-containing reconstituted OBs (ROBs) were partially protected from dextran sodium sulfate (DSS)-induced colitis and associated weight loss, while mortality and inflammatory scores revealed an overall anti-inflammatory effect that was likely mediated by impaired DC immune responses. Our study indicates that the administration of reconstituted quercetin and piperine-containing OBs may represent an effective and potent anti-inflammatory strategy to treat acute intestinal inflammation. PMID:24558444

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

    PubMed Central

    2010-01-01

    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. PMID:20109187

  1. Inflammatory reaction as an occlusive mechanism in aortocoronary bypass grafts?

    PubMed

    Svendsen, E; Dalen, H; Moland, J; Engedal, H

    1986-01-01

    Morphological changes in aortocoronary vein grafts are described in two cases; one dying 5 hours post operatively and the other reoperated 8 months after aortocoronary bypass surgery for graft occlusion. Occlusive thrombi and fibrin deposition on the intimal surface and a focal inflammatory process in the wall of the vein grafts were found in the former. Thrombotic encrustation and organization similar to the manifestations of the thrombogenic theory of atherosclerosis were demonstrated in the latter. PMID:3489720

  2. The effects of levan on the acute inflammatory response.

    PubMed Central

    Sedgwick, A. D.; Rutman, A.; Sin, Y. M.; Mackay, A. R.; Willoughby, D. A.

    1984-01-01

    The fructose polymer levan has been shown to affect the accumulation of leucocytes in inflammatory lesions. The present study has investigated the effect of levan on experimental pleurisy induced by carrageenan and calcium pyrophosphate dihydrate (CPPD) crystals. Total pleural polymorphonuclear leucocyte counts and exudate volumes were significantly reduced by levan treatment. We were, however, unable to detect any effect on mononuclear cell numbers. Furthermore, levan treatment significantly reduced peripheral leucocyte numbers. The counter-irritant activity of levan was compared with that of a known counter-irritant, dextran. The ability of levan to reduce pleural polymorph numbers and exudate volume could not be accounted for totally by counter-irritation. Studies using an in-vitro leucocyte adhesion assay system indicate that levan affects leucocyte adhesion to vascular endothelium. PMID:6201184

  3. 5-Aminolevulinic acid regulates the inflammatory response and alloimmune reaction.

    PubMed

    Fujino, Masayuki; Nishio, Yoshiaki; Ito, Hidenori; Tanaka, Tohru; Li, Xiao-Kang

    2016-08-01

    5-Aminolevulinic acid (5-ALA) is a naturally occurring amino acid and precursor of heme and protoporphyrin IX (PpIX). Exogenously administrated 5-ALA increases the accumulation of PpIX in tumor cells specifically due to the compromised metabolism of 5-ALA to heme in mitochondria. PpIX emits red fluorescence by the irradiation of blue light and the formation of reactive oxygen species and singlet oxygen. Thus, performing a photodynamic diagnosis (PDD) and photodynamic therapy (PDT) using 5-ALA have given rise to a new strategy for tumor diagnosis and therapy. In addition to the field of tumor therapy, 5-ALA has been implicated in the treatment of inflammatory disease, autoimmune disease and transplantation due to the anti-inflammation and immunoregulation properties that are elicited with the expression of heme oxygenase (HO)-1, an inducible enzyme that catalyzes the rate-limiting step in the oxidative degradation of heme to free iron, biliverdin and carbon monoxide (CO), in combination with sodium ferrous citrate (SFC), because an inhibitor of HO-1 abolishes the effects of 5-ALA. Furthermore, NF-E2-related factor 2 (Nrf2), mitogen-activated protein kinase (MAPK), and heme are involved in the HO-1 expression. Biliverdin and CO are also known to have anti-apoptotic, anti-inflammatory and immunoregulatory functions. We herein review the current use of 5-ALA in inflammatory diseases, transplantation medicine, and tumor therapy. PMID:26643355

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

    SciTech Connect

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

    1983-08-01

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

  5. Acute disseminated encephalomyelitis: Updates on an inflammatory CNS syndrome.

    PubMed

    Pohl, Daniela; Alper, Gulay; Van Haren, Keith; Kornberg, Andrew J; Lucchinetti, Claudia F; Tenembaum, Silvia; Belman, Anita L

    2016-08-30

    Acute disseminated encephalomyelitis (ADEM) is an immune-mediated demyelinating CNS disorder with predilection to early childhood. ADEM is generally considered a monophasic disease. However, recurrent ADEM has been described and defined as multiphasic disseminated encephalomyelitis. ADEM often occurs postinfectiously, although a causal relationship has never been established. ADEM and multiple sclerosis are currently viewed as distinct entities, generally distinguishable even at disease onset. However, pathologic studies have demonstrated transitional cases of yet unclear significance. ADEM is clinically defined by acute polyfocal neurologic deficits including encephalopathy. MRI typically demonstrates reversible, ill-defined white matter lesions of the brain and often also the spinal cord, along with frequent involvement of thalami and basal ganglia. CSF analysis may reveal a mild pleocytosis and elevated protein, but is generally negative for intrathecal oligoclonal immunoglobulin G synthesis. In the absence of a specific diagnostic test, ADEM is considered a diagnosis of exclusion, and ADEM mimics, especially those requiring a different treatment approach, have to be carefully ruled out. The role of biomarkers, including autoantibodies like anti-myelin oligodendrocyte glycoprotein, in the pathogenesis and diagnosis of ADEM is currently under debate. Based on the presumed autoimmune etiology of ADEM, the current treatment approach consists of early immunotherapy. Outcome of ADEM in pediatric patients is generally favorable, but cognitive deficits have been reported even in the absence of other neurologic sequelae. This review summarizes the current knowledge on epidemiology, pathology, clinical presentation, neuroimaging features, CSF findings, differential diagnosis, therapy, and outcome, with a focus on recent advances and controversies. PMID:27572859

  6. Association of inflammatory bowel disease risk loci with sarcoidosis, and its acute and chronic subphenotypes.

    PubMed

    Fischer, A; Nothnagel, M; Franke, A; Jacobs, G; Saadati, H R; Gaede, K I; Rosenstiel, P; Schürmann, M; Müller-Quernheim, J; Schreiber, S; Hofmann, S

    2011-03-01

    Sarcoidosis is a complex granulomatous inflammatory disorder that shares several clinical and pathogenic features with inflammatory bowel disease (IBD). Postulating a common genetic basis of inflammatory diseases, we tested 106 single-nucleotide polymorphisms (SNPs) that are known or have been suggested to be associated with IBD for a potential association with sarcoidosis and its acute and chronic subphenotypes. We genotyped 1,996 German sarcoidosis patients, comprising 648 acutely and 1,161 chronically affected individuals, 2,622 control subjects, and 342 German trios with affected offspring using SNPlex™ technology. The nonsynonymous SNP rs11209026 (Arg381Gln) in the interleukin (IL)-23 receptor (IL23R) gene was associated with chronic sarcoidosis (OR 0.63; p = 5.58×10(-5)), which was supported by the result of a transmission disequilibrium test analysis in the independent family sample (OR 0.50; p = 0.031). Marker rs12035082 located at chromosome 1q24.3 was found to be associated with the acute subphenotype (OR 1.36; p = 6.80×10(-7)) and rs916977 (HERC2 locus; OR 1.30; p = 4.49×10(-5)) was associated with sarcoidosis. Our results highlight the potential importance of the IL-23 signalling pathway for the development of chronic sarcoidosis. The finding links sarcoidosis pathogenesis to other inflammatory conditions and may contribute to new hypotheses on disease mechanisms. PMID:20650992

  7. Hippocampal protection in mice with an attenuated inflammatory monocyte response to acute CNS picornavirus infection

    PubMed Central

    Howe, Charles L.; LaFrance-Corey, Reghann G.; Sundsbak, Rhianna S.; Sauer, Brian M.; LaFrance, Stephanie J.; Buenz, Eric J.; Schmalstieg, William F.

    2012-01-01

    Neuronal injury during acute viral infection of the brain is associated with the development of persistent cognitive deficits and seizures in humans. In C57BL/6 mice acutely infected with the Theiler's murine encephalomyelitis virus, hippocampal CA1 neurons are injured by a rapid innate immune response, resulting in profound memory deficits. In contrast, infected SJL and B6xSJL F1 hybrid mice exhibit essentially complete hippocampal and memory preservation. Analysis of brain-infiltrating leukocytes revealed that SJL mice mount a sharply attenuated inflammatory monocyte response as compared to B6 mice. Bone marrow transplantation experiments isolated the attenuation to the SJL immune system. Adoptive transfer of B6 inflammatory monocytes into acutely infected B6xSJL hosts converted these mice to a hippocampal damage phenotype and induced a cognitive deficit marked by failure to recognize a novel object. These findings show that inflammatory monocytes are the critical cellular mediator of hippocampal injury during acute picornavirus infection of the brain. PMID:22848791

  8. Characterization of Inflammatory Response in Acute-on-Chronic Liver Failure and Relationship with Prognosis

    PubMed Central

    Solé, Cristina; Solà, Elsa; Morales-Ruiz, Manuel; Fernàndez, Guerau; Huelin, Patricia; Graupera, Isabel; Moreira, Rebeca; de Prada, Gloria; Ariza, Xavier; Pose, Elisa; Fabrellas, Núria; Kalko, Susana G.; Jiménez, Wladimiro; Ginès, Pere

    2016-01-01

    ACLF is characterized by a systemic inflammatory response, but the cytokines involved in this process have not been well studied. The aim of this study was to characterize the systemic inflammatory response in patients with cirrhosis and ACLF and its relationship with prognosis. Fifty-five patients with cirrhosis, 26 with ACLF, were studied prospectively. Systemic inflammatory response was analyzed by measuring a large array of plasma cytokines by using a multiplex kit. A principal component analysis show noticeable differences between ACLF and decompensated cirrhosis without ACLF. Patients with ACLF had significant abnormal levels of 12 cytokines compared to those without ACLF, including: VCAM-1, VEGF-A, Fractalkine, MIP-1α, Eotaxin, IP-10, RANTES, GM-CSF, IL-1β, IL-2, ICAM-1, and MCP-1. Cytokines showing the most marked relationship with ACLF were VCAM-1 and VEGF-A (AUCROC 0.77; p = 0.001). There was a significant relationship between some of inflammatory mediators and 3-month mortality, particularly VCAM-1, ICAM-1, and GM-CSF (AUCROC>0.7; p < 0.05). Functional Enrichment Analysis showed that inflammatory markers differentially expressed in ACLF patients were enriched in leukocyte migration, particularly monocytes and macrophages, and chemotaxis pathways. In conclusion, ACLF is characterized by a marked inflammatory reaction with activation of mediators of adhesion and migration of leukocytes. The intensity of the inflammatory reaction correlates with prognosis. PMID:27578545

  9. Characterization of Inflammatory Response in Acute-on-Chronic Liver Failure and Relationship with Prognosis.

    PubMed

    Solé, Cristina; Solà, Elsa; Morales-Ruiz, Manuel; Fernàndez, Guerau; Huelin, Patricia; Graupera, Isabel; Moreira, Rebeca; de Prada, Gloria; Ariza, Xavier; Pose, Elisa; Fabrellas, Núria; Kalko, Susana G; Jiménez, Wladimiro; Ginès, Pere

    2016-01-01

    ACLF is characterized by a systemic inflammatory response, but the cytokines involved in this process have not been well studied. The aim of this study was to characterize the systemic inflammatory response in patients with cirrhosis and ACLF and its relationship with prognosis. Fifty-five patients with cirrhosis, 26 with ACLF, were studied prospectively. Systemic inflammatory response was analyzed by measuring a large array of plasma cytokines by using a multiplex kit. A principal component analysis show noticeable differences between ACLF and decompensated cirrhosis without ACLF. Patients with ACLF had significant abnormal levels of 12 cytokines compared to those without ACLF, including: VCAM-1, VEGF-A, Fractalkine, MIP-1α, Eotaxin, IP-10, RANTES, GM-CSF, IL-1β, IL-2, ICAM-1, and MCP-1. Cytokines showing the most marked relationship with ACLF were VCAM-1 and VEGF-A (AUCROC 0.77; p = 0.001). There was a significant relationship between some of inflammatory mediators and 3-month mortality, particularly VCAM-1, ICAM-1, and GM-CSF (AUCROC>0.7; p < 0.05). Functional Enrichment Analysis showed that inflammatory markers differentially expressed in ACLF patients were enriched in leukocyte migration, particularly monocytes and macrophages, and chemotaxis pathways. In conclusion, ACLF is characterized by a marked inflammatory reaction with activation of mediators of adhesion and migration of leukocytes. The intensity of the inflammatory reaction correlates with prognosis. PMID:27578545

  10. Bcr and Abr Cooperate in Negatively Regulating Acute Inflammatory Responses▿

    PubMed Central

    Cunnick, Jess M.; Schmidhuber, Sabine; Chen, Gang; Yu, Min; Yi, Sun-Ju; Cho, Young Jin; Kaartinen, Vesa; Minoo, Parviz; Warburton, David; Groffen, John; Heisterkamp, Nora

    2009-01-01

    Bcr and Abr are GTPase-activating proteins for the small GTPase Rac. Both proteins are expressed in cells of the innate immune system, including neutrophils and macrophages. The function of Bcr has been linked to the negative regulation of neutrophil reactive oxygen species (ROS) production, but the function of Abr in the innate immune system was unknown. Here, we report that mice lacking both proteins are severely affected in two models of experimental endotoxemia, including exposure to Escherichia coli lipopolysaccharide and polymicrobial sepsis, with extensive microvascular leakage, resulting in severe pulmonary edema and hemorrhage. Additionally, in vivo-activated neutrophils of abr and bcr null mutant mice produced excessive tissue-damaging myeloperoxidase (MPO), elastase, and ROS. Moreover, the secretion of the tissue metalloproteinase MMP9 by monocytes and ROS by elicited macrophages was abnormally high. In comparison, ROS production from bone marrow monocytes was not significantly different from that of controls, and the exocytosis of neutrophil secondary and tertiary granule products, including lactoferrin, was normal. These data show that Abr and Bcr normally curb very specific functions of mature tissue innate immune cells, and that each protein has distinct as well as partly overlapping functions in the downregulation of inflammatory processes. PMID:19703997

  11. Acute inflammatory response in spinal cord following impact injury.

    PubMed

    Carlson, S L; Parrish, M E; Springer, J E; Doty, K; Dossett, L

    1998-05-01

    Numerous factors are involved in the spread of secondary damage in spinal cord after traumatic injury, including ischemia, edema, increased excitatory amino acids, and oxidative damage to the tissue from reactive oxygen species. Neutrophils and macrophages can produce reactive oxygen species when activated and thus may contribute to the lipid peroxidation that is known to occur after spinal cord injury. This study examined the rostral-caudal distribution of neutrophils and macrophages/microglia at 4, 6, 24, and 48 h after contusion injury to the T10 spinal cord of rat (10 g weight, 50 mm drop). Neutrophils were located predominantly in necrotic regions, with a time course that peaked at 24 h as measured with assays of myeloperoxidase activity (MPO). The sharpest peak of MPO activity was localized between 4 mm rostral and caudal to the injury. Macrophages/microglia were visualized with antibodies against ED1 and OX-42. Numerous cells with a phagocytic morphology were present by 24 h, with a higher number by 48 h. These cells were predominantly located within the gray matter and dorsal funiculus white matter. The number of cells gradually declined through 6 mm rostral and caudal to the lesion. OX-42 staining also revealed reactive microglia with blunt processes, particularly at levels distant to the lesion. The number of macrophages/microglia was significantly correlated with the amount of tissue damage at each level. Treatments to decrease the inflammatory response are likely to be beneficial to recovery of function after traumatic spinal cord injury. PMID:9582256

  12. Acute Inflammatory Responses of Nanoparticles in an Intra-Tracheal Instillation Rat Model

    PubMed Central

    Armstead, Andrea L.; Minarchick, Valerie C.; Porter, Dale W.; Nurkiewicz, Timothy R.; Li, Bingyun

    2015-01-01

    Exposure to hard metal tungsten carbide cobalt (WC-Co) “dusts” in enclosed industrial environments is known to contribute to the development of hard metal lung disease and an increased risk for lung cancer. Currently, the influence of local and systemic inflammation on disease progression following WC-Co exposure remains unclear. To better understand the relationship between WC-Co nanoparticle (NP) exposure and its resultant effects, the acute local pulmonary and systemic inflammatory responses caused by WC-Co NPs were explored using an intra-tracheal instillation (IT) model and compared to those of CeO2 (another occupational hazard) NP exposure. Sprague-Dawley rats were given an IT dose (0-500 μg per rat) of WC-Co or CeO2 NPs. Following 24-hr exposure, broncho-alveolar lavage fluid and whole blood were collected and analyzed. A consistent lack of acute local pulmonary inflammation was observed in terms of the broncho-alveolar lavage fluid parameters examined (i.e. LDH, albumin, and macrophage activation) in animals exposed to WC-Co NP; however, significant acute pulmonary inflammation was observed in the CeO2 NP group. The lack of acute inflammation following WC-Co NP exposure contrasts with earlier in vivo reports regarding WC-Co toxicity in rats, illuminating the critical role of NP dose and exposure time and bringing into question the potential role of impurities in particle samples. Further, we demonstrated that WC-Co NP exposure does not induce acute systemic effects since no significant increase in circulating inflammatory cytokines were observed. Taken together, the results of this in vivo study illustrate the distinct differences in acute local pulmonary and systemic inflammatory responses to NPs composed of WC-Co and CeO2; therefore, it is important that the outcomes of pulmonary exposure to one type of NPs may not be implicitly extrapolated to other types of NPs. PMID:25738830

  13. Acute inflammatory responses of nanoparticles in an intra-tracheal instillation rat model.

    PubMed

    Armstead, Andrea L; Minarchick, Valerie C; Porter, Dale W; Nurkiewicz, Timothy R; Li, Bingyun

    2015-01-01

    Exposure to hard metal tungsten carbide cobalt (WC-Co) "dusts" in enclosed industrial environments is known to contribute to the development of hard metal lung disease and an increased risk for lung cancer. Currently, the influence of local and systemic inflammation on disease progression following WC-Co exposure remains unclear. To better understand the relationship between WC-Co nanoparticle (NP) exposure and its resultant effects, the acute local pulmonary and systemic inflammatory responses caused by WC-Co NPs were explored using an intra-tracheal instillation (IT) model and compared to those of CeO2 (another occupational hazard) NP exposure. Sprague-Dawley rats were given an IT dose (0-500 μg per rat) of WC-Co or CeO2 NPs. Following 24-hr exposure, broncho-alveolar lavage fluid and whole blood were collected and analyzed. A consistent lack of acute local pulmonary inflammation was observed in terms of the broncho-alveolar lavage fluid parameters examined (i.e. LDH, albumin, and macrophage activation) in animals exposed to WC-Co NP; however, significant acute pulmonary inflammation was observed in the CeO2 NP group. The lack of acute inflammation following WC-Co NP exposure contrasts with earlier in vivo reports regarding WC-Co toxicity in rats, illuminating the critical role of NP dose and exposure time and bringing into question the potential role of impurities in particle samples. Further, we demonstrated that WC-Co NP exposure does not induce acute systemic effects since no significant increase in circulating inflammatory cytokines were observed. Taken together, the results of this in vivo study illustrate the distinct differences in acute local pulmonary and systemic inflammatory responses to NPs composed of WC-Co and CeO2; therefore, it is important that the outcomes of pulmonary exposure to one type of NPs may not be implicitly extrapolated to other types of NPs. PMID:25738830

  14. Genetic or Pharmacologic Amplification of Nrf2 Signaling Inhibits Acute Inflammatory Liver Injury in Mice

    PubMed Central

    Osburn, William O.; Yates, Melinda S.; Dolan, Patrick D.; Liby, Karen T.; Sporn, Michael B.; Taguchi, Keiko; Yamamoto, Masayuki; Kensler, Thomas W.

    2008-01-01

    Oxidative stress-mediated destruction of normal parenchymal cells during hepatic inflammatory responses contributes to the pathogenesis of immune-mediated hepatitis and is implicated in the progression of acute inflammatory liver injury to chronic inflammatory liver disease. The transcription factor NF-E2-related factor 2 (Nrf2) regulates the expression of a battery of antioxidative enzymes and Nrf2 signaling can be activated by small-molecule drugs that disrupt Keap1-mediated repression of Nrf2 signaling. Therefore, genetic and pharmacologic approaches were used to activate Nrf2 signaling to assess protection against inflammatory liver injury. Profound increases in ind of cell death were observed in both Nrf2 wild-type (Nrf2-WT) mice and Nrf2-disrupted (Nrf2-KO) mice 24-hr following intravenous injection of concanavalin A (12.5 mg/kg, ConA), a model for T cell-mediated acute inflammatory liver injury. However, hepatocyte-specific conditional Keap1 null (Alb-Cre:Keap1flox/−, cKeap1-KO) mice with constitutively enhanced expression of Nrf2-regulated antioxidative genes as well as Nrf2-WT mice but not Nrf2-KO mice pretreated with three daily doses of a triterpenoid that potently activates Nrf2 (30 µmole/kg, CDDO-Im) were highly resistant to ConA-mediated inflammatory liver injury. CDDO-Im pretreatment of both Nrf2-WT and Nrf2-KO mice resulted in equivalent suppression of serum pro-inflammatory soluble proteins suggesting that the hepatoprotection afforded by CDDO-Im pretreatment of Nrf2-WT mice but not Nrf2-KO mice was not due to suppression of systemic pro-inflammatory signaling, but instead was due to activation of Nrf2 signaling in the liver. Enhanced hepatic expression of Nrf2-regulated antioxidative genes inhibited inflammation-mediated oxidative stress, thereby preventing hepatocyte necrosis. Attenuation of hepatocyte death in cKeap1-KO mice and CDDO-Im pretreated Nrf2-WT mice resulted in decreased late-phase pro-inflammatory gene expression in the liver

  15. Acute contrast reaction management by radiologists: a local audit study.

    PubMed

    Bartlett, Murray J; Bynevelt, Michael

    2003-12-01

    Consultant radiologists and trainees must possess knowledge of optimal acute management of anaphylactic/anaphylactoid contrast reactions because patient survival depends upon prompt initial management. The aim of the present study is to assess the knowledge of first-line management of these reactions among radiologists. Within one working day, and without prior knowledge, radiology consultants and trainees within four teaching hospitals in a major Australian capital city were asked to complete a confidential questionnaire regarding acute resuscitation management. Scenarios were presented of an adult who developed life-threatening symptoms of anaphylaxis immediately after intravenous contrast administration, ventricular fibrillation and profound bradycardia. Questions were asked with regards to adrenaline, corticosteroid, antihistamines, intravenous volume expansion, cardio-pulmonary rescuscitation and knowledge of the emergency telephone number. Sites were assessed for presence of an anaphylaxis management chart and also when each participant last completed a resuscitation course. Forty-two participants were recruited. Overall, 53% of questions were answered correctly. Only 43% knew the adrenaline dose and if an incorrect dose was administered it was more likely to be an overdose. Notable inadequacies were also discovered with corticosteroid, atropine, antihistamine doses and intravenous fluid use. Only 26% had completed a resuscitation course in the past 2 years. Forty-five percent knew the emergency telephone number and 55% of rooms using intravenous contrast contained an immediately visible chart for contrast reaction management. Radiologist and trainee knowledge of immediate life-threatening contrast reaction management is deficient. Severe contrast reactions are uncommon with today's use of non-ionic contrast, but they still occur. Experience in the management of anaphylaxis can only come from regular, compulsory training. PMID:14641186

  16. Reduction of the systemic inflammatory induced by acute cerebral infarction through ultra-early thrombolytic therapy

    PubMed Central

    YE, LICHAO; CAI, RUOWEI; YANG, MEILI; QIAN, JIAQIANG; HONG, ZHILIN

    2015-01-01

    Acute ischemic stroke induces systemic inflammation, exhibited as changes in body temperature, white blood cell counts and C-reactive protein (CRP) levels. The aim of the present study was to observe the effects of intravenous thrombolytic therapy on inflammatory indices in order to investigate the hypothesis that post-stroke systemic inflammatory response occurs in response to the necrosis of brain tissues. In this study, 62 patients with acute cerebral infarction and indications for intravenous thrombolysis were divided into three groups on the basis of their treatment and response: Successful thrombolysis (n=36), failed thrombolysis (n=12) and control (n=14) groups. The body temperature, white blood cell counts and high-sensitivity (hs)-CRP levels were recorded pre-treatment and on post-stroke days 1, 3, 5 and 7. Spearman's correlation analysis showed that the pre-treatment National Institutes of Health Stroke Scale (NIHSS) score positively correlated with body temperature, white blood cell count and hs-CRP levels. On day 3 of effective intravenous thrombolysis, the body temperature and white blood cell were decreased and on days 3 and 5, the serum levels of hs-CRP were reduced compared with those in the failed thrombolysis and control groups. The results indicate that the systemic inflammatory response following acute cerebral infarction was mainly caused by ischemic injury of local brain tissue; the more serious the stroke, the stronger the inflammatory response. Ultra-early thrombolytic therapy may inhibit the necrosis of brain tissue and thereby reduce the inflammatory response. PMID:26622513

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

    PubMed Central

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

    2015-01-01

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

  18. Sexual dimorphism of stress response and immune/ inflammatory reaction: the corticotropin releasing hormone perspective

    PubMed Central

    Vamvakopoulos, Nicholas V.

    1995-01-01

    This review higlghts key aspects of corticotropin releasing hormone (CRH) biology of potential relevance to the sexual dimorphism of the stress response and immune/inflammatory reaction, and introduces two important new concepts based on the regulatory potential of the human (h) CRH gene: (1) a proposed mechanism to account for the tissue-specific antithetical responses of hCRH gene expression to glucocorticolds, that may also explain the frequently observed antithetical effects of chronic glucocorticoid administration in clinical practice and (2) a heuristic diagram to illustrate the proposed modulation of the stress response and immune/ inflammatory reaction by steroid hormones, from the perspective of the CRH system. PMID:18475634

  19. Changes of hepatic lactoferrin gene expression in two mouse models of the acute phase reaction.

    PubMed

    Ahmad, Ghayyor; Sial, Gull Zareen Khan; Ramadori, Pierluigi; Dudas, Jozsef; Batusic, Danko S; Ramadori, Giuliano

    2011-12-01

    Lactoferrin (Ltf), an iron binding glycoprotein, is a pleiotropic molecule whose serum concentration increases under acute phase conditions. The physiological roles of this protein have been well elucidated, but the source and serum regulation of Ltf gene expression have not been investigated in detail as part of the acute phase reaction (APR). In the current work, the changes in hepatic Ltf-gene-expression during turpentine oil- (TO-) or LPS-induced APR were investigated. Ltf was upregulated at both the mRNA and protein levels in the liver of TO- and LPS-treated wild type (WT) mice. The pattern of induction however was different in both animal models indicating distinctive signalling patterns resulting in an acute phase reaction. Cytokines are the core regulators of APR. Among the major cytokines, IL-6 is an important signalling molecule, which also regulates iron homeostasis in response to an inflammatory situation. In this study, the administration of IL-6 induced Ltf gene expression in the liver of WT mice, in murine hepatocytes and in hepa 1-6 cells. Ltf-gene-expression was upregulated also in the liver of TO- and LPS-treated IL-6 knockout (KO) mice. The increase in serum Ltf after LPS injection was greater than after TO-injection both in WT and IL-6-KO mice. To evaluate the contribution of other acute phase cytokines in the regulation of Ltf-gene-expression in the liver, both in vitro and in vivo studies with IL-1β, TNF-α, or IFN-γ were performed. The results demonstrate that TNF-α and IFN-γ also upregulated Ltf-gene-expression, while IL-1β has no role in the regulation of Ltf-gene-expression. PMID:21963450

  20. Effect of IMOD™ on the inflammatory process after acute ischemic stroke: a randomized clinical trial

    PubMed Central

    2013-01-01

    Background and purpose of the study Considering the role of inflammation in acute cerebrovascular accidents, anti-inflammatory treatment has been considered as an option in cerebrovascular diseases. Regarding the properties of Setarud (IMOD™) in immune regulation, the aim of the present study was to evaluate the role of this medication in treating patients with acute ischemic stroke. Methods In this randomized clinical trial, 99 patients with their first ever acute ischemic stroke were divided into two groups of IMOD™ (n = 49) and control (n = 50). The control group underwent routine treatment and the intervention group underwent routine treatment plus daily intermittent infusion of IMOD™ (250mg on the first day and then 375mg into DW5% serum during a 30-minute period for 7 days). The serum levels of inflammatory markers were evaluated on the first day (baseline) and on 4th and 7th days. Data were analyzed and the results were compared. Results and major conclusion 58 males (58.6%) and 41 females (41.4%) with a mean age of 67.00 ± 8.82 years, who had their first ever stroke attack, were enrolled in this trial. Treatment with IMOD™ showed a decreasing trend in IL-6 levels compared to the control group (p = 0.04). In addition, the treatment resulted in the control of increasing serum levels of hsCRP after 7 days compared to the control group (p = 0.02). There was an insignificant decrease in TNF-α and IL-1 levels in the IMOD™ group. Considering the prominent role of inflammation after an ischemic cerebral damage, it appears that treatment with IMOD™ improves the inflammatory profile. Therefore, IMOD™ (Setarud) might be considered as a therapeutic option in the acute ischemic stroke. However, future studies are necessary on its long-term results and clinical efficacy. PMID:23514014

  1. Early Identification of Acute Hemolytic Transfusion Reactions: Realistic Implications for Best Practice in Patient Monitoring.

    PubMed

    Menendez, Juliet Battard; Edwards, Barbara

    2016-01-01

    Acute hemolytic transfusion reactions can result in severe complications and death. Through early identification and prompt intervention, nurses can reduce the risks associated with these serious reactions. Realistic evidence-based patient monitoring protocols can help guide identification of acute hemolytic transfusion reactions and facilitate lifesaving interventions to avert critical patient situations. PMID:27323466

  2. IL-6 promotes acute and chronic inflammatory disease in the absence of SOCS3

    PubMed Central

    Croker, Ben A; Kiu, Hiu; Pellegrini, Marc; Toe, Jesse; Preston, Simon; Metcalf, Donald; O’Donnell, Joanne A; Cengia, Louise H; McArthur, Kate; Nicola, Nicos A; Alexander, Warren S; Roberts, Andrew W

    2011-01-01

    The lack of expression of the Suppressor of Cytokine Signalling-3 (SOCS3) or inactivation of the negative regulatory capacity of SOCS3 has been well documented in rheumatoid arthritis, viral hepatitis and cancer. The specific qualitative and quantitative consequences of SOCS3-deficiency on IL-6-mediated pro- and anti-inflammatory responses remain controversial in vitro and unknown in vivo. Mice with a conditional deletion of SOCS3 in hematopoietic cells develop lethal inflammatory disease during adult life and develop gross histopathological changes during experimental arthritis, typified by elevated IL-6 levels. To clarify the nature of the IL-6 responses in vivo, we generated mice deficient in SOCS3 (SOCS3−/Δvav) or both SOCS3 and IL-6 (IL-6−/−/SOCS3−/Δ vav) and examined responses in models of acute and chronic inflammation. Acute responses to IL-1β were lethal to SOCS3−/Δ vav mice but not IL-6−/−/SOCS3−/Δ vav mice, indicating that IL-6 was required for the lethal inflammation induced by IL-1β. Administration of IL-1β to SOCS3−/Δ vav mice induced systemic apoptosis of lymphocytes in the thymus, spleen and lymph nodes that was dependent on the presence of IL-6. IL-6-deficiency prolonged survival of SOCS3−/Δ vav mice and ameliorated spontaneous inflammatory disease developing during adult life. Infection of SOCS3−/Δ vav mice with LCMV induced a lethal inflammatory response that was dependent on IL-6, despite SOCS3−/Δ vav mice controlling viral replication. We conclude that SOCS3 is required for survival during inflammatory responses and is a critical regulator of IL-6 in vivo. PMID:21519345

  3. Synthesis, acute toxicity and anti-inflammatory effect of bornyl salicylate, a salicylic acid derivative.

    PubMed

    Vasconcelos, Renata Marcia Costa; Leite, Fagner Carvalho; Leite, Jacqueline Alves; Rodrigues Mascarenhas, Sandra; Rodrigues, Luis Cezar; Piuvezam, Marcia Regina

    2012-12-01

    Bornyl salicylate (BS) is a salicylic derivative, obtained by sterification of salicylic acid and monoterpene (-)-borneol, and its topical use in inflammatory diseases was described in the early 20th century. It is also known that borneol presents neuroprotective, genoprotective and analgesic properties. The purpose of this study was to evaluate BS in experimental models of acute inflammation. The toxicity of BS was analyzed by measuring water and food intake, weight, mortality and weight of main organs. To assess its anti-inflammatory effect, BS-treated mice were challenged with carrageenan, prostaglandin E2 (PGE2), bradikynin (BK) or histamine (HIS)-induced paw edema, zymosan-induced peritonitis and vascular permeability induced by acetic acid. Nitric oxide (NO) production was analyzed in peritoneal macrophage cultures. There was no sign of acute toxicity of BS in male and female mice. Furthermore, treatment with BS was significantly (p < 0.05) effective in reducing paw edema induced by carrageenan in early and late phases; this effect was related to PGE2 and BK, but HIS independent. Neutrophil migration and cytokine release (TNF-α, IL-1β and IL-6) induced by zymosan and fluid leakage induced by acetic acid were also reduced in BS-treated animals. In vitro, BS (10 µg/mL) reduced NO production in LPS-stimulated macrophages. These data suggest that BS has an anti-inflammatory effect, which is related, at least in part, with decrease of mediators as PGE2, NO and pro-inflammatory cytokines. However, further studies should be done to explore its potential as an anti-inflammatory drug. PMID:22712758

  4. Inflammatory reaction following bovine pericardium graft augmentation for posterior vaginal wall defect repair.

    PubMed

    Lazarou, George; Powers, Kenneth; Pena, Carlos; Bruck, Lance; Mikhail, Magdy S

    2005-01-01

    Graft augmentation for repair of recurrent pelvic organ prolapse is commonly used in reconstructive pelvic surgery. The reported complications are mainly late onset. We report a case of early-onset inflammatory reaction following bovine pericardium graft augmentation for posterior vaginal wall defect repair. A 49-year-old presented with a recurrent and symptomatic posterior vaginal wall defect. She underwent an uneventful site-specific repair and bovine graft augmentation. Her early postoperative course was complicated by inflammatory response to the graft presenting as intense pelvic floor spasm and urinary retention. The condition was managed conservatively and resolved subsequently. One year later, the patient continues to be asymptomatic. Transient intense pelvic floor spasm and urinary retention can be the result of inflammatory reaction following graft augmentation with bovine pericardium for posterior vaginal wall defect repair. PMID:15378236

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

    PubMed

    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 < 25) groups, and blood samples were collected for enzyme-linked immunosorbent assay analysis. The acute mental 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. PMID:26511907

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

    PubMed Central

    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. Impairment of T cell development and acute inflammatory response in HIV-1 Tat transgenic mice

    PubMed Central

    Fiume, Giuseppe; Scialdone, Annarita; Albano, Francesco; Rossi, Annalisa; Maria Tuccillo, Franca; Rea, Domenica; Palmieri, Camillo; Caiazzo, Elisabetta; Cicala, Carla; Bellevicine, Claudio; Falcone, Cristina; Vecchio, Eleonora; Pisano, Antonio; Ceglia, Simona; Mimmi, Selena; Iaccino, Enrico; Laurentiis, Annamaria de; Pontoriero, Marilena; Agosti, Valter; Troncone, Giancarlo; Mignogna, Chiara; Palma, Giuseppe; Arra, Claudio; Mallardo, Massimo; Maria Buonaguro, Franco; Scala, Giuseppe; Quinto, Ileana

    2015-01-01

    Immune activation and chronic inflammation are hallmark features of HIV infection causing T-cell depletion and cellular immune dysfunction in AIDS. Here, we addressed the issue whether HIV-1 Tat could affect T cell development and acute inflammatory response by generating a transgenic mouse expressing Tat in lymphoid tissue. Tat-Tg mice showed thymus atrophy and the maturation block from DN4 to DP thymic subpopulations, resulting in CD4+ and CD8+ T cells depletion in peripheral blood. In Tat-positive thymus, we observed the increased p65/NF-κB activity and deregulated expression of cytokines/chemokines and microRNA-181a-1, which are involved in T-lymphopoiesis. Upon LPS intraperitoneal injection, Tat-Tg mice developed an abnormal acute inflammatory response, which was characterized by enhanced lethality and production of inflammatory cytokines. Based on these findings, Tat-Tg mouse could represent an animal model for testing adjunctive therapies of HIV-1-associated inflammation and immune deregulation. PMID:26343909

  8. Impairment of T cell development and acute inflammatory response in HIV-1 Tat transgenic mice.

    PubMed

    Fiume, Giuseppe; Scialdone, Annarita; Albano, Francesco; Rossi, Annalisa; Tuccillo, Franca Maria; Rea, Domenica; Palmieri, Camillo; Caiazzo, Elisabetta; Cicala, Carla; Bellevicine, Claudio; Falcone, Cristina; Vecchio, Eleonora; Pisano, Antonio; Ceglia, Simona; Mimmi, Selena; Iaccino, Enrico; de Laurentiis, Annamaria; Pontoriero, Marilena; Agosti, Valter; Troncone, Giancarlo; Mignogna, Chiara; Palma, Giuseppe; Arra, Claudio; Mallardo, Massimo; Buonaguro, Franco Maria; Scala, Giuseppe; Quinto, Ileana

    2015-01-01

    Immune activation and chronic inflammation are hallmark features of HIV infection causing T-cell depletion and cellular immune dysfunction in AIDS. Here, we addressed the issue whether HIV-1 Tat could affect T cell development and acute inflammatory response by generating a transgenic mouse expressing Tat in lymphoid tissue. Tat-Tg mice showed thymus atrophy and the maturation block from DN4 to DP thymic subpopulations, resulting in CD4(+) and CD8(+) T cells depletion in peripheral blood. In Tat-positive thymus, we observed the increased p65/NF-κB activity and deregulated expression of cytokines/chemokines and microRNA-181a-1, which are involved in T-lymphopoiesis. Upon LPS intraperitoneal injection, Tat-Tg mice developed an abnormal acute inflammatory response, which was characterized by enhanced lethality and production of inflammatory cytokines. Based on these findings, Tat-Tg mouse could represent an animal model for testing adjunctive therapies of HIV-1-associated inflammation and immune deregulation. PMID:26343909

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

    PubMed

    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

  10. Hypersensitivity to Nonsteroidal Anti-inflammatory Drugs in Children and Adolescents: Cross-Intolerance Reactions.

    PubMed

    Blanca-López, N; Cornejo-García, J A; Plaza-Serón, M C; Doña, I; Torres-Jaén, M J; Canto, G; Padilla-España, L; Kidon, M; Perkins, J R; Blanca, M

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are used worldwide and are responsible for several types of drug hypersensitivity reactions (DHRs) in all age groups. The 2 major groups of DHRs to NSAIDs are those induced by immunological mechanisms (selective reactions) and those where inflammatory mediators are released through activation of the prostaglandin-leukotriene pathway without specific immunological recognition (cross-intolerance). In the present review, we focus on cross-intolerance reactions, which are the most frequent DHRs and are becoming a topic of major interest in children and adolescents. Paracetamol and ibuprofen are the drugs that most frequently cause DHRs in children; other NSAIDs are responsible for reactions in adolescents. In vivo and in vitro tests are of limited diagnostic value, with some exceptions for the less common selective reactions. In cross-intolerance, the clinical history and controlled administration are in many instances the only way to establish a diagnosis and look for alternatives. The clinical history is diagnostic when consistent symptoms occur repeatedly after exposure to NSAIDs with different chemical structures. Cutaneous and respiratory symptoms often co-occur in young children. The natural history of these reactions in children is unknown, and some patients can develop tolerance over time. Atopy remains a major risk factor for cross-intolerant reactions. The increasing interest in hypersensitivity to NSAIDs with improvements in patient phenotyping and the information provided by pharmacogenetics will improve our understanding and management of these reactions in the near future. PMID:26310040

  11. Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain

    PubMed Central

    Wang, Xiao-Min; Wu, Tian-Xia; Hamza, May; Ramsay, Edward S.; Wahl, Sharon M.; Dionne, Raymond A.

    2007-01-01

    New insights into the biological properties of cyclooxygenase-2 (COX-2) and its response pathway challenge the hypothesis that COX-2 is simply pro-inflammatory and inhibition of COX-2 solely prevents the development of inflammation and ameliorates inflammatory pain. The present study performed a comprehensive analysis of gene/protein expression induced by a selective inhibitor of COX-2, rofecoxib, compared with a non-selective COX inhibitor, ibuprofen, and placebo in a clinical model of acute inflammatory pain (the surgical extraction of impacted third molars) using microarray analysis followed by quantitative RT-PCR verification and Western blotting. Inhibition of COX-2 modulated gene expression related to inflammation and pain, the arachidonic acid pathway, apoptosis/angiogenesis, cell adhesion and signal transduction. Compared to placebo, rofecoxib treatment increased the gene expression of ANXA3 (annexin 3), SOD2 (superoxide dismutase 2), SOCS3 (suppressor of cytokine signaling 3) and IL1RN (IL1 receptor antagonist) which are associated with inhibition of phospholipase A2 and suppression of cytokine signaling cascades, respectively. Both rofecoxib and ibuprofen treatment increased the gene expression of the pro-inflammatory mediators, IL6 and CCL2 (chemokine C-C motif ligand 2), following tissue injury compared to the placebo treatment. These results indicate a complex role for COX-2 in the inflammatory cascade in addition to the well-characterized COX-dependent pathway, as multiple pathways are also involved in rofecoxib-induced anti-inflammatory and analgesic effects at the gene expression level. These findings may also suggest an alternative hypothesis for the adverse effects attributed to selective inhibition of COX-2. PMID:17070997

  12. Trait Hostility and Acute Inflammatory Responses to Stress in the Laboratory.

    PubMed

    Girard, Dominique; Tardif, Jean-Claude; Boisclair Demarble, Julie; D'Antono, Bianca

    2016-01-01

    Hostility has been associated with higher basal levels of inflammation. The present study evaluated the association of hostility with acute stress-induced changes in inflammatory activity. One hundred and ninety-nine healthy men and women, aged 19-64 years, were exposed to a stress protocol involving four interpersonal stressors. Participants completed the Cook-Medley Hostility questionnaire and provided two blood samples for the measurement of inflammatory biomarkers (CRP, Il-6, MPO, TNF-α, MCP-1, Il-8, Il-10, and Il-18), prior to and following exposure to a standardized stress protocol. In univariate analyses, hostility was associated with significantly higher TNF-α, but lower Il-8 and Il-18 values post-stress, though only Il-8 remained significant after controlling for baseline differences. In multivariate analyses, a significant Age by Hostility interaction emerged for Il-6, while sex moderated the relation between hostility and Il-10 reactivity. Following stress, hostility was associated with greater pro-inflammatory Il-6 activity among younger individuals and to decreased anti-inflammatory Il-10 activity in women. Future research is needed to replicate these findings and to evaluate their implication for disease. PMID:27270459

  13. Trait Hostility and Acute Inflammatory Responses to Stress in the Laboratory

    PubMed Central

    Girard, Dominique; Tardif, Jean-Claude; Boisclair Demarble, Julie; D’Antono, Bianca

    2016-01-01

    Hostility has been associated with higher basal levels of inflammation. The present study evaluated the association of hostility with acute stress-induced changes in inflammatory activity. One hundred and ninety-nine healthy men and women, aged 19–64 years, were exposed to a stress protocol involving four interpersonal stressors. Participants completed the Cook-Medley Hostility questionnaire and provided two blood samples for the measurement of inflammatory biomarkers (CRP, Il-6, MPO, TNF-α, MCP-1, Il-8, Il-10, and Il-18), prior to and following exposure to a standardized stress protocol. In univariate analyses, hostility was associated with significantly higher TNF-α, but lower Il-8 and Il-18 values post-stress, though only Il-8 remained significant after controlling for baseline differences. In multivariate analyses, a significant Age by Hostility interaction emerged for Il-6, while sex moderated the relation between hostility and Il-10 reactivity. Following stress, hostility was associated with greater pro-inflammatory Il-6 activity among younger individuals and to decreased anti-inflammatory Il-10 activity in women. Future research is needed to replicate these findings and to evaluate their implication for disease. PMID:27270459

  14. Temporal expression of pro-inflammatory cytokines and inducible nitric oxide synthase in experimental acute Chagasic cardiomyopathy.

    PubMed Central

    Chandrasekar, B.; Melby, P. C.; Troyer, D. A.; Colston, J. T.; Freeman, G. L.

    1998-01-01

    To characterize the kinetics of myocardial cytokine and inducible nitric oxide synthase (iNOS) expression in acute Chagasic cardiomyopathy, we studied a rat model of acute Trypanosoma cruzi infection. Rats were euthanized 36 hours and 5, 10, and 15 days after infection, and hearts were collected for histology, mRNA, and protein analyses. Histological analysis of myocardium showed a progressive increase in the number of amastigotes and mononuclear inflammatory cells. Organisms were first detected 5 days after intraperitoneal inoculation as isolated nests and became numerous by day 15. Northern blot analysis of total RNA revealed no signal for interleukin (IL)-1beta or tumor necrosis factor (TNF)-alpha and a weak signal for IL-6 in control hearts. High levels of expression for the three genes were detected in the infected animals at 36 hours after infection. Although IL-1beta and IL-6 levels increased steadily up to 10 days, TNF-alpha levels were the highest at 5 days, remained high at 10 days, and declined thereafter. Western blot analysis showed similar results to that of mRNA expression. No signal was detected for iNOS in the controls, but both its mRNA and protein were found in the infected animals, with levels being highest at 15 days after infection. Immunohistochemistry revealed no iNOS immunoreactivity in uninfected animals, but intense iNOS staining was detected in blood vessels of infected animals, which decreased progressively with period of infection. Positive staining for iNOS in cardiomyocytes was first detected at 36 hours after infection (at a time when there was no histological inflammatory reaction), which steadily increased, being the highest at 15 days after infection. These results indicate that, in addition to mechanical damage by T. cruzi, substantial pro-inflammatory cytokine production within the myocardium is likely to participate in the pathophysiology of acute Chagasic cardiomyopathy. Images Figure 1 Figure 3 Figure 5 Figure 6 Figure 7

  15. Relative contribution of contact and complement activation to inflammatory reactions in arthritic joints.

    PubMed Central

    Abbink, J J; Kamp, A M; Nuijens, J H; Erenberg, A J; Swaak, A J; Hack, C E

    1992-01-01

    Although both the complement and contact system are thought to contribute to the inflammatory reaction in arthritic joints, only activation of complement has so far been well established, whereas contact activation and its contribution to arthritis has not been systematically explored. Complement and contact activation were assessed in 71 patients with inflammatory arthropathies and 11 with osteoarthritis using sensitive assays for C3a, and C1-inhibitor (C1INH)-kallikrein and C1INH-factor XIIa complexes respectively. Increased plasma concentrations of kallikrein-and factor XIIa-C1INH complexes were found in two and seven of the 71 patients with inflammatory arthropathies, respectively, and in none of the patients with osteoarthritis. Increased synovial fluid concentrations of kallikrein and factor XIIa complexes occurred in 13 and 15 patients with inflammatory joint diseases respectively, and in two patients with osteoarthritis. Contact system parameters did not correlate with clinical symptoms, local activity, or neutrophil activation. In contrast, synovial fluid concentrations of C3a and C1INH-C1 complexes were increased in all patients and in 20 patients with inflammatory arthropathies respectively, and were higher in patients with a higher local activity score. Synovial fluid C3a correlated with parameters of neutrophil activation such as lactoferrin. Increased plasma concentrations of C3a and C1INH-C1 complexes occurred in 13 and 11 patients with inflammatory joint diseases, and in one and two patients with osteoarthritis respectively. Plasma concentrations of C3a correlated with the number of painful joints. Thus contact activation occurs only sporadically in patients with arthritis and contributes little if anything to the local inflammatory reaction and neutrophil activation. These latter events are significantly related to the extent of complement activation. PMID:1444625

  16. Estimation of the prevalence and rate of acute transfusion reactions occurring in Windhoek, Namibia

    PubMed Central

    Meza, Benjamin P.L.; Lohrke, Britta; Wilkinson, Robert; Pitman, John P.; Shiraishi, Ray W.; Bock, Naomi; Lowrance, David W.; Kuehnert, Matthew J.; Mataranyika, Mary; Basavaraju, Sridhar V.

    2014-01-01

    Background Acute transfusion reactions are probably common in sub-Saharan Africa, but transfusion reaction surveillance systems have not been widely established. In 2008, the Blood Transfusion Service of Namibia implemented a national acute transfusion reaction surveillance system, but substantial under-reporting was suspected. We estimated the actual prevalence and rate of acute transfusion reactions occurring in Windhoek, Namibia. Methods The percentage of transfusion events resulting in a reported acute transfusion reaction was calculated. Actual percentage and rates of acute transfusion reactions per 1,000 transfused units were estimated by reviewing patients’ records from six hospitals, which transfuse >99% of all blood in Windhoek. Patients’ records for 1,162 transfusion events occurring between 1st January – 31st December 2011 were randomly selected. Clinical and demographic information were abstracted and Centers for Disease Control and Prevention National Healthcare Safety Network criteria were applied to categorize acute transfusion reactions1. Results From January 1 – December 31, 2011, there were 3,697 transfusion events (involving 10,338 blood units) in the selected hospitals. Eight (0.2%) acute transfusion reactions were reported to the surveillance system. Of the 1,162 transfusion events selected, medical records for 785 transfusion events were analysed, and 28 acute transfusion reactions were detected, of which only one had also been reported to the surveillance system. An estimated 3.4% (95% confidence interval [CI]: 2.3–4.4) of transfusion events in Windhoek resulted in an acute transfusion reaction, with an estimated rate of 11.5 (95% CI: 7.6–14.5) acute transfusion reactions per 1,000 transfused units. Conclusion The estimated actual rate of acute transfusion reactions is higher than the rate reported to the national haemovigilance system. Improved surveillance and interventions to reduce transfusion-related morbidity and mortality

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

    PubMed

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

    2013-10-01

    Menthol, the cooling natural product of peppermint, is widely used in medicinal preparations for the relief of acute and inflammatory pain in sports injuries, arthritis, and other painful conditions. Menthol induces the sensation of cooling by activating TRPM8, an ion channel in cold-sensitive peripheral sensory neurons. Recent studies identified additional targets of menthol, including the irritant receptor, TRPA1, voltage-gated ion channels and neurotransmitter receptors. It remains unclear which of these targets contribute to menthol-induced analgesia, or to the irritating side effects associated with menthol therapy. Here, we use genetic and pharmacological approaches in mice to probe the role of TRPM8 in analgesia induced by L-menthol, the predominant analgesic menthol isomer in medicinal preparations. L-menthol effectively diminished pain behavior elicited by chemical stimuli (capsaicin, acrolein, acetic acid), noxious heat, and inflammation (complete Freund's adjuvant). Genetic deletion of TRPM8 completely abolished analgesia by L-menthol in all these models, although other analgesics (acetaminophen) remained effective. Loss of L-menthol-induced analgesia was recapitulated in mice treated with a selective TRPM8 inhibitor, AMG2850. Selective activation of TRPM8 with WS-12, a menthol derivative that we characterized as a specific TRPM8 agonist in cultured sensory neurons and in vivo, also induced TRPM8-dependent analgesia of acute and inflammatory pain. L-menthol- and WS-12-induced analgesia was blocked by naloxone, suggesting activation of endogenous opioid-dependent analgesic pathways. Our data show that TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. In contrast to menthol, selective TRPM8 agonists may produce analgesia more effectively, with diminished side effects. PMID:23820004

  18. TRPM8 is the Principal Mediator of Menthol-induced Analgesia of Acute and Inflammatory Pain

    PubMed Central

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

    2013-01-01

    Menthol, the cooling natural product of peppermint, is widely used in medicinal preparations for the relief of acute and inflammatory pain in sports injuries, arthritis and other painful conditions. Menthol induces the sensation of cooling by activating TRPM8, an ion channel in cold-sensitive peripheral sensory neurons. Recent studies identified additional targets of menthol, including the irritant receptor, TRPA1, voltage-gated ion channels and neurotransmitter receptors. It remains unclear which of these targets contribute to menthol-induced analgesia, or to the irritating side effects associated with menthol therapy. Here, we use genetic and pharmacological approaches in mice to probe the role of TRPM8 in analgesia induced by L-menthol, the predominant analgesic menthol isomer in medicinal preparations. L-menthol effectively diminished pain behavior elicited by chemical stimuli (capsaicin, acrolein, acetic acid), noxious heat and inflammation (complete Freund's adjuvant). Genetic deletion of TRPM8 completely abolished analgesia by L-menthol in all these models, while other analgesics (acetaminophen) remained effective. Loss of L-menthol-induced analgesia was recapitulated in mice treated with a selective TRPM8 inhibitor, AMG2850. Selective activation of TRPM8 with WS-12, a menthol derivative we characterized as a specific TRPM8 agonist in cultured sensory neurons and in vivo, also induced TRPM8-dependent analgesia of acute and inflammatory pain. L-menthol and WS-12 induced analgesia was blocked by naloxone, suggesting activation of endogenous opioid-dependent analgesic pathways. Our data show that TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. In contrast to menthol, selective TRPM8 agonists may produce analgesia more effectively with diminished side effects. PMID:23820004

  19. Pain Relief for Acute Urolithiasis: The Case for Non-Steroidal Anti-Inflammatory Drugs.

    PubMed

    Steinberg, Peter L; Chang, Steven L

    2016-07-01

    Pain from renal colic is often severe and incapacitating. Many patients require emergent hospitalization and aggressive analgesia to relieve such discomfort. For many years, the optimal analgesic strategy has been sought to manage such severe pain. One of the mainstays of therapy for acute renal colic is with non-steroidal anti-inflammatory drugs (NSAIDs). This paper reviews the mechanism by which NSAIDs allow pain relief in renal colic, the evidence for their use in this condition, and the use of NSAIDs combined with other agents in renal colic. PMID:27286841

  20. Inflammatory response, neutrophil activation, and free radical production after acute myocardial infarction: effect of thrombolytic treatment.

    PubMed Central

    Bell, D; Jackson, M; Nicoll, J J; Millar, A; Dawes, J; Muir, A L

    1990-01-01

    Activated neutrophils releasing proteolytic enzymes and oxygen free radicals have been implicated in extending myocardial injury after myocardial infarction. Neutrophil elastase was used as a marker of neutrophil activation and the non-peroxide diene conjugate of linoleic acid was used as an indicator of free radical activity in 32 patients after acute myocardial infarction; 17 were treated by intravenous thrombolysis. Patients with acute myocardial infarction had higher plasma concentrations of neutrophil elastase and the non-peroxide diene conjugated isomer of linoleic acid than normal volunteers or patients with stable ischaemic heart disease. Patients treated by thrombolysis had an early peak of neutrophil elastase at eight hours while those who had not been treated by thrombolysis showed a later peak 40 hours after infarction. The plasma concentration of non-peroxide conjugated diene of linoleic acid was highest 16 hours after the infarction irrespective of treatment by thrombolysis. Quantitative imaging with single photon emission tomography showed decreased uptake of indium-111 labelled neutrophils in the infarcted myocardium (as judged from technetium-99m pyrophosphate) in those who had received thrombolysis, suggesting a decreased inflammatory response. The results indicate increased neutrophil activation and free radical production after myocardial infarction; they also suggest that thrombolysis does not amplify the inflammatory response and may indeed suppress it. Images PMID:2317413

  1. ω-3 PUFAs and Resveratrol Differently Modulate Acute and Chronic Inflammatory Processes

    PubMed Central

    Schwager, Joseph; Richard, Nathalie; Riegger, Christoph; Salem, Norman

    2015-01-01

    ω-3 PUFAs and polyphenols have multiple effects on inflammation in vivo and in vitro. The effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and resveratrol (RV) were investigated in LPS-stimulated peripheral blood leukocytes (PBLs) (i.e., acute inflammation) and IL-1β activated human chondrocytes (i.e., chronic inflammation). Inflammatory mediators including chemokines, cytokines, interleukins, and PGE2 were measured by multiplex analysis and gene expression was quantified by RT-PCR. In PBLs, RV decreased the secretion of PGE2, CCL5/RANTES, and CXCL8/IL-8 but increased IL-1β, IL-6, and IL-10. In contrast to RV, ω-3 PUFAs augmented the production of PGE2 and CXCL8/IL-8. EPA and DHA similarly affected the pattern of inflammatory mediators. Combination of RV and ω-3 PUFAs exerted synergistic effects on CCL5/RANTES and had additive effects on IL-6 or CXCL8/IL-8. Both ω-3 PUFAs and RV reduced catabolic gene expression (e.g., MMPs, ADAMTS-4, IL-1β, and IL-6) in activated chondrocytes. The data suggest that ω-3 PUFAs and RV differ in the regulation of acute inflammation of peripheral blood leukocytes but have common properties in modulating features related to chronic inflammation of chondrocytes. PMID:26301248

  2. Urinary 1-hydroxypyrene is associated with oxidative stress and inflammatory biomarkers in acute Myocardial Infarction.

    PubMed

    Freitas, Fernando; Brucker, Natália; Durgante, Juliano; Bubols, Guilherme; Bulcão, Rachel; Moro, Angela; Charão, Mariele; Baierle, Marília; Nascimento, Sabrina; Gauer, Bruna; Sauer, Elisa; Zimmer, Marcelo; Thiesen, Flávia; Castro, Iran; Saldiva, Paulo; Garcia, Solange C

    2014-09-01

    Several studies have associated exposure to environmental pollutants, especially polycyclic aromatic hydrocarbons (PAHs), with the development of cardiovascular diseases. Considering that 1-hydroxypyrene (1-OHP) is the major biomarker of exposure to pyrenes, the purpose of this study was to evaluate the potential association between 1-OHP and oxidative stress/inflammatory biomarkers in patients who had suffered an acute myocardial infarction (AMI). After adopting the exclusion criteria, 58 post-infarction patients and 41 controls were sub-divided into smokers and non-smokers. Urinary 1-OHP, hematological and biochemical parameters, oxidative stress biomarkers (MDA, SOD, CAT, GPx and exogenous antioxidants) and the inflammatory biomarker (hs-CRP) were analyzed. 1-OHP levels were increased in post-infarct patients compared to controls (p < 0.05) and were correlated to MDA (r = 0.426, p < 0.01), CAT (r = 0.474, p < 0.001) and β-carotene (r = -0.309; p < 0.05) in non-smokers. Furthermore, post-infarction patients had elevated hs-CRP, MDA, CAT and GPx levels compared to controls for both smokers and non-smokers. Besides, β-carotene levels and SOD activity were decreased in post-infarction patients. In summary, our findings indicate that the exposure to pyrenes was associated to lipid damage and alterations of endogenous and exogenous antioxidants, demonstrating that PAHs contribute to oxidative stress and are associated to acute myocardial infarction. PMID:25257356

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

    PubMed Central

    Freitas, Fernando; Brucker, Natália; Durgante, Juliano; Bubols, Guilherme; Bulcão, Rachel; Moro, Angela; Charão, Mariele; Baierle, Marília; Nascimento, Sabrina; Gauer, Bruna; Sauer, Elisa; Zimmer, Marcelo; Thiesen, Flávia; Castro, Iran; Saldiva, Paulo; Garcia, Solange C.

    2014-01-01

    Several studies have associated exposure to environmental pollutants, especially polycyclic aromatic hydrocarbons (PAHs), with the development of cardiovascular diseases. Considering that 1-hydroxypyrene (1-OHP) is the major biomarker of exposure to pyrenes, the purpose of this study was to evaluate the potential association between 1-OHP and oxidative stress/inflammatory biomarkers in patients who had suffered an acute myocardial infarction (AMI). After adopting the exclusion criteria, 58 post-infarction patients and 41 controls were sub-divided into smokers and non-smokers. Urinary 1-OHP, hematological and biochemical parameters, oxidative stress biomarkers (MDA, SOD, CAT, GPx and exogenous antioxidants) and the inflammatory biomarker (hs-CRP) were analyzed. 1-OHP levels were increased in post-infarct patients compared to controls (p < 0.05) and were correlated to MDA (r = 0.426, p < 0.01), CAT (r = 0.474, p < 0.001) and β-carotene (r = −0.309; p < 0.05) in non-smokers. Furthermore, post-infarction patients had elevated hs-CRP, MDA, CAT and GPx levels compared to controls for both smokers and non-smokers. Besides, β-carotene levels and SOD activity were decreased in post-infarction patients. In summary, our findings indicate that the exposure to pyrenes was associated to lipid damage and alterations of endogenous and exogenous antioxidants, demonstrating that PAHs contribute to oxidative stress and are associated to acute myocardial infarction. PMID:25257356

  4. Response and habituation of pro and anti inflammatory gene expression to repeated acute stress

    PubMed Central

    McInnis, Christine M.; Wang, Diana; Gianferante, Danielle; Hanlin, Luke; Chen, Xuejie; Thoma, Myriam V.; Rohleder, Nicolas

    2015-01-01

    Introduction Acute stress induces increases in plasma inflammatory mediators, which do not habituate to repeated stress. Inflammation is a risk factor for age-related illnesses, highlighting the need to understand factors controlling inflammation. No studies have examined changes in pro- and anti-inflammatory gene expression in response to repeated acute stress in humans. Methods RNA was isolated from peripheral blood before, 30 and 120 minutes after exposure of n=32 healthy human participants to the Trier Social Stress Test (TSST) on two days. Gene expression of interleukin (IL)-6, IL-1β, nuclear factor (NF)-κB and IκB was measured repeatedly on both days. We further assessed leukocyte numbers, plasma IL-6, and salivary cortisol. Results Stress induced IL-6 (F=44.7; p<0.001) and cortisol responses (F=18.6; p<0.001). Cortisol responses habituated (F=5.1, p=0.003), but IL-6 responses did not (n.s.). All genes increased in response to initial stress (IL-6: F=3.8; p=0.029; IL-1β: F=7.1; p=0.008; NF-κB: F=5.1; p=0.009; IκB; F=4.7; p=0.013) and showed habituation to repeated stress (IL-6: t=2.3; p=0.03; IL-1β: t=3.9; p=0.001; NF-κB: t=2.1; p=0.041; IκB: t=3.1; p=0.005). Day 1 responses of IL-1β and IκB were not explained by changes in leukocyte populations, but IL-6 and NF-κB, as well as most day 2 changes were not independent of leukocyte populations. Conclusions Stress response and habituation of pro- and anti-inflammatory gene expression as found here might indicate that even on an intracellular level, inflammatory responses to acute stress are adaptive in that they respond to initial, but habituate to repeated, similar stress. Future studies will need to test whether non-habituation is predictive of disease. PMID:25683696

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

    PubMed

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

    2016-08-01

    Although the relationship between environmental cold temperature and susceptibility to respiratory infection is generally accepted, the effect of ambient cold temperature on host reactivity in lung inflammation has not been fully studied. To examine the function of ambient cold temperature on lung inflammation, mice were exposed to 4 °C for 8 h each day for 14 days. In the lungs of mice exposed to cold stress, inflammatory cells in bronchoalveolar lavage (BAL) fluid and lung tissues were slightly increased by about twofold. However, the structures of pulmonary epithelial cells were kept within normal limits. Next, we examined the effect of cold stress on the inflammatory responses in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. The infiltration of neutrophils and inflammation of lung tissue determined by histology were significantly increased by exposure to ambient cold temperature. In addition, the production of pro-inflammatory cytokines including interleukin (IL)-12, IL-17, and monokine induced by gamma interferon (MIG) was elevated by exposure to cold stress. Therefore, we suggest that cold stress is a factor that exacerbates lung inflammation including ALI. To our knowledge, this is the first report on the relationship between cold stress and severity of lung inflammation. PMID:26617279

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

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

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

    PubMed Central

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

    2015-01-01

    Vitamin D receptor (VDR) is highly expressed in human and mouse kidneys. Nevertheless, its functions remain obscure. This study investigated the effects of vitamin D3 (VitD3) pretreatment on renal inflammation during lipopolysaccharide (LPS)-induced acute kidney injury. Mice were intraperitoneally injected with LPS. In VitD3 + LPS group, mice were pretreated with VitD3 (25 μg/kg) at 48, 24 and 1 h before LPS injection. As expected, an obvious reduction of renal function and pathological damage was observed in LPS-treated mice. VitD3 pretreatment significantly alleviated LPS-induced reduction of renal function and pathological damage. Moreover, VitD3 pretreatment attenuated LPS-induced renal inflammatory cytokines, chemokines and adhesion molecules. In addition, pretreatment with 1,25(OH)2D3, the active form of VitD3, alleviated LPS-induced up-regulation of inflammatory cytokines and chemokines in human HK-2 cells, a renal tubular epithelial cell line, in a VDR-dependent manner. Further analysis showed that VitD3, which activated renal VDR, specifically repressed LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 subunit in the renal tubules. LPS, which activated renal NF-κB, reciprocally suppressed renal VDR and its target gene. Moreover, VitD3 reinforced the physical interaction between renal VDR and NF-κB p65 subunit. These results provide a mechanistic explanation for VitD3-mediated anti-inflammatory activity during LPS-induced acute kidney injury. PMID:26691774

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

    PubMed

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

    2015-01-01

    Vitamin D receptor (VDR) is highly expressed in human and mouse kidneys. Nevertheless, its functions remain obscure. This study investigated the effects of vitamin D3 (VitD3) pretreatment on renal inflammation during lipopolysaccharide (LPS)-induced acute kidney injury. Mice were intraperitoneally injected with LPS. In VitD3 + LPS group, mice were pretreated with VitD3 (25 μg/kg) at 48, 24 and 1 h before LPS injection. As expected, an obvious reduction of renal function and pathological damage was observed in LPS-treated mice. VitD3 pretreatment significantly alleviated LPS-induced reduction of renal function and pathological damage. Moreover, VitD3 pretreatment attenuated LPS-induced renal inflammatory cytokines, chemokines and adhesion molecules. In addition, pretreatment with 1,25(OH)2D3, the active form of VitD3, alleviated LPS-induced up-regulation of inflammatory cytokines and chemokines in human HK-2 cells, a renal tubular epithelial cell line, in a VDR-dependent manner. Further analysis showed that VitD3, which activated renal VDR, specifically repressed LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 subunit in the renal tubules. LPS, which activated renal NF-κB, reciprocally suppressed renal VDR and its target gene. Moreover, VitD3 reinforced the physical interaction between renal VDR and NF-κB p65 subunit. These results provide a mechanistic explanation for VitD3-mediated anti-inflammatory activity during LPS-induced acute kidney injury. PMID:26691774

  10. Interleukin-1 polymorphisms are associated with the inflammatory response in human muscle to acute resistance exercise

    PubMed Central

    Dennis, Richard A; Trappe, Todd A; Simpson, Pippa; Carroll, Chad; Emma Huang, B; Nagarajan, Radhakrishnan; Bearden, Edward; Gurley, Cathy; Duff, Gordon W; Evans, William J; Kornman, Kenneth; Peterson, Charlotte A

    2004-01-01

    Inflammation appears to play an important role in the repair and regeneration of skeletal muscle after damage. We tested the hypothesis that the severity of the inflammatory response in muscle after an acute bout of resistance exercise is associated with single nucleotide polymorphisms (SNPs) previously shown to alter interleukin-1 (IL-1) activity. Using a double-blind prospective design, sedentary young men were screened (n = 100) for enrolment (n = 24) based upon having 1 of 4 haplotype patterns composed of five polymorphic sites in the IL-1 gene cluster: IL-1A (+4845), IL-1B (+3954), IL-1B (−511), IL-1B (−3737) and IL-1RN (+2018). Subjects performed a standard bout of resistance leg exercise and vastus lateralis biopsies were obtained pre-, and at 24, and 72 h post-exercise. Inflammatory marker mRNAs (IL-1β, IL-6 and tumor necrosis factor-α (TNF-α)) and the number of CD68+ macrophages were quantified. Considerable variation was observed in the expression of these gene products between subjects. At 72 h post-exercise, IL-1β had increased in a number of subjects (n = 10) and decreased (n = 4) or did not change (n = 10) in others. Inflammatory responses were significantly associated with specific haplotype patterns and were also influenced by individual SNPs. Subjects with genotypes 1.1 at IL-1B (+3954) or 2.2 at IL-1B (−3737) had approximately a 2-fold higher median induction of several markers, but no increase in macrophages, suggesting that cytokine gene expression is elevated per macrophage. The IL-1RN (+2018) SNP maximized the response specifically within these groups and was associated with increased macrophage recruitment. This is the first report that IL-1 genotype is associated with the inflammation of skeletal muscle following acute resistance exercise that may potentially affect the adaptations to chronic resistance exercise. PMID:15331687

  11. Evidence that mesothelial cells regulate the acute inflammatory response in talc pleurodesis.

    PubMed

    Marchi, E; Vargas, F S; Acencio, M M; Antonangelo, L; Genofre, E H; Teixeira, L R

    2006-11-01

    Intrapleural instillation of talc is used to produce pleurodesis in cases of recurrent malignant pleural effusions. The mechanisms by which pleurodesis is produced remain unknown but may involve either injury or activation of the mesothelium. The aim of the current study was to assess the inflammatory response of pleural mesothelial cells to talc in an experimental model in rabbits. A group of 10 rabbits were injected intrapleurally with talc (200 mg.kg(-1)) and undiluted pleural fluid was collected after 6, 24 or 48 h for measurement of interleukin (IL)-8, vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-beta1. Samples of pleura were studied to assess the inflammatory infiltrate and mesothelial cell viability. The pleural fluid IL-8 concentration peaked at 6 h, whereas VEGF and TGF-beta1 concentrations increased steadily over 48 h. Immunohistochemistry for cytokeratin showed a preserved layer of mesothelial cells despite the intense inflammatory pleural reaction. In conclusion, it is proposed that the mesothelial cell, although injured by the talc, may actively mediate the primary inflammatory pleural response in talc-induced pleurodesis. PMID:16870666

  12. Rapamycin protects neurons from brain contusion-induced inflammatory reaction via modulation of microglial activation

    PubMed Central

    SONG, QI; XIE, DUJIANG; PAN, SHIYONG; XU, WEIJUN

    2015-01-01

    The inflammatory reaction is important in secondary injury following traumatic brain injury (TBI). Rapamycin has been demonstrated as a neuroprotective agent in a mouse model of TBI, however, there is a lack of data regarding the effects of rapamycin on the inflammatory reaction following TBI. Therefore, the present study was designed to assess the effects of treatment with rapamycin on inflammatory reactions and examine the possible involvement of microglial activation following TBI. Male imprinting control region mice were randomly divided into four groups: Sham group (n=23), TBI group (n=23), TBI + dimethyl sulfoxide (DMSO) group (n=31) and TBI + rapamycin group (n=31). Rapamycin was dissolved in DMSO (50 mg/ml) and injected 30 min after TBI (2 mg/Kg; intraperitoneally). A weight-drop model of TBI was induced, and the brain tissues were harvested 24 h after TBI. The findings indicated that the administration of rapamycin following TBI was associated with decreased levels of activated microglia and neuron degeneration at the peri-injury site, reduced levels of proinflammatory cytokines and increased neurobehavioral function, possibly mediated by inactivation of the mammalian target of rapamycin pathway. The results of the present study offer novel insight into the mechanisms responsible for the anti-neuroinflammatory effects of rapamycin, possibly involving the modulation of microglial activation. PMID:26458361

  13. Inflammatory biomarkers predicting prognosis in patients with acute dyspnea☆☆☆★

    PubMed Central

    Wiklund, Karolin; Gränsbo, Klas; Lund, Nathalie; Peyman, Marjaneh; Tegner, Lena; Toni-Bengtsson, Maria; Wieloch, Mattias; Melander, Olle

    2016-01-01

    Objective/Purpose The objective was to identify inflammatory biomarkers that predict risk of 90-day mortality in patients with acute dyspnea. Method We analyzed 25 inflammatory biomarkers, in plasma, in 407 adult patients admitted to the emergency department (ED) with acute dyspnea and related them to risk of 90-day mortality using Cox proportional hazard models adjusted for age, sex, oxygen saturation, respiratory rate, C-reactive protein, and Medical Emergency Triage and Treatment System–Adult score. Results Fifty patients (12%) died within 90 day from admission. Two strong and independent biomarker signals were detected: The hazard ratio (95% confidence interval) for 90-day mortality per 1-SD increment of interleukin-8 (IL-8) was 2.20 (1.67-2.90) (P = 2.5 × 10− 8) and for growth differentiation factor–15 (GDF-15) was 3.45 (2.18-5.45) (P = 1.3 × 10− 7) A Biomarker Mortality Risk Score (BMRS) summing standardized and weighted values of IL-8 and GDF-15 revealed that of patients belonging to quartile 1 (Q1) of the BMRS, only 1 patient died, whereas 32 patients died among those belonging to quartile 4. Each 1-SD increment of the BMRS was associated with a hazard ratio of 3.79 (2.50-5.73) (P = 2 × 10− 10) for 90-day mortality, and the point estimate was 13 times higher in Q4 as compared with Q1 of the BMRS (Ptrend over quartiles = 2 × 10− 6). Conclusion Interleukin-8 and GDF-15 are strongly and independently related to risk of 90-day mortality in unselected patients admitted to the ED because of acute dyspnea, suggesting that they may guide first-line physicians at the ED in risk assessment which in turn could lead to more accurate level of care and treatment intensity. PMID:26740417

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

    PubMed

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

    2016-05-01

    Based on former studies showing an antagonism between angiopoietin-2 (Ang-2) and bacterial endotoxins (LPS), we investigated the role of Ang-2 as immunomodulatory treatment. At first, kinetics of circulating LPS in Gram-negative pyelonephritis developing after urinary obstruction was studied. Serum LPS, interleukin (IL)-6 and Ang-2 were measured in 25 patients with acute pyelonephritis and sepsis before and after removal of the obstruction performed either with insertion of a pigtail catheter (n=12) or percutaneous drainage (n=13). At a second stage, Ang-2 was given as anti-inflammatory treatment in 40 rabbits one hour after induction of acute pyelonephritis by ligation of the ureter at the level of pelvo-ureteral junction and upstream bacterial inoculation. Survival was recorded; blood mononuclear cells were isolated and stimulated for the production of tumour necrosis factor-alpha (TNFα). The decrease in circulating LPS was significantly greater among patients undergoing drainage than pigtail insertion. This was accompanied by reciprocal changes of Ang-2 and IL-6. Treatment with Ang-2 prolonged survival from Escherichia coli pyelonephritis despite high levels of circulating LPS. When Ang-2 was given as treatment of Pseudomonas aeruginosa pyelonephritis, sepsis-induced decrease of TNFα production by circulating mononuclear cells was reversed without an effect on tissue bacterial overgrowth. It is concluded that Ang-2 and LPS follow reverse kinetics in acute pyelonephritis. When given as experimental treatment, Ang-2 prolongs survival through an effect on mononuclear cells. PMID:26844659

  15. Acinar inflammatory response to lipid derivatives generated in necrotic fat during acute pancreatitis.

    PubMed

    Mateu, A; Ramudo, L; Manso, M A; Closa, D; De Dios, I

    2014-09-01

    Lipids play a role in acute pancreatitis (AP) progression. We investigate the ability of pancreatic acinar cells to trigger inflammatory response in the presence of lipid compounds generated in necrotic areas of peripancreatic adipose tissue (AT) during AP induced in rats by 5% sodium taurocholate. Lipid composition of AT was analyzed by HPLC-mass spectrometry. Acinar inflammatory response to total lipids as well as to either the free fatty acid (FFA) fraction or their chlorinated products (Cl-FFAs) was evaluated. For this, mRNA expression of chemokine (C-C motif) ligand 2 (CCL2) and P-selectin as well as the activation of MAPKs, NF-κB and STAT-3 were analyzed in pancreatic acini. Myeloperoxidase (MPO) activity, as an inducer of Cl-FFA generation, was also analyzed in AT. MPO activity significantly increased in necrotic (AT-N) induced changes in lipid composition of necrotic fat, such as increase in FFA and phospholipid (PL) content, generation of Cl-FFAs and increases in saturated FFAs and in the poly-:mono-unsaturated FFA ratio. Total lipids from AT-N induced overexpression of CCL2 and P-selectin in pancreatic acini as well as MAPKs phosphorylation and activation of NF-κB and STAT3. FFAs, but not Cl-FFAs, up-regulated CCL2 and P-selectin in acinar cells. We conclude that FFAs are capable of up-regulating inflammatory mediators in pancreatic acini and given that they are highly produced during AP, mainly may contribute to the inflammatory response triggered in acinar cells by fat necrosis. No role is played by Cl-FFAs generated as a result of neutrophil infiltration. PMID:24959971

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

    PubMed Central

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

    2015-01-01

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

  17. Senescence of human skeletal muscle impairs the local inflammatory cytokine response to acute eccentric exercise.

    PubMed

    Hamada, Koichiro; Vannier, Edouard; Sacheck, Jennifer M; Witsell, Alice L; Roubenoff, Ronenn

    2005-02-01

    The impact of aging on the cytokine response of human skeletal muscle to exercise-induced injury remains poorly understood. We enrolled physically active, young (23-35 years old, n=15) and old (66-78 years old, n=15) men to perform 45 min of downhill running (16% descent) at 75% VO2max. Biopsies of vastus lateralis were obtained 24 h before and 72 h after acute eccentric exercise. Transcripts for inflammatory (TNF-alpha, IL-1beta) and anti-inflammatory cytokines (IL-6, TGF-beta1) were quantified by real-time PCR. Before exercise, cytokine transcripts did not differ with age. At old age, exercise induced a blunted accumulation of transcripts encoding the pan-leukocyte surface marker CD18 (young: 10.1-fold increase, P<0.005; old: 4.7-fold increase, P=0.02; young vs. old: P<0.05). In both age groups, CD18 transcript accumulation strongly correlated with TNF-alpha (young, r=0.87, P<0.001; old, r=0.72, P=0.002) and TGF-beta1 transcript accumulation (young, r=0.80, P<0.001; old, r=0.64, P=0.008). At old age, there was no correlation between IL-1beta and CD18 transcript accumulation. Furthermore, exercise induced IL-6 transcript accumulation in young (3.6-fold, P=0.057) but not in old men. Our results suggest that aging impairs the adaptive response of human skeletal muscle to eccentric exercise by differential modulation of a discrete set of inflammatory and anti-inflammatory cytokine genes. PMID:15556970

  18. The role of TLR2 in the acute inflammatory response induced by Bothrops atrox snake venom.

    PubMed

    Moreira, Vanessa; Teixeira, Catarina; Borges da Silva, Henrique; D'Império Lima, Maria Regina; Dos-Santos, Maria Cristina

    2016-08-01

    Envenomation by snakes of the species Bothrops atrox induces local and systemic effects. Local effects include drastic tissue damage and a marked inflammatory response as a result of the synthesis and release of a variety of protein and lipid mediators. Toll-like receptor (TLR) signaling pathways can play an important role in this response, leading to synthesis of these inflammatory mediators. This study investigated the influence of TLR2 on the acute inflammatory response induced by Bothrops atrox venom. Wild-type C57BL/6 mice (WT) and TLR2 gene knockout mice (TLR2(-/-)) were injected with Bothrops atrox venom (BaV), and the following responses to the venom were assessed in peritoneal exudate: leukocyte accumulation; release of mediators, including CCL-2, IL-10, IL-1β, IL-6 and LTB4; protein expression of COX-1 and COX-2; and quantification of their products PGE2 and TXA2. After injection with BaV, the TLR2(-/-) mice (TLR2(-/-)BaV) had higher levels of IL-6 and CCL-2 than WT animals kept under the same conditions (WTBaV), together with an accumulation of polymorphonuclear leukocytes (PMNs), inhibition of IL-1β and LTB4 and reduced mononuclear leukocyte influx. However, no significant differences in COX-2 protein expression or PGE2, TXA2 and IL-10 production between the TLR2(-/-)BaV and WTBav animals were observed. Together, these results indicate that the signaling pathway activated by TLR2 acts by modulating the induced inflammatory response to BaV through the direct action of venom-associated molecular patterns (VAMPs) or indirectly by forming damage-associated molecular patterns (DAMPs) and that this may have important therapeutic implications. PMID:27109323

  19. Cell population kinetic parameters for acute epidermal reactions in man

    SciTech Connect

    Cohen, L.

    1986-11-01

    Cell population kinetic parameters for acute reactions in squamous epithelium were estimated using available data on skin tolerance doses. Roughly equivalent doses for kilovoltage radiation delivered in equal daily fractions, as reported by F. Ellis (Br. J. Radiol. 15, 348-350 (1942)) and by R. Paterson (The Treatment of Malignant Disease by Radium and X-Rays. Edward Arnold, London, 1948), were combined with data for nonstandard fractionation at longer intervals of 1 or 2 weeks. By analyzing the combined data set, well-determined parameters could be derived. The data show that repopulation, with a potential cell doubling time of about 7 days, must occur in irradiated human skin, though this may possibly be limited to no more than seven doublings. The parameters derived are distinctly different from those associated with late-reacting dose-limiting tissues. The main difference is the steeper initial slope of the computed survival curve, that is a larger J parameter (multitarget model) or a larger alpha component (linear-quadratic model).

  20. Inflammatory reactions in onchocerciasis: a report on current knowledge and recommendations for further study*

    PubMed Central

    Henson, P. M.; Mackenzie, C. D.; Spector, W. G.

    1979-01-01

    This report concerns the host's reactions to the presence of the parasite both in the course of the natural disease and during drug treatment. The various stages of Onchocerca volvulus are discussed in terms of the type of tissue reaction seen. The discussion then turns to basic hypotheses concerning the etiology of these reactions, emphasis being placed on the fact that while pathological changes are considerable in some locations there is a remarkable lack of reaction in others. Some of the mechanisms possibly involved in this apparent absence of host response are discussed, including anti-complement factors, poor antigenicity, acquisition of host antigen, immune tolerance, and blocking antibodies. In any study of the inflammatory response it is recommended that critical evaluations be made of histological material, haematological studies, the definition of the antigenic nature of O. volvulus, characterization of immunological reactivity of patients, and the definition of the migratory pathways of the parasite. The marked host reactions seen following chemotherapy, especially those related to the interaction of the drug diethylcarbamazine with microfilariae, are discussed at some length. The etiology of these reactions is considered and recommendations are made for the experimental elucidation of the mechanisms involved. Emphasis is placed on the necessity for detailed sequential histopathological and immunopathological studies in the definition of the tissue lesions found in onchocerciasis. Characterization of these lesions will assist greatly the approach to control of the adverse reactions seen during treatment. The use of anti-inflammatory agents in clinical trials is discussed and comments are made concerning the most suitable clinical situations for testing drugs and the types of drug that should be tested. PMID:396050

  1. Levels of acute inflammatory biomarkers in advanced prostate cancer patients with α2-macroglobulin deficiency.

    PubMed

    Kanoh, Yuhsaku; Ohtani, Hideki; Egawa, Shin; Baba, Shiro; Akahoshi, Tohru

    2011-12-01

    C-reactive protein (CRP), serum amyloid A (SAA), interleukin-6 (IL-6), α1-antitrypsin (α1AT), α1-acid glycoprotein (α1AG) and ceruloplasmin (CP) are acute inflammatory biomarkers that increase in various conditions including infection, inflammation, malignancy and tissue disturbance. In contrast, α2-macroglobulin (α2M) is involved in inflammation through its function as a carrier protein of IL-6. We had previously reported on advanced prostate cancer (PCa) patients with multiple distant bone metastases in whom serum α2M levels were markedly decreased (α2M deficiency). However, the relationship between serum levels of α2M and acute inflammatory biomarkers in PCa patients with or without α2M deficiency has not been demonstrated. In the present study, we examined serum levels of CRP, SAA, IL-6, α1AT, α1AG and CP in PCa patients with or without α2M deficiency to establish clinical significance and changes in these biomarkers during PCa disease progression. We found that upon addition of recombinant IL-6 (rIL-6) to serum from PCa patients with α2M deficiency, since a function of α2M is to bind and stabilize IL-6, the α2M-IL-6 complex and free endogenous IL-6 were not detectable. Serum levels of the α2M-independent markers, α1AT, α1AG and CP, in all PCa patients regardless of α2M deficiency were significantly higher than in healthy controls, but those of the α2M-dependent molecules, CRP, SAA and IL-6, were not increased in PCa patients with α2M deficiency. Therefore, quantitation of both α2M-dependent (CRP, SAA and IL-6) and α2M-independent (α1AT, α1AG and CP) acute inflammatory biomarkers in advanced PCa patients may be an auxiliary indicator, together with prostate-specific antigen (PSA), to monitor PCa disease progression. PMID:21894431

  2. Intracellular Hmgb1 Inhibits Inflammatory Nucleosome Release and Limits Acute Pancreatitis in Mice

    PubMed Central

    Kang, Rui; Zhang, Qiuhong; Hou, Wen; Yan, Zhenwen; Chen, Ruochan; Bonaroti, Jillian; Bansal, Preeti; Billiar, Timothy R.; Tsung, Allan; Wang, Qingde; Bartlett, David L.; Whitcomb, David C; Chang, Eugene B.; Zhu, Xiaorong; Wang, Haichao; Lu, Ben; Tracey, Kevin J.; Cao, Lizhi; Fan, Xue-Gong; Lotze, Michael T.; Zeh, Herbert J.; Tang, Daolin

    2014-01-01

    BACKGROUND & AIMS: High mobility group box 1 (HMGB1) is an abundant protein that regulates chromosome architecture and also functions as a damage-associated molecular pattern molecule. Little is known about its intracellular roles in response to tissue injury or during subsequent local and systemic inflammatory responses. We investigated the function of Hmgb1 in mice following induction of acute pancreatitis. METHODS: We utilized a Cre/LoxP system to create mice with pancreas-specific disruption in Hmbg1 (Pdx1-Cre; HMGB1flox/flox mice). Acute pancreatitis was induced in these mice (HMGB1flox/flox mice served as controls) following injection of L-arginine or cerulein. Pancreatic tissues and acinar cells were collected and analyzed by histologic, immunoblot, and immunohistochemical analyses. RESULTS: Following injection of L-arginine or cerulein, Pdx1-Cre; HMGB1flox/flox mice developed acute pancreatitis more rapidly than controls, with increased mortality. Pancreatic tissues of these mice also had higher levels of serum amylase, acinar cell death, leukocyte infiltration, and interstitial edema than controls. Pancreatic tissues and acinar cells collected from the Pdx1-Cre; HMGB1flox/flox mice following L-arginine- or cerulein injection demonstrated nuclear catastrophe with greater nucleosome release when compared with controls, along with increased phosphorylation/activation of RELA Nfκb, degradation of Iκb, and phosphorylation of Mapk. Inhibitors of reactive oxygen species (N-acetyl-L-cysteine) blocked L-arginine–induced DNA damage, necrosis, apoptosis, release of nucleosomes, and activation of Nfκb in pancreatic tissues and acinar cells from Pdx1-Cre; HMGB1flox/flox and control mice. Exogenous genomic DNA and recombinant histone H3 proteins significantly induced release of HMGB1 from mouse macrophages; administration of antibodies against H3 to mice reduced serum levels of HMGB1 and increased survival following L-arginine injection. CONCLUSIONS: In 2 mouse

  3. Acute inflammatory demyelinating polyradiculoneuropathy in a patient receiving oxaliplatin-based chemotherapy.

    PubMed

    Yoon, Ju Young; Nam, Tai Seung; Kim, Myeong Kyu; Hwang, Jun Eul; Shim, Hyun-Jeong; Cho, Sang Hee; Chung, Ik Joo; Bae, Woo Kyun

    2012-06-01

    We report a case of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) that developed in a patient with cholangiocarcinoma after receiving oxaliplatin-based chemotherapy. A 62-year-old man had multiple hypodense lesions with delayed enhancement in the both lobes of the liver on abdominal computed tomography. He was treated with 5-fluorouracil, leucovorin and oxaliplatin (100 mg/m(2)). After eight cycles of treatment and a cumulative oxaliplatin dose of 780 mg/m(2), he developed an unsteady gait, dysphagia, weakness of both the upper and lower limbs and impairment of all sensory modalities. Nerve conduction studies confirmed the diagnosis of AIDP. Immunoglobulin G i.v. was administered for 5 days but the neurological deficits of both his upper and lower limbs did not improve. This case highlights unusual peripheral nervous system manifestations in a patient who received chemotherapy with oxaliplatin. PMID:22524580

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

    PubMed

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

    2014-12-01

    This study aims to evaluate the possible mechanisms responsible for the anti-inflammatory effects of apigenin lipopolysaccharide (LPS)-induced inflammatory in acute lung injury. In this study, the anti-inflammatory effects of apigenin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and the possible mechanisms involved in this protection were investigated. Pretreatment with apigenin prior to the administration of intratracheal LPS significantly induced a decrease in lung wet weight/dry weight ratio in total leukocyte number and neutrophil percent in the bronchoalveolar lavage fluid (BALF) and in IL-6 and IL-1β, the tumor neurosis factor-α (TNF-α) in the BALF. These results showed that anti-inflammatory effects of apigenin against the LPS-induced ALI may be due to its ability of primary inhibition of cyclooxygenase-2 (COX-2) gene expression and nuclear factor kB (NF-kB) gene expression of lung. The results presented here suggest that the protective mechanism of apigenin may be attributed partly to decreased production of proinflammatory cytokines through the inhibition of COX-2 and NF-kB activation. The results support that use of apigenin is beneficial in the treatment of ALI. PMID:24958013

  5. Low-level laser therapy attenuates the acute inflammatory response induced by muscle traumatic injury.

    PubMed

    Silveira, Paulo Cesar Lock; Scheffer, Debora da Luz; Glaser, Viviane; Remor, Aline Pertile; Pinho, Ricardo Aurino; Aguiar Junior, Aderbal Silva; Latini, Alexandra

    2016-01-01

    The purpose of this work was to investigate the effect of early and long-term low-level laser therapy (LLLT) on oxidative stress and inflammatory biomarkers after acute-traumatic muscle injury in Wistar rats. Animals were randomly divided into the following four groups: control group (CG), muscle injury group (IG), CG + LLLT, and IG + LLLT: laser treatment with doses of 3 and 5 J/cm(2). Muscle traumatic injury was induced by a single-impact blunt trauma in the rat gastrocnemius. Irradiation for 3 or 5 J/cm(2) was initiated 2, 12, and 24 h after muscle trauma induction, and the treatment was continued for five consecutive days. All the oxidant markers investigated. namely thiobarbituric acid-reactive substance, carbonyl, superoxide dismutase, glutathione peroxidase, and catalase, were increased as soon as 2 h after muscle injury and remained increased up to 24 h. These alterations were prevented by LLLT at a 3 J/cm(2) dose given 2 h after the trauma. Similarly, LLLT prevented the trauma-induced proinflammatory state characterized by IL-6 and IL-10. In parallel, trauma-induced reduction in BDNF and VEGF, vascular remodeling and fiber-proliferating markers, was prevented by laser irradiation. In order to test whether the preventive effect of LLLT was also reflected in muscle functionality, we tested the locomotor activity, by measuring distance traveled and the number of rearings in the open field test. LLLT was effective in recovering the normal locomotion, indicating that the irradiation induced biostimulatory effects that accelerated or resolved the acute inflammatory response as well as the oxidant state elicited by the muscle trauma. PMID:26983894

  6. Exposure to welding fumes is associated with acute systemic inflammatory responses

    PubMed Central

    Kim, J; Chen, J; Boyce, P; Christiani, D

    2005-01-01

    Aims: To investigate the acute systemic inflammatory response to welding fume exposure. Methods: Twenty four welders (42% smokers) and 13 non-exposed controls (23% smokers) were monitored at a welding school. Exposure to fine particulate matter (PM2.5) was assessed using cyclone samplers. Markers of systemic inflammation, including C-reactive protein (CRP), fibrinogen, and white blood cell (WBC) levels, were determined in peripheral blood samples collected at baseline and after 5.3 (SD 1.0) hours of exposure. Results: The median PM2.5 concentration for welders was 1.66 mg/m3, which was significantly greater than that for controls (0.04 mg/m3). Compared to non-smokers, smokers had a significantly higher baseline WBC count, but comparable levels of CRP and fibrinogen. In non-smokers, welding fume exposure was associated with a significant increase in WBC and neutrophil counts immediately following exposure (+0.8x103/µl, 95% CI 0.1 to 1.6, and +1.0x103/µl, 95% CI 0.4 to 1.7, respectively). A significant decrease in fibrinogen levels was observed in non-smokers (–32 mg/dl, 95% CI –63 to –1). No significant changes in WBC, neutrophil, and fibrinogen levels were found in smokers. Sixteen hours after welding exposure, CRP levels were found to be significantly increased in both non-smokers and smokers (0.90 mg/l, 95% CI 0.17 to 1.64). PM2.5 concentrations were found to be significantly associated with absolute neutrophil counts in non-smokers, and CRP levels in both non-smokers and smokers. Conclusions: High levels of welding fume exposure induce acute systemic inflammation in a relatively young, healthy working population. These results also suggest that smoking may modify the effect of welding fume exposure on specific inflammatory markers. PMID:15723880

  7. An unexpected cause of an acute hypersensitivity reaction during recovery from anaesthesia.

    PubMed

    Thong, C L; Lambros, M; Stewart, M G; Kam, P C A

    2005-08-01

    Acute hypersensitivity reactions to chlorhexidine in the operating room are probably more likely to occur during the early phases of anaesthesia because chlorhexidine is often used for cleaning the surgical field or during placement of indwelling catheters. We report a case of an acute hypersensitivity reaction that occurred in the post anaesthetic care unit. Subsequent skin testing suggested sensitivity to chlorhexidine, which had been applied over the vaginal mucosa at the end of surgery. Relevant issues in the investigation of acute hypersensitivity reactions in the post anaesthetic period are discussed. PMID:16119497

  8. Effects of anesthetic regimes on inflammatory responses in a rat model of acute lung injury

    PubMed Central

    Fortis, Spyridon; Spieth, Peter M.; Lu, Wei-Yang; Parotto, Matteo; Haitsma, Jack J; Slutsky, Arthur S.; Zhong, Nanshan; Mazer, C. David; Zhang, Haibo

    2016-01-01

    Background Gamma amino butyric acid (GABA) is the major inhibitory neurotransmitter through activation of GABA receptors. Volatile anesthetics activate type A (GABAA) receptors resulting in inhibition of synaptic transmission. Lung epithelial cells have been recently found to express GABAA receptors that exert anti-inflammatory properties. We hypothesized that the volatile anesthetic sevoflurane (SEVO) attenuates lung inflammation through activation of lung epithelial GABAA receptors. Methods Sprague-Dawley rats were anesthetized with SEVO or ketamine/xylazine (KX). Acute lung inflammation was induced by intratracheal instillation of endotoxin, followed by mechanical ventilation for 4 h at a tidal volume of 15 mL/kg without positive end-expiratory pressure (two-hit lung injury model). To examine the specific effects of GABA, healthy human bronchial epithelial cells (BEAS-2B) were challenged with endotoxin in the presence and absence of GABA with and without addition of the GABAA receptor antagonist picrotoxin. Results Anesthesia with SEVO improved oxygenation and reduced pulmonary cytokine responses compared to KX. This phenomenon was associated with increased expression of the π subunit of GABAA receptors and glutamic acid decarboxylase (GAD). The endotoxin-induced cytokine release from BEAS-2B cells was attenuated by the treatment with GABA, which was reversed by the administration of picrotoxin. Conclusion Anesthesia with SEVO suppresses pulmonary inflammation thus protects the lung from the two-hit injury. The anti-inflammatory effect of SEVO is likely due to activation of pulmonary GABAA signaling pathways. PMID:22711173

  9. Endothelial Fas-Ligand in Inflammatory Bowel Diseases and in Acute Appendicitis.

    PubMed

    Kokkonen, Tuomo S; Karttunen, Tuomo J

    2015-12-01

    Fas-mediated induction of apoptosis is a major factor in the selection of lymphocytes and downregulation of immunological processes. In the present study, we have assessed endothelial Fas-ligand (FasL) expression in normal human ileum, appendix, and colon, and compared the expression levels with that in inflammatory bowel disease and in acute appendicitis. In a normal appendix, endothelial FasL levels were constant in almost half of the mucosal vessels; but, in the normal ileum and colon, endothelial FasL was practically restricted to areas in close proximity to lymphatic follicles, and was expressed mainly in the submucosal aspect of the follicles in the vessels with high endothelium. In samples from subjects with either Crohn's disease or ulcerative colitis, the extent of endothelial FasL expression was elevated in the submucosa and associated with an elevated number of lymphoid follicles. In inflammatory bowel disease, ulcers and areas with a high density of mononuclear cells expressing FasL also showed an elevated density of blood vessels with endothelial FasL expression. Although the function of endothelial FasL remains unclear, such a specific expression pattern suggests that endothelial FasL expression has a role in the regulation of lymphocyte access to the peripheral lymphoid tissues, including the intestinal mucosa. PMID:26374830

  10. Evaluation of the analgesic effect of low-power optical radiation in acute inflammatory process

    NASA Astrophysics Data System (ADS)

    Ferreira, Denise M.; Zangaro, Renato A.; Cury, Yara; Frigo, Lucio; Barbosa, Daniella G.; da Silva Melo, Milene; Munin, Egberto

    2004-07-01

    Many research works have explored the use of the low power laser as a tool for the control of inflammatory processes. The anti-inflammatory effect of low power optical radiation and its ability to induce analgesia has been reported for different experimental conditions. Many published works are very qualitative in nature. In this work the action of low power laser radiation on acute inflammatory process is evaluated. The time evolution of rat paw edema and pain induced by carrageenan was experimentally monitored. A 632.8 nm He-Ne laser was used for the treatment. The laser treatment, at a dosage of 2,5 J/cm2, was applied at the first, second and third hour after the induction of the inflammation. A hydroplethysmometer was used for the evaluation of the inflammation. The measurement of pain sensitivity was performed according to the method described by Randall and Selito, (1957). The laser treatment was capable of inhibiting the carrageenan-induced hyperalgesia by 49% (p<0,001) at the second hour after the induction, as compared to the non-treated group. At the fourth hour (peak of the carrageenan action on hyperalgesia) and at the sixth hour, the achieved inhibition was 49% (p<0,001) and 61% (p<0,001), respectively. In the treated groups, the edema evolution was inhibited by 38% (p<0,01), at the second hour after induction, as compared to the non-treated groups. At the fourth hour (peak of the carrageenan action on leakage) and at sixth hour the achieved inhibition was 35% (p<0,01) and 30% (p<0,05) respectively.

  11. Acute gastrointestinal permeability responses to different non-steroidal anti-inflammatory drugs

    PubMed Central

    Smecuol, E; Bai, J; Sugai, E; Vazquez, H; Niveloni, S; Pedreira, S; Maurino, E; Meddings, J

    2001-01-01

    BACKGROUND AND AIMS—Non-steroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal damage both in the upper and lower gastrointestinal tract. New anti-inflammatory drugs have been developed in an attempt to improve their gastrointestinal side effect profile. Our objective was to compare the effect on gastrointestinal permeability of acute equieffective doses of four different NSAIDs; three were designed to reduce gastrointestinal mucosal injury.
MATERIALS—Healthy volunteers underwent sugar tests in a randomised fashion, 15 days apart, at: (1) baseline; (2) after two days of 75 mg slow release (microspheres) indomethacin; (3) after two days of 7.5 mg oral meloxicam which preferentially inhibits cyclooxygenase 2; and (4) after two days of 750 mg naproxen. A subgroup of subjects was tested after two days of 200 mg celecoxib. In each test, subjects ingested a solution containing sucrose, lactulose, and mannitol and sucralose, to evaluate gastroduodenal, intestinal, and colonic permeability, respectively.
RESULTS—Gastric permeability was significantly affected by naproxen (p<0.05) but not by slow release indomethacin, meloxicam, or celecoxib. Intestinal permeability was significantly increased by the first three NSAIDs (p<0.05) but not by celecoxib. Abnormal lactulose/mannitol ratios were observed in 42% of meloxicam treatments, in 62% during indomethacin, and in 75% of subjects treated with naproxen. Finally, colonic permeability, as measured by sucralose, was not significantly increased by any of the four drugs.
CONCLUSION—Our study provides evidence that the newly developed NSAIDs reduce gastric mucosal permeability significantly. However, most produced significant alteration of small intestinal permeability. In contrast, our results suggest that celecoxib seems to exhibit the most desirable gastrointestinal side effect profile.


Keywords: permeability; non-steroidal anti-inflammatory drugs; celecoxib; meloxican; small intestine

  12. Chronic inflammatory systemic diseases: An evolutionary trade-off between acutely beneficial but chronically harmful programs.

    PubMed

    Straub, Rainer H; Schradin, Carsten

    2016-01-01

    It has been recognized that during chronic inflammatory systemic diseases (CIDs) maladaptations of the immune, nervous, endocrine and reproductive system occur. Maladaptation leads to disease sequelae in CIDs. The ultimate reason of disease sequelae in CIDs remained unclear because clinicians do not consider bodily energy trade-offs and evolutionary medicine. We review the evolution of physiological supersystems, fitness consequences of genes involved in CIDs during different life-history stages, environmental factors of CIDs, energy trade-offs during inflammatory episodes and the non-specificity of CIDs. Incorporating bodily energy regulation into evolutionary medicine builds a framework to better understand pathophysiology of CIDs by considering that genes and networks used are positively selected if they serve acute, highly energy-consuming inflammation. It is predicted that genes that protect energy stores are positively selected (as immune memory). This could explain why energy-demanding inflammatory episodes like infectious diseases must be terminated within 3-8 weeks to be adaptive, and otherwise become maladaptive. Considering energy regulation as an evolved adaptive trait explains why many known sequelae of different CIDs must be uniform. These are, e.g. sickness behavior/fatigue/depressive symptoms, sleep disturbance, anorexia, malnutrition, muscle wasting-cachexia, cachectic obesity, insulin resistance with hyperinsulinemia, dyslipidemia, alterations of steroid hormone axes, disturbances of the hypothalamic-pituitary-gonadal (HPG) axis, hypertension, bone loss and hypercoagulability. Considering evolved energy trade-offs helps us to understand how an energy imbalance can lead to the disease sequelae of CIDs. In the future, clinicians must translate this knowledge into early diagnosis and symptomatic treatment in CIDs. PMID:26817483

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  14. Calcitriol inhibits tumor necrosis factor alpha and macrophage inflammatory protein-2 during lipopolysaccharide-induced acute lung injury in mice.

    PubMed

    Tan, Zhu-Xia; Chen, Yuan-Hua; Xu, Shen; Qin, Hou-Ying; Wang, Hua; Zhang, Cheng; Xu, De-Xiang; Zhao, Hui

    2016-08-01

    Acute lung injury is a common complication of sepsis in intensive care unit patients with an extremely high mortality. The present study investigated the effects of calcitriol, the active form of vitamin D, on tumor necrosis factor alpha (TNF-α) and macrophage inflammatory protein-2 (MIP-2) in sepsis-induced acute lung injury. Mice were intraperitoneally (i.p.) injected with lipopolysaccharide (LPS, 1.0mg/kg) to establish the animal model of sepsis-induced acute lung injury. Some mice were i.p. injected with calcitriol (1.0μg/kg) before LPS injection. An obvious infiltration of inflammatory cells in the lungs was observed beginning at 1h after LPS injection. Correspondingly, TNF-α and MIP-2 in sera and lung homogenates were markedly elevated in LPS-treated mice. Interestingly, calcitriol obviously alleviated LPS-induced infiltration of inflammatory cells in the lungs. Moreover, calcitriol markedly attenuated LPS-induced elevation of TNF-α and MIP-2 in sera and lung homogenates. Further analysis showed that calcitriol repressed LPS-induced p38 mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) phosphorylation. In addition, calcitriol blocked LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 and p50 subunit in the lungs. Taken together, these results suggest that calcitriol inhibits inflammatory cytokines production in LPS-induced acute lung injury. PMID:27216047

  15. Effect of Surgical Castration with or without Oral Meloxicam on the Acute Inflammatory Response in Yearling Beef Bulls

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  16. Metabonomic analysis of the anti-inflammatory effects of volatile oils of Angelica sinensis on rat model of acute inflammation.

    PubMed

    Zhang, Wen-Quan; Hua, Yong-Li; Zhang, Man; Ji, Peng; Li, Jin-Xia; Zhang, Ling; Li, Peng-Ling; Wei, Yan-Ming

    2015-06-01

    Metabonomics based on GC-MS was used to study the possible anti-inflammatory mechanisms of volatile oils of Angelica sinensis (VOAS) in rats with acute inflammation. Acute inflammation was induced by subcutaneous injection of carrageenan in rats. The levels of prostaglandin E2 (PGE2 ), histamine (HIS) and 5-hydroxytryptamine (5-HT) in the inflammatory fluid were detected. Principal component analysis and orthogonal partial least squares-discriminant analysis models were performed for pattern recognition analysis. After the administration of VOAS, the levels of PGE2 , HIS, and 5-HT returned to levels observed in normal group. According to GC-MS analysis, the intervention of VOAS in rats with acute inflammation induced substantial and characteristic changes in their metabolic profiles. Fourteen metabolite biomarkers, namely, lactic acid, malic acid, citric acid, trans-dehydroandrosterone, aldosterone, linoleic acid, hexadecanoic acid, pregnenolone, octadecenoic acid, myristic acid, l-histidine, octadecanoic acid, arachidonic acid (AA) and l-tryptophan, were detected in the inflammatory fluid. The levels of all biomarkers either increased or decreased significantly in model groups. VOAS possibly intervened in the metabolic process of inflammation by altering histidine metabolism, tryptophan metabolism, AA metabolism, steroid hormone biosynthesis, fatty acid metabolism and energy metabolism. Metabonomics was used to reflect an organism's physiological and metabolic state comprehensively, and it is a potentially powerful tool that reveals the anti-acute-inflammatory mechanism of VOAS. PMID:25515821

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  18. The Effect of Acute and Chronic Morphine on Some Blood Biochemical Parameters in an Inflammatory Condition in Gonadectomized Male Rats

    PubMed Central

    Chahkandi, Mohadeseh; Askari, Nayerreh; Asadikaram, Gholamreza

    2015-01-01

    Background Opiates affect blood factors as well as pain and inflammation in a gender-dependent manner. The aim of the present study was to evaluate the effects of morphine on serum glucose, cholesterol, triglycerides, and urea in gonadectomized and inflammation conditions. Methods Animals were divided as follows: control group, carrageenan and chronic morphine recipients, acute morphine recipients, chronic morphine recipients, carrageenan recipients, acute morphine and carrageenan recipients, gonadectomized group, gonadectomized recipients of carrageenan, gonadectomized recipients of morphine, gonadectomized recipients of chronic morphine, gonadectomized recipients of carrageenan and chronic morphine, gonadectomized recipients of acute morphine and carrageenan. Findings Our results have shown that acute and chronic morphine elevates blood glucose level in the acute and chronic morphine group. Cholesterol level has shown to be increasing in the morphine and carrageenan recipient group compared with a group which merely received morphine. Triglyceride has shown to be decreasing in acute and chronic morphine recipient group compared with control group. A significant increase in serum urea was observed in acute and chronic morphine recipients compared with the carrageenan recipient group. Conclusion Morphine alters the serum glucose, cholesterol, triglyceride, and urea in the normal and inflammatory conditions differently, hence, this finding should be considered in the patients who use morphine as a relief of pain, especially in an inflammatory condition. PMID:26885349

  19. Systemic Lupus Erythematosus With Acute Inflammatory Demyelinating Polyneuropathy: A Case Report and Review of the Literature

    PubMed Central

    Li, Xiangling; Wang, Yanqiang

    2016-01-01

    We recently encountered a patient with acute inflammatory demyelinating polyneuropathy (AIDP) that was associated with systemic lupus erythematosus (SLE). A 34-year-old Chinese female with a 3-year history of SLE presented with acute bilateral leg weakness and paraparesis, and lost the ability to walk 1 day after noticing bilateral leg numbness and pain for 12 days. Physical examination revealed bilateral facial muscle paralysis, muscle strength in the legs with graded 1/5 proximally and 2/5 distally bilaterally and absence of deep tendon reflex in both knees and ankles. Paresthesia was observed in distal limbs with glove and stocking distribution. Cerebrospinal fluid analysis demonstrated albuminocytologic dissociation. Electrophysiologic survey also indicated sensory-motor demyelinating polyneuropathy. The diagnosis of SLE was established based on her initial symptoms including intermittent fevers, hair loss, oral ulcers, malar rash and arthritis affecting the elbow, wrist and hand joints; positive immunologic findings for antinuclear antibody (ANA), anti-DNA antibody, anti-Smith (anti-Sm) antibody, low serum complement levels, and the kidney biopsy specimen showed glomerular mesangial proliferation with focal endothelial cell proliferation (ISN/PPS 2004 classification lupus nephritis, class III). Treatment with intravenous immunoglobulin, methylprednisolone and cyclophosphamide resulted in clinical and electrophysiological improvement. PMID:27298667

  20. Systemic Lupus Erythematosus With Acute Inflammatory Demyelinating Polyneuropathy: A Case Report and Review of the Literature.

    PubMed

    Li, Xiangling; Wang, Yanqiang

    2016-07-01

    We recently encountered a patient with acute inflammatory demyelinating polyneuropathy (AIDP) that was associated with systemic lupus erythematosus (SLE). A 34-year-old Chinese female with a 3-year history of SLE presented with acute bilateral leg weakness and paraparesis, and lost the ability to walk 1 day after noticing bilateral leg numbness and pain for 12 days. Physical examination revealed bilateral facial muscle paralysis, muscle strength in the legs with graded 1/5 proximally and 2/5 distally bilaterally and absence of deep tendon reflex in both knees and ankles. Paresthesia was observed in distal limbs with glove and stocking distribution. Cerebrospinal fluid analysis demonstrated albuminocytologic dissociation. Electrophysiologic survey also indicated sensory-motor demyelinating polyneuropathy. The diagnosis of SLE was established based on her initial symptoms including intermittent fevers, hair loss, oral ulcers, malar rash and arthritis affecting the elbow, wrist and hand joints; positive immunologic findings for antinuclear antibody (ANA), anti-DNA antibody, anti-Smith (anti-Sm) antibody, low serum complement levels, and the kidney biopsy specimen showed glomerular mesangial proliferation with focal endothelial cell proliferation (ISN/PPS 2004 classification lupus nephritis, class III). Treatment with intravenous immunoglobulin, methylprednisolone and cyclophosphamide resulted in clinical and electrophysiological improvement. PMID:27298667

  1. Analysis of the inflammatory reaction induced by the catfish (Cathorops spixii) venoms.

    PubMed

    Junqueira, Marcos Emerson Pinheiro; Grund, Lidiane Zito; Orii, Noêmia M; Saraiva, Tânia Cristina; de Magalhães Lopes, Carlos Alberto; Lima, Carla; Lopes-Ferreira, Mônica

    2007-06-01

    Cathorops spixii is one of the most abundant venomous fish of the southeastern coast of the State of São Paulo, and consequently causes a great part of the accidents seen there. The accidents affect mainly fishermen, swimmers and tourists and are characterized by punctiform or wide wounds, erythema, edema, pain, sudoresis, indisposition, fever, nausea, vomiting and secondary infection. The objective of this work was to characterize the inflammatory response induced in mice by both venoms (mucus and sting) of the catfish C. spixii. Our results demonstrated that both venoms induced a great number of rolling and adherent leukocytes in the post-capillary venules of cremaster muscle of mice, and an increase in the vascular permeability in peritoneal cavity. Mucus induced the recruitment of neutrophils immediately after injection followed later by macrophage infiltration. In contrast, the cellular infiltration elicited by sting venom was rapidly resolved. The peritonitis reaction provoked by venoms was characterized by cytokine (IL-6), chemokines (MCP-1 and KC) or lipid mediator (LTB4) production in the peritoneal cavity. The macrophages from 7-day mucus venom-induced exudates upon in vitro mucus venom stimulation, expressed CD11c x MHC class II and release bioactive IL-12p70. On the other hand, sting venom-elicited peritoneal macrophages lost the ability to differentiate into dendritic cells, following re-stimulation in vitro with sting venom, they do not express CD11c, nor do they exhibit sufficient levels of MHC class II. In conclusion, both types of venoms (mucus or sting) promote inflammatory reaction with different profiles, and the inflammatory reaction induced by the first was characterized by antigen persistence in peritoneal cavity that allowed the activation of phagocytic cells with capacity of antigenic presentation. PMID:17321559

  2. The Effect of Oxandrolone on the Endocrinologic, Inflammatory, and Hypermetabolic Responses During the Acute Phase Postburn

    PubMed Central

    Jeschke, Marc G.; Finnerty, Celeste C.; Suman, Oscar E.; Kulp, Gabriela; Mlcak, Ronald P.; Herndon, David N.

    2007-01-01

    Objective and Summary Background Data: Postburn long-term oxandrolone treatment improves hypermetabolism and body composition. The effects of oxandrolone on clinical outcome, body composition, endocrine system, and inflammation during the acute phase postburn in a large prospective randomized single-center trial have not been studied. Methods: Burned children (n = 235) with >40% total body surface area burn were randomized (block randomization 4:1) to receive standard burn care (control, n = 190) or standard burn care plus oxandrolone for at least 7 days (oxandrolone 0.1 mg/kg body weight q.12 hours p.o, n = 45). Clinical parameters, body composition, serum hormones, and cytokine expression profiles were measured throughout acute hospitalization. Statistical analysis was performed by Student t test, or ANOVA followed by Bonferroni correction with significance accepted at P < 0.05. Results: Demographics and clinical data were similar in both groups. Length of intensive care unit stay was significantly decreased in oxandrolone-treated patients (0.48 ± 0.02 days/% burn) compared with controls (0.56 ± 0.02 days/% burn), (P < 0.05). Control patients lost 8 ± 1% of their lean body mass (LBM), whereas oxandrolone-treated patients had preserved LBM (+9 ± 4%), P < 0.05. Oxandrolone significantly increased serum prealbumin, total protein, testosterone, and AST/ALT, whereas it significantly decreased α2-macroglobulin and complement C3, P < 0.05. Oxandrolone did not adversely affect the endocrine and inflammatory response as we found no significant differences in the hormone panels and cytokine expression profiles. Conclusions: In this large prospective, double-blinded, randomized single-center study, oxandrolone shortened length of acute hospital stay, maintained LBM, improved body composition and hepatic protein synthesis while having no adverse effects on the endocrine axis postburn, but was associated with an increase in AST and ALT. PMID:17717439

  3. Activation of Endogenous Anti-Inflammatory Mediator Cyclic AMP Attenuates Acute Pyelonephritis in Mice Induced by Uropathogenic Escherichia coli

    PubMed Central

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

    2015-01-01

    The pathogenesis of pyelonephritis caused by uropathogenic Escherichia coli (UPEC) is not well understood. Here, we show that besides UPEC virulence, the severity of the host innate immune response and invasion of renal epithelial cells are important pathogenic factors. Activation of endogenous anti-inflammatory mediator cAMP significantly attenuated acute pyelonephritis in mice induced by UPEC. Administration of forskolin (a potent elevator of intracellular cAMP) reduced kidney infection (ie, bacterial load, tissue destruction); this was associated with attenuated local inflammation, as evidenced by the reduction of renal production of proinflammatory mediators, renal infiltration of inflammatory cells, and renal myeloperoxidase activity. In primary cell culture systems, forskolin not only down-regulated UPEC-stimulated production of proinflammatory mediators by renal tubular epithelial cells and inflammatory cells (eg, monocyte/macrophages) but also reduced bacterial internalization by renal tubular epithelial cells. Our findings clearly indicate that activation of endogenous anti-inflammatory mediator cAMP is beneficial for controlling UPEC-mediated acute pyelonephritis in mice. The beneficial effect can be explained at least in part by limiting excessive inflammatory responses through acting on both renal tubular epithelial cells and inflammatory cells and by inhibiting bacteria invasion of renal tubular epithelial cells. PMID:25478807

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

    PubMed

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

    2015-02-01

    The pathogenesis of pyelonephritis caused by uropathogenic Escherichia coli (UPEC) is not well understood. Here, we show that besides UPEC virulence, the severity of the host innate immune response and invasion of renal epithelial cells are important pathogenic factors. Activation of endogenous anti-inflammatory mediator cAMP significantly attenuated acute pyelonephritis in mice induced by UPEC. Administration of forskolin (a potent elevator of intracellular cAMP) reduced kidney infection (ie, bacterial load, tissue destruction); this was associated with attenuated local inflammation, as evidenced by the reduction of renal production of proinflammatory mediators, renal infiltration of inflammatory cells, and renal myeloperoxidase activity. In primary cell culture systems, forskolin not only down-regulated UPEC-stimulated production of proinflammatory mediators by renal tubular epithelial cells and inflammatory cells (eg, monocyte/macrophages) but also reduced bacterial internalization by renal tubular epithelial cells. Our findings clearly indicate that activation of endogenous anti-inflammatory mediator cAMP is beneficial for controlling UPEC-mediated acute pyelonephritis in mice. The beneficial effect can be explained at least in part by limiting excessive inflammatory responses through acting on both renal tubular epithelial cells and inflammatory cells and by inhibiting bacteria invasion of renal tubular epithelial cells. PMID:25478807

  5. Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response. Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures.

    PubMed Central

    Van Lenten, B J; Hama, S Y; de Beer, F C; Stafforini, D M; McIntyre, T M; Prescott, S M; La Du, B N; Fogelman, A M; Navab, M

    1995-01-01

    We previously reported that high density lipoprotein (HDL) protects against the oxidative modification of low density lipoprotein (LDL) induced by artery wall cells causing these cells to produce pro-inflammatory molecules. We also reported that enzyme systems associated with HDL were responsible for this anti-inflammatory property of HDL. We now report studies comparing HDL before and during an acute phase response (APR) in both humans and a croton oil rabbit model. In rabbits, from the onset of APR the protective effect of HDL progressively decreased and was completely lost by day three. As serum amyloid A (SAA) levels in acute phase HDL (AP-HDL) increased, apo A-I levels decreased 73%. Concomitantly, paraoxonase (PON) and platelet activating factor acetylhydrolase (PAF-AH) levels in HDL declined 71 and 90%, respectively, from days one to three. After day three, there was some recovery of the protective effect of HDL. AP-HDL from human patients and rabbits but not normal or control HDL (C-HDL) exhibited increases in ceruloplasmin (CP). This increase in CP was not seen in acute phase VLDL or LDL. C-HDL incubated with purified CP and re-isolated (CP-HDL), lost its ability to inhibit LDL oxidation. Northern blot analyses demonstrated enhanced expression of MCP-1 in coculture cells treated with AP-HDL and CP-HDL compared to C-HDL. Enrichment of human AP-HDL with purified PON or PAF-AH rendered AP-HDL protective against LDL modification. We conclude that under basal conditions HDL serves an anti-inflammatory role but during APR displacement and/or exchange of proteins associated with HDL results in a pro-inflammatory molecule. Images PMID:8675645

  6. Vcsa1 gene peptides for the treatment of inflammatory and allergic reactions.

    PubMed

    Morris, Katherine; Kuo, Byron; Wilkinson, Mark D; Davison, Joseph S; Befus, A Dean; Mathison, Ronald D

    2007-06-01

    The recently emerged Vcsa1 gene is one member of the variable coding sequence (VCS) multigene family of Rattus norvegicus. This gene encodes the precursor prohormone SMR1 (submandibular rat-1), which on enzymatic processing gives rise to several 5 to 11 amino acid peptides that modulate a variety of physiological functions. The analgesic pentapeptide sialorphin and anti-inflammatory heptapeptide submandibular gland peptide-T (TDIFEGG) are the most intensively studied. Although the Vcsa1 gene and its protein product are unique to rats, TDIFEGG or a derivative acts on all species examined to date, including human cells, in functions related to allergic reactions and inflammation. In this review, the patent and academic literature on SMR1 and its natural peptides and their derivatives are reviewed for consideration of biological targets and relevance to the development of novel therapeutic agents. The VCS gene family is discussed and we speculate on possible human homologs of these potent anti-inflammatory rat-derived peptides. The biologically active peptide products of SMR1 are considered and the mechanism of action and structure-activity relationships of the anti-inflammatory submandibular gland peptide-T and its derivatives are discussed. PMID:19075974

  7. Inflammatory reaction in chronic periodontopathies in patients with diabetes mellitus. Histological and immunohistochemical study.

    PubMed

    Camen, Georgiana Cristiana; Caraivan, O; Olteanu, Mădălina; Camen, A; Bunget, Adina; Popescu, Florina Carmen; Predescu, Anca

    2012-01-01

    Chronic periodontopathies and diabetes mellitus are two clinical entities, which reciprocally condition one another. The periodontal disease is considered a major complication, which induces an unfavorable evolution of diabetes mellitus. Diabetes mellitus is an endocrine disease which favors the occurrence of periodontopathy through gum's microvascular disorders, the selection and development of an aggressive bacterial plaque and through an exaggerate inflammatory response to the microflora within the oral cavity. Both diabetes mellitus and periodontal disease have an increasing incidence in the whole world. Development of periodontopathy is related to the aggression of bacterial flora in dental plaque, flora that is influenced on its turn by the evolution of diabetes mellitus. In our study, we have evaluated the inflammatory reaction in periodontium in patients with slowly and progressive periodontitis in patients with diabetes mellitus who had diabetes longer than five years. It has been found that all patients presented a chronic inflammatory infiltrate, abundant, with round mononuclear cells of lymphocyte, plasma cells and macrophage type, with non-homogenous arrangement, more intensely where the covering epithelium presented erosions or necrotic areas. Out of the immunity system cells, the most numerous where of T-lymphocytes type. PMID:22395500

  8. Granulomatous reaction in hepatic inflammatory angiomyolipoma after chemoembolization and spontaneous rupture

    PubMed Central

    Kai, Keita; Miyosh, Atsushi; Aishima, Shinichi; Wakiyama, Kota; Nakashita, Shunya; Iwane, Shinji; Azama, Shinya; Irie, Hiroyuki; Noshiro, Hirokazu

    2015-01-01

    A 77-year-old Japanese woman was transported to a nearby hospital due to sudden abdominal pain and transient loss of consciousness. Abdominal computed tomography (CT) suggested hemoperitoneum and hepatic nodule. She was conservatively treated. Contrast-enhanced CT two months later revealed an increased mass size, and the enhancement pattern suggested the possibility of hepatocellular carcinoma (HCC). Under a clinical diagnosis of HCC, transcatheter arterial chemoembolization (TACE) was performed. A subsequent imaging study revealed that most of the lipiodol used for the embolization was washed out. Therefore, surgical resection was performed. Histologically, the nodule contained numerous inflammatory cells including small lymphocytes, plasma cells and macrophages. Notably, epithelioid granulomatous features with multinucleated giant cells were observed in both the nodule and background liver. Some of the multinucleated giant cells contained oil lipid. Among the infiltrating inflammatory cells, spindle-shaped, histiocytoid or myoid tumor cells with eosinophilic cytoplasm were found. The tumor cells were positive for Melan A and HMB45. The nodule contained many IgG4-positive plasma cells; these were counted and found to number 72.6 cells/HPF (range: 61-80). The calculated IgG4:IgG ratio was 33.2%. The nodule was finally diagnosed as previously ruptured inflammatory angiomyolipoma modified by granulomatous reaction after TACE. PMID:26327777

  9. Inflammatory eye reactions with bisphosphonates and other osteoporosis medications: what are the risks?

    PubMed

    Clark, Emma M; Durup, Darshana

    2015-02-01

    Inflammatory eye reactions (IERs) are rare but have been associated with medications to treat osteoporosis. The aim of this review is to summarize the current literature on the association between IERs and specific medications to treat osteoporosis (bisphosphonates, selective estrogen receptor modulators, strontium, denosumab and teriparatide). We cover the known epidemiology, potential pathogenic mechanisms and a resume of unanswered questions. Briefly, this review highlights that none of the existing randomized clinical trials were powered to identify these rare adverse events, and the majority of the information available is from spontaneous case reports and case series reporting associations between bisphosphonates and IERs. No case reports describe IERs after other anti-osteoporosis medications. Importantly, some case reports describe recurrence of the IER after affected patients were rechallenged with the same or another bisphosphonate, and that no reported cases resolved without discontinuation of the bisphosphonate. However, three large population-based cohort studies have shown conflicting results between osteoporosis treatments and IERs, but overall these studies suggest that IERs may actually be part of underlying inflammatory disease processes that also cause osteoporosis, rather than due to the medications used to treat osteoporosis themselves. There are no clear pathogenic mechanisms for how bisphosphonates could potentially cause IERs. However, the drug is secreted into the tears by the lacrimal gland and could cause irritation to the mucous membranes with subsequent release of inflammatory mediators, similar to the systemic response typically seen after infusion of bisphosphonates. However, in summary it is still not known whether there is a true causal association between bisphosphonates or other anti-osteoporosis medications and IERs, or whether it is confounding by indication and is actually due to underlying inflammatory diseases that cause both

  10. Local inflammatory reaction induced by Scolopendra viridicornis centipede venom in mice.

    PubMed

    Kimura, Louise Faggionato; Prezotto-Neto, José Pedro; Távora, Bianca de Carvalho Lins Fernandes; Antoniazzi, Marta Maria; Knysak, Irene; Gióia Guizze, Samuel Paulo; Santoro, Marcelo Larami; Barbaro, Katia Cristina

    2013-12-15

    Centipede envenomation is generally mild, and human victims usually manifest burning pain, erythema and edema. Despite the abundance and ubiquity of these animals, centipede venom has been poorly characterized in literature. For this reason, the aim of this work was to investigate local inflammatory features induced by Scolopendra viridicornis centipede envenomation in mice, evaluating edema formation, leukocyte infiltration, production of inflammatory mediators, and also performing histological analysis. The highest edematogenic activity induced by the venom, determined by plethysmometry, was noticed 0.5 h after injection in mice footpad. At 24 h, edema was still detected in animals that received 15 and 60 μg of venom, and at 48 h, only in animals injected with 60 μg of venom. In relation to leukocyte count, S. viridicornis venom induced cell recruitment, mainly neutrophils and monocytes/macrophages, in all doses and time periods analyzed in comparison with PBS-injected mice. An increase in lymphocytes was detected especially between 1 and 24 h at 60 μg dose. Besides, eosinophil recruitment was observed mainly for 15 and 60 μg doses in early time periods. Edema formation and cell recruitment were also confirmed by histological analysis. Moreover, S. viridicornis venom stimulated the release of IL-6, MCP-1, KC, and IL-1β. Conversely, S. viridicornis venom did not induce the release of detectable levels of TNF-α. We demonstrated that the edematogenic activity induced by S. viridicornis venom was of rapid onset, and the venom stimulated secretion of pro-inflammatory mediators which contribute to the inflammatory reaction induced by S. viridicornis venom in an experimental model. PMID:24140924

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

    PubMed

    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. PMID:27091601

  12. Retrosternal mass: An interesting allergic reaction to intravenous thrombolytic therapy for acute ischemic stroke

    PubMed Central

    Motamed, Mohammad Reza; Aghaei, Mahboubeh; Badi, Zahra

    2013-01-01

    Stroke is an important cause of disability and death worldwide, with the majority of strokes occurring in older people. Thrombolysis with recombinant tissue plasminogen activator (r-TPA) is the approved treatment for acute ischemic stroke. A major concern of physicians, who treat acute ischemic stroke with recombinant tissue plasminogen activator (r-TPA,) is the risk of intracerebral hemorrhage. However, other adverse reactions, including anaphylaxis and angioedema, can also occur. Here we report an interesting soft tissue reaction to intravenous r-TPA in an 80 year-old male who was treated for acute ischemic stroke. PMID:24250917

  13. Retrosternal mass: An interesting allergic reaction to intravenous thrombolytic therapy for acute ischemic stroke.

    PubMed

    Mehrpour, Masoud; Motamed, Mohammad Reza; Aghaei, Mahboubeh; Badi, Zahra

    2013-01-01

    Stroke is an important cause of disability and death worldwide, with the majority of strokes occurring in older people. Thrombolysis with recombinant tissue plasminogen activator (r-TPA) is the approved treatment for acute ischemic stroke. A major concern of physicians, who treat acute ischemic stroke with recombinant tissue plasminogen activator (r-TPA,) is the risk of intracerebral hemorrhage. However, other adverse reactions, including anaphylaxis and angioedema, can also occur. Here we report an interesting soft tissue reaction to intravenous r-TPA in an 80 year-old male who was treated for acute ischemic stroke. PMID:24250917

  14. Acute inflammatory response to transgastric natural orifice transluminal endoscopic surgery peritoneoscopy: An experimental study in swine

    PubMed Central

    Rezende, Marcelo; Montero, Edna Frasson de Souza; Salomão, Reinaldo; Brunialti, Milena; Rodrigues, Rodrigo; Gomes, Gustavo; Libera, Alice Della; Ferrari, Angelo; Libera, Ermelindo Della

    2013-01-01

    OBJECTIVE: To investigate the impact of transgastric peritoneal access on plasma biomarkers of acute inflammatory response in comparison to laparoscopy. METHODS: This was a prospective and comparative study in a porcine model. Transgastric peritoneal access performed by natural orifice transluminal endoscopic surgery was compared with laparoscopy. Laparotomy and sham groups were used as positive and negative controls, respectively. Thirty-four pigs were assigned to receive transgastric natural orifice transluminal endoscopic surgery (n = 12), laparoscopy (n = 8), laparotomy (n = 8) or a sham procedure involving only anesthesia (n = 6). In the natural orifice transluminal endoscopic surgery group, peritoneoscopy was performed with a gastroscope via transgastric access. Blood samples were collected at baseline and 1, 3, 6, 9 and 24 h after the surgical procedure for measurement of interleukins 1β, 6 and 10 and tumor necrosis factor-α. A complete blood count was performed, and C-reactive protein levels were measured at baseline and at 24 h. RESULTS: All surgical and endoscopic procedures were performed without major complications. Peritoneal cavity inventory showed no signs of peritonitis in any animal. Interleukin 1β, interleukin 10 and tumor necrosis factor-α levels were below the threshold of detection. The mean level of interleukin 6 was statistically significantly higher in the laparotomy group than in the other groups (p<0.05), with no significant differences among the sham, laparoscopy and natural orifice transluminal endoscopic surgery groups (p>0.05). C-reactive protein analysis indicated significant increases in all groups, with no differences among the groups. Complete blood count analysis showed no differences among the groups. CONCLUSIONS: Based on the observed interleukin 6 patterns, the systemic inflammatory response resulting from transgastric peritoneal access by natural orifice transluminal endoscopic surgery is similar in

  15. Acute Endotoxin-Induced Thymic Atrophy Is Characterized By Intrathymic Inflammatory and Wound Healing Responses

    PubMed Central

    Billard, Matthew J.; Gruver, Amanda L.; Sempowski, Gregory D.

    2011-01-01

    Background Productive thymopoiesis is essential for a robust and healthy immune system. Thymus unfortunately is acutely sensitive to stress resulting in involution and decreased T cell production. Thymic involution is a complication of many clinical settings, including infection, malnutrition, starvation, and irradiation or immunosuppressive therapies. Systemic rises in glucocorticoids and inflammatory cytokines are known to contribute to thymic atrophy. Little is known, however, about intrathymic mechanisms that may actively contribute to thymus atrophy or initiate thymic recovery following stress events. Methodology/Principal Findings Phenotypic, histologic and transcriptome/pathway analysis of murine thymic tissue during the early stages of endotoxemia-induced thymic involution was performed to identify putative mechanisms that drive thymic involution during stress. Thymus atrophy in this murine model was confirmed by down-regulation of genes involved in T cell development, cell activation, and cell cycle progression, correlating with observed phenotypic and histologic thymus involution. Significant gene changes support the hypothesis that multiple key intrathymic pathways are differentially activated during stress-induced thymic involution. These included direct activation of thymus tissue by LPS through TLR signaling, local expression of inflammatory cytokines, inhibition of T cell signaling, and induction of wound healing/tissue remodeling. Conclusions/Significance Taken together, these observations demonstrated that in addition to the classic systemic response, a direct intrathymic response to endotoxin challenge concurrently contributes to thymic involution during endotoxemia. These findings are a substantial advancement over current understanding of thymus response to stress and may lead to the development of novel therapeutic approaches to ameliorate immune deficiency associated with stress events. PMID:21437240

  16. Effect of hydrogen sulfide on inflammatory cytokines in acute myocardial ischemia injury in rats

    PubMed Central

    LIU, FANG; LIU, GUANG-JIE; LIU, NA; ZHANG, GANG; ZHANG, JIAN-XIN; LI, LAN-FANG

    2015-01-01

    Hydrogen sulfide (H2S) is believed to be involved in numerous physiological and pathophysiological processes, and now it is recognized as the third endogenous signaling gasotransmitter, following nitric oxide and carbon monoxide; however, the effects of H2S on inflammatory factors in acute myocardial ischemia injury in rats have not been clarified. In the present study, sodium hydrosulfide (NaHS) was used as the H2S donor. Thirty-six male Sprague Dawley rats were randomly divided into five groups: Sham, ischemia, ischemia + low-dose (0.78 mg/kg) NaHS, ischemia + medium-dose (1.56 mg/kg) NaHS, ischemia + high-dose (3.12 mg/kg) NaHS and ischemia + propargylglycine (PPG) (30 mg/kg). The rats in each group were sacrificed 6 h after the surgery for sample collection. Compared with the ischemia group, the cardiac damage in the rats in the ischemia + NaHS groups was significantly reduced, particularly in the high-dose group; in the ischemia + PPG group, the myocardial injury was aggravated compared with that in the ischemia group. Compared with the ischemia group, the levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in the serum of rats in the ischemia + medium- and high-dose NaHS groups were significantly reduced, and the expression of intercellular adhesion molecule-1 (ICAM-1) mRNA and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) protein in the myocardial tissues of rats was significantly reduced. In the ischemia + PPG group, the TNF-α, IL-1β and IL-6 levels in the serum were significantly increased, the expression of ICAM-1 mRNA was increased, although without a significant difference, and the expression of NF-κB was increased. The findings of the present study provide novel evidence for the dual effects of H2S on acute myocardial ischemia injury via the modulation of inflammatory factors. PMID:25667680

  17. Individual Radiosensitivity Measured With Lymphocytes May Predict the Risk of Acute Reaction After Radiotherapy

    SciTech Connect

    Borgmann, Kerstin; Hoeller, Ulrike; Nowack, Sven; Bernhard, Michael; Roeper, Barbara; Brackrock, Sophie; Petersen, Cordula; Szymczak, Silke; Ziegler, Andreas; Feyer, Petra; Alberti, Winfried; Dikomey, Ekkehard

    2008-05-01

    Purpose: We tested whether the chromosomal radiosensitivity of in vitro irradiated lymphocytes could be used to predict the risk of acute reactions after radiotherapy. Methods and Materials: Two prospective studies were performed: study A with 51 patients included different tumor sites and study B included 87 breast cancer patients. Acute reaction was assessed using the Radiation Therapy Oncology Group score. In both studies, patients were treated with curative radiotherapy, and the mean tumor dose applied was 55 Gy (40-65) {+-} boost with 11 Gy (6-31) in study A and 50.4 Gy {+-} boost with 10 Gy in study B. Individual radiosensitivity was determined with lymphocytes irradiated in vitro with X-ray doses of either 3 or 6 Gy and scoring the number of chromosomal deletions. Results: Acute reactions displayed a typical spectrum with 57% in study A and 53% in study B showing an acute reaction of Grade 2-3. Individual radiosensitivity in both studies was characterized by a substantial variation and the fraction of patients with Grade 2-3 reaction was found to increase with increasing individual radiosensitivity measured at 6 Gy (study A, p = 0.238; study B, p = 0.023). For study B, this fraction increased with breast volume, and the impact of individual radiosensitivity on acute reaction was especially pronounced (p = 0.00025) for lower breast volume. No such clear association with acute reaction was observed when individual radiosensitivity was assessed at 3 Gy. Conclusion: Individual radiosensitivity determined at 6 Gy seems to be a good predictor for risk of acute effects after curative radiotherapy.

  18. Best evidence topic report. Rectal or intravenous non-steroidal anti-inflammatory drugs in acute renal colic.

    PubMed

    Lee, Caroline; Gnanasegaram, Dhurga; Maloba, Margaret

    2005-09-01

    A short cut review was carried out to establish whether rectal non-steroidal anti-inflammatory drugs (NSAIDs) are as effective as IV NSAIDs in the management of acute renal colic. Altogether 179 papers were found using the reported search, of which two represent the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. Rectal NSAIDs are an effective form of analgesia for patients with acute renal colic and have fewer side effects compared with intravenous NSAIDs. PMID:16113190

  19. Pitavastatin is a potent anti-inflammatory agent in the rat paw model of acute inflammation.

    PubMed

    Qadir, Farida; Alam, Syed Mahboob; Siddiqi, Abeer Qamar; Kamran, Afshan

    2014-11-01

    Statins are used extensively as anti-hyperlipidemic agents. In addition to curtailing cholesterol synthesis they have been found to have multiple actions unrelated to cholesterol lowering "the pleiotropic effects," which includes inhibition of inflammation. We aimed at investigating the effect of pitavastatin a 3rd generation statin, in suppressing acute inflammation in rat paw edema model. Male Sprague-Dawley rats were randomly assigned to one of five groups (n=8): Control, indomethacin and pitavastatin (0.2mg/kg, 0.4mg/kg, 0.8mg/kg) treated. 1hour following treatment, inflammation was induced by sub-planter injection of egg albumin into the hind paw. Anti-inflammatory effect was evaluated by measurement of edema formation every half hour for three hours, assessment of polymorphonuclear leukocyte (PMNL) infiltration and measurement of tissue damage in skin biopsies. Ascending doses of pitavastatin were found to attenuate these parameters. The lowest dose of pitavastatin (0.2mg/kg) was found to significantly reduce edema volume, PMNL infiltration and tissue damage. The efficacy of the smallest dose was found comparable to indomethacin. PMID:26045381

  20. Non-steroidal anti-inflammatory drugs with adverse psychiatric reactions: five case reports.

    PubMed

    Jiang, H K; Chang, D M

    1999-01-01

    Adverse drug reactions of non-steroidal anti-inflammatory drugs (NSAIDs) are quite prevalent, but there are few reports about possible adverse psychiatric reactions, which may be ignored or underestimated. We describe here five psychiatric outpatients, two with major depressive disorders, one bipolar disorder, one schizophrenic disorder and one anxiety disorder, who were treated with NSAIDs for pain due to rheumatoid arthritis, osteoarthritis or other painful neuromuscular conditions. All five patients developed a moderate to severe depressive state, three patients became obviously paranoid, and four had either thoughts of suicide or an attempt while undergoing co-administration of NSAIDs. The psychiatric symptoms remitted when the NSAIDs were stopped. The depressive and paranoid symptoms returned on seven occasions of re-use or re-challenge with the same or a different type of NSAID in all five patients. When the NSAIDs were stopped again, the patients had another remission of the adverse psychiatric reactions, and eventually recovered to their baseline mental states in clear temporal relationships. The cases presented suggest that NSAIDs can induce or exacerbate idiosyncratic reproducible adverse psychiatric symptoms in certain vulnerable patients, including those with a variety of psychotic or neurotic disorders, and also in elderly persons, but these undesirable side-effects were generally transient and disappeared on withdrawal of the NSAIDs. PMID:10468178

  1. The acute phase protein serum amyloid A (SAA) as an inflammatory marker in equine influenza virus infection.

    PubMed

    Hultén, C; Sandgren, B; Skiöldebrand, E; Klingeborn, B; Marhaug, G; Forsberg, M

    1999-01-01

    The acute phase protein serum amyloid A (SAA) has proven potentially useful as an inflammatory marker in the horse, but the knowledge of SAA responses in viral diseases is limited. The aim of this study was to evaluate SAA as a marker for acute equine influenza A2 (H3N8) virus infection. This is a highly contagious, serious condition that inflicts suffering on affected horses and predisposes them to secondary bacterial infections and impaired performance. Seventy horses, suffering from equine influenza, as verified by clinical signs and seroconversion, were sampled in the acute (the first 48 h) and convalescent (days 11-22) stages of the disease, and SAA concentrations were determined. Clinical signs and rectal temperature were recorded. Secondary infections, that could have influenced SAA concentrations, were clinically suspected in 4 horses. SAA concentrations were higher in the acute stage than in the convalescent stage, and there was a statistically positive relationship between acute stage SAA concentrations and clinical signs and between acute stage SAA concentrations and maximal rectal temperature. Horses sampled early in the acute stage had lower SAA concentrations than those sampled later, indicating increasing concentrations during the first 48 h. There was a statistically positive relationship between convalescent SAA concentrations and degree of clinical signs during the disease process. The results of this investigation indicate that equine SAA responds to equine influenza infection by increasing in concentration during the first 48 h of clinical signs and returning to baseline within 11-22 days in uncomplicated cases. PMID:10918902

  2. Eriodictyol, a plant flavonoid, attenuates LPS-induced acute lung injury through its antioxidative and anti-inflammatory activity

    PubMed Central

    ZHU, GUANG-FA; GUO, HONG-JUAN; HUANG, YAN; WU, CHUN-TING; ZHANG, XIANG-FENG

    2015-01-01

    Acute lung injury (ALI) is characterized by excessive inflammatory responses and oxidative injury in the lung tissue. It has been suggested that anti-inflammatory or antioxidative agents could have therapeutic effects in ALI, and eriodictyol has been reported to exhibit antioxidative and anti-inflammatory activity in vitro. The aim of the present study was to investigate the effect of eriodictyol on lipopolysaccharide (LPS)-induced ALI in a mouse model. The mice were divided into four groups: Phosphate-buffered saline-treated healthy control, LPS-induced ALI, vehicle-treated ALI (LPS + vehicle) and eriodictyol-treated ALI (LPS + eriodictyol). Eriodictyol (30 mg/kg) was administered orally once, 2 days before the induction of ALI. The data showed that eriodictyol pretreatment attenuated LPS-induced ALI through its antioxidative and anti-inflammatory activity. Furthermore, the eriodictyol pretreatment activated the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway in the ALI mouse model, which attenuated the oxidative injury and inhibited the inflammatory cytokine expression in macrophages. In combination, the results of the present study demonstrated that eriodictyol could alleviate the LPS-induced lung injury in mice by regulating the Nrf2 pathway and inhibiting the expression of inflammatory cytokines in macrophages, suggesting that eriodictyol could be used as a potential drug for the treatment of LPS-induced lung injury. PMID:26668626

  3. Naringin Alleviates Diabetic Kidney Disease through Inhibiting Oxidative Stress and Inflammatory Reaction

    PubMed Central

    Chen, Fenqin; Zhang, Ning; Ma, Xiaoyu; Huang, Ting; Shao, Ying; Wu, Can; Wang, Qiuyue

    2015-01-01

    Naringin, a flavanone glycoside extracted from Citrus grandis Osbeck, has a wide range of pharmacological effects. In the present study we aimed at demonstrating the protective effect of naringin against diabetic kidney disease (DKD) and elucidating its possible molecular mechanism underlying. The beneficial effect of naringin was assessed in rats with streptozotocin (STZ)-induced diabetes and high glucose-induced HBZY-1 cells. According to our results, first we found that naringin relieved kidney injury, improved renal function and inhibited collagen formation and renal interstitial fibrosis. Second, we confirmed that naringin restrained oxidative stress by activating Nrf2 antioxidant pathway. Moreover, the results suggested that naringin significantly resisted inflammatory reaction by inhibiting NF- κ B signaling pathway. Taken together, our results demonstrate that naringin effectively alleviates DKD, which provide theoretical basis for naringin clinically used to treatment of DKD. PMID:26619044

  4. Age, Predisposing Diseases, and Ultrasonographic Findings in Determining Clinical Outcome of Acute Acalculous Inflammatory Gallbladder Diseases in Children.

    PubMed

    Yi, Dae Yong; Chang, Eun Jae; Kim, Ji Young; Lee, Eun Hye; Yang, Hye Ran

    2016-10-01

    We evaluated clinical factors such as age, gender, predisposing diseases and ultrasonographic findings that determine clinical outcome of acute acalculous inflammatory gallbladder diseases in children. The patients were divided into the four age groups. From March 2004 through February 2014, clinical data from 131 children diagnosed as acute acalculous inflammatory gallbladder disease by ultrasonography were retrospectively reviewed. Systemic infectious diseases were the most common etiology of acute inflammatory gallbladder disease in children and were identified in 50 patients (38.2%). Kawasaki disease was the most common predisposing disease (28 patients, 21.4%). The incidence was highest in infancy and lowest in adolescence. The age groups were associated with different predisposing diseases; noninfectious systemic disease was the most common etiology in infancy and early childhood, whereas systemic infectious disease was the most common in middle childhood and adolescence (P = 0.001). Gallbladder wall thickening was more commonly found in malignancy (100%) and systemic infection (94.0%) (P = 0.002), whereas gallbladder distension was more frequent in noninfectious systemic diseases (60%) (P = 0.000). Ascites seen on ultrasonography was associated with a worse clinical course compared with no ascites (77.9% vs. 37.7%, P = 0.030), and the duration of hospitalization was longer in patients with ascites (11.6 ± 10.7 vs. 8.0 ± 6.6 days, P = 0.020). In conclusion, consideration of age and predisposing disease in addition to ultrasonographic gallbladder findings in children suspected of acute acalculous inflammatory gallbladder disease might result in better outcomes. PMID:27550491

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

    PubMed Central

    Popovic, Ljiljana M.; Mitic, Nebojsa R.; Bisevac, Boban; Miric, Mirjana; Popovic, Brankica

    2015-01-01

    Exercise induces a multitude of physiological and biochemical changes in blood affecting its redox status. Tissue damage resulting from exercise induces activation of inflammatory cells followed by the increased activity of myeloperoxidase (MPO) in circulation. Vitamin C readily scavenges free radicals and may thereby prevent oxidative damage of important biological macromolecules. The aim of this study was to examine the effect of vitamin C supplementation on oxidative stress and neutrophil inflammatory response induced by acute and regular exercise. Experiment was conducted on acute exercise group (performing Bruce Treadmill Protocol (BTP)) and regular training group. Markers of lipid peroxidation, malondialdehyde (MDA), MPO activity, and vitamin C status were estimated at rest and after BTP (acute exercise group) and before and after vitamin C supplementation in both groups. Our results showed increased postexercise Asc in serum independently of vitamin supplementation. They also showed that vitamin C can significantly decrease postexercise MDA level in both experimental groups. Increased postexercise MPO activity has been found in both groups and was not affected by vitamin C supplementation. We concluded that vitamin C supplementation can suppress lipid peroxidation process during exercise but cannot affect neutrophil inflammatory response in either exercise group. PMID:25802681

  6. Influence of vitamin C supplementation on oxidative stress and neutrophil inflammatory response in acute and regular exercise.

    PubMed

    Popovic, Ljiljana M; Mitic, Nebojsa R; Miric, Dijana; Bisevac, Boban; Miric, Mirjana; Popovic, Brankica

    2015-01-01

    Exercise induces a multitude of physiological and biochemical changes in blood affecting its redox status. Tissue damage resulting from exercise induces activation of inflammatory cells followed by the increased activity of myeloperoxidase (MPO) in circulation. Vitamin C readily scavenges free radicals and may thereby prevent oxidative damage of important biological macromolecules. The aim of this study was to examine the effect of vitamin C supplementation on oxidative stress and neutrophil inflammatory response induced by acute and regular exercise. Experiment was conducted on acute exercise group (performing Bruce Treadmill Protocol (BTP)) and regular training group. Markers of lipid peroxidation, malondialdehyde (MDA), MPO activity, and vitamin C status were estimated at rest and after BTP (acute exercise group) and before and after vitamin C supplementation in both groups. Our results showed increased postexercise Asc in serum independently of vitamin supplementation. They also showed that vitamin C can significantly decrease postexercise MDA level in both experimental groups. Increased postexercise MPO activity has been found in both groups and was not affected by vitamin C supplementation. We concluded that vitamin C supplementation can suppress lipid peroxidation process during exercise but cannot affect neutrophil inflammatory response in either exercise group. PMID:25802681

  7. Application of Molecular Topology for the Prediction of Reaction Yields and Anti-Inflammatory Activity of Heterocyclic Amidine Derivatives

    PubMed Central

    Pla-Franco, Jordi; Gálvez-Llompart, María; Gálvez, Jorge; García-Domenech, Ramón

    2011-01-01

    Topological-mathematical models based on multiple linear regression analyses have been built to predict the reaction yields and the anti-inflammatory activity of a set of heterocylic amidine derivatives, synthesized under environmental friendly conditions, using microwave irradiation. Two models with three variables each were selected. The models were validated by cross-validation and randomization tests. The final outcome demonstrates a good agreement between the predicted and experimental results, confirming the robustness of the method. These models also enabled the screening of virtual libraries for new amidine derivatives predicted to show higher values of reaction yields and anti-inflammatory activity. PMID:21541058

  8. Characteristics and clinical outcome of nonsteroidal anti-inflammatory drug-induced acute hepato-nephrotoxicity among Chinese patients

    PubMed Central

    Cao, Ya-Li; Tian, Zhi-Gang; Wang, Fang; Li, Wen-Ge; Cheng, Dan-Ying; Yang, Yan-Fang; Gao, Hong-Mei

    2014-01-01

    AIM: To determine the clinicopathological characteristics of nonsteroidal anti-inflammatory drug (NSAID)-induced acute hepato-nephrotoxicity among Chinese patients. METHODS: We conducted a retrospective chart review of patients using the International Classification of Diseases, Ninth Revision diagnosis code for acute kidney injury (AKI) (584.5 or 584.9) and for acute liver injury (ALI) (570.0 or 573.3) from January 2004 to December 2013. Medical records were reviewed to confirm the diagnosis of AKI and ALI and to quantify NSAID administration. RESULTS: Seven of 59 patients (11.8%) were identified with acute hepato-nephrotoxicity induced by NSAIDs. Five patients (71.4%) received over the recommended NSAIDs dose. Compared with NSAIDs-associated mere AKI, the risk factors of NSAIDs-induced acute hepato-nephrotoxicity are age older than 60 years (57.1%), a high prevalence of alcohol use (71.4%) and positive hepatitis B virus (HBV) markers (85.7%). Compared with NSAIDs-associated mere ALI, the risk factors of NSAIDs-induced acute hepato-nephrotoxicity are age older than 60 years (57.1%), increased extracellular volume depletion (71.4%), and renin-angiotensin-aldosterone system (RAAS) inhibitor combined use (57.1%). Acute interstitial nephritis and acute tubulointerstitial disease were apparent in three out of six (42.9%) kidney biopsy patients, respectively. Acute hepatitis was found in four out of six (66.7%) liver biopsy patients. Overall complete recovery occurred in four patients within a mean of 118.25 ± 55.42 d. CONCLUSION: The injury typically occurred after an overdose of NSAIDs. The risk factors include age older than 60 years, alcohol use, positive HBV markers, extracellular volume depletion and RAAS inhibitor combined use. PMID:25320533

  9. Acute physical exercise under hypoxia improves sleep, mood and reaction time.

    PubMed

    de Aquino-Lemos, Valdir; Santos, Ronaldo Vagner T; Antunes, Hanna Karen Moreira; Lira, Fabio S; Luz Bittar, Irene G; Caris, Aline V; Tufik, Sergio; de Mello, Marco Tulio

    2016-02-01

    This study aimed to assess the effect of two sessions of acute physical exercise at 50% VO2peak performed under hypoxia (equivalent to an altitude of 4500 m for 28 h) on sleep, mood and reaction time. Forty healthy men were randomized into 4 groups: Normoxia (NG) (n = 10); Hypoxia (HG) (n = 10); Exercise under Normoxia (ENG) (n = 10); and Exercise under Hypoxia (EHG) (n = 10). All mood and reaction time assessments were performed 40 min after awakening. Sleep was reassessed on the first day at 14 h after the initiation of hypoxia; mood and reaction time were measured 28 h later. Two sessions of acute physical exercise at 50% VO2peak were performed for 60 min on the first and second days after 3 and 27 h, respectively, after starting to hypoxia. Improved sleep efficiency, stage N3 and REM sleep and reduced wake after sleep onset were observed under hypoxia after acute physical exercise. Tension, anger, depressed mood, vigor and reaction time scores improved after exercise under hypoxia. We conclude that hypoxia impairs sleep, reaction time and mood. Acute physical exercise at 50% VO2peak under hypoxia improves sleep efficiency, reversing the aspects that had been adversely affected under hypoxia, possibly contributing to improved mood and reaction time. PMID:26522742

  10. Anti-B7-H3 monoclonal antibody ameliorates the damage of acute experimental pancreatitis by attenuating the inflammatory response.

    PubMed

    Zhuang, Xiaohui; Shen, Jiaqing; Jia, Zhengyu; Wu, Airong; Xu, Ting; Shi, Yuqi; Xu, Chunfang

    2016-06-01

    B7-H3, a recently discovered B7 family member, is documented as a regulator in the inflammatory response as well as T cell-mediated immune responses. In this paper, we find that patients with acute pancreatitis revealed overwhelming levels of serum soluble B7-H3 (sB7-H3) associated with the clinical outcomes. Furthermore, B7-H3 protein was marked increased in l-arginine-induced acute experimental pancreatitis. Anti-B7-H3 monoclonal antibody treatment attenuated the proinflammatory cytokine production, downregulated the activation of the NF-κB signaling pathway, and ameliorated the pancreas disruption in l-arginine-induced pancreatitis. In addition, although l-arginine alone failed to induce the production of proinflammatory cytokine and anti-B7-H3 mAb had no effect on the proinflammatory cytokine production of acinar cells, administration of anti-B7-H3 mAb in the coculture model of acinar cells and macrophages stimulated by l-arginine displayed the similar effects. On the whole, B7-H3 participates in the development of acute pancreatitis, and anti-B7-H3 monoclonal antibody ameliorates severity of acute experimental pancreatitis via attenuation of the inflammatory response. PMID:27003113

  11. Evaluation of the systemic acute phase response and endometrial gene expression of serum amyloid A and pro- and anti-inflammatory cytokines in mares with experimentally induced endometritis.

    PubMed

    Christoffersen, Mette; Mette, Christoffersen; Baagoe, Camilla Dooleweerdt; Camilla Dooleweerdt, Baagoe; Jacobsen, Stine; Stine, Jacobsen; Bojesen, Anders Miki; Anders Miki, Bojesen; Petersen, Morten Roenn; Morten Roenn, Petersen; Lehn-Jensen, Henrik; Henrik, Lehn-Jensen

    2010-11-15

    Infectious infertility in the mare is clinically well described, little is however known about the systemic acute phase reaction (APR) and local immunological responses accompanying equine endometritis. The aim of this study was to monitor selected markers of the APR in the systemic circulation and to correlate them to the local innate immune response in the uterus during infectious endometritis. Six adult standard bred mares received an intrauterine infusion of 10(9)CFU Escherichia coli. Blood samples were obtained before (0 h) and 3, 6, 12, 24, 36, 48, 72, 96 and 120 h post inoculation (pi), and endometrial biopsies were sampled before, and 3, 12, 24, 48 and 72 h pi. The infectious endometritis elicited a systemic APR with significantly increased concentrations of the acute phase proteins (APPs) serum amyloid A (SAA) and fibrinogen. Relative gene expression analyses were performed on extracted RNA from endometrial biopsies using quantitative real-time PCR and specific primers for SAA and pro- and anti-inflammatory cytokines. Expression of SAA was significantly up-regulated at 3 and 12h pi, and a significant up-regulated expression of IL-1β, TNFα, IL-8 and IL-10 was observed at 3h pi. Plasma concentration of SAA was significantly correlated to endometrial SAA expression. The results of the present study demonstrate that endometritis gives rise to a systemic APR and an up-regulated endometrial gene expression of SAA and several pro-and anti-inflammatory cytokines. Understanding endometrial expression of acute phase proteins and selected cytokines contributing to uterine immunity in equine endometritis could improve understanding of events leading to infertility in the mare and help identify candidate genes of mediators/markers for diagnostic use. PMID:20728224

  12. Rapidly Progressing Severe Cutaneous Adverse Reaction With Acute Kidney Injury After Drug Exposure: An Uncommon Presentation.

    PubMed

    Rodgers, Bradley K; Kumar, Avinash B

    2016-01-01

    Toxic epidermal necrolysis syndrome (TEN) is a rare severe cutaneous adverse drug reaction that involves skin and mucous membranes. We describe a case of TEN presenting with stage III acute kidney injury, rhabdomyolysis, and acute respiratory failure likely triggered by allopurinol for recently diagnosed gout. Prompt diagnosis, multidisciplinary management, including aggressive resuscitation, cardiorespiratory support, intravenous immunoglobulin therapy, and daily wound care resulted in a positive outcome despite a predicted mortality greater than 60%. Although allopurinol is a known triggering agent, TEN presenting with rhabdomyolysis and acute kidney injury is rare. PMID:24832386

  13. Changing Patterns of Acute Phase Proteins and Inflammatory Mediators in Experimental Caprine Coccidiosis

    PubMed Central

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

    2011-01-01

    This experiment was conducted to assess the changing patterns and relative values of acute phase proteins and inflammatory cytokines in experimental caprine coccidiosis. Eighteen newborn kids were allocated to 3 equal groups. Two groups, A and B, were inoculated with a single dose of 1×103 and1×105 sporulated oocysts of Eimeria arloingi, respectively. The third group, C, received distilled water as the control. Blood samples were collected from the jugular vein of each kid in both groups before inoculation and at days 7, 14, 21, 28, 35, and 42 post-inoculation (PI), and the levels of haptoglobin (Hp), serum amyloid A (SAA), TNF-α, and IFN-γ were measured. For histopathological examinations, 2 kids were selected from each group, euthanized, and necropsied on day 42 PI. Mean Hp concentrations in groups A and B (0.34 and 0.68 g/L) at day 7 PI were 3.2 and 6.3 times higher than the levels before inoculation. The mean SAA concentrations in groups A and B (25.6 and 83.5 µg/ml) at day 7 PI were 4.2 and 13.7 times higher than the levels before inoculation. The magnitude and duration of the Hp and SAA responses correlated well with the inoculation doses and the severity of the clinical signs and diarrhea in kids. These results were consistent with the histopathological features, which showed advanced widespread lesions in group B. In both groups, significant correlations were observed for TNF-α and IFN-γ with SAA and Hp, respectively. In conclusion, Hp and SAA can be useful non-specific diagnostic indicators in caprine coccidiosis. PMID:22072820

  14. Assessment of Inflammation in an Acute on Chronic Model of Inflammatory Bowel Disease with Ultrasound Molecular Imaging

    PubMed Central

    Machtaler, Steven; Knieling, Ferdinand; Luong, Richard; Tian, Lu; Willmann, Jürgen K.

    2015-01-01

    Background: Ultrasound (US) molecular imaging has shown promise in assessing inflammation in preclinical, murine models of inflammatory bowel disease. These models, however, initiated acute inflammation on previously normal colons, in contrast to patients where acute exacerbations are often in chronically inflamed regions. In this study, we explored the potential of dual P- and E-selectin targeted US imaging for assessing acute inflammation on a murine quiescent chronic inflammatory background. Methods: Chronic colitis was induced using three cycles of 4% DSS in male FVB mice. Acute inflammation was initiated 2 weeks after the final DSS cycle through rectal administration of 1% TNBS. Mice at different stages of inflammation were imaged using a small animal ultrasound system following i.v. injection of microbubbles targeted to P- and E-selectin. In vivo imaging results were correlated with ex vivo immunofluorescence and histology. Results: Induction of acute inflammation resulted in an increase in the targeted US signal from 5.5 ± 5.1 arbitrary units (a.u.) at day 0 to 61.0 ± 45.2 a.u. (P < 0.0001) at day 1, 36.3 ± 33.1 a.u. at day 3, returning to levels similar to control at day 5. Immunofluorescence showed significant increase in the percentage of P- and E-selectin positive vessels at day 1 (P-selectin: 21.0 ± 7.1% of vessels; P < 0.05; E-selectin: 16.4 ±3.7%; P < 0.05) compared to day 0 (P-selectin: 10.3 ± 5.7%; E-selectin: 7.3 ± 7.0%). Conclusions: Acute inflammation can be accurately measured in a clinically relevant murine model of chronic IBD using ultrasound molecular imaging with a dual P- and E- selectin-targeted contrast agent. PMID:26379784

  15. Progranulin protects against endotoxin-induced acute kidney injury by downregulating renal cell death and inflammatory responses in mice.

    PubMed

    Xu, Xiaoying; Gou, Linfeng; Zhou, Meng; Yang, Fusheng; Zhao, Yihan; Feng, Tingting; Shi, Peikun; Ghavamian, Armin; Zhao, Weiming; Yu, Yuan; Lu, Yi; Yi, Fan; Liu, Guangyi; Tang, Wei

    2016-09-01

    Progranulin (PGRN), a pluripotent secreted growth factor, is involved in various physiologic and disease processes. However, the role of PGRN in endotoxin-induced septic acute kidney injury (AKI) remains unknown. The objective of this study is to investigate the protective effects of PGRN on an endotoxin-induced AKI mouse model by using PGRN-deficient mice and recombinant PGRN (rPGRN) pretreatment. PGRN levels were increased in kidneys of wild-type (WT) mice at 6 and 24h after lipopolysaccharide (LPS) injection. Renal function detection, hematoxylin and eosin staining, immunohistochemical staining, ELISA and in situ terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick-end labeling were used to reveal tissue injury, inflammatory cell infiltration, production of inflammatory mediators and cell death in mouse kidneys after LPS injection. PGRN deficiency resulted in severe kidney injury and increased apoptotic death, inflammatory cell infiltration, production of pro-inflammatory mediators and the expression and nucleus-to-cytoplasmic translocation of HMGB1 in the kidney. In addition, rPGRN administration before LPS treatment ameliorated the endotoxin-induced AKI in WT mice. PGRN may be a novel biologic agent with therapeutic potential for endotoxin-induced septic AKI possibly by inhibiting LPS-induced renal cell death and inflammatory responses in mice. PMID:27367257

  16. Characterization of the acute inflammatory response in the hybrid tambacu (Piaractus mesopotamicus male x Colossoma macropomum female) (Osteichthyes).

    PubMed

    Martins, M L; Myiazaki, D M Y; Tavares-Dias, M; Fenerick, J; Onaka, E M; Bozzo, F R; Fujimoto, R Y; Moraes, F R

    2009-08-01

    This work evaluated the acute inflammatory response induced by injections of 0.5 mL saline solution (control), 500 microg carrageenin and 0.5 mL thioglycollate 3% in the swim bladder of juvenile tambacu hybrid. Fish were distributed in three treatments, three replications and acclimated for a period of 10 days before assay. The cell characterization from the inflammatory exudate was performed in Giemsa and PAS stained smears. Carrageenin, injected in fish, showed an increase on the total number of cells in the inflammatory exudate when compared to saline and thioglycollate injected. Whereas, for carrageenin-injected fish, the percentage of thrombocyte was higher than thioglycollate. On the other hand, granulocyte percentage in thioglycollate-injected fish was higher than the ones injected using carrageenin. Carrageenin provoked the highest migration of macrophage to the inflammatory site. The PAS method confirmed the presence of three types of granulocytes: eosinophilic granular cell (EGC) type 1 with the characteristics of a special granulocytic cell commonly found in the circulating blood; EGC type 2 shorter than the last one and neutrophil. This study contributes to a better understanding of the inflammatory response and infectious processes in native fish. PMID:19802458

  17. [Ischemic stroke as reaction to an acute stressful event].

    PubMed

    Ibrahimagić, Omer C; Sinanović, Osman; Cickusić, Amra; Smajlović, Dzevdet

    2005-01-01

    The period following ischemic stroke can be considered as a reaction to a stressful event. Changes in cortisol secretion are one of the indicators of stress reaction. The aim of the study was to determine morning serum levels of cortisol in stroke patients within 48 hours and 15 days of ischemic stroke onset. Study group included 40 patients, 20 of them were females, mean age 65.3 +/- 10.3 years. The patients did not receive any corticosteroid agents or spironolactone, and did not suffer from Cushing's or Addison's syndrome. Ischemic stroke was verified by computed tomography of the brain. The fluorometric method with DELFIA Cortisol immunoassay was used to determine morning serum cortisol levels. Reference values of the measured hormone were 201-681 nmol/l. The mean level of serum cortisol within 48 hours of stroke was 560.9 +/- 318.9 nmol/l, and on day 15 it was 426.2 +/- 159.3 nmol/l, i.e. significantly lower (p < 0.02). On the first measurement, the level of serum cortisol was elevated in 32%, and on the second measurement in only 7.5% patients, which was also significantly lower (p < 0.001). It was concluded that the stress reaction in ischemic stroke patients was more pronounced within the first 48 hours of stroke onset. Judging from the morning cortisol levels, the reaction to stress was considerably less pronounced 15 days after stroke onset. PMID:15875466

  18. LPS-Induced Lung Inflammation in Marmoset Monkeys – An Acute Model for Anti-Inflammatory Drug Testing

    PubMed Central

    Seehase, Sophie; Lauenstein, Hans-Dieter; Schlumbohm, Christina; Switalla, Simone; Neuhaus, Vanessa; Förster, Christine; Fieguth, Hans-Gerd; Pfennig, Olaf; Fuchs, Eberhard; Kaup, Franz-Josef; Bleyer, Martina; Hohlfeld, Jens M.; Braun, Armin

    2012-01-01

    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 (IC50). 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. PMID:22952743

  19. Acute Pro- and Anti-Inflammatory Responses to Resistance Exercise in Patients with Coronary Artery Disease: A Pilot Study

    PubMed Central

    Volaklis, Konstantinos A.; Smilios, Ilias; Spassis, Apostolos T.; Zois, Christos E.; Douda, Helen T.; Halle, Martin; Tokmakidis, Savvas P.

    2015-01-01

    Little is known about the inflammatory effects of resistance exercise in healthy and even less in diseased individuals such as cardiac patients. The purpose of this study was to examine the acute pro- and anti-inflammatory responses during resistance exercise (RE) in patients with coronary artery disease. Eight low risk patients completed two acute RE protocols at low (50% of 1 RM; 2x18 rps) and moderate intensity (75% of 1 RM; 3x8 rps) in random order. Both protocols included six exercises and had the same total load volume. Blood samples were obtained before, immediately after and 60 minutes after each protocol for the determination of lactate, TNFα, INF-γ, IL-6, IL-10, TGF-β1, and hsCRP concentrations. IL-6 and IL-10 levels increased (p < 0.05) immediately after both RE protocols with no differences between protocols. INF-γ was significantly lower (p < 0.05) 60 min after the low intensity protocol, whereas TGF-β1 increased (p < 0.05) immediately after the low intensity protocol. There were no differences in TNF-& and hs-CRP after both RE protocols or between protocols. The above data indicate that acute resistance exercise performed at low to moderate intensity in low risk, trained CAD patients is safe and does not exacerbate the inflammation associated with their disease. Key points Acute resistance exercise is safe without exacerbating inflammation in patients with CAD. Both exercise intensities (50 and 75% of 1 RM) elicit desirable pro-and anti-inflammatory responses. With both exercise intensities (50 and 75% of 1 RM) acceptable clinical hemodynamic alterations were observed. PMID:25729295

  20. Immunology of infusion reactions in the treatment of patients with acute lymphoblastic leukemia.

    PubMed

    Asselin, Barbara

    2016-07-01

    Infusion reactions are potentially dose-limiting adverse events associated with intravenous administration of several common agents used to treat patients with acute lymphoblastic leukemia. True clinical hypersensitivity reactions are antibody-mediated and can occur only after repeated exposure to an antigen. Conversely, anaphylactoid infusion reactions are nonantibody-mediated and often occur on the initial exposure to a drug. Cytokine-release syndrome comprises a subset of nonantibody-mediated infusion reactions associated with the use of monoclonal antibodies and immune therapies. Clinical symptoms of hypersensitivity reactions and nonantibody-mediated infusion reactions heavily overlap and can be difficult to distinguish in practice. Regardless of the underlying mechanism, any infusion reaction can negatively affect treatment efficacy and patient safety. These events require prompt response, and potentially, modification of subsequent therapy. PMID:27086555

  1. Acute adverse reactions to magnetic resonance contrast media--gadolinium chelates.

    PubMed

    Li, A; Wong, C S; Wong, M K; Lee, C M; Au Yeung, M C

    2006-05-01

    The objective of this study was to evaluate the clinical safety of intravenous gadolinium-based contrast media used in patients who underwent MRI at a single institution. Acute adverse reactions to intravenous gadolinium-based contrast media used for MRI at the Princess Margaret Hospital, Hong Kong, SAR, from January 1999 to November 2004 were recorded in an incidence log book. The medical records of patients' demographics were retrospectively reviewed and the nature, frequency and severity of the adverse reactions were investigated and documented. The incidence of acute adverse reactions to intravenous gadolinium-based contrast media was 0.48% (45 patients with 46 adverse reactions). The severity of these adverse reactions were 96% mild, 2% moderate (one patient developed shortness of breath that required oxygen supplementation and intravenous steroidal management) and 2% severe (one patient developed an anaphylactoid reaction, but successfully recovered through timely resuscitation). No patients were recorded as having contrast extravasation and none died as a result of any adverse reaction. Among the 45 patients who developed adverse reactions, three patients (6.7%) had prior adverse reactions to iodinated contrast media, three (6.7%) had prior reactions to a different gadolinium-based contrast agent, one (2%) had asthma and nine (20%) had a history of drug/food allergy. Overall, 41% of the adverse reactions were not documented in the final MRI report or the clinical medical records. Gadolinium-based contrast media are safe and well tolerated by the vast majority of patients. In our study, the adverse reaction rate (0.48%) and the incidence of severe anaphylactoid reaction (0.01%) concur with those reported in the literature. Although most of the symptoms are mild and transient, these adverse reactions must be accurately documented and managed. PMID:16632615

  2. Severe inflammatory reaction induced by peritoneal trauma is the key driving mechanism of postoperative adhesion formation

    PubMed Central

    2011-01-01

    Background Many factors have been put forward as a driving mechanism of surgery-triggered adhesion formation (AF). In this study, we underline the key role of specific surgical trauma related with open surgery (OS) and laparoscopic (LS) conditions in postoperative AF and we aimed to study peritoneal tissue inflammatory reaction (TIR), remodelling specific complications of open surgery (OS) versus LS and subsequently evaluating AF induced by these conditions. Methods A prospective randomized study was done in 80 anaesthetised female Wistar rats divided equally into 2 groups. Specific traumatic OS conditions were induced by midline incision line (MIL) extension and tissue drying and specific LS conditions were remodelled by intraperitoneal CO2 insufflation at the 10 cm of water. TIR was evaluated at the 24th, 72nd, 120th and 168th hour by scoring scale. Statistical analysis was performed by the non-parametric t test and two-way ANOVA using Bonferroni post-tests. Results More pronounced residual TIR was registered after OS than after LS. There were no significant TIR interactions though highly significant differences were observed between the OS and LS groups (p < 0.0001) with regard to surgical and time factors. The TIR change differences between the OS and LS groups were pronounced with postoperative time p < 0.05 at the 24th and 72nd; p < 0.01 - 120th and p < 0.001 - 168th hrs. Adhesion free wounds were observed in 20.0 and 31.0% of cases after creation of OS and LS conditions respectively; with no significant differences between these values (p > 0.05). However larger adhesion size (41.67 ± 33.63) was observed after OS in comparison with LS (20.31 ± 16.38). The upper-lower 95% confidential limits ranged from 60.29 to 23.04 and from 29.04 to 11.59 respectively after OS and LS groups with significant differences (p = 0.03). Analogous changes were observed in adhesion severity values. Subsequently, severe TIR parameters were followed by larger sizes of severe

  3. Traumeel – an emerging option to nonsteroidal anti-inflammatory drugs in the management of acute musculoskeletal injuries

    PubMed Central

    Schneider, Christian

    2011-01-01

    Musculoskeletal injuries are on the rise. First-line management of such injuries usually employs the RICE (rest, ice, compression, and elevation) approach to limit excessive inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) are also commonly used to limit inflammation and to control pain. Traumeel®, a preparation with bioregulatory effects is also used to treat the symptoms associated with acute musculoskeletal injuries, including pain and swelling. Traumeel is a fixed combination of biological and mineral extracts, which aims to apply stimuli to multiple targets to restore normal functioning of regulatory mechanisms. This paper presents the accumulating evidence of Traumeel’s action on the inflammatory process, and of its efficacy and tolerability in randomized trials, as well as observational and surveillance studies for the treatment of musculoskeletal injuries. Traumeel has shown comparable effectiveness to NSAIDs in terms of reducing symptoms of inflammation, accelerating recovery, and improving mobility, with a favorable safety profile. While continued research and development is ongoing to broaden the clinical evidence of Traumeel in acute musculoskeletal injury and to further establish its benefits, current information suggests that Traumeel may be considered as an anti-inflammatory agent that is at least as effective and appears to be better tolerated than NSAIDs. PMID:21556350

  4. The role of MRI in the diagnosis of acute radiation reaction in breast cancer patient

    NASA Astrophysics Data System (ADS)

    Startseva, Zh A.; Musabaeva, L. I.; Usova, AV; Frolova, I. G.; Simonov, K. A.; Velikaya, V. V.

    2016-02-01

    A clinical case with acute radiation reaction of the left breast after organ-preserving surgery with 10 Gy IORT (24.8 Gy) conventional radiation therapy has been presented. Comprehensive MRI examination showed signs of radiation- induced damage to skin, soft tissues and vessels of the residual breast.

  5. Specific inflammatory response of Anemonia sulcata (Cnidaria) after bacterial injection causes tissue reaction and enzymatic activity alteration.

    PubMed

    Trapani, M R; Parisi, M G; Parrinello, D; Sanfratello, M A; Benenati, G; Palla, F; Cammarata, M

    2016-03-01

    The evolution of multicellular organisms was marked by adaptations to protect against pathogens. The mechanisms for discriminating the ''self'' from ''non-self" have evolved into a long history of cellular and molecular strategies, from damage repair to the co-evolution of host-pathogen interactions. We investigated the inflammatory response in Anemonia sulcata (Cnidaria: Anthozoa) following injection of substances that varied in type and dimension, and observed clear, strong and specific reactions, especially after injection of Escherichia coli and Vibrio alginolyticus. Moreover, we analyzed enzymatic activity of protease, phosphatase and esterase, showing how the injection of different bacterial strains alters the expression of these enzymes and suggesting a correlation between the appearance of the inflammatory reaction and the modification of enzymatic activities. Our study shows for the first time, a specific reaction and enzymatic responses following injection of bacteria in a cnidarian. PMID:26836977

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

    PubMed Central

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

    2015-01-01

    Objectives 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. Methods 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. Results 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. Conclusion 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. PMID:26378783

  7. Dual Islet Transplantation Modeling of the Instant Blood-Mediated Inflammatory Reaction

    PubMed Central

    Martin, BM; Samy, KP; Lowe, MC; Thompson, PW; Cano, J; Farris, AB; Song, M; Dove, CR; Leopardi, FV; Strobert, EA; Jenkins, JB; Collins, BH; Larsen, CP; Kirk, AD

    2015-01-01

    Islet xenotransplantation is a potential treatment for diabetes without the limitations of tissue availability. Although successful experimentally, early islet loss remains substantial and attributed to an instant blood mediated inflammatory reaction (IBMIR). This syndrome of islet destruction has been incompletely defined and characterization in pig-to-primate models has been hampered by logistical and statistical limitations of large animal studies. To further investigate IBMIR, we developed a novel in vivo dual islet transplant model to precisely characterize IBMIR as proof-of-concept that this model can serve to properly control experiments comparing modified xenoislet preparations. Wild-type (WT) and α1,3-galactosyltransferase knockout (GTKO) neonatal porcine islets (NPIs) were studied in non-immunosuppressed rhesus macaques. Inert polyethylene microspheres served as a control for the effects of portal embolization. Digital analysis of immunohistochemistry targeting IBMIR mediators was performed at one and 24 hours after intraportal islet infusion. Early findings observed in transplanted islets include complement and antibody deposition, and infiltration by neutrophils, macrophages, and platelets. Insulin, complement, antibody, neutrophils, macrophages, and platelets were similar between GTKO and WT islets, with increasing macrophage infiltration at 24 hours in both phenotypes. This model provides an objective and internally controlled study of distinct islet preparations and documents the temporal histology of IBMIR. PMID:25702898

  8. Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1

    PubMed Central

    Vettorazzi, Sabine; Bode, Constantin; Dejager, Lien; Frappart, Lucien; Shelest, Ekaterina; Klaßen, Carina; Tasdogan, Alpaslan; Reichardt, Holger M.; Libert, Claude; Schneider, Marion; Weih, Falk; Henriette Uhlenhaut, N.; David, Jean-Pierre; Gräler, Markus; Kleiman, Anna; Tuckermann, Jan P.

    2015-01-01

    Acute lung injury (ALI) is a severe inflammatory disease for which no specific treatment exists. As glucocorticoids have potent immunosuppressive effects, their application in ALI is currently being tested in clinical trials. However, the benefits of this type of regimen remain unclear. Here we identify a mechanism of glucocorticoid action that challenges the long-standing dogma of cytokine repression by the glucocorticoid receptor. Contrarily, synergistic gene induction of sphingosine kinase 1 (SphK1) by glucocorticoids and pro-inflammatory stimuli via the glucocorticoid receptor in macrophages increases circulating sphingosine 1-phosphate levels, which proves essential for the inhibition of inflammation. Chemical or genetic inhibition of SphK1 abrogates the therapeutic effects of glucocorticoids. Inflammatory p38 MAPK- and mitogen- and stress-activated protein kinase 1 (MSK1)-dependent pathways cooperate with glucocorticoids to upregulate SphK1 expression. Our findings support a critical role for SphK1 induction in the suppression of lung inflammation by glucocorticoids, and therefore provide rationales for effective anti-inflammatory therapies. PMID:26183376

  9. CD99-like 2 (CD99L2)-deficient mice are defective in the acute inflammatory response.

    PubMed

    Rutledge, Nakisha S; Weber, Evan W; Winger, Ryan; Tourtellotte, Warren G; Park, Seong Hoe; Muller, William A

    2015-12-01

    CD99-Like 2 (CD99L2) is a Type I glycoprotein expressed on leukocytes and endothelial cells as well as other cell types. It is related to CD99, although it shows only 38% sequence identity. CD99L2 has been shown to play a role in leukocyte extravasation in mice under various inflammatory conditions using anti-CD99L2 antibodies and, in one case by targeted deletion of CD99L2. We report here studies on an independently made CD99L2 "knockout mouse" that extend our knowledge of the role of CD99L2 in inflammation. CD99L2 deficiency did not affect the total or relative numbers of circulating leukocyte subsets, red blood cells, or platelets. Neither did CD99L2 deficiency affect the expression of ICAM-1, PECAM, or CD99 on endothelial cells. Mice lacking CD99L2 had a defective inflammatory response in the thioglycollate peritonitis model with a greater than 80% block in neutrophil infiltration and a nearly complete block in monocyte emigration into the peritoneal cavity measured 16h after the inflammatory challenge. The mice will be a useful resource to study the role of CD99L2 in various acute and chronic inflammatory diseases. PMID:26321243

  10. Acute inflammatory response of the male breasts secondary to self-injection of petroleum jelly: a case report.

    PubMed

    Chen, Ming; Yalamanchili, Chandana; Hamous, James; Piskun, Mary A; Weis, Brian

    2008-04-01

    The injection of liquid foreign materials such as petroleum jelly and paraffin oil was used as an early medical intervention for the augmentation of body contour in the late 19th century. These practices were associated with severe late onset complications and they have been abandoned by plastic surgeons today. This article discusses a male-to-female transsexual patient with an acute inflammatory response with early sclerosing lipogranuloma of breasts associated with the self-injection of large amounts of petroleum jelly. The inflammation is successfully controlled with the early administration of prophylactic broad-spectrum antibiotics, steroids, and nonsteroid anti-inflammatory agents followed by a subcutaneous mastectomy. The importance of medical education and psychology counseling is discussed. PMID:18360333

  11. Non–Muscle Myosin Light Chain Kinase Isoform Is a Viable Molecular Target in Acute Inflammatory Lung Injury

    PubMed Central

    Mirzapoiazova, Tamara; Moitra, Jaideep; Moreno-Vinasco, Liliana; Sammani, Saad; Turner, Jerry R.; Chiang, Eddie T.; Evenoski, Carrie; Wang, Ting; Singleton, Patrick A.; Huang, Yong; Lussier, Yves A.; Watterson, D. Martin; Dudek, Steven M.; Garcia, Joe G. N.

    2011-01-01

    Acute lung injury (ALI) and mechanical ventilator-induced lung injury (VILI), major causes of acute respiratory failure with elevated morbidity and mortality, are characterized by significant pulmonary inflammation and alveolar/vascular barrier dysfunction. Previous studies highlighted the role of the non–muscle myosin light chain kinase isoform (nmMLCK) as an essential element of the inflammatory response, with variants in the MYLK gene that contribute to ALI susceptibility. To define nmMLCK involvement further in acute inflammatory syndromes, we used two murine models of inflammatory lung injury, induced by either an intratracheal administration of lipopolysaccharide (LPS model) or mechanical ventilation with increased tidal volumes (the VILI model). Intravenous delivery of the membrane-permeant MLC kinase peptide inhibitor, PIK, produced a dose-dependent attenuation of both LPS-induced lung inflammation and VILI (∼50% reductions in alveolar/vascular permeability and leukocyte influx). Intravenous injections of nmMLCK silencing RNA, either directly or as cargo within angiotensin-converting enzyme (ACE) antibody–conjugated liposomes (to target the pulmonary vasculature selectively), decreased nmMLCK lung expression (∼70% reduction) and significantly attenuated LPS-induced and VILI-induced lung inflammation (∼40% reduction in bronchoalveolar lavage protein). Compared with wild-type mice, nmMLCK knockout mice were significantly protected from VILI, with significant reductions in VILI-induced gene expression in biological pathways such as nrf2-mediated oxidative stress, coagulation, p53-signaling, leukocyte extravasation, and IL-6–signaling. These studies validate nmMLCK as an attractive target for ameliorating the adverse effects of dysregulated lung inflammation. PMID:20139351

  12. Amelioration of Acute Kidney Injury in Lipopolysaccharide-Induced Systemic Inflammatory Response Syndrome by an Aldose Reductase Inhibitor, Fidarestat

    PubMed Central

    Takahashi, Kazunori; Mizukami, Hiroki; Kamata, Kosuke; Inaba, Wataru; Kato, Noriaki; Hibi, Chihiro; Yagihashi, Soroku

    2012-01-01

    Background Systemic inflammatory response syndrome is a fatal disease because of multiple organ failure. Acute kidney injury is a serious complication of systemic inflammatory response syndrome and its genesis is still unclear posing a difficulty for an effective treatment. Aldose reductase (AR) inhibitor is recently found to suppress lipopolysaccharide (LPS)-induced cardiac failure and its lethality. We studied the effects of AR inhibitor on LPS-induced acute kidney injury and its mechanism. Methods Mice were injected with LPS and the effects of AR inhibitor (Fidarestat 32 mg/kg) before or after LPS injection were examined for the mortality, severity of renal failure and kidney pathology. Serum concentrations of cytokines (interleukin-1β, interleukin-6, monocyte chemotactic protein-1 and tumor necrosis factor-α) and their mRNA expressions in the lung, liver, spleen and kidney were measured. We also evaluated polyol metabolites in the kidney. Results Mortality rate within 72 hours was significantly less in LPS-injected mice treated with AR inhibitor both before (29%) and after LPS injection (40%) than untreated mice (90%). LPS-injected mice showed marked increases in blood urea nitrogen, creatinine and cytokines, and AR inhibitor treatment suppressed the changes. LPS-induced acute kidney injury was associated with vacuolar degeneration and apoptosis of renal tubular cells as well as infiltration of neutrophils and macrophages. With improvement of such pathological findings, AR inhibitor treatment suppressed the elevation of cytokine mRNA levels in multiple organs and renal sorbitol accumulation. Conclusion AR inhibitor treatment ameliorated LPS-induced acute kidney injury, resulting in the lowered mortality. PMID:22253906

  13. Developmental endothelial locus-1 modulates platelet-monocyte interactions and instant blood-mediated inflammatory reaction in islet transplantation.

    PubMed

    Kourtzelis, Ioannis; Kotlabova, Klara; Lim, Jong-Hyung; Mitroulis, Ioannis; Ferreira, Anaisa; Chen, Lan-Sun; Gercken, Bettina; Steffen, Anja; Kemter, Elisabeth; Klotzsche-von Ameln, Anne; Waskow, Claudia; Hosur, Kavita; Chatzigeorgiou, Antonios; Ludwig, Barbara; Wolf, Eckhard; Hajishengallis, George; Chavakis, Triantafyllos

    2016-04-01

    Platelet-monocyte interactions are strongly implicated in thrombo-inflammatory injury by actively contributing to intravascular inflammation, leukocyte recruitment to inflamed sites, and the amplification of the procoagulant response. Instant blood-mediated inflammatory reaction (IBMIR) represents thrombo-inflammatory injury elicited upon pancreatic islet transplantation (islet-Tx), thereby dramatically affecting transplant survival and function. Developmental endothelial locus-1 (Del-1) is a functionally versatile endothelial cell-derived homeostatic factor with anti-inflammatory properties, but its potential role in IBMIR has not been previously addressed. Here, we establish Del-1 as a novel inhibitor of IBMIR using a whole blood-islet model and a syngeneic murine transplantation model. Indeed, Del-1 pre-treatment of blood before addition of islets diminished coagulation activation and islet damage as assessed by C-peptide release. Consistently, intraportal islet-Tx in transgenic mice with endothelial cell-specific overexpression of Del-1 resulted in a marked decrease of monocytes and platelet-monocyte aggregates in the transplanted tissues, relative to those in wild-type recipients. Mechanistically, Del-1 decreased platelet-monocyte aggregate formation, by specifically blocking the interaction between monocyte Mac-1-integrin and platelet GPIb. Our findings reveal a hitherto unknown role of Del-1 in the regulation of platelet-monocyte interplay and the subsequent heterotypic aggregate formation in the context of IBMIR. Therefore, Del-1 may represent a novel approach to prevent or mitigate the adverse reactions mediated through thrombo-inflammatory pathways in islet-Tx and perhaps other inflammatory disorders involving platelet-leukocyte aggregate formation. PMID:26676803

  14. Sex-dimorphic adverse drug reactions to immune suppressive agents in inflammatory bowel disease

    PubMed Central

    Zelinkova, Zuzana; Bultman, Evelien; Vogelaar, Lauran; Bouziane, Cheima; Kuipers, Ernst J; van der Woude, C Janneke

    2012-01-01

    AIM: To analyze sex differences in adverse drug reactions (ADR) to the immune suppressive medication in inflammatory bowel disease (IBD) patients. METHODS: All IBD patients attending the IBD outpatient clinic of a referral hospital were identified through the electronic diagnosis registration system. The electronic medical records of IBD patients were reviewed and the files of those patients who have used immune suppressive therapy for IBD, i.e., thiopurines, methotrexate, cyclosporine, tacrolimus and anti-tumor necrosis factor agents (anti-TNF); infliximab (IFX), adalimumab (ADA) and/or certolizumab, were further analyzed. The reported ADR to immune suppressive drugs were noted. The general definition of ADR used in clinical practice comprised the occurrence of the ADR in the temporal relationship with its disappearance upon discontinuation of the medication. Patients for whom the required information on drug use and ADR was not available in the electronic medical record and patients with only one registered contact and no further follow-up at the outpatient clinic were excluded. The difference in the incidence and type of ADR between male and female IBD patients were analyzed statistically by χ2 test. RESULTS: In total, 1009 IBD patients were identified in the electronic diagnosis registration system. Out of these 1009 patients, 843 patients were eligible for further analysis. There were 386 males (46%), mean age 42 years (range: 16-87 years) with a mean duration of the disease of 14 years (range: 0-54 years); 578 patients with Crohn’s disease, 244 with ulcerative colitis and 21 with unclassified colitis. Seventy percent (586 pts) of patients used any kind of immune suppressive agents at a certain point of the disease course, the majority of the patients (546 pts, 65%) used thiopurines, 176 pts (21%) methotrexate, 46 pts (5%) cyclosporine and one patient tacrolimus. One third (240 pts, 28%) of patients were treated with anti-TNF, the majority of patients (227

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

    PubMed Central

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

    2012-01-01

    The possible role of β-2 adrenergic receptors in modulation of inflammatory and nociceptive conditions suggests that the β-2 adrenergic receptor agonist, salbutamol, may have beneficial anti-inflammatory and analgesic effects. Therefore, in this study, we induced inflammatory and nociceptive responses with carrageenan-induced paw edema or cotton-pellet-induced granuloma models, both of which result in oxidative stress. We hypothesized that salbutamol would prevent inflammatory and nociceptive responses by stimulating β-2 adrenergic receptors and the prevention of generation of ROS during the acute inflammation process in rats. Both doses of salbutamol used in the study (1 and 2 mg/kg) effectively blocked the acute inflammation and inflammatory nociception induced by carrageenan. In the cotton-pellet-induced granuloma test, both doses of salbutamol also significantly decreased the weight of granuloma tissue on the cotton pellets when compared to the control. Anti-inflammatory and analgesic effects of salbutamol were found to be comparable with those of indomethacin. Salbutamol decreased myeloperoxidase (MPO) activity and lipid peroxidation (LPO) level and increased the activity of superoxide dismutase (SOD) and level of glutathione (GSH) during the acute phase of inflammation. In conclusion, salbutamol can decrease acute and chronic inflammation, possibly through the stimulation of β-2 adrenergic receptors. This anti-inflammatory effect may be of significance in asthma treatment, where inflammation also takes part in the etiopathology. This study reveals that salbutamol has significant antioxidative effects, which at least partially explain its anti-inflammatory capabilities. These findings presented here may also shed light on the roles of β-2 adrenergic receptors in inflammatory and hyperalgesic conditions. PMID:22665951

  16. Role of Cystathionine Gamma-Lyase in Immediate Renal Impairment and Inflammatory Response in Acute Ischemic Kidney Injury.

    PubMed

    Markó, Lajos; Szijártó, István A; Filipovic, Milos R; Kaßmann, Mario; Balogh, András; Park, Joon-Keun; Przybyl, Lukasz; N'diaye, Gabriele; Krämer, Stephanie; Anders, Juliane; Ishii, Isao; Müller, Dominik N; Gollasch, Maik

    2016-01-01

    Hydrogen sulfide (H2S) is known to act protectively during renal ischemia/reperfusion injury (IRI). However, the role of the endogenous H2S in acute kidney injury (AKI) is largely unclear. Here, we analyzed the role of cystathionine gamma-lyase (CTH) in acute renal IRI using CTH-deficient (Cth(-/-)) mice whose renal H2S levels were approximately 50% of control (wild-type) mice. Although levels of serum creatinine and renal expression of AKI marker proteins were equivalent between Cth(-/-) and control mice, histological analysis revealed that IRI caused less renal tubular damage in Cth(-/-) mice. Flow cytometric analysis revealed that renal population of infiltrated granulocytes/macrophages was equivalent in these mice. However, renal expression levels of certain inflammatory cytokines/adhesion molecules believed to play a role in IRI were found to be lower after IRI only in Cth(-/-) mice. Our results indicate that the systemic CTH loss does not deteriorate but rather ameliorates the immediate AKI outcome probably due to reduced inflammatory responses in the kidney. The renal expression of CTH and other H2S-producing enzymes was markedly suppressed after IRI, which could be an integrated adaptive response for renal cell protection. PMID:27273292

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

    PubMed

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

    2015-10-01

    The inflammatory response aims to restore homeostasis by means of removing a biological stress, such as an invading bacterial pathogen. In cases of acute systemic inflammation, the possibility of collateral tissue damage arises, which leads to a necessary down-regulation of the response. A reduced ordinary differential equations (ODE) model of acute inflammation was presented and investigated in [10]. That system contains multiple positive and negative feedback loops and is a highly coupled and nonlinear ODE. The implementation of nonlinear model predictive control (NMPC) as a methodology for determining proper therapeutic intervention for in silico patients displaying complex inflammatory states was initially explored in [5]. Since direct measurements of the bacterial population and the magnitude of tissue damage/dysfunction are not readily available or biologically feasible, the need for robust state estimation was evident. In this present work, we present results on the nonlinear reachability of the underlying model, and then focus our attention on improving the predictability of the underlying model by coupling the NMPC with a particle filter. The results, though comparable to the initial exploratory study, show that robust state estimation of this highly nonlinear model can provide an alternative to prior updating strategies used when only partial access to the unmeasurable states of the system are available. PMID:26280180

  18. Systemic inflammatory response syndrome in nonhuman primates culminating in multiple organ failure, acute lung injury, and disseminated intravascular coagulation.

    PubMed

    Hukkanen, Renee R; Liggitt, H Denny; Murnane, Robert D; Frevert, Charles W

    2009-10-01

    The systemic inflammatory response syndrome (SIRS) is a clinicopathological manifestation of overexuberant acute-phase inflammation caused by infectious or noninfectious etiologies. The systemic release of pro-inflammatory cytokines, chemokines, and lipid and vasoactive mediators induces endothelial damage and microvascular thrombosis, potentially culminating in disseminated intravascular coagulation (DIC), acute respiratory distress syndrome (ARDS), and multiple organ dysfunction (MOD) or failure (MOF). We present five cases in the pig-tailed macaque and olive baboon where SIRS resulted in MOF, ARDS, DIC, and the Waterhouse-Friderichsen syndrome; each with gross and histological elements manifested as edema, deposition of fibrin, hemorrhage, and thrombosis. In the described cases, SIRS was the end-common pathway for multiple risk factors that parallel those documented in humans: major surgery, obstetric complications, and infection. The diagnosis of SIRS should be considered when evaluating nonhuman primate (NHP) cases of MOF manifesting with histological evidence of vascular leakage. Experimental manipulation of NHP models may be complicated by SIRS and accompanying rapid clinical decompensation. Such adverse events may compromise toxicological studies and should be avoided when possible. PMID:19773593

  19. Role of Cystathionine Gamma-Lyase in Immediate Renal Impairment and Inflammatory Response in Acute Ischemic Kidney Injury

    PubMed Central

    Markó, Lajos; Szijártó, István A.; Filipovic, Milos R.; Kaßmann, Mario; Balogh, András; Park, Joon-Keun; Przybyl, Lukasz; N’diaye, Gabriele; Krämer, Stephanie; Anders, Juliane; Ishii, Isao; Müller, Dominik N.; Gollasch, Maik

    2016-01-01

    Hydrogen sulfide (H2S) is known to act protectively during renal ischemia/reperfusion injury (IRI). However, the role of the endogenous H2S in acute kidney injury (AKI) is largely unclear. Here, we analyzed the role of cystathionine gamma-lyase (CTH) in acute renal IRI using CTH-deficient (Cth−/−) mice whose renal H2S levels were approximately 50% of control (wild-type) mice. Although levels of serum creatinine and renal expression of AKI marker proteins were equivalent between Cth−/− and control mice, histological analysis revealed that IRI caused less renal tubular damage in Cth−/− mice. Flow cytometric analysis revealed that renal population of infiltrated granulocytes/macrophages was equivalent in these mice. However, renal expression levels of certain inflammatory cytokines/adhesion molecules believed to play a role in IRI were found to be lower after IRI only in Cth−/− mice. Our results indicate that the systemic CTH loss does not deteriorate but rather ameliorates the immediate AKI outcome probably due to reduced inflammatory responses in the kidney. The renal expression of CTH and other H2S-producing enzymes was markedly suppressed after IRI, which could be an integrated adaptive response for renal cell protection. PMID:27273292

  20. Pyruvate dehydrogenase kinase 2 and 4 gene deficiency attenuates nociceptive behaviors in a mouse model of acute inflammatory pain.

    PubMed

    Jha, Mithilesh Kumar; Rahman, Md Habibur; Park, Dong Ho; Kook, Hyun; Lee, In-Kyu; Lee, Won-Ha; Suk, Kyoungho

    2016-09-01

    Pyruvate dehydrogenase (PDH) kinases (PDKs) 1-4, expressed in peripheral and central tissues, regulate the activity of the PDH complex (PDC). The PDC is an important mitochondrial gatekeeping enzyme that controls cellular metabolism. The role of PDKs in diverse neurological disorders, including neurometabolic aberrations and neurodegeneration, has been described. Implications for a role of PDKs in inflammation and neurometabolic coupling led us to investigate the effect of genetic ablation of PDK2/4 on nociception in a mouse model of acute inflammatory pain. Deficiency in Pdk2 and/or Pdk4 in mice led to attenuation of formalin-induced nociceptive behaviors (flinching, licking, biting, or lifting of the injected paw). Likewise, the pharmacological inhibition of PDKs substantially diminished the nociceptive responses in the second phase of the formalin test. Furthermore, formalin-provoked paw edema formation and mechanical and thermal hypersensitivities were significantly reduced in Pdk2/4-deficient mice. Formalin-driven neutrophil recruitment at the site of inflammation, spinal glial activation, and neuronal sensitization were substantially lessened in the second or late phase of the formalin test in Pdk2/4-deficient animals. Overall, our results suggest that PDK2/4 can be a potential target for the development of pharmacotherapy for the treatment of acute inflammatory pain. © 2016 Wiley Periodicals, Inc. PMID:26931482

  1. Prophylaxis and management of acute radiation-induced skin reactions: a systematic review of the literature

    PubMed Central

    Salvo, N.; Barnes, E.; van Draanen, J.; Stacey, E.; Mitera, G.; Breen, D.; Giotis, A.; Czarnota, G.; Pang, J.; De Angelis, C.

    2010-01-01

    Radiation therapy is a common treatment for cancer patients. One of the most common side effects of radiation is acute skin reaction (radiation dermatitis) that ranges from a mild rash to severe ulceration. Approximately 85% of patients treated with radiation therapy will experience a moderate-to-severe skin reaction. Acute radiation-induced skin reactions often lead to itching and pain, delays in treatment, and diminished aesthetic appearance—and subsequently to a decrease in quality of life. Surveys have demonstrated that a wide variety of topical, oral, and intravenous agents are used to prevent or to treat radiation-induced skin reactions. We conducted a literature review to identify trials that investigated products for the prophylaxis and management of acute radiation dermatitis. Thirty-nine studies met the pre-defined criteria, with thirty-three being categorized as prophylactic trials and six as management trials. For objective evaluation of skin reactions, the Radiation Therapy Oncology Group criteria and the U.S. National Cancer Institute Common Toxicity Criteria were the most commonly used tools (65% of the studies). Topical corticosteroid agents were found to significantly reduce the severity of skin reactions; however, the trials of corticosteroids evaluated various agents, and no clear indication about a preferred corticosteroid has emerged. Amifostine and oral enzymes were somewhat effective in preventing radiation-induced skin reactions in phase ii and phase iii trials respectively; further large randomized controlled trials should be undertaken to better investigate those products. Biafine cream (Ortho–McNeil Pharmaceuticals, Titusville, NJ, U.S.A.) was found not to be superior to standard regimes in the prevention of radiation-induced skin reactions (n = 6). In conclusion, the evidence is insufficient to support the use of a particular agent for the prevention and management of acute radiation-induced skin reactions. Future trials should focus

  2. Prophylaxis and management of acute radiation-induced skin reactions: a systematic review of the literature.

    PubMed

    Salvo, N; Barnes, E; van Draanen, J; Stacey, E; Mitera, G; Breen, D; Giotis, A; Czarnota, G; Pang, J; De Angelis, C

    2010-08-01

    Radiation therapy is a common treatment for cancer patients. One of the most common side effects of radiation is acute skin reaction (radiation dermatitis) that ranges from a mild rash to severe ulceration. Approximately 85% of patients treated with radiation therapy will experience a moderate-to-severe skin reaction. Acute radiation-induced skin reactions often lead to itching and pain, delays in treatment, and diminished aesthetic appearance-and subsequently to a decrease in quality of life. Surveys have demonstrated that a wide variety of topical, oral, and intravenous agents are used to prevent or to treat radiation-induced skin reactions. We conducted a literature review to identify trials that investigated products for the prophylaxis and management of acute radiation dermatitis. Thirty-nine studies met the pre-defined criteria, with thirty-three being categorized as prophylactic trials and six as management trials.For objective evaluation of skin reactions, the Radiation Therapy Oncology Group criteria and the U.S. National Cancer Institute Common Toxicity Criteria were the most commonly used tools (65% of the studies). Topical corticosteroid agents were found to significantly reduce the severity of skin reactions; however, the trials of corticosteroids evaluated various agents, and no clear indication about a preferred corticosteroid has emerged. Amifostine and oral enzymes were somewhat effective in preventing radiation-induced skin reactions in phase II and phase III trials respectively; further large randomized controlled trials should be undertaken to better investigate those products. Biafine cream (Ortho-McNeil Pharmaceuticals, Titusville, NJ, U.S.A.) was found not to be superior to standard regimes in the prevention of radiation-induced skin reactions (n = 6).In conclusion, the evidence is insufficient to support the use of a particular agent for the prevention and management of acute radiation-induced skin reactions. Future trials should focus on

  3. Acute inflammatory response in the mouse: exacerbation by immunoneutralization of lipocortin 1.

    PubMed Central

    Perretti, M.; Ahluwalia, A.; Harris, J. G.; Harris, H. J.; Wheller, S. K.; Flower, R. J.

    1996-01-01

    1. An immuno-neutralization strategy was employed to investigate the role of endogenous lipocortin 1 (LC1) in acute inflammation in the mouse. 2. Mice were treated subcutaneously with phosphate-buffered solution (PBS), non-immune sheep serum (NSS) or with one of two sheep antisera raised against LC1 (LCS3), or its N-terminal peptide (LCPS1), three times over a period of seven days. Twenty four hours after the last injection several parameters of acute inflammation were measured including zymosan-induced inflammation in 6-day-old air-pouches, zymosan-activated serum (ZAS)-induced oedema in the skin, platelet-activating factor (PAF)-induced neutrophilia and interleukin-1 beta (IL-1 beta)-induced corticosterone (CCS) release. 3. At the 4 h time-point of the zymosan inflamed air-pouch model, treatment with LCS3 did not modify the number of polymorphonuclear leucocytes (PMN) recruited: 7.84 +/- 1.01 and 7.00 +/- 0.77 x 10(6) PMN per mouse for NSS- and LCS3 group, n = 7. However, several other parameters of cell activation including myeloperoxidase (MPO) and elastase activities were increased (2.2 fold, P < 0.05, and 6.5 fold, P < 0.05, respectively) in the lavage fluids of these mice. Similarly, a significant increase in the amount of immunoreactive prostaglandin E2 (PGE2; 1.81 fold, P < 0.05) and IL-1 alpha (2.75 fold, P < 0.05), but not tumour necrosis factor-alpha (TNF-alpha), was also observed in LCS3-treated mice. 4. The recruitment of PMN into the zymosan inflamed air-pouches by 24 h had declined substantially (4.13 +/- 0.61 x 10(6) PMN per mouse, n = 12) in the NSS-treated mice, whereas high values were still measured in those treated with LCS3 (9.35 +/- 1.20 x 10(6) PMN per mouse, n = 12, P < 0.05). A similar effect was also found following sub-chronic treatment of mice with LCPS1: 6.48 +/- 0.10 x 10(6) PMN per mouse, vs. 2.77 +/- 1.20 and 2.64 +/- 0.49 x 10(6) PMN per mouse for PBS- and NSS-treated groups (n = 7, P < 0.05). Most markers of inflammation were

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

    SciTech Connect

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

    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.

  5. Pro-inflammatory potential of Escherichia coli strains K12 and Nissle 1917 in a murine model of acute ileitis.

    PubMed

    Bereswill, S; Fischer, A; Dunay, I R; Kühl, A A; Göbel, U B; Liesenfeld, O; Heimesaat, M M

    2013-06-01

    Non-pathogenic Escherichia coli (Ec) strains K12 (EcK12) and Nissle 1917 (EcN) are used for gene technology and probiotic treatment of intestinal inflammation, respectively. We investigated intestinal colonization and potential pro-inflammatory properties of EcK12, EcN, and commensal E. coli (EcCo) strains in Toxoplasma (T.) gondii-induced acute ileitis. Whereas gnotobiotic animals generated by quintuple antibiotic treatment were protected from ileitis, mice replenished with conventional microbiota suffered from small intestinal necrosis 7 days post-T. gondii infection (p.i.). Irrespective of the Ec strain, recolonized mice revealed mild to moderate histopathological changes in their ileal mucosa. Upon stable recolonization with EcK12, EcN, or EcCo, development of inflammation was accompanied by pro-inflammatory responses at day 7 p.i., including increased ileal T lymphocyte and apoptotic cell numbers compared to T. gondii-infected gnotobiotic controls. Strikingly, either Ec strain was capable to translocate to extra-intestinal locations, such as MLN, spleen, and liver. Taken together, Ec strains used in gene technology and probiotic treatment are able to exert inflammatory responses in a murine model of small intestinal inflammation. In conclusion, the therapeutic use of Ec strains in patients with broad-spectrum antibiotic treatment and/or intestinal inflammation should be considered with caution. PMID:24265929

  6. Pro-inflammatory cytokines and soluble receptors in response to acute psychosocial stress: differential reactivity in bipolar disorder.

    PubMed

    Wieck, Andrea; Grassi-Oliveira, Rodrigo; do Prado, Carine Hartmann; Rizzo, Lucas Bortolotto; de Oliveira, Agatha Schommer; Kommers-Molina, Júlia; Viola, Thiago Wendt; Marciano Vieira, Erica Leandro; Teixeira, Antônio Lúcio; Bauer, Moisés Evandro

    2014-09-19

    Mounting evidence suggests a chronic pro-inflammatory state in individuals with bipolar disorder (BD). Stress exposure is known to exacerbate several inflammatory conditions as well as psychiatric disorders. Here, we analyzed plasma levels of pro-inflammatory cytokines and their soluble receptors to realistic acute psychosocial stress challenge in BD. Thirteen euthymic type 1 BD patients and 15 matched controls underwent the Trier Social Stress Test protocol (TSST). Blood samples were collected before and after TSST and plasma cytokines interleukin IL-2, IL-6, IL-33, and tumor necrosis factor alpha (TNF-α) were measured. In addition TNF-α soluble receptors TNFR1 and TNFR2, and IL-33 soluble receptor sST2 were assessed. Increased IL-33 and reduced sST2 levels were observed in BD subjects as compared to controls, independently of stress exposure. Following TSST, there were higher levels of IL-2 and reduced levels of sTNFR1 in both groups. However, the magnitude change for both cytokines was found higher in controls than BD subjects. Our data suggest that BD patients have differential stress reactivity as compared to controls, possibly related to an immunologic imbalance and failure of regulatory mechanisms. PMID:25092610

  7. Unfractionated bone marrow cells attenuate paraquat-induced glomerular injury and acute renal failure by modulating the inflammatory response

    PubMed Central

    Gu, Sing-Yi; Yeh, Ti-Yen; Lin, Shih-Yi; Peng, Fu-Chuo

    2016-01-01

    The aim of this study was to evaluate the efficacy of unfractionated bone marrow cells (BMCs) in attenuating acute kidney injury (AKI) induced by paraquat (PQ) in a mouse model. PQ (55 mg/kg BW) was intraperitoneally injected into C57BL/6 female mice to induce AKI, including renal function failure, glomerular damage and renal tubule injury. Glomerular podocytes were the first target damaged by PQ, which led to glomerular injury. Upon immunofluorescence staining, podocytes depletion was validated and accompanied by increased urinary podocin levels, measured on days 1 and 6. A total of 5.4 × 106 BMCs obtained from the same strain of male mice were injected into AKI mice through the tail vein at 3, 24, and 48 hours after PQ administration. As a result, renal function increased, tubular and glomerular injury were ameliorated, podocytes loss improved, and recipient mortality decreased. In addition, BMCs co-treatment decreased the extent of neutrophil infiltration and modulated the inflammatory response by shifting from pro-inflammatory Th1 to an anti-inflammatory Th2 profile, where IL-1β, TNF-α, IL-6 and IFN-γ levels declined and IL-10 and IL-4 levels increased. The present study provides a platform to investigate PQ-induced AKI and repeated BMCs injection represents an efficient therapeutic strategy. PMID:26988026

  8. In vivo analysis of THz wave irradiation induced acute inflammatory response in skin by laser-scanning confocal microscopy.

    PubMed

    Hwang, Yoonha; Ahn, Jinhyo; Mun, Jungho; Bae, Sangyoon; Jeong, Young Uk; Vinokurov, Nikolay A; Kim, Pilhan

    2014-05-19

    The recent development of THz sources in a wide range of THz frequencies and power levels has led to greatly increased interest in potential biomedical applications such as cancer and burn wound diagnosis. However, despite its importance in realizing THz wave based applications, our knowledge of how THz wave irradiation can affect a live tissue at the cellular level is very limited. In this study, an acute inflammatory response caused by pulsed THz wave irradiation on the skin of a live mouse was analyzed at the cellular level using intravital laser-scanning confocal microscopy. Pulsed THz wave (2.7 THz, 4 μs pulsewidth, 61.4 μJ per pulse, 3Hz repetition), generated using compact FEL, was used to irradiate an anesthetized mouse's ear skin with an average power of 260 mW/cm(2) for 30 minutes using a high-precision focused THz wave irradiation setup. In contrast to in vitro analysis using cultured cells at similar power levels of CW THz wave irradiation, no temperature change at the surface of the ear skin was observed when skin was examined with an IR camera. To monitor any potential inflammatory response, resident neutrophils in the same area of ear skin were repeatedly visualized before and after THz wave irradiation using a custom-built laser-scanning confocal microscopy system optimized for in vivo visualization. While non-irradiated control skin area showed no changes in the number of resident neutrophils, a massive recruitment of newly infiltrated neutrophils was observed in the THz wave irradiated skin area after 6 hours, which suggests an induction of acute inflammatory response by the pulsed THz wave irradiation on the skin via a non-thermal process. PMID:24921268

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

    PubMed

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

    2016-04-01

    The outcome of intracerebral hemorrhage (ICH) is mainly determined by the volume of the hemorrhage core and the secondary brain damage to penumbral tissues due to brain swelling, microcirculation disturbance and inflammation. The present study aims to investigate the protective effects of cerebrolysin on brain edema and inhibition of the inflammation response surrounding the hematoma core in the acute stage after ICH. The ICH model was induced by administration of type VII bacterial collagenase into the stratum of adult rats, which were then randomly divided into three groups: ICH + saline; ICH + Cerebrolysin (5 ml/kg) and sham. Cerebrolysin or saline was administered intraperitoneally 1 h post surgery. Neurological scores, extent of brain edema content and Evans blue dye extravasation were recorded. The levels of pro-inflammatory factors (IL-1β, TNF-α and IL-6) were assayed by Real-time PCR and Elisa kits. Aquaporin-4 (AQP4) and tight junction proteins (TJPs; claudin-5, occludin and zonula occluden-1) expression were measured at multiple time points. The morphological and intercellular changes were characterized by Electron microscopy. It is found that cerebrolysin (5 ml/kg) improved the neurological behavior and reduced the ipsilateral brain water content and Evans blue dye extravasation. After cerebrolysin treated, the levels of pro-inflammatory factors and AQP4 in the peri-hematomal areas were markedly reduced and were accompanied with higher expression of TJPs. Electron microscopy showed the astrocytic swelling and concentrated chromatin in the ICH group and confirmed the cell junction changes. Thus, early cerebrolysin treatment ameliorates secondary injury after ICH and promotes behavioral performance during the acute phase by reducing brain edema, inflammatory response, and blood-brain barrier permeability. PMID:26498936

  10. Treatment of acute soft tissue trauma with a topical non-steroidal anti-inflammatory drug (biphenylacetic acid 3% gel).

    PubMed

    Lee, E H; Lee, P Y; Ngai, A T; Chiu, E H

    1991-08-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective in the treatment of acute soft tissue injuries. However, taken orally, NSAIDs have a definite incidence of gastro-intestinal toxicity. Since acute soft tissue trauma is normally localised, use of a topical NSAID may eliminate this undesirable side-effect. This study was designed to evaluate the efficacy and safety of a topical NSAID, biphenylacetic acid 3% gel (Traxam) in the treatment of soft tissue trauma. Thirty-two patients (22 males and 10 females) with acute soft tissue trauma were enrolled at the Department of Orthopaedic Surgery, National University Hospital, Singapore from 7 June 1988 to 28 March 1989. Each patient was treated for a period of one week with bipenylacetic acid 3% gel (Traxam), 60 mg three times a day. Statistically significant improvement was found in pain, swelling and functional impairment in all patients assessed at day 3 and day 7 after the injury. The speed of recovery was enhanced. The medication was found to be well tolerated and safe. PMID:1776001

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    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

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

    PubMed Central

    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

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

    PubMed

    Ikeda, Y; Ito, M; Matsuu, M; Shichijo, K; Fukuda, E; Nakayama, T; Nakashima, M; Naito, S; Sekine, I

    2000-09-01

    Inflammatory cell infiltration of the colon is observed at an early stage of radiation-induced colitis. The emigration of inflammatory cells from the circulation requires interactions between cell adhesion molecules on the vascular endothelium and molecules on the surface of leukocytes. To elucidate this process, the present work analyzes the kinetics of the expression of intercellular adhesion molecule-1 (ICAM-1) and the accumulation of inflammatory myeloperoxidase (MPO)-positive cells in relation to the appearance of acute radiation colitis prior to an overt radiation-induced ulcer. Colon tissues were obtained from Wistar Kyoto rats at various times after 22.5 Gy irradiation to the rectum. Histologically, crypt depletion and numerous inflammatory cells were observed 4 days after irradiation, and mucosal ulcer 6 days after irradiation. ICAM-1 immunopositivity was present in the endothelial cells of small vessels in the mucosa of both control and irradiated rats. ICAM-1 mRNA expression was detected in normal colon and irradiated colon by reverse transcription-PCR. In Northern blotting, ICAM-1 mRNA levels were found to increase markedly in the irradiated colon compared to the normal colon. In Western blotting. ICAM-1 protein expression also increased with a peak one day after irradiation, and remained elevated up to 6 days thereafter. The number of MPO-positive cells in lamina propria mucosa increased in a time-dependent fashion from 6 h to 6 days after irradiation. These data suggest that up-regulation of ICAM-1 in endothelial cells and accumulation of MPO positive cells play important roles in the development of radiation-induced colonic ulcer. PMID:11210829

  15. Bioassay-guided evaluation of Dioscorea villosa – an acute and subchronic toxicity, antinociceptive and anti-inflammatory approach

    PubMed Central

    2013-01-01

    Background Dioscorea villosa (DV) has been used in Brazil as an alternative medicine to attenuate menopause symptoms, as well as for the treatment of joint pain and rheumatoid arthritis. In spite of the popular use of DV for the treatment of various disorders, there are limited scientific data regarding safety aspects of this herb. In this regard, we carried out to evaluated both antinociceptive and anti-inflammatory activities in experimental models and assess the toxic effects of the acute (single dose) and subchronic (30 days) oral administration of dry extract of Dioscorea villosa in rodents. Methods The LC analyses were performed to assess the presence of the diosgenin in samples of DV. The antinociceptive study of DV was performed using models of acetic acid-induced writhing and formalin-induced pain in mice. The anti-inflammatory study was accomplished by leukocyte migration to the peritoneal cavity. A dry extract of DV was tested at doses of 100, 200 and 400 mg/kg (per os or p.o.). The toxicological properties of the dry extract were evaluated by toxicity assays of acute (5 g/kg, single dose) and subchronic (1 g/kg/day, 30 days) treatment. Haematological, biochemical, and histopathological parameters were studied. The results are expressed as mean ± S.D., and statistical analysis of the data were performed with the Student’s t-test or one-way analysis of variance (ANOVA) followed by Tukey’s test. In all cases differences were considered significant if p < 0.05. Results HPLC-DAD analysis of the extract from DV revealed the presence of diosgenin as the major compound. Doses of 200 and 400 mg⁄kg significantly reduced the amount of acetic acid-induced writhing in relation to the vehicle (p < 0.0001). In the first phase, using the formalin-induced neurogenic pain test, only the 400 mg/kg dose of DV showed significant inhibition of neurogenic pain (p < 0.001). In the second phase, 200 and 400 mg/kg of DV showed significant

  16. The serpentine path to a novel mechanism-based inhibitor of acute inflammatory lung injury

    PubMed Central

    2014-01-01

    The Comroe lecture on which this review is based described my research path during the past 45 years, beginning with studies of oxidant stress (hyperoxia) and eventuating in the discovery of a synthetic inhibitor of phospholipase A2 activity (called MJ33) that prevents acute lung injury in mice exposed to lipopolysaccharide. In between were studies of lung ischemia, lung surfactant metabolism, the protein peroxiredoxin 6 and its phospholipase A2 activity, and mechanisms for NADPH oxidase activation. These seemingly unrelated research activities provided the nexus for identification of a novel target and a potentially novel therapeutic agent for prevention or treatment of acute lung injury. PMID:24744383

  17. Inflammatory reaction and changes in expression of coagulation proteins on lung endothelial cells after total-body irradiation in mice.

    PubMed

    Van der Meeren, Anne; Vandamme, Marie; Squiban, Claire; Gaugler, Marie-Hélène; Mouthon, Marc-André

    2003-12-01

    Inflammatory reaction is a classical feature of radiation exposure, and pneumonitis is a dose-limiting complication in the handling of hematological disorders treated with total-body irradiation. In the present study, we first evaluated the inflammatory response in C57BL6/J mice exposed to lethal doses of gamma rays treated with antibiotics or not. Both interleukin 6 and KC (also known as Gro1) were increased in the plasma 10 to 18 days after radiation exposure, independent of bacterial infection, whereas fibrinogen release was linked to a bacterial infection. Furthermore, both Il6 and KC were increased in the lungs of irradiated mice. Our second objective was to characterize the endothelial cell changes in the lungs of total-body-irradiated mice. For this purpose, a quantitative RT-PCR was used to determine the expression of genes involved in inflammatory and coagulation processes. We found that the adhesion molecules P-selectin and platelet endothelial cell adhesion molecule 1 were up-regulated, whereas E-selectin remained unchanged. Tissue factor expression was up-regulated as well, and thrombomodulin gene expression was down-regulated. The investigation by immunohistochemistry of adhesion molecules confirmed the increase in the basal expression of both P-selectin and platelet endothelial cell adhesion molecule 1 on pulmonary endothelial cells. All together, our results suggest the involvement of endothelial cells in the development of radiation-induced inflammatory and thrombotic processes. PMID:14640783

  18. Active Hemovigilance Significantly Improves Reporting of Acute Non-infectious Adverse Reactions to Blood Transfusion.

    PubMed

    Agnihotri, Naveen; Agnihotri, Ajju

    2016-09-01

    One of the key purposes of a hemovigilance program is to improve reporting of transfusion related adverse events and subsequent data-driven improvement in blood transfusion (BT) practices. We conducted a study over 3 years to assess the impact of healthcare worker training and an active feedback programme on reporting of adverse reactions to BTs. All hospitalized patients who required a BT were included in the study. Healthcare workers involved in BT to patients were sensitized and trained in adverse reaction reporting by conducting training sessions and meetings. All the transfused patients were 'actively' monitored for any acute adverse reaction by using a uniquely coded blood issue form. A total of 18,914 blood components transfused to 5785 different patients resulted in 61 adverse reaction episodes. This incidence of 0.32 % in our study was found to be significantly higher (p < 0.005) than that reported from the same region in the past. Red blood cell units were the most frequently transfused component and thus most commonly involved in an adverse reaction (42.6 %), however apheresis platelets had the highest chance of reaction per unit transfused (0.66 %). There was no mortality associated with the BT during the study period. An active surveillance program significantly improves reporting and management of adverse reactions to BTs. PMID:27429527

  19. Ampelopsis japonica Makino Extract Inhibits the Inflammatory Reaction Induced by Pathogen-Associated Molecular Patterns in Epidermal Keratinocytes

    PubMed Central

    Choi, Mi-Ra; Choi, Dae-Kyoung; Kim, Ki-Duck; Kim, Sue Jeong; Kim, Dong-Il; Im, Myung; Lee, Young; Seo, Young-Joon; Kim, Chang Deok

    2016-01-01

    Background Keratinocytes are the major cells in epidermis, providing barrier components such as cornified cells through the sophisticated differentiation process. In addition, keratinocytes exerts their role as the defense cells via activation of innate immunity. It has been known that pathogen-associated molecular patterns (PAMPs) including double-strand RNA and nucleotides can provoke inflammatory reaction in keratinocytes. Objective The aim of this study is to evaluate the effect of Ampelopsis japonica Makino extract (AE) on PAMPs-induced inflammatory reaction of keratinocytes. Methods The effects of AE were determined using poly (I:C)-induced inflammation and imiquimod-induced psoriasiform dermatitis models. Results In cultured keratinocytes, AE significantly inhibited poly(I:C)-induced expression of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor-α. AE significantly inhibited poly(I:C)-induced release of caspase-1 active form (p20), and down-regulated nuclear factor-κB signaling pathway. In imiquimod-induced psoriasiform dermatitis model, topical application of AE resulted in significant reduction of epidermal hyperplasia. Conclusion These results suggest that AE may be a potential candidate for the treatment of skin inflammation. PMID:27274634

  20. Macrophage Polarization in AIDS: Dynamic Interface between Anti-Viral and Anti-Inflammatory Macrophages during Acute and Chronic Infection

    PubMed Central

    Burdo, Tricia H; Walker, Joshua; Williams, Kenneth C

    2015-01-01

    Monocyte and macrophage inflammation in parenchymal tissues during acute and chronic HIV and SIV infection plays a role in early anti-viral immune responses and later in restorative responses. Macrophage polarization is observed in such responses in the central nervous system (CNS) and the heart and cardiac vessels that suggest early responses are M1 type antiviral responses, and later responses favor M2 restorative responses. Macrophage polarization is unique to different tissues and is likely dictated as much by the local microenvironment as well as other inflammatory cells involved in the viral responses. Such polarization is found in HIV infected humans, and the SIV infected animal model of AIDS, and occurs even with effective anti-retroviral therapy. Therapies that directly target macrophage polarization in HIV infection have recently been implemented, as have therapies to directly block traffic and accumulation of macrophages in tissues. PMID:26500805

  1. β-Nicotinamide adenine dinucleotide attenuates lipopolysaccharide-induced inflammatory effects in a murine model of acute lung injury.

    PubMed

    Umapathy, Nagavedi Siddaramappa; Gonzales, Joyce; Fulzele, Sadanand; Kim, Kyung-mi; Lucas, Rudolf; Verin, Alexander Dimitrievich

    2012-06-01

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) occur in approximately 200,000 patients per year. Studies indicate that lung endothelium plays a significant role in ALI. The authors' recent in vitro studies demonstrate a novel mechanism of β-nicotinamide adenine dinucleotide (β-NAD)-induced protection against gram-positive (pneumolysin, PLY) and gram-negative (lipopolysaccharide, LPS) toxin-induced lung endothelial cell (EC) barrier dysfunction. The objective of the current study was to evaluate the protective effect of β-NAD against LPS-induced ALI in mice. C57BL/6J mice were randomly divided into 4 groups: vehicle, β-NAD, LPS, and LPS/β-NAD. After surgery, mice were allowed to recover for 24 hours. Evans blue dye-albumin (EBA) was given through the internal jugular vein 2 hours prior to the termination of the experiments. Upon sacrificing the animals, bronchoalveolar lavage fluid (BALF) was collected and the lungs were harvested. β-NAD treatment significantly attenuated the inflammatory response by means of reducing the accumulation of cells and protein in BALF, blunting the parenchymal neutrophil infiltration, and preventing capillary leak. In addition, the histological examination demonstrated decreased interstitial edema in the LPS/β-NAD specimens, as compared to the LPS-only specimens. The mRNA levels of the anti-inflammatory cytokines were up-regulated in the LPS group treated with β-NAD compared to the LPS-only-treated group. β-NAD treatment down-regulated the mRNA levels of the proinflammatory cytokines. These findings suggest that β-NAD could be investigated as a therapeutic option against bacterial toxin-induced lung inflammation and ALI in mice. PMID:22563684

  2. Inflammatory and metabolic markers and short-time outcome in patients with acute ischemic stroke in relation to TOAST subtypes.

    PubMed

    Lehmann, Marcio Francisco; Kallaur, Ana Paula; Oliveira, Sayonara Rangel; Alfieri, Daniela Frizon; Delongui, Franciele; de Sousa Parreira, Johnathan; de Araújo, Maria Caroline Martins; Rossato, Carolina; de Almeida, Jéssica Tavares; Pelegrino, Larissa Moliterno; Bragato, Erick Frank; Lehmann, Ana Lucia Cruz Fürstenberger; Morimoto, Helena Kaminami; Lozovoy, Marcell Alysson Batisti; Simão, Andrea Name Colado; Kaimen-Maciel, Damácio Ramon; Reiche, Edna Maria Vissoci

    2015-12-01

    The aim of this study was to evaluate the association between inflammatory and metabolic markers and short-time outcome with acute ischemic stroke subtypes. A total of 121 patients was classified according to TOAST criteria, such as large artery atherosclerosis (LAAS), lacunar infarct (LAC), cardioembolic infarct (CEI), other determined etiology (ODE), and undetermined etiology (UDE). The functional impairment was evaluated within the first eight hours of stroke and the outcome after three-month follow-up using the modified Rankin Scale. Blood samples were obtained up to 24 h of stroke. Compared with 96 controls, patients with LAAS, CEI, and LAC subtypes showed higher levels of white blood cells, high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), metalloproteinase 9 (MMP-9), glucose, and iron (p < 0.05); and lower high-density lipoprotein cholesterol (HDL-C) (p < 0.0001); platelets, insulin, insulin resistance, and homocysteine were higher in LAC (p < 0.0001); ferritin was higher in LAAS (p < 0.0001); and total cholesterol (TC) was lower in LAAS and CEI (p < 0.01). When stroke subtypes were compared, insulin was higher in LAAS vs. LAC and in LAC vs. CEI (p < 0.05); and TC was lower in LAAS vs. LAC (p < 0.05). Outcome and rate of mortality after three-month were higher in LAAS vs. LAC (p < 0.001 and p = 0.0391 respectively). The results underscored the important role of the inflammatory response and metabolic changes in the pathogenesis of ischemic stroke subtypes that might be considered on the initial evaluation of stroke patients to identify those that could benefit with individualized therapeutic strategies that taken into account these markers after acute ischemic event. PMID:26359121

  3. A quantitative immunohistochemical study on the time-dependent course of acute inflammatory cellular response to human brain injury.

    PubMed

    Hausmann, R; Kaiser, A; Lang, C; Bohnert, M; Betz, P

    1999-01-01

    The time-dependent inflammatory cell reaction in human cortical contusions has been investigated during the first 30 weeks after blunt head injury. Immunohistochemical staining was carried out using CD 15 for granulocytes and LCA, CD 3 and UCHL-1 for mononuclear leucocytes. In order to provide reliable data for a forensic wound age estimation, the intensity of the cellular reaction was evaluated with a quantitative image analysis system. CD 15-labelled granulocytes were detectable earliest 10 min after brain injury, whereas significantly increased numbers of mononuclear leucocytes occurred in cortical contusions after a postinfliction interval of at least 1.1 days (LCA), 2 days (CD 3) or 3.7 days (UCHL-1), respectively. PMID:10433032

  4. Activation of P2X7 Receptor by ATP Plays an Important Role in Regulating Inflammatory Responses during Acute Viral Infection

    PubMed Central

    Lee, Benjamin H.; Hwang, David M.; Palaniyar, Nades; Grinstein, Sergio; Philpott, Dana J.; Hu, Jim

    2012-01-01

    Acute viral infection causes damages to the host due to uncontrolled viral replication but even replication deficient viral vectors can induce systemic inflammatory responses. Indeed, overactive host innate immune responses to viral vectors have led to devastating consequences. Macrophages are important innate immune cells that recognize viruses and induce inflammatory responses at the early stage of infection. However, tissue resident macrophages are not easily activated by the mere presence of virus suggesting that their activation requires additional signals from other cells in the tissue in order to trigger inflammatory responses. Previously, we have shown that the cross-talk between epithelial cells and macrophages generates synergistic inflammatory responses during adenoviral vector infection. Here, we investigated whether ATP is involved in the activation of macrophages to induce inflammatory responses during an acute adenoviral infection. Using a macrophage-epithelial cell co-culture system we demonstrated that ATP signaling through P2X7 receptor (P2X7R) is required for induction of inflammatory mediators. We also showed that ATP-P2X7R signaling regulates inflammasome activation as inhibition or deficiency of P2X7R as well as caspase-1 significantly reduced IL-1β secretion. Furthermore, we found that intranasal administration of replication deficient adenoviral vectors in mice caused a high mortality in wild-type mice with symptoms of acute respiratory distress syndrome but the mice deficient in P2X7R or caspase-1 showed increased survival. In addition, wild-type mice treated with apyrase or inhibitors of P2X7R or caspase-1 showed higher rates of survival. The improved survival in the P2X7R deficient mice correlated with diminished levels of IL-1β and IL-6 and reduced neutrophil infiltration in the early phase of infection. These results indicate that ATP, released during viral infection, is an important inflammatory regulator that activates the

  5. Mosla dianthera inhibits mast cell-mediated allergic reactions through the inhibition of histamine release and inflammatory cytokine production

    SciTech Connect

    Lee, Dong-Hee; Kim, Sang-Hyun . E-mail: shkim72@knu.ac.kr; Eun, Jae-Soon; Shin, Tae-Yong . E-mail: tyshin@woosuk.ac.kr

    2006-11-01

    In this study, we investigated the effect of the aqueous extract of Mosla dianthera (Maxim.) (AEMD) on the mast cell-mediated allergy model and studied the possible mechanism of action. Mast cell-mediated allergic disease is involved in many diseases such as asthma, sinusitis and rheumatoid arthritis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. AEMD inhibited compound 48/80-induced systemic reactions in mice. AEMD decreased immunoglobulin E-mediated local allergic reactions, passive cutaneous anaphylaxis. AEMD attenuated intracellular calcium level and release of histamine from rat peritoneal mast cells activated by compound 48/80. Furthermore, AEMD attenuated the phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-stimulated TNF-{alpha}, IL-8 and IL-6 secretion in human mast cells. The inhibitory effect of AEMD on the pro-inflammatory cytokines was nuclear factor-{kappa}B (NF-{kappa}B) dependent. AEMD decreased PMA and A23187-induced degradation of I{kappa}B{alpha} and nuclear translocation of NF-{kappa}B. Our findings provide evidence that AEMD inhibits mast cell-derived immediate-type allergic reactions and involvement of pro-inflammatory cytokines and NF-{kappa}B in these effects.

  6. The predictive value of Alvarado score, inflammatory parameters and ultrasound imaging in the diagnosis of acute appendicitis

    PubMed Central

    Tanrıkulu, Ceren Şen; Karamercan, Mehmet Akif; Tanrıkulu, Yusuf; Öztürk, Miraç; Yüzbaşıoğlu, Yücel; Coşkun, Figen

    2016-01-01

    Objective: Acute appendicitis (AA) is one of the most common surgical emergencies. Despite extraordinary advances in modern investigations, the accurate diagnosis of AA remains an enigmatic challenge. The aim of this study was to compare and evaluate the diagnostic accuracy of inflammatory parameters [C-reactive protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR)], ultrasound (US) and Alvarado score (AS) in reducing the rate of negative appendectomies. Material and Methods: Two hundred seventy-eight patients were included in this study. Patients were separated into two main groups as the surgery group (n=184) and non-operative group (n=94). Complete blood count, ESR and PCT levels were assessed, abdominal US was performed and AS was calculated for all patients. Results: In the surgery group, clinical predictive factors for histopathologic results such as AS ≥7, AA signs on US, neutrophilia and leukocytosis were significant. Neutrophilia and leukocytosis had the highest accuracy rate among these factors. Inflammatory parameters were not predictive for histopathologic results, although higher CRP and PCT levels were significant in perforated and necrotizing appendicitis. Multifactorial regression analyses showed that AS was not of significant predictive value in the non-operative group. Conclusion: There was no superiority of AS and/or US in the diagnosis of AA. Recent findings have shown the most reliable parameters in the diagnosis of AA to be primarily ‘neutrophilia’ and secondarily ‘leukocytosis’. Other results of this study indicated that inflammatory parameters (CRP, PCT, ESR) were not superior to other parameters but CRP and PCT levels were significantly high in complicated cases.

  7. Staphylococcal enterotoxin B-induced microRNA-155 targets SOCS1 to promote acute inflammatory lung injury.

    PubMed

    Rao, Roshni; Rieder, Sadiye Amcaoglu; Nagarkatti, Prakash; Nagarkatti, Mitzi

    2014-07-01

    Staphylococcal enterotoxin B (SEB) causes food poisoning in humans. It is considered a biological weapon, and inhalation can trigger lung injury and sometimes respiratory failure. Being a superantigen, SEB initiates an exaggerated inflammatory response. While the role of microRNAs (miRNAs) in immune cell activation is getting increasing recognition, their role in the regulation of inflammatory disease induced by SEB has not been studied. In this investigation, we demonstrate that exposure to SEB by inhalation results in acute inflammatory lung injury accompanied by an altered miRNA expression profile in lung-infiltrating cells. Among the miRNAs that were significantly elevated, miR-155 was the most overexpressed. Interestingly, miR-155(-/-) mice were protected from SEB-mediated inflammation and lung injury. Further studies revealed a functional link between SEB-induced miR-155 and proinflammatory cytokine gamma interferon (IFN-γ). Through the use of bioinformatics tools, suppressor of cytokine signaling 1 (SOCS1), a negative regulator of IFN-γ, was identified as a potential target of miR-155. While miR-155(-/-) mice displayed increased expression of Socs1, the overexpression of miR-155 led to its suppression, thereby enhancing IFN-γ levels. Additionally, the inhibition of miR-155 resulted in restored Socs1expression. Together, our data demonstrate an important role for miR-155 in promoting SEB-mediated inflammation in the lungs through Socs1 suppression and suggest that miR-155 may be an important target in preventing SEB-mediated inflammation and tissue injury. PMID:24778118

  8. Neutrophils counteract autophagy-mediated anti-inflammatory mechanisms in alveolar macrophage: role in posthemorrhagic shock acute lung inflammation.

    PubMed

    Wen, Zongmei; Fan, Liyan; Li, Yuehua; Zou, Zui; Scott, Melanie J; Xiao, Guozhi; Li, Song; Billiar, Timothy R; Wilson, Mark A; Shi, Xueyin; Fan, Jie

    2014-11-01

    Acute lung injury (ALI) is a major component of multiple organ dysfunction syndrome after hemorrhagic shock (HS) resulting from major surgery and trauma. The increased susceptibility in HS patients to the development of ALI suggests not yet fully elucidated mechanisms that enhance proinflammatory responses and/or suppress anti-inflammatory responses in the lung. Alveolar macrophages (AMϕ) are at the center of the pathogenesis of ALI after HS. We have previously reported that HS-activated polymorphonuclear neutrophils (PMNs) interact with macrophages to influence inflammation progress. In this study, we explore a novel function of PMNs regulating AMϕ anti-inflammatory mechanisms involving autophagy. Using a mouse "two-hit" model of HS/resuscitation followed by intratracheal injection of muramyl dipeptide, we demonstrate that HS initiates high mobility group box 1/TLR4 signaling, which upregulates NOD2 expression in AMϕ and sensitizes them to subsequent NOD2 ligand muramyl dipeptide to augment lung inflammation. In addition, upregulated NOD2 signaling induces autophagy in AMϕ, which negatively regulates lung inflammation through feedback suppression of NOD2-RIP2 signaling and inflammasome activation. Importantly, we further demonstrate that HS-activated PMNs that migrate in alveoli counteract the anti-inflammatory effect of autophagy in AMϕ, possibly through NAD(P)H oxidase-mediated signaling to enhance I-κB kinase γ phosphorylation, NF-κB activation, and nucleotide-binding oligomerization domain protein 3 inflammasome activation, and therefore augment post-HS lung inflammation. These findings explore a previously unidentified complexity in the mechanisms of ALI, which involves cell-cell interaction and receptor cross talk. PMID:25267975

  9. Discovery of new MD2 inhibitor from chalcone derivatives with anti-inflammatory effects in LPS-induced acute lung injury

    PubMed Central

    Zhang, Yali; Wu, Jianzhang; Ying, Shilong; Chen, Gaozhi; Wu, Beibei; Xu, Tingting; Liu, Zhiguo; Liu, Xing; Huang, Lehao; Shan, Xiaoou; Dai, Yuanrong; Liang, Guang

    2016-01-01

    Acute lung injury (ALI) is a life-threatening acute inflammatory disease with limited options available for therapy. Myeloid differentiation protein 2, a co-receptor of TLR4, is absolutely required for TLR4 sense LPS, and represents an attractive target for treating severe inflammatory diseases. In this study, we designed and synthesized 31 chalcone derivatives that contain the moiety of (E)-4-phenylbut-3-en-2-one, which we consider the core structure of current MD2 inhibitors. We first evaluated the anti-inflammatory activities of these compounds in MPMs. For the most active compound 20, we confirmed that it is a specific MD2 inhibitor through a series of biochemical experiments and elucidated that it binds to the hydrophobic pocket of MD2 via hydrogen bonds with Arg90 and Tyr102 residues. Compound 20 also blocked the LPS-induced activation of TLR4/MD2 -downstream pro-inflammatory MAPKs/NF-κB signaling pathways. In a rat model with ALI induced by intracheal LPS instillation, administration with compound 20 exhibited significant protective effect against ALI, accompanied by the inhibition of TLR4/MD2 complex formation in lung tissues. Taken together, the results of this study suggest the specific MD2 inhibitor from chalcone derivatives we identified is a potential candidate for treating acute inflammatory diseases. PMID:27118147

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

    PubMed

    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. PMID:25299597

  11. Lipopolysaccharide-induced anti-inflammatory acute phase response is enhanced in spermidine/spermine N1-acetyltransferase (SSAT) overexpressing mice.

    PubMed

    Pirnes-Karhu, Sini; Sironen, Reijo; Alhonen, Leena; Uimari, Anne

    2012-02-01

    Bacterial lipopolysaccharide (LPS) is an effective activator of the components of innate immunity. It has been shown that polyamines and their metabolic enzymes affect the LPS-induced immune response by modulating both pro- and anti-inflammatory actions. On the other hand, LPS causes changes in cellular polyamine metabolism. In this study, the LPS-induced inflammatory response in spermidine/spermine N(1)-acetyltransferase overexpressing transgenic mice (SSAT mice) was analyzed. In liver and kidneys, LPS enhanced the activity of the polyamine biosynthetic enzyme ornithine decarboxylase and increased the intracellular putrescine content in both SSAT overexpressing and wild-type mice. In survival studies, the enhanced polyamine catabolism and concomitantly altered cellular polyamine pools in SSAT mice did not affect the LPS-induced mortality of these animals. However, in the acute phase of LPS-induced inflammatory response, the serum levels of proinflammatory cytokines interleukin-1β and interferon-γ were significantly reduced and, on the contrary, anti-inflammatory cytokine interleukin-10 was significantly increased in the sera of SSAT mice compared with the wild-type animals. In addition, hepatic acute-phase proteins C-reactive protein, haptoglobin and α(1)-acid glycoprotein were expressed in higher amounts in SSAT mice than in the wild-type animals. In summary, the study suggests that SSAT overexpression obtained in SSAT mice enhances the anti-inflammatory actions in the acute phase of LPS-induced immune response. PMID:21814792

  12. Mass-Spectrometric Identification of T-Kininogen I/Thiostatin as an Acute-Phase Inflammatory Protein Suppressed by Curcumin and Capsaicin

    PubMed Central

    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. PMID:25299597

  13. [Acute rheumatic fever and infectious-inflammatory diseases of the pharynx: the relationship, treatment, and prophylaxis].

    PubMed

    Belov, B S

    2015-01-01

    The relationship between pharyngeal infections, such as tonsillitis and pharyngitis, caused by group A beta-hemolytic streptococci (BHSA) and acute rheumatic fever (ARF) is a well-established fact confirmed by numerous studies carried out along the following lines: epidemiological, immunological, therapeutic, and prophylactic. The currently available data provide an opportunity to discuss the existence of «rheumatogenic» BHSA strains exhibiting a number of characteristic clinical and morphological properties. According to the current recommendations penicillins remain the means of first-line therapy for the treatment of acute forms of BHSA-induced tonsillitis and pharyngitis, whereas the macrolides should be applied only as the alternative medications in the patients with intolerance to beta-lactam antibiotics. This article contains characteristics of BHSA-carrier state and the principal indications for the prescription of antibiotics to the patients with these conditions. The key principle of secondary medicamental prophylaxis of acute respiratory infections are expounded along with the main fines of future research on the problems associated with BHSA-induced pharyngeal infections. PMID:26870861

  14. Inhibition of Group IIA Secretory Phospholipase A2 and its Inflammatory Reactions in Mice by Ethanolic Extract of Andrographis paniculata, a Well-known Medicinal Food

    PubMed Central

    Kishore, V.; Yarla, N. S.; Zameer, F.; Nagendra Prasad, M. N.; Santosh, M. S.; More, S. S.; Rao, D. G.; Dhananjaya, Bhadrapura Lakkappa

    2016-01-01

    Andrographis paniculata Nees is an important medicinal plant found in the tropical regions of the world, which has been traditionally used in Indian and Chinese medicinal systems. It is also used as medicinal food. A. paniculata is found to exhibit anti-inflammatory activities; however, its inhibitory potential on inflammatory Group IIA phospholipases A2 (PLA2) and its associated inflammatory reactions are not clearly understood. The aim of the present study is to evaluate the inhibitory/neutralizing potential of ethanolic extract of A. paniculata on the isolated inflammatory PLA2 (VRV-PL-VIIIa) from Daboii rusellii pulchella (belonging to Group IIA inflammatory secretory PLA2 [sPLA2]) and its associated edema-induced activities in Swiss albino mice. A. paniculata extract dose dependently inhibited the Group IIA sPLA2 enzymatic activity with an IC50 value of 10.3 ± 0.5 μg/ml. Further, the extract dose dependently inhibited the edema formation, when co-injected with enzyme indicating that a strong correlation exists between lipolytic and pro-inflammatory activities of the enzyme. In conclusion, results of this study shows that the ethanolic extract of A. paniculata effectively inhibits Group IIA sPLA2 and its associated inflammatory activities, which substantiate its anti-inflammatory properties. The results of the present study warranted further studies to develop bioactive compound (s) in ethanolic extract of A. paniculata as potent therapeutic agent (s) for inflammatory diseases. SUMMARY This study emphasis the anti-inflammatory effect of A. paniculata by inhibiting the inflammatory Group IIA sPLA2 and its associated inflammatory activities such as edema. It was found that there is a strong correlation between lipolytic activity and pro-inflammatory activity inhibition. Therefore, the study suggests that the extract processes potent anti-inflammatory agents, which could be developed as a potential therapeutic agent against inflammatory and related diseases

  15. The acute phase of inflammatory response involved in the wound-healing process after excimer laser treatment

    PubMed Central

    Resan, Mirko; Vukosavljevic, Miroslav; Vojvodic, Danilo; Pajic-Eggspuehler, Brigitte; Pajic, Bojan

    2016-01-01

    Purpose To evaluate the participation of proinflammatory cytokines in the acute phase of corneal wound-healing response after excimer laser treatment. Methods The study included 68 myopic eyes up to −3.0 diopters divided into two groups: 1) eyes treated with laser in situ keratomileusis (LASIK) (n=31) and 2) eyes treated with photorefractive keratectomy (PRK) (n=37). Each group was then divided into three subgroups based on tear sampling times: before (0 hours), 1 hour after, and 24 hours after treatment. The tear fluid was sampled from lower lateral tear meniscus using a cellulose microsurgical sponge. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8 in tear fluid were determined by flow cytometry method. Results Statistical significance was observed in the concentrations of TNF-α (P=0.0421) and IL-1β (P=0.0225) between samples collected 1 and 24 hours after PRK treatment in favor of samples collected 1 hour after treatment. IL-6 concentration changes showed a significant increase in the PRK group in both time intervals following treatment compared to pretreatment (0 hour/1 hour, P=0.0031; 0 hour/24 hours, P=0.0059). For IL-8 concentrations, significant differences were observed between control and experimental groups in samples collected 1 hour after LASIK and 1 hour after PRK treatment (P<0.001 for both groups), and IL-8 concentrations between control and experimental groups in samples collected 24 hours after LASIK and 24 hours after PRK treatment were greater after PRK treatment (P=0.0005). Comparison of average concentration values of proinflammatory cytokines in all the tested samples between LASIK and PRK groups showed significantly higher levels of IL-1β in the LASIK group 24 hours after treatment (P=0.0134), and of IL-6 in the PRK group 24 hours after treatment (P=0.0031). Conclusion The acute phase of corneal wound healing after excimer laser treatment is defined by an intensive inflammatory response. After PRK

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

    PubMed

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

    2016-09-01

    Background Resistance exercise is emerging as a potential adjunct therapy to aid in the management of breast cancer-related lymphedema (BCRL). However, the mechanisms underlying the relationships between the acute and long-term benefits of resistance exercise on BCRL are not well understood. Purpose To examine the acute inflammatory response to upper-body resistance exercise in women with BCRL and to compare these effects between resistance exercises involving low, moderate, and high loads. The impact on lymphedema status and associated symptoms was also compared. Methods A total of 21 women, 62 ± 10 years old, with BCRL participated in the study. Participants completed low-load (15-20 repetition maximum [RM]), moderate-load (10-12 RM), and high-load (6-8 RM) exercise sessions consisting of 3 sets of 6 upper-body resistance exercises. Sessions were completed in a randomized order separated by a 7- to 10-day wash-out period. Venous blood samples were obtained to assess markers of exercise-induced muscle damage and inflammation. Lymphedema status was assessed using bioimpedance spectroscopy and arm circumferences, and associated symptoms were assessed using Visual Analogue Scales for pain, heaviness, and tightness. Measurements were conducted before and 24 hours after the exercise sessions. Results No significant changes in creatine kinase, C-reactive protein, interleukin-6, and tumor necrosis factor-α were observed following the 3 resistance exercise sessions. There were no significant changes in arm swelling or symptom severity scores across the 3 resistance exercise conditions. Conclusions The magnitude of acute exercise-induced inflammation following upper-body resistance exercise in women with BCRL does not vary between resistance exercise loads. PMID:26582633

  17. Promoting inflammatory lymphangiogenesis by vascular endothelial growth factor-C (VEGF-C) aggravated intestinal inflammation in mice with experimental acute colitis

    PubMed Central

    Wang, X.L.; Zhao, J.; Qin, L.; Qiao, M.

    2016-01-01

    Angiogenesis and lymphangiogenesis are thought to play a role in the pathogenesis of inflammatory bowel diseases (IBD). However, it is not understood if inflammatory lymphangiogenesis is a pathological consequence or a productive attempt to resolve the inflammation. This study investigated the effect of lymphangiogenesis on intestinal inflammation by overexpressing a lymphangiogenesis factor, vascular endothelial growth factor-C (VEGF-C), in a mouse model of acute colitis. Forty eight-week-old female C57BL/6 mice were treated with recombinant adenovirus overexpressing VEGF-C or with recombinant VEGF-C156S protein. Acute colitis was then established by exposing the mice to 5% dextran sodium sulfate (DSS) for 7 days. Mice were evaluated for disease activity index (DAI), colonic inflammatory changes, colon edema, microvessel density, lymphatic vessel density (LVD), and VEGFR-3mRNA expression in colon tissue. When acute colitis was induced in mice overexpressing VEGF-C, there was a significant increase in colonic epithelial damage, inflammatory edema, microvessel density, and neutrophil infiltration compared to control mice. These mice also exhibited increased lymphatic vessel density (73.0±3.9 vs 38.2±1.9, P<0.001) and lymphatic vessel size (1974.6±104.3 vs 1639.0±91.5, P<0.001) compared to control mice. Additionally, the expression of VEGFR-3 mRNA was significantly upregulated in VEGF-C156S mice compared to DSS-treated mice after induction of colitis (42.0±1.4 vs 3.5±0.4, P<0.001). Stimulation of lymphangiogenesis by VEGF-C during acute colitis promoted inflammatory lymphangiogenesis in the colon and aggravated intestinal inflammation. Inflammatory lymphangiogenesis may have pleiotropic effects at different stages of IBD. PMID:27074165

  18. Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress

    PubMed Central

    Picard, Martin; McManus, Meagan J.; Gray, Jason D.; Nasca, Carla; Moffat, Cynthia; Kopinski, Piotr K.; Seifert, Erin L.; McEwen, Bruce S.; Wallace, Douglas C.

    2015-01-01

    The experience of psychological stress triggers neuroendocrine, inflammatory, metabolic, and transcriptional perturbations that ultimately predispose to disease. However, the subcellular determinants of this integrated, multisystemic stress response have not been defined. Central to stress adaptation is cellular energetics, involving mitochondrial energy production and oxidative stress. We therefore hypothesized that abnormal mitochondrial functions would differentially modulate the organism’s multisystemic response to psychological stress. By mutating or deleting mitochondrial genes encoded in the mtDNA [NADH dehydrogenase 6 (ND6) and cytochrome c oxidase subunit I (COI)] or nuclear DNA [adenine nucleotide translocator 1 (ANT1) and nicotinamide nucleotide transhydrogenase (NNT)], we selectively impaired mitochondrial respiratory chain function, energy exchange, and mitochondrial redox balance in mice. The resulting impact on physiological reactivity and recovery from restraint stress were then characterized. We show that mitochondrial dysfunctions altered the hypothalamic–pituitary–adrenal axis, sympathetic adrenal–medullary activation and catecholamine levels, the inflammatory cytokine IL-6, circulating metabolites, and hippocampal gene expression responses to stress. Each mitochondrial defect generated a distinct whole-body stress-response signature. These results demonstrate the role of mitochondrial energetics and redox balance as modulators of key pathophysiological perturbations previously linked to disease. This work establishes mitochondria as stress-response modulators, with implications for understanding the mechanisms of stress pathophysiology and mitochondrial diseases. PMID:26627253

  19. Enhanced inflammatory response to acute ozone exposure in rats during pregnancy and lactation

    SciTech Connect

    Gunnison, A.F.; Weideman, P.A.; Sobo, M. )

    1992-11-01

    Experimental evidence from several studies suggests that pregnant animals and women are more susceptible to oxidants than nonpregnant controls. In the study reported here, we sought to determine whether pregnant rats are more sensitive than age-matched virgin females to the inflammatory effects of ozone, a gaseous oxidant of considerable environmental significance. Rats at several stages of pregnancy and lactation, as well as age-matched virgin females, were exposed to 1 ppm ozone for 6 hr. Controls were sham-exposed to pure air for an identical period of time. Bronchoalveolar lavage was performed 24 hr after the beginning of exposure, and components of the lavage fluid considered to be indicators of inflammation were used to assess the severity of pulmonary inflammation. The results of this experiment showed that significantly enhanced sensitivity to ozone-induced pulmonary inflammation develops during pregnancy, is maintained during lactation, and disappears following lactation. Implicit in this pattern of differential sensitivity in rats is the possibility of a similar pattern of inflammatory response in analogous groups of humans as well as the potential for applicability to other oxidative pollutants.

  20. Design, synthesis and biological evaluation of paralleled Aza resveratrol-chalcone compounds as potential anti-inflammatory agents for the treatment of acute lung injury.

    PubMed

    Chen, Wenbo; Ge, Xiangting; Xu, Fengli; Zhang, Yali; Liu, Zhiguo; Pan, Jialing; Song, Jiao; Dai, Yuanrong; Zhou, Jianmin; Feng, Jianpeng; Liang, Guang

    2015-08-01

    Acute lung injury (ALI) is a major cause of acute respiratory failure in critically-ill patients. It has been reported that both resveratrol and chalcone derivatives could ameliorate lung injury induced by inflammation. A series of paralleled Aza resveratrol-chalcone compounds (5a-5m, 6a-6i) were designed, synthesized and screened for anti-inflammatory activity. A majority showed potent inhibition on the IL-6 and TNF-α expression-stimulated by LPS in macrophages, of which compound 6b is the most potent analog by inhibition of LPS-induced IL-6 release in a dose-dependent manner. Moreover, 6b exhibited protection against LPS-induced acute lung injury in vivo. These results offer further insight into the use of Aza resveratrol-chalcone compounds for the treatment of inflammatory diseases, and the use of compound 6b as a lead compound for the development of anti-ALI agents. PMID:26048788

  1. [IRIS: a paradoxical inflammatory reaction in patients treated simultaneously for tuberculosis and HIV].

    PubMed

    Chakrabarti, Lisa A; Lortholary, Olivier

    2015-01-01

    Co-infection with Mycobacterium tuberculosis (Mtb) and human immunodeficiency virus (HIV) represents a major threat to public health worldwide. The treatment of patients coinfected by Mtb and HIV is often complicated by the occurrence of an immune reconstitution inflammatory syndrome (IRIS), resulting in the unexpected resumption of tuberculosis symptoms after the initiation of antiretroviral therapy. IRIS is associated with a rapid reconstitution of CD4(+) T cell responses specific for Mtb, which is promoted by the control of HIV replication and a high concentration of available interleukin-7. Macrophages, whose activity is suddenly stimulated by CD4(+) T cell help, respond by an exacerbated inflammatory response in Mtb-rich tissues. A major research objective remains to identify biomarkers which could allow a reliable prediction of IRIS occurrence, in order to optimize medical care for the many patients affected by both HIV and tuberculosis in resource-limited settings. PMID:25658731

  2. Plasticity of the Systemic Inflammatory Response to Acute Infection during Critical Illness: Development of the Riboleukogram

    PubMed Central

    Burykin, Anton; Ruan, Jianhua; Li, Qing; Schierding, William; Lin, Nan; Dixon, David; Zhang, Weixiong; Coopersmith, Craig M.; Dunne, W. Michael; Colonna, Marco; Ghosh, Bijoy K.; Cobb, J. Perren

    2008-01-01

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

  3. Bone Marrow Mesenchymal Stem Cells Inhibit Lipopolysaccharide-Induced Inflammatory Reactions in Macrophages and Endothelial Cells

    PubMed Central

    Li, Dequan; Wang, Cong; Chi, Chuang; Wang, Yuanyuan; Zhao, Jing; Fang, Jun; Pan, Jingye

    2016-01-01

    Background. Systemic inflammatory response syndrome (SIRS) accompanied by trauma can lead to multiple organ dysfunction syndrome (MODS) and even death. Early inhibition of the inflammation is necessary for damage control. Bone marrow mesenchymal stem cells (BMSCs), as a novel therapy modality, have been shown to reduce inflammatory responses in human and animal models. Methods. In this study, we used Western blot, quantitative PCR, and enzyme-linked immunosorbent assay (ELISA) to assess the activity of BMSCs to suppress the inflammation induced by lipopolysaccharide (LPS) in human umbilical cord endothelial cells (HUVECs) and alveolar macrophages. Results. Our results demonstrated that LPS caused an inflammatory response in alveolar macrophages and HUVECs, increased permeability of HUVEC, upregulated expression of toll-like receptor (TLR) 2, TLR4, phosphorylated p65, downregulated release of IL10, and promoted release of TNF-α in both cells. Coculture with BMSCs attenuated all of these activities induced by LPS in the two tested cell types. Conclusions. Together, our results demonstrate that BMSCs dosage dependently attenuates the inflammation damage of alveolar macrophages and HUVECs induced by LPS. PMID:27057093

  4. Composition of PM Affects Acute Vascular Inflammatory and Coagulative Markers - The RAPTES Project

    PubMed Central

    Strak, Maciej; Hoek, Gerard; Godri, Krystal J.; Gosens, Ilse; Mudway, Ian S.; van Oerle, René; Spronk, Henri M. H.; Cassee, Flemming R.; Lebret, Erik; Kelly, Frank J.; Harrison, Roy M.; Brunekreef, Bert; Steenhof, Maaike; Janssen, Nicole A. H.

    2013-01-01

    Background Exposure to ambient particulate matter (PM) has been associated with adverse cardiovascular effects in epidemiological studies. Current knowledge of independent effects of individual PM characteristics remains limited. Methods Using a semi-experimental design we investigated which PM characteristics were consistently associated with blood biomarkers believed to be predictive of the risk of cardiovascular events. We exposed healthy adult volunteers at 5 different locations chosen to provide PM exposure contrasts with reduced correlations among PM characteristics. Each of the 31 volunteers was exposed for 5 h, exercising intermittently, 3–7 times at different sites from March to October 2009. Extensive on-site exposure characterization included measurements of PM mass and number concentration, elemental- (EC) and organic carbon (OC), trace metals, sulfate, nitrate, and PM oxidative potential (OP). Before and 2 h and 18 h after exposure we measured acute vascular blood biomarkers - C-reactive protein, fibrinogen, platelet counts, von Willebrand Factor, and tissue plasminogen activator/plasminogen activator inhibitor-1 complex. We used two-pollutant models to assess which PM characteristics were most consistently associated with the measured biomarkers. Results and Conclusion We found OC, nitrate and sulfate to be most consistently associated with different biomarkers of acute cardiovascular risk. Associations with PM mass concentrations and OP were less consistent, whereas other measured components of the air pollution mixture, including PNC, EC, trace metals and NO2, were not associated with the biomarkers after adjusting for other pollutants. PMID:23516583

  5. A retinoic acid receptor agonist Am80 rescues neurons, attenuates inflammatory reactions, and improves behavioral recovery after intracerebral hemorrhage in mice.

    PubMed

    Matsushita, Hideaki; Hijioka, Masanori; Hisatsune, Akinori; Isohama, Yoichiro; Shudo, Koichi; Katsuki, Hiroshi

    2011-01-01

    Am80 (tamibarotene) is a retinoic acid receptor (RAR) agonist clinically available for treatment of acute promyelocytic leukemia. As intracerebral hemorrhage (ICH) accompanies inflammatory reactions in the brain and also because retinoids may suppress activation of microglia, we investigated the effect of Am80 on collagenase-induced experimental model of ICH in adult mice. Daily oral administration of Am80 (5 mg/kg) starting from 1 day before or from up to 6 hours after intrastriatal injection of collagenase significantly inhibited the decrease in the number of striatal neurons at 3 days after the insult. Am80 showed no significant effect on the hematoma size and the extent of edema associated with hemorrhage. Prominent expression of RARα was observed in activated microglia/macrophages, and the number of activated microglia/macrophages in the perihematoma region was lower in Am80-treated mice than in vehicle-treated mice. Am80 treatment also reduced areas affected by hemorrhage-associated oxidative stress as indicated by nitrotyrosine immunoreactivity, and attenuated heme oxygenase-1 expression in activated microglia/macrophages. Moreover, Am80-treated mice exhibited better recovery from hemorrhage-induced neurologic deficits than vehicle-treated mice. These results suggest that RAR is a promising target of neuroprotective therapy for ICH. PMID:20551971

  6. A retinoic acid receptor agonist Am80 rescues neurons, attenuates inflammatory reactions, and improves behavioral recovery after intracerebral hemorrhage in mice

    PubMed Central

    Matsushita, Hideaki; Hijioka, Masanori; Hisatsune, Akinori; Isohama, Yoichiro; Shudo, Koichi; Katsuki, Hiroshi

    2011-01-01

    Am80 (tamibarotene) is a retinoic acid receptor (RAR) agonist clinically available for treatment of acute promyelocytic leukemia. As intracerebral hemorrhage (ICH) accompanies inflammatory reactions in the brain and also because retinoids may suppress activation of microglia, we investigated the effect of Am80 on collagenase-induced experimental model of ICH in adult mice. Daily oral administration of Am80 (5 mg/kg) starting from 1 day before or from up to 6 hours after intrastriatal injection of collagenase significantly inhibited the decrease in the number of striatal neurons at 3 days after the insult. Am80 showed no significant effect on the hematoma size and the extent of edema associated with hemorrhage. Prominent expression of RARα was observed in activated microglia/macrophages, and the number of activated microglia/macrophages in the perihematoma region was lower in Am80-treated mice than in vehicle-treated mice. Am80 treatment also reduced areas affected by hemorrhage-associated oxidative stress as indicated by nitrotyrosine immunoreactivity, and attenuated heme oxygenase-1 expression in activated microglia/macrophages. Moreover, Am80-treated mice exhibited better recovery from hemorrhage-induced neurologic deficits than vehicle-treated mice. These results suggest that RAR is a promising target of neuroprotective therapy for ICH. PMID:20551971

  7. Acute aerobic exercise and information processing: energizing motor processes during a choice reaction time task.

    PubMed

    Audiffren, Michel; Tomporowski, Phillip D; Zagrodnik, James

    2008-11-01

    The immediate and short-term after effects of a bout of aerobic exercise on young adults' information processing were investigated. Seventeen participants performed an auditory two-choice reaction time (RT) task before, during, and after 40 min of ergometer cycling. In a separate session, the same sequence of testing was completed while seated on an ergometer without pedalling. Results indicate that exercise (1) improves the speed of reactions by energizing motor outputs; (2) interacts with the arousing effect of a loud auditory signal suggesting a direct link between arousal and activation; (3) gradually reduces RT and peaks between 15 and 20 min; (4) effects on RT disappear very quickly after exercise cessation; and (5) effects on motor processes cannot be explained by increases in body temperature caused by exercise. Taken together, these results support a selective influence of acute aerobic exercise on motor adjustment stage. PMID:18930445

  8. Acute psychosocial stress and emotion regulation skills modulate empathic reactions to pain in others.

    PubMed

    Buruck, Gabriele; Wendsche, Johannes; Melzer, Marlen; Strobel, Alexander; Dörfel, Denise

    2014-01-01

    Psychosocial stress affects resources for adequate coping with environmental demands. A crucial question in this context is the extent to which acute psychosocial stressors impact empathy and emotion regulation. In the present study, 120 participants were randomly assigned to a control group vs. a group confronted with the Trier Social Stress Test (TSST), an established paradigm for the induction of acute psychosocial stress. Empathy for pain as a specific subgroup of empathy was assessed via pain intensity ratings during a pain-picture task. Self-reported emotion regulation skills were measured as predictors using an established questionnaire. Stressed individuals scored significantly lower on the appraisal of pain pictures. A regression model was chosen to find variables that further predict the pain ratings. These findings implicate that acute psychosocial stress might impair empathic processes to observed pain in another person and the ability to accept one's emotion additionally predicts the empathic reaction. Furthermore, the ability to tolerate negative emotions modulated the relation between stress and pain judgments, and thus influenced core cognitive-affective functions relevant for coping with environmental challenges. In conclusion, our study emphasizes the necessity of reducing negative emotions in terms of empathic distress when confronted with pain of another person under psychosocial stress, in order to be able to retain pro-social behavior. PMID:24910626

  9. Acute psychosocial stress and emotion regulation skills modulate empathic reactions to pain in others

    PubMed Central

    Buruck, Gabriele; Wendsche, Johannes; Melzer, Marlen; Strobel, Alexander; Dörfel, Denise

    2014-01-01

    Psychosocial stress affects resources for adequate coping with environmental demands. A crucial question in this context is the extent to which acute psychosocial stressors impact empathy and emotion regulation. In the present study, 120 participants were randomly assigned to a control group vs. a group confronted with the Trier Social Stress Test (TSST), an established paradigm for the induction of acute psychosocial stress. Empathy for pain as a specific subgroup of empathy was assessed via pain intensity ratings during a pain-picture task. Self-reported emotion regulation skills were measured as predictors using an established questionnaire. Stressed individuals scored significantly lower on the appraisal of pain pictures. A regression model was chosen to find variables that further predict the pain ratings. These findings implicate that acute psychosocial stress might impair empathic processes to observed pain in another person and the ability to accept one's emotion additionally predicts the empathic reaction. Furthermore, the ability to tolerate negative emotions modulated the relation between stress and pain judgments, and thus influenced core cognitive-affective functions relevant for coping with environmental challenges. In conclusion, our study emphasizes the necessity of reducing negative emotions in terms of empathic distress when confronted with pain of another person under psychosocial stress, in order to be able to retain pro-social behavior. PMID:24910626

  10. Neuroendocrine, metabolic, and immune functions during the acute phase response of inflammatory stress in monosodium L-glutamate-damaged, hyperadipose male rat.

    PubMed

    Castrogiovanni, Daniel; Gaillard, Rolf C; Giovambattista, Andrés; Spinedi, Eduardo

    2008-01-01

    In rats, neonatal treatment with monosodium L-glutamate (MSG) induces several metabolic and neuroendocrine abnormalities, which result in hyperadiposity. No data exist, however, regarding neuroendocrine, immune and metabolic responses to acute endotoxemia in the MSG-damaged rat. We studied the consequences of MSG treatment during the acute phase response of inflammatory stress. Neonatal male rats were treated with MSG or vehicle (controls, CTR) and studied at age 90 days. Pituitary, adrenal, adipo-insular axis, immune, metabolic and gonadal functions were explored before and up to 5 h after single sub-lethal i.p. injection of bacterial lipopolysaccharide (LPS; 150 microg/kg). Our results showed that, during the acute phase response of inflammatory stress in MSG rats: (1) the corticotrope-adrenal, leptin, insulin and triglyceride responses were higher than in CTR rats, (2) pro-inflammatory (TNFalpha) cytokine response was impaired and anti-inflammatory (IL-10) cytokine response was normal, and (3) changes in peripheral estradiol and testosterone levels after LPS varied as in CTR rats. These data indicate that metabolic and neroendocrine-immune functions are altered in MSG-damaged rats. Our study also suggests that the enhanced corticotrope-corticoadrenal activity in MSG animals could be responsible, at least in part, for the immune and metabolic derangements characterizing hypothalamic obesity. PMID:18382067

  11. Provocation tests with the offending nonsteroidal anti-inflammatory drugs in patients with urticaria/angioedema reactions.

    PubMed

    Zisa, Giuliana; Riccobono, Francesca; Bommarito, Luisa; D'Antonio, Cristian; Calamari, Ambra Marianna; Poppa, Mariangela; Moschella, Maria Adele; Di Pietrantonj, Carlo; Galimberti, Maurizio

    2012-01-01

    The provocation test (PT) with the suspected drug represents the gold standard in the diagnosis of non-IgE hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs). Nevertheless, there is no consensus regarding the clinical management of suspected NSAID-sensitive patients. This study assessed if a PT with the suspected drug is a reliable and safe proceeding to confirm NSAID hypersensitivity in patients with a clinical history of urticaria/angioedema (Urt/AE). It also analyzed different patient characteristics (such as gender, age, atopy, dermographism, time interval between the last drug reaction, and number of previous NSAID reactions) in relation to PT positivity. One hundred fifty-nine patients with Urt/AE apparently related to assumption of one or more NSAIDs underwent PT with the suspected drugs. Moreover, to distinguish single/multiple NSAID reactivity in patients who did not tolerate the offending NSAID, another strong cyclooxygenase-1 inhibitor PT was performed. PT was negative in 142/159 patients (89.31%), ruling out a diagnosis of NSAIDs hypersensitivity; 17/159 patients (10.69%) experienced a reaction of Urt/AE during the PT: 8 patients were diagnosed as single reactors to NSAIDs and 4 as multiple reactors to NSAIDs. Those with a history of multiple NSAID reactions and male patients were both more likely to have a positive PT. Our results suggest that in all patients with history of NSAID cutaneous reactions, the NSAID hypersensitivity should be confirmed by an oral PT and that the diagnostic proceeding can safely start with the offending NSAID. PMID:23026184

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

    PubMed Central

    Petersen, Rebecca Y.; Royse, Emily; Kemp, Matthew W.; Miura, Yuichiro; Noe, Andres; Jobe, Alan H.; Hillman, Noah H.

    2016-01-01

    Background Mechanical ventilation at birth causes airway injury and lung inflammation in preterm sheep. Continuous positive airway pressure (CPAP) is being increasingly used clinically to transition preterm infants at birth. Objective To test if distending pressures will activate acute phase reactants and inflammatory changes in the airways of fetal, preterm lambs. Methods The head and chest of fetal lambs at 128±1 day GA were surgically exteriorized. With placental circulation intact, fetal lambs were then randomized to one of five 15 minute interventions: PEEP of 0, 4, 8, 12, or 16 cmH2O. Recruitment volumes were recorded. Fetal lambs remained on placental support for 30 min after the intervention. The twins of each 0 cmH2O animal served as controls. Fetal lung fluid (FLF), bronchoalveolar lavage fluid (BAL), right mainstem bronchi and peripheral lung tissue were evaluated for inflammation. Results Recruitment volume increased from 0.4±0.04 mL/kg at 4 cmH2O to 2.4±0.3 mL/kg at 16 cmH2O. The lambs were surfactant deficient, and all pressures were below the opening inflection pressure on pressure-volume curve. mRNA expression of early response genes and pro-inflammatory cytokines did not increase in airway tissue or lung tissue at any pressure compared to controls. FLF and BAL also did not have increases in early response proteins. No histologic changes or Egr-1 activation was present at the pressures used. Conclusion Distending pressures as high as 16 cmH2O did not recruit lung volume at birth and did not increase markers of injury in the lung or airways in non-breathing preterm fetal sheep. PMID:27463520

  13. HDAC9 regulates ox-LDL-induced endothelial cell apoptosis by participating in inflammatory reactions.

    PubMed

    Han, Xu; Han, Xiang; Wang, Zheng; Shen, Junjun; Dong, Qiang

    2016-01-01

    Atherosclerosis is the most common cause of cardiovascular diseases worldwide. The endothelial cell apoptosis elicited by oxidized low-density lipoprotein (ox-LDL), which contributes to endothelial damage and inflammation, is a particularly important event in the early stage of atherosclerosis. However, the mechanism underlying ox-LDL-induced endothelial cell apoptosis remains unclear. Here we found that HDAC9 expression was increased at both the mRNA and protein levels accompanied by dose-dependent ox-LDL-induced endothelial cell apoptosis. Depletion of HDAC9 by its specific shRNA significantly antagonized ox-LDL-induced cell apoptosis and suppressed the expression of ox-LDL-induced inflammatory factors, such as TNF-alpha and MCP1. These data suggest that HDAC9 is an important epigenetic factor regulating ox-LDL-induced endothelial cell apoptosis and inflammatory factor expression. These results suggest that HDAC9 may participate in ox-LDL-induced endothelial damage and inflammation during atherosclerosis development. PMID:27100479

  14. Comparison of allergic reactions to intravenous and intramuscular pegaspargase in children with acute lymphoblastic leukemia.

    PubMed

    Petersen, William C; Clark, Dana; Senn, Stacy L; Cash, W Thomas; Gillespie, Scott E; McCracken, Courtney E; Keller, Frank G; Lew, Glen

    2014-05-01

    Pegaspargase (PEG) is a standard component of therapy for pediatric acute lymphoblastic leukemia (ALL). Because PEG preparations are bacterially derived, they are highly immunogenic. PEG has traditionally been delivered intramuscularly (IM), but over the last several years, more PEG has been given intravenously (IV) in order to provide a less painful and more convenient means of delivery. However, there are limited data comparing allergic reactions between IV and IM PEG recipients, especially in a large cohort of patients. We reviewed the charts of pediatric ALL patients diagnosed from 2006 to 2011 who received PEG at our institution and compared the incidence, time to onset of symptoms, reaction grade, and hospitalization rate for patients who had allergic reactions to PEG. Of 318 evaluable patients, 159 received IV and 159 received IM PEG. Thirty-one (19.5%) IV patients had an allergic reaction, compared to 17 (10.7%) IM patients (P = .028). Time to onset of symptoms was ≤ 30 minutes for 26 of 27 evaluable IV patients (96.3%) versus only two of 11 evaluable IM patients (18.2%; P < .001). Four of 31 IV patients (12.9%) and six of 17 IM patients (35.5%) required hospitalization (P = .134). There is increased incidence of allergy in patients who received IV PEG compared to IM. Grade of reaction was similar between IV and IM, but allergic reactions to IV PEG had a more rapid onset. While the risk of allergy may be increased, IV delivery appears to have an acceptable safety profile for administration in ALL patients. PMID:24498943

  15. Acute Transfusion Reactions (ATRs) in Intensive Care Unit (ICU): A Retrospective Study

    PubMed Central

    Kumar, Rajesh; Gupta, Manvi; Gupta, Varun; Kaur, Amarjit; Gupta, Sonia

    2014-01-01

    Background: Blood transfusion is a frequent and integral part of critical care. Although life saving, it can occasionally be unsafe and result in a spectrum of adverse events. Acute transfusion reactions (ATRs) are probably under diagnosed in critically ill patients due to confusion of the symptoms with the underlying disease. Aim: To analyze the incidence and spectrum of ATRs occuring in critically ill patients. Materials and Methods: This was a retrospective review conducted from 1st April 2011 till 31st March 2013. The ATRs related to the administration of blood components in the patients admitted in various Intensive Care Units (ICUs) were recorded, analyzed and classified on the basis of their clinical features and laboratory tests. Results: During the study period 98651 blood components were issued. Out of these 21971 were issued to various ICUs. A total of 225 transfusion reactions were reported from the various critical care departments during this period. The most frequent were Febrile Non Hemolytic Transfusion Reactions (FNHTR) 136 (60.4%), allergic reactions 70 (31.2%), hemolytic reactions 1(0.4%) and non specific reactions 18 (8%). The incidence of ATRs in our study was found to be 1.09% in adult ICUs and 0.36% in pediatric ICUs. Conclusions: Blood transfusion is a vital therapeutic procedure with a potential risk to already critical patients. So a strict vigilance has to be kept and each transfusion has to be monitored carefully with prompt recognition and treatment of ATRs. A rational use of these products considering their deleterious effects can decrease transfusion related morbidity and mortality in the critically ill patients. PMID:24701502

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

    PubMed

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

    2012-07-01

    In this study, the anti-nociceptive and anti-inflammatory effects of cyanocobalamin (Vit B12) against acute and chronic pain and inflammation were evaluated in mice. Vit B12 (0.87, 1 and 1.77 mg/kg) were injected intraperitoneally. The anti-nociceptive effects against acute pain were examined using hot-plate and writhing tests. The chronic pain was examined 14 days after sciatic nerve ligation using the hot-plate test. Morphine (10 mg/kg) was used as a positive control. Anti-inflammatory effects of Vit B12 against acute and chronic inflammation were assessed using xylene-induced edema in ears and granuloma caused by compressed cotton implantation, respectively. In these tests, sodium diclofenac (15 mg/kg) was used as a positive control. Vit B12 showed a dose related effect in acute anti-nociceptive test and increased the anti-nociceptive effect of morphine in chronic treatment. Vit B12 demonstrated an anti-nociceptive effect in chronic studies as single or continues daily treatment and increased significantly the anti-nociceptive effect of morphine. All doses of Vit B12 significantly decreased xylene-induced ear edema. Maximum anti-inflammatory effect (37.5%) was obtained at dose of 1 mg/kg. In chronic inflammation, Vit B12 significantly decreased granuloma formation in mice. In conclusion our work presents some experimental evidence supporting the administration of cyanocobalamin in controlling acute and chronic neuropathic pain. Cyanocobalamin may have anti-inflammatory effect. It may reduce tolerance to anti-nociceptive effect of morphine as well. PMID:22588629

  17. Lycopene protects against acute zearalenone-induced oxidative, endocrine, inflammatory and reproductive damages in male mice.

    PubMed

    Boeira, Silvana Peterini; Funck, Vinícius Rafael; Borges Filho, Carlos; Del'Fabbro, Lucian; de Gomes, Marcelo Gomes; Donato, Franciele; Royes, Luiz Fernando Freire; Oliveira, Mauro Schneider; Jesse, Cristiano Ricardo; Furian, Ana Flávia

    2015-03-25

    Male mice received lycopene for 10 days before a single oral administration of zearalenone (ZEA). After 48 h testes and blood were collected. Mice treated with lycopene/ZEA exhibited amelioration of the hematological changes. Lycopene prevented the reduction in the number and motility of spermatozoa and testosterone levels, indicating a protective effect in the testicular damage induced by ZEA. Lycopene was also effective in protecting against the decrease in glutathione-S-transferase, glutathione peroxidase, glutathione reductase and δ-aminolevulinic acid dehydratase activities caused by ZEA in the testes. Exposure of animals to ZEA induced modification of antioxidant and inflammatory status with increase of reduced glutathione (GSH) levels and increase of the oxidized glutathione, interleukins 1β, 2, 6, 10, tumor necrosis factor-α and bilirubin levels. Lycopene prevented ZEA-induced changes in GSH levels and inhibited the processes of inflammation, reducing the damage induced by ZEA. Altogether, our results indicate that lycopene was able to prevent ZEA-induced damage in the mice. PMID:25682699

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

    PubMed

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

    2016-07-01

    The disease profile in the Indian population provides a unique opportunity for studying the host microbiome interaction in both infectious (amebiasis) and autoimmune diseases like inflammatory bowel disease (IBD) from a similar environment and genetic background. Analysis of fecal samples from untreated amebic liver abscess (ALA) patients, Entamoeba histolytica (Eh)-negative and -positive asymptomatic individuals, and pus samples from naive ALA patients revealed a significant reduction in Lactobacillus in asymptomatic individuals (Eh +ve) and ALA patients. Two anaerobic genera, namely Bacteroides and Peptostreptococcus, were detected in naive ALA pus samples. Analysis of fecal samples from amoebic colitis patients showed a significant decline in population of Bacteroides, Clostridium coccoides and leptum subgroup, Lactobacillus, Campylobacter, and Eubacterium, whereas a significant increase in Bifidobacterium was observed. Mucosa-associated bacterial flora analysis from IBD patients and healthy controls revealed a significant difference in concentration of bacteria among predominating and subdominating genera between ulcerative colitis (UC), Crohn's disease (CD) patients, and controls. In contrast to the mucosal studies, we found a significant increase in lactobacilli population in fecal samples of active UC patients. Another study revealed a significant decrease of Clostridium coccoides and leptum clusters in fecal samples of active UC patients along with decreased concentrations of fecal SCFAs, especially of n-butyrate, iso-butyrate, and acetate. We therefore found similar perturbations in gut microbiome in both infectious and autoimmune diseases, indicating inflammation to be the major driver for changes in gut microbiome. PMID:26994772

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

    PubMed Central

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

    2014-01-01

    Exogenous aldehydes can cause pain in animal models, suggesting that aldehyde dehydrogenase 2 (ALDH2), which metabolizes many aldehydes, may regulate nociception. To test this hypothesis, we generated a knock-in mouse with an inactivating point mutation in ALDH2 (ALDH2*2), which is also present in human ALDH2 of ~540 million East Asians. The ALDH2*1/*2 heterozygotic mice exhibited a larger response to painful stimuli than their wild-type littermates, and this heightened nociception was inhibited by an ALDH2-selective activator (Alda-1). No effect on inflammation per se was observed. Using a rat model, we then showed that nociception tightly correlated with ALDH activity (R2=0.90) and that reduced nociception was associated with less early growth response protein 1 (EGR1) in the spinal cord and less reactive aldehyde accumulation at the insult site (including acetaldehyde and 4-hydroxynonenal). Further, acetaldehyde and formalin-induced nociceptive behavior was greater in the ALDH2*1/*2 mice than wild-type mice. Finally, Alda-1 treatment was also beneficial when given even after the inflammatory agent was administered. Our data in rodent models suggest that the mitochondrial enzyme ALDH2 regulates nociception and could serve as a molecular target for pain control, with ALDH2 activators, such as Alda-1, as potential non-narcotic cardiac-safe analgesics. Furthermore, our results suggest a possible genetic basis for East Asians’ apparent lower pain tolerance. PMID:25163478

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

    PubMed Central

    Cai, Guohui; Dinan, Tara; Barwood, Joanne M.; De Luca, Simone N.; Soch, Alita; Ziko, Ilvana; Chan, Stanley M. H.; Zeng, Xiao-Yi; Li, Songpei; Molero, Juan; Spencer, Sarah J.

    2015-01-01

    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. PMID:25628527

  1. Effects of nitric oxide synthase inhibitor ω-Nitro-L-Arginine Methyl Ester, on silica-induced inflammatory reaction and apoptosis

    PubMed Central

    Wang, He; Leigh, James

    2006-01-01

    Background Although nitric oxide is overproduced by macrophages and neutrophils after exposure to silica, its role in silica-induced inflammatory reaction and apoptosis needs further clarification. In this study, rats were intratracheally instilled with either silica suspension or saline to examine inflammatory reactions and intraperitoneally injected with ω-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthases, or saline to examine the possible role of nitric oxide production in the reaction. Results Results showed that silica instillation induced a strong inflammatory reaction indicated by increased total cell number, number of neutrophils, protein concentration and lactate dehydrogenase (LDH) activity in bronchoalveolar lavage fluid (BALF). There were no significant differences in these indices between silica-instilled groups with and without L-NAME injection (p > 0.05) except LDH level. The results also showed that apoptotic leucocytes were identified in BALF cells of silica-instilled groups whereas no significant difference was found between silica-instilled groups with and without L-NAME injection in the apoptotic reaction (p > 0.05). Silica instillation significantly increased the level of BALF nitrite/nitrate and L-NAME injection reduced this increase. Conclusion Intratracheal instillation of silica caused an obvious inflammatory reaction and leucocyte apoptosis, but these reactions were not influenced by intraperitoneal injection of L-NAME and reduced production of NO. This supports the possibility that silica-induced lung inflammation and BALF cell apoptosis are via NO-independent mechanisms. PMID:17090306

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

    SciTech Connect

    Marchini, T.; Magnani, N.D.; Paz, M.L.; Vanasco, V.; Tasat, D.; González Maglio, D.H.; 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

  3. Baclofen, a GABABR Agonist, Ameliorates Immune-Complex Mediated Acute Lung Injury by Modulating Pro-Inflammatory Mediators

    PubMed Central

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

    2015-01-01

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

  4. Acute effects of single-dose olanzapine on metabolic, endocrine, and inflammatory markers in healthy controls.

    PubMed

    Hahn, Margaret Karolina; Wolever, Tom M S; Arenovich, Tamara; Teo, Celine; Giacca, Adria; Powell, Valerie; Clarke, Leigh; Fletcher, Paul; Cohn, Tony; McIntyre, Roger S; Gomes, Sylvia; Chintoh, Araba; Remington, Gary J

    2013-12-01

    Atypical antipsychotics may "directly" influence glucose homeostasis, increasing risk of type 2 diabetes independently of changes in adiposity. Animal models suggest direct effects after even a single dose of certain atypical antipsychotics on glucose dysregulation. Here, we investigated effects of a single-dose olanzapine (OLA) on glucose metabolism in healthy volunteers, thereby minimizing confounding effects of the illness of schizophrenia and adiposity. In a randomized double-blind crossover design, 15 subjects were administered 10 mg of OLA or placebo at 7:00 A.M. on separate study dates. A frequently sampled intravenous glucose tolerance test was initiated 4.25 hours later to assess changes in glucose homeostasis, including an index of insulin sensitivity, disposition index, glucose effectiveness, and acute insulin response to glucose. We also examined effects on cortisol, prolactin, fasting free fatty acids (FFAs), insulin-mediated suppression of FFAs, and adipocytokines (leptin, adiponectin, C-reactive protein, interleukin 6, and tumor necrosis factor α). Complete data for both visits were analyzed for 12 subjects. Olanzapine treatment significantly decreased glucose effectiveness (P = 0.041) and raised fasting glucose over 4.25 hours (P = 0.03) as compared to placebo. Olanzapine was associated with lower serum cortisol (P = 0.003), lower fasting FFA (P = 0.042), and increased prolactin levels (P < 0.0001). We therefore suggest that a single dose of OLA may invoke early changes in some parameters of glucose and lipid metabolism, as well as endocrine indices. PMID:24100786

  5. [Treatment of acute inflammatory pathology of the upper airway with morniflumate].

    PubMed

    Marchioni, C F; Livi, E; Oliani, C; Guerzoni, P; Corona, M

    1990-12-01

    Sixty patients, 33 men and 27 women (mean age about 45 years; range 25-60), affected by acute influenza syndrome of the upper airways were admitted to a controlled single-blind study with three drugs under parallel conditions. According to a balanced randomized sequence, the subjects were treated over a 7-10 day period with morniflumate sachets (700 mg bid) or with tiaprofenic acid sachets (300 mg bid) or with paracetamol (10 ml syrup equivalent to 500 mg tid). The efficacy of the test drugs was assessed by determining the local and general signs and symptoms before starting the treatments, in basal conditions, and on the 3rd, 5th and last day of treatment. At the doses and formulations used, morniflumate proved to be equivalent to paracetamol and more effective than tiaprofenic acid as for its antipyretic action in the first days of treatment. On the other hand, both morniflumate and tiaprofenic acid showed a significantly higher antiinflammatory effect compared to paracetamol. Pain was effectively and equally controlled in all the treatment groups. The drugs administered were generally well tolerated. A greater incidence of adverse GI events was reported in the group treated with tiaprofenic acid. PMID:2132289

  6. Inflammatory Transcriptome Profiling of Human Monocytes Exposed Acutely to Cigarette Smoke

    PubMed Central

    Wright, William R.; Parzych, Katarzyna; Crawford, Damian; Mein, Charles; Mitchell, Jane A.; Paul-Clark, Mark J.

    2012-01-01

    Background Cigarette smoking is responsible for 5 million deaths worldwide each year, and is a major risk factor for cardiovascular and lung diseases. Cigarette smoke contains a complex mixture of over 4000 chemicals containing 1015 free radicals. Studies show smoke is perceived by cells as an inflammatory and xenobiotic stimulus, which activates an immune response. The specific cellular mechanisms driving cigarette smoke-induced inflammation and disease are not fully understood, although the innate immune system is involved in the pathology of smoking related diseases. Methodology/Principle findings To address the impact of smoke as an inflammagen on the innate immune system, THP-1 cells and Human PBMCs were stimulated with 3 and 10% (v/v) cigarette smoke extract (CSE) for 8 and 24 hours. Total RNA was extracted and the transcriptome analysed using Illumina BeadChip arrays. In THP-1 cells, 10% CSE resulted in 80 genes being upregulated and 37 downregulated by ≥1.5 fold after 8 hours. In PBMCs stimulated with 10% CSE for 8 hours, 199 genes were upregulated and 206 genes downregulated by ≥1.5 fold. After 24 hours, the number of genes activated and repressed by ≥1.5 fold had risen to 311 and 306 respectively. The major pathways that were altered are associated with cell survival, such as inducible antioxidants, protein chaperone and folding proteins, and the ubiquitin/proteosome pathway. Conclusions Our results suggest that cigarette smoke causes inflammation and has detrimental effects on the metabolism and function of innate immune cells. In addition, THP-1 cells provide a genetically stable alternative to primary cells for the study of the effects of cigarette smoke on human monocytes. PMID:22363418

  7. Early High-dosage Atorvastatin Treatment Improved Serum Immune-inflammatory Markers and Functional Outcome in Acute Ischemic Strokes Classified as Large Artery Atherosclerotic Stroke

    PubMed Central

    Tuttolomondo, Antonino; Di Raimondo, Domenico; Pecoraro, Rosaria; Maida, Carlo; Arnao, Valentina; Corte, Vittoriano Della; Simonetta, Irene; Corpora, Francesca; Di Bona, Danilo; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio

    2016-01-01

    Abstract Statins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. The primary hypothesis of this randomized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators. We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke (LAAS) randomly assigned in a randomized parallel trial to the following groups: Group A, 22 patients treated with atorvastatin 80 mg (once-daily) from admission day until discharge; Group B, 20 patients not treated with atorvastatin 80 mg until discharge, and after discharge, treatment with atorvastatin has been started. At 72 hours and at 7 days after acute ischemic stroke, subjects of group A showed significantly lower plasma levels of tumor necrosis factor-α, interleukin (IL)-6, vascular cell adhesion molecule-1, whereas no significant difference with regard to plasma levels of IL-10, E-Selectin, and P-Selectin was observed between the 2 groups. At 72 hours and 7 days after admission, stroke patients treated with atorvastatin 80 mg in comparison with stroke subjects not treated with atorvastatin showed a significantly lower mean National Institutes of Health Stroke Scale and modified Rankin scores. Our findings provide the first evidence that atorvastatin acutely administered immediately after an atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory activation of the acute phase of stroke and that its early use is associated to a better functional and prognostic profile. PMID:27043681

  8. Differences in cerebrospinal fluid inflammatory cell reaction of patients with leptomeningeal involvement by lymphoma and carcinoma.

    PubMed

    Illán, Julia; Simo, Marta; Serrano, Cristina; Castañón, Susana; Gonzalo, Raquel; Martínez-García, María; Pardo, Javier; Gómez, Lidia; Navarro, Miguel; Altozano, Javier Pérez; Alvarez, Ruth; Bruna, Jordi; Subirá, Dolores

    2014-12-01

    Dissemination of neoplastic cells into the cerebrospinal fluid (CSF) and leptomeninges is a devastating complication in patients with epithelial cell neoplasia (leptomeningeal carcinomatosis [LC]) and lymphomas (lymphomatous meningitis [LyM]). Information about the surrounding inflammatory cell populations is scarce. In this study, flow cytometry immunophenotyping was used to describe the distribution of the main leukocyte populations in the CSF of 83 patients diagnosed with neoplastic meningitis (LC, n = 65; LyM, n = 18). These data were compared with those obtained in the CSF from 55 patients diagnosed with the same groups of neoplasia without meningeal involvement (solid tumors, n = 36; high-grade lymphoma, n = 19). Median (interquartile) rates of lymphocytes, monocytes, and polymorphonuclear (PMN) cells were 59.7% (range, 35-76.6%), 24% (range, 16-53%), and 1.5% (range, 0-7.6%) in LC, respectively, and 98.5% (range, 70.8-100%), 1.5% (range, 0-29.3%), and 0% in LyM, respectively (P < 0.001). No difference was observed between patients with breast adenocarcinoma (n = 30) and lung adenocarcinoma (n = 21), nor with different rates of malignant CSF involvement. Patients with lymphoma (with or without LyM) had a similar CSF leukocyte distribution, but cancer patients with LC and without LC had a distinctive PMN cell rate (P = 0.002). These data show that CSF samples from patients with LC have a greater number of inflammatory cells and a different leukocyte distribution than seen in the CSF from patients with LyM. Description of PMN cells is a distinctive parameter of patients with LC, compared with the CSF from patients with LyM and patients with cancer but without LC. PMID:24746871

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

    PubMed Central

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

    2015-01-01

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

  10. Anti-inflammatory and anti-oxidative effects of corilagin in a rat model of acute cholestasis

    PubMed Central

    2013-01-01

    Background Nowadays, treatments for cholestasis remain largely nonspecific and often ineffective. Recent studies showed that inflammatory injuries and oxidative stress occur in the liver with cholestasis. In this study, we would use corilagin to treat the animal model of acute cholestasis in order to define the activity to interfere with inflammation-related and oxidative stress pathway in cholestatic pathogenesis. Methods Rats were administrated with alpha-naphthylisothiocyanate to establish model of cholestasis and divided into corilagin, ursodeoxycholic acid, dexamethasone, model and normal groups with treatment of related agent. At 24h, 48h and 72h time points after administration, living condition, serum markers of liver damage, pathological changes of hepatic tissue, nuclear factor (NF)-kappaB, myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) were examined and observed. Results Compared to model group, corilagin had remarkable effect on living condition, pathological manifestation of liver tissue, total bilirubin, direct bilirubin, (P<0.01), but no effect on alanine aminotransferase (ALT) and aspartate aminotransferase (AST). With corilagin intervention, levels of MPO, MDA and translocation of NF-κB were notably decreased, and levels of SOD and NO were markedly increased (P<0.05 or P<0.01). Conclusions It is shown that corilagin is a potential component to relieve cholestasis through inflammation-related and oxidation-related pathway. PMID:23641818

  11. Anti-inflammatory and anti-apoptotic effects of oxysophoridine on lipopolysaccharide-induced acute lung injury in mice

    PubMed Central

    Fu, Junjing; Wang, Yongtao; Zhang, Jianxin; Wu, Wei; Chen, Xiyan; Yang, Yanrong

    2015-01-01

    Oxysophoridine (OSR) is an alkaloid with multiple pharmacological activities. This study aimed to investigate the protective effects and underlying mechanisms of OSR on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Here, we found that OSR treatment markedly mitigated LPS-induced body weight loss and significant lung injury characterized by the deterioration of histopathology, histologic scores, wet-to-dry ratio, exduate volume, and protein leakage. OSR dramatically attenuated LPS-induced lung inflammation, as evidenced by the reduced levels of total cells, neutrophils, lymphocytes, and macrophages and pro-inflammatory cytokines (i.e., tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein-1) in bronchoalveolar lavage fluid and of their mRNA expression in lung tissues. OSR also inhibited LPS-induced expression and activation of nuclear factor-κB p65 in pulmonary tissue. Additionally, OSR administration markedly prevented LPS-induced pulmonary cell apoptosis in mice, as reflected by the decrease in expression of procaspase-8, procaspase-3, cleaved caspase-8, and cleaved caspase-3, and Bcl-2-associated X/B-cell lymphoma 2 ratio. These results indicate that OSR is a potential therapeutic drug for treating LPS-induced ALI. PMID:26885265

  12. Antioxidant and Anti-Inflammatory Effects of Coenzyme Q10 on L-Arginine-Induced Acute Pancreatitis in Rat

    PubMed Central

    Mirmalek, Seyed Abbas; Gholamrezaei Boushehrinejad, Ala; Yavari, Hassan; Kardeh, Bahareh; Parsa, Yekta; Salimi-Tabatabaee, Seyed Alireza; Yadollah-Damavandi, Soheila; Parsa, Tina; Shahverdi, Ehsan

    2016-01-01

    This study was aimed at evaluating the protective effect of coenzyme Q10 on L-arginine-induced acute pancreatitis in rats regarding biomarkers and morphologic changes. Thirty-two male Sprague-Dawley rats were divided into 4 equal groups. Control group received intraperitoneal normal saline, while in sham and experimental groups 1 and 2 pancreatitis was induced with L-arginine. E1 and E2 groups were treated with a single dose of 100 and 200 mg/kg Q10, respectively. Serum lipase and amylase, along with pancreas IL-10, IL-1β, and TNF-α, were measured. For evaluation of oxidative stress, pancreatic superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and myeloperoxidase (MPO) were assessed. Histopathological examination for morphologic investigation was conducted. Serum amylase and lipase, as well as TNF-α and IL-1β cytokines, reverted with administration of Q10 in consistence with dosage. In contrast, Q10 assisted in boosting of IL-10 with higher dosage (200 mg/kg). A similar pattern for oxidative stress markers was noticed. Both MDA and MPO levels declined with increased dosage, contrary to elevation of SOD and GSH. Histopathology was in favor of protective effects of Q10. Our findings proved the amelioration of pancreatic injury by Q10, which suggest the anti-inflammatory and antioxidant property of Q10 and its potential therapeutic role. PMID:27190575

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

    PubMed

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

    2016-08-01

    Protein interacting with C kinase 1 (PICK1) is a scaffolding protein mainly implicated in neurological diseases, however, the function of PICK1 in acute liver injury (ALI) remains unknown. Our study found a dramatical decrease in mRNA and protein levels of PICK1 in liver tissues and isolated Kupffer cells (KCs) from the liver in mice with ALI. Furthermore, pretreatment the mice with ALI with FSC-231, a pharmacological inhibitor of PICK1, could significantly augment inflammatory response. Furthermore, in vitro studies showed that both lipopolysaccharide (LPS) and interferon gamma (IFN-γ) significantly reduced the expression of PICK1, while IL-4 elevated its expression in RAW 264.7 cells. Additionally, over-expression of PICK1 inhibited the expression of M1 biomarkers by suppressing NF-κB activity, and enhanced the expression of M2 biomarkers by promoting STAT6 activity. In contrast, knockdown of PICK1 or FSC-231 pretreatment promoted M1 polarization and suppressed M2 polarization. Besides, caveolin-1 was identified as a potential target gene controlled by PICK1 in RAW 264.7 cells. Mechanistic investigation revealed a dual role of PICK1 in regulating macrophage polarization and implied PICK1 as a potential therapeutic target in ALI. PMID:27157267

  14. Cytokine profile of a Holstein calf with bovine leukocyte adhesion deficiency during the acute-phase inflammatory response.

    PubMed

    Nagahata, Hajime; Hagiwara, Katsuro; Kasamatsu, Masahiko; Higuchi, Hidetoshi; Kurosawa, Takashi

    2002-12-01

    Changes in interleukin (IL)-1beta, IL-6 and IL-8 in serum, and their mRNA expression on neutrophils from a 4.6-month old Holstein young calf with bovine leukocyte adhesion deficiency (BLAD) during the acute phase were evaluated. IL-1beta concentrations in the serum of the calf with BLAD at age 143-162 days ranged from 8.7 to 16.6 ng/ml, whereas the values were less than 2.7 ng/ml in control calves. Serum IL-6 (0.04 ng/ml) was only detected on the 1st day when the animal was diagnosed with the BLAD. IL-1beta and IL-8 mRNA expression on neutrophils from the affected calf appeared to be similar to those of controls. Serum cytokine levels and their mRNA expression on neutrophils from the calf with BLAD appeared to be little affected by the deficient expression of beta(2)-integrin on leukocytes, and are considered to be modulated by the inflammatory stimuli. PMID:12520109

  15. Modeling the Pro-inflammatory Tumor Microenvironment in Acute Lymphoblastic Leukemia Predicts a Breakdown of Hematopoietic-Mesenchymal Communication Networks

    PubMed Central

    Enciso, Jennifer; Mayani, Hector; Mendoza, Luis; Pelayo, Rosana

    2016-01-01

    Lineage fate decisions of hematopoietic cells depend on intrinsic factors and extrinsic signals provided by the bone marrow microenvironment, where they reside. Abnormalities in composition and function of hematopoietic niches have been proposed as key contributors of acute lymphoblastic leukemia (ALL) progression. Our previous experimental findings strongly suggest that pro-inflammatory cues contribute to mesenchymal niche abnormalities that result in maintenance of ALL precursor cells at the expense of normal hematopoiesis. Here, we propose a molecular regulatory network interconnecting the major communication pathways between hematopoietic stem and progenitor cells (HSPCs) and mesenchymal stromal cells (MSCs) within the BM. Dynamical analysis of the network as a Boolean model reveals two stationary states that can be interpreted as the intercellular contact status. Furthermore, simulations describe the molecular patterns observed during experimental proliferation and activation. Importantly, our model predicts instability in the CXCR4/CXCL12 and VLA4/VCAM1 interactions following microenvironmental perturbation due by temporal signaling from Toll like receptors (TLRs) ligation. Therefore, aberrant expression of NF-κB induced by intrinsic or extrinsic factors may contribute to create a tumor microenvironment where a negative feedback loop inhibiting CXCR4/CXCL12 and VLA4/VCAM1 cellular communication axes allows for the maintenance of malignant cells. PMID:27594840

  16. Modeling the Pro-inflammatory Tumor Microenvironment in Acute Lymphoblastic Leukemia Predicts a Breakdown of Hematopoietic-Mesenchymal Communication Networks.

    PubMed

    Enciso, Jennifer; Mayani, Hector; Mendoza, Luis; Pelayo, Rosana

    2016-01-01

    Lineage fate decisions of hematopoietic cells depend on intrinsic factors and extrinsic signals provided by the bone marrow microenvironment, where they reside. Abnormalities in composition and function of hematopoietic niches have been proposed as key contributors of acute lymphoblastic leukemia (ALL) progression. Our previous experimental findings strongly suggest that pro-inflammatory cues contribute to mesenchymal niche abnormalities that result in maintenance of ALL precursor cells at the expense of normal hematopoiesis. Here, we propose a molecular regulatory network interconnecting the major communication pathways between hematopoietic stem and progenitor cells (HSPCs) and mesenchymal stromal cells (MSCs) within the BM. Dynamical analysis of the network as a Boolean model reveals two stationary states that can be interpreted as the intercellular contact status. Furthermore, simulations describe the molecular patterns observed during experimental proliferation and activation. Importantly, our model predicts instability in the CXCR4/CXCL12 and VLA4/VCAM1 interactions following microenvironmental perturbation due by temporal signaling from Toll like receptors (TLRs) ligation. Therefore, aberrant expression of NF-κB induced by intrinsic or extrinsic factors may contribute to create a tumor microenvironment where a negative feedback loop inhibiting CXCR4/CXCL12 and VLA4/VCAM1 cellular communication axes allows for the maintenance of malignant cells. PMID:27594840

  17. Circadian characteristics of permissive and suppressive effects of cortisol and their role in homeostasis and the acute inflammatory response.

    PubMed

    Mavroudis, Panteleimon D; Corbett, Siobhan A; Calvano, Steven E; Androulakis, Ioannis P

    2015-02-01

    In this work we explore a semi-mechanistic model that considers cortisol's permissive and suppressive effects through the regulation of cytokine receptors and cytokines respectively. Our model reveals the proactive role of cortisol during the resting period and its reactive character during the body's activity phase. Administration of an acute LPS dose during the night, when cortisol's permissive effects are higher than suppressive, leads to increased cytokine levels compared to LPS administration at morning when cortisol's suppressive effects are higher. Interestingly, our model presents a hysteretic behavior where the relative predominance of permissive or suppressive effects results not only from cortisol levels but also from the previous states of the model. Therefore, for the same cortisol levels, administration of an inflammatory stimulus at cortisol's ascending phase, that follows a time period where cytokine receptor expression is elevated ultimately sensitizing the body for the impending stimulus, leads to higher cytokine expression compared to administration of the same stimulus at cortisol's descending phase. PMID:25445574

  18. Paired Ig-Like Type 2 Receptor-Derived Agonist Ligands Ameliorate Inflammatory Reactions by Downregulating β1 Integrin Activity

    PubMed Central

    Lee, Kyoung-Jin; Lim, Dongyoung; Yoo, Yeon Ho; Park, Eun-Ji; Lee, Sun-Hee; Yadav, Birendra Kumar; Lee, Yong-Ki; Park, Jeong Hyun; Kim, Daejoong; Park, Kyeong Han; Hahn, Jang-Hee

    2016-01-01

    The paired immunoglobulin-like type 2 receptor (PILR) family consists of two functionally opposite members, inhibitory PILRα and activating PILRβ receptors. PILRs are widely expressed in various immune cells and interact with their ligands, especially CD99 expressed on activated T cells, to participate in immune responses. Here we investigated whether PILR-derived agonists inhibit β1 integrin activity as ligands for CD99. PILR-derived peptides as well as PILR-Fc fusion proteins prevented cell adhesion to fibronectin through the regulation of β1 integrin activity. Especially, PILRpep3, a representative 3-mer peptide covering the conserved motifs of the PILR extracellular domain, prevented the clustering and activation of β1 integrin by dephosphorylating FAK and vinculin, which are major components of focal adhesion. In addition, PILRpep3 inhibited transendothelial migration of monocytes as well as endothelial cell tube formation. Furthermore, upon intraperitoneal injection of PILRpep3 into mice with collagen-induced arthritis, the inflammatory response of rheumatoid arthritis was strongly suppressed. Taken together, these results suggest that PILR-derived agonist ligands may prevent the inflammatory reactions of rheumatoid arthritis by activating CD99. PMID:27306643

  19. Adenovirus-delivered angiopoietin-1 suppresses NF-κB and p38 MAPK and attenuates inflammatory responses in phosgene-induced acute lung injury.

    PubMed

    He, Dai-Kun; Shao, Yi-Ru; Zhang, Lin; Shen, Jie; Zhong, Zhi-Yue; Wang, Jing; Xu, Guoxiong

    2014-02-01

    Animals exposed to phosgene (Psg) result in acute lung injury (ALI). We have recently reported that angiopoietin-1 (Ang1) reduces inflammation and vascular hyperpermeability in ALI animals. In this study, we examined whether the beneficial effects of adenovirus-delivered Ang1 (Ad/Ang1) on inflammatory responses in Psg-induced ALI rats are due to the suppression of the nuclear factor-kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) pathways, which play crucial roles in inflammatory responses in ALI. We demonstrated that Psg increased Ang2 and inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-4 (IL-4), IL-6, IL-8, and IL-10, in the serum and bronchoalveolar lavage fluid of ALI rats, determined by ELISA. Ang1 inhibits pro-inflammatory mediators (TNF-α, IL-6 and IL-8) and has no effect on anti-inflammatory mediators (IL-4 and IL-10). Furthermore, the inhibitory action of Ang1 was mediated by the suppression of the NF-κB and p38 MAPK pathways, leading to the attenuation of inflammatory responses of ALI. Thus, Ad/Ang1 may provide a useful tool for the effective treatment in Psg-induced ALI. PMID:24517841

  20. [Role of anti-inflammatory drugs in the treatment of acute coronary syndromes. From athero-inflammation to athero-thrombosis].

    PubMed

    Altman, Raúl; Scazziota, Alejandra

    2003-01-01

    Coronary thrombosis is the most important cause of morbidity and mortality and the most severe manifestation of atherosclerosis. Knowledge of the pathophysiology of atheroma formation and the causes of atheroma accidents have allowed the development of new therapeutic measures for reducing thrombotic events after a coronary episode. Treating the thrombosis after plaque rupture is useful, but a late measure once coronary flow is disturbed. Therefore, treatment at an earlier stage, which we call athero-inflammation, a central event in atheroma progression leading to atherothrombosis, seems wise. There is evidence of an inflammatory component in the pathogenesis of atheroma rupture in acute coronary events. Earlier studies of anti-inflammatory medication have not demonstrated a reduction in thrombotic complications after an acute coronary episode. However, there are pathophysiological arguments and clinical findings that suggest that it would be advisable to include anti-inflammatory medications, especially those that inhibit preferentially COX-2, in the therapeutic arsenal for this pathology. We postulated that blocking athero-inflammation could prevent thrombosis. A pilot study was carried out in 120 patients with acute coronary syndrome without ST-segment elevation in which 60 patients were treated with meloxicam, a preferential COX-2 inhibitor. All patients received heparin and aspirin. During the stay in the coronary care unit, as well as after 90 days, meloxicam lowered composite outcomes (myocardial infarction, death and revascularization procedures) compared with the control group. These results and available pathophysiological and clinical evidence support the hypothesis of potential benefits of non-steroidal anti-inflammatory drugs with preferential inhibitory activity on COX-2 in patients with acute coronary syndromes. More trials are needed to confirm their preventive effect. PMID:12549993

  1. Pseudoephedrine/ephedrine shows potent anti-inflammatory activity against TNF-α-mediated acute liver failure induced by lipopolysaccharide/D-galactosamine.

    PubMed

    Wu, Zhongping; Kong, Xiangliang; Zhang, Tong; Ye, Jin; Fang, Zhaoqin; Yang, Xuejun

    2014-02-01

    The anti-inflammatory effects of pseudoephedrine/ephedrine were investigated using the experimental model of lipopolysaccharide (LPS)-induced acute liver failure in D-galactosamine (D-GalN)-sensitised male rats in order to elucidate effects other than sympathomimetic effects. Rats were intraperitoneally injected with D-GalN (400 mg/kg) and LPS (40 μg/kg) to induce acute liver failure. The treatment groups were then intraperitoneally administered pseudoephedrine/ephedrine at 0 h and 4 h after induction and the activation induced by treatment with pseudoephedrine and/or LPS on the primary Kupffer cells (KCs) was monitored. Compared with controls induced by GalN/LPS alone, pseudoephedrine dramatically reduced the infiltration of inflammatory cells and bile ductular hyperplasia and hepatic necrosis observed in liver sections. It inhibited both hepatocellular apoptosis and the expression of monocyte chemotactic protein-1. It lowered the production of tumour necrosis factor-α (TNF-α) in the beginning of acute liver failure induced by D-GalN/LPS. Correspondingly, levels of alanine aminotransferase (ALT), total bilirubin (TBIL) and malondialdehyde were attenuated. Ephedrine demonstrated all these identical protective effects as well. In addition, pseudoephedrine significantly suppressed the production of p-IκB-α, reducing the degradation of sequestered nuclear factor kappa B (NF-κB) in the cytoplasm, and inhibited the translocation of NF-κB/p65 to the nucleus, the transcription of TNF-α mRNA and the production of TNF-α in primary KCs. These results suggest that pseudoephedrine and ephedrine have a potent anti-inflammatory activity against D-GalN/LPS-induced acute liver failure in rats, and this comprehensive anti-inflammatory effect may result from the inhibition of TNF-α production. PMID:24365491

  2. Inflammatory reaction after traumatic brain injury: Therapeutic potential of targeting cell-cell communication by chemokines

    PubMed Central

    Gyoneva, Stefka; Ransohoff, Richard M.

    2015-01-01

    Traumatic brain injury (TBI) affects millions of people worldwide every year. The primary impact initiates the secretion of pro- and anti-inflammatory factors, subsequent recruitment of peripheral immune cells and activation of brain-resident microglia and astrocytes. Chemokines are major mediators of peripheral blood cell recruitment to damaged tissue, including the TBI brain. Here we review the involvement of specific chemokine pathways in TBI pathology and attempts to modulate these pathways for therapeutic purposes. We focus on chemokine (C-C motif) ligand 2/chemokine (C-C motif) receptor 2 (CCL2/CCR2) and chemokine (C-X-C motif) ligand 12/chemokine (C-X-C motif) receptor 4 (CXCL12/CXCR4). Recent micro-array and multiplex expression profiling have also implicated CXCL10 and CCL5 in TBI pathology. Chemokine (C-X3-C motif) ligand 1/ chemokine (C-X3-C motif) receptor 1 (CX3CL1/CX3CR1) signaling in the context of TBI is also discussed. Current literature suggests that modulating chemokine signaling, especially CCL2/CCR2, may be beneficial in TBI treatment. PMID:25979813

  3. Adverse respiratory reactions to aspirin and nonsteroidal anti-inflammatory drugs.

    PubMed

    Simon, Ronald A

    2004-01-01

    Aspirin-exacerbated respiratory disease (AERD) is an adult-onset condition that manifests as asthma, rhinosinusitis/nasal polyps, and sensitivity to aspirin and other cyclooxygenase-1 (COX-1)-inhibitor nonsteroidal anti-inflammatory drugs (NSAIDs). There is no cross-sensitivity to highly selective COX-2 inhibitors. AERD is chronic and does not improve with avoidance of COX-1 inhibitors. The diagnosis of AERD is made through provocative challenge testing. Following a positive aspirin challenge, patients can be desensitized to aspirin and NSAIDs. The desensitized state can be maintained indefinitely with continued daily administration. After desensitization, there is an approximately 48-hour refractory period to adverse effects from aspirin. The pathogenesis of AERD remains unknown, but these patients have been shown to have multiple abnormalities in arachidonic acid metabolism and in cysteinyl leukotriene 1 receptors. AERD patients can take up to 650 mg of acetaminophen for analgesic or antipyretic relief. Patients can also use weak COX-1 inhibitors, such as sodium salicylate or choline magnesium trisalicylate. Treatment of AERD patients with antileukotriene medications has been helpful but not preferential when compared with non-AERD patients. An alternative treatment for many AERD patients is aspirin desensitization. This is particularly effective in reducing upper-airway mucosal congestion, nasal polyp formation, and systemic steroids. PMID:14680616

  4. Recognition of Borrelia burgdorferi by NOD2 is central for the induction of an inflammatory reaction.

    PubMed

    Oosting, Marije; Berende, Anneleen; Sturm, Patrick; Ter Hofstede, Hadewych J M; de Jong, Dirk J; Kanneganti, Thirumala-Devi; van der Meer, Jos W M; Kullberg, Bart-Jan; Netea, Mihai G; Joosten, Leo A B

    2010-06-15

    Toll-like receptor 2 (TLR2) plays an important role in the recognition of Borrelia bacteria, the causative agent of Lyme disease, but the existence and importance of additional receptors in this process has been hypothesized. In the present study, we confirmed the role played by TLR2 in the recognition of Borrelia bacteria but also demonstrated a crucial role for the intracellular peptidoglycan receptor NOD2 for sensing the spirochete. Cells from individuals who were homozygous for the loss-of-function mutation 3020insC in the NOD2 gene were defective with respect to cytokine release after stimulation with Borrelia species, and this was confirmed in peritoneal macrophages from mice lacking RICK, the adaptor molecule used by NOD2. In contrast, NOD1 played no major role in the recognition of Borrelia spirochetes. This raises the intriguing possibility that recognition of Borrelia spirochetes is exerted by TLR2 in combination with NOD2 and that both receptors are necessary for an effective induction of cytokines by Borrelia species. The interplay between TLR2 and NOD2 might not only be necessary for the induction of a proper immune response but may also contribute to inflammatory-induced pathology. PMID:20441518

  5. Taxanes as a Risk Factor for Acute Adverse Reactions to Iodinated Contrast Media in Cancer Patients

    PubMed Central

    Farolfi, Alberto; Della Luna, Corradina; Ragazzini, Angela; Carretta, Elisa; Gentili, Nicola; Casadei, Carla; Aquilina, Michele; Barone, Domenico; Minguzzi, Martina; Amadori, Dino; Nanni, Oriana

    2014-01-01

    Background. The impact of cytotoxic agents on the risk of acute allergy-like adverse reactions (ARs) to intravenous iodinated contrast media (ICM) injections is unknown. Methods. We retrospectively reviewed 13,565 computed tomography (CT) scans performed in a consecutive cohort of cancer patients from January 1, 2010 to December 31, 2012. Episodes of acute ICM-related ARs were reported to the pharmacovigilance officer. The following matched comparisons were made: tax code, gender, primary tumor, antineoplastic therapy, and date of last cycle. Concomitant antineoplastic treatment was classified into five groups: platinum, taxane, platinum plus taxane, other, and no treatment group (no therapy had been administered in the previous 24 months). Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) to evaluate the risk of acute ICM-related ARs. Results. Of 10,472 contrast-enhanced CT scans, 97 (0.93%; 95% CI: 0.74–1.11) ICM-related ARs were reported, 11 of which (0.1%) were severe, including one fatality. The overall incidence was significantly higher in patients aged <65 years (p = .0062) and in the platinum plus taxane and taxane groups (p = .007), whereas no correlation was found with gender, number of previous CT scans, site of disease, or treatment setting. Multivariate analysis confirmed an increased risk for patients aged <65 years (OR: 1.73; 95% CI: 1.14–2.63) and for the taxane group (in comparison with the no treatment group; OR: 2.06; 95% CI: 1.02–4.16). Conclusion. Among cancer patients, concomitant treatment with taxanes and younger age would seem to be risk factors for ICM-related ARs. PMID:25063226

  6. Effect of Acute Exercise on Clinically Measured Reaction Time in Collegiate Athletes

    PubMed Central

    Reddy, Shailesh; Eckner, James T.; Kutcher, Jeffrey S

    2014-01-01

    Purpose We have developed a reliable and valid clinical test of reaction time (RTclin) that is sensitive to the acute effects of concussion. If RTclin is to be used as a sideline concussion assessment tool then the acute effects of exercise on RTclin may need to be controlled for. The purpose of this study is therefore to determine the effect of exercise on RTclin. Methods A gender balanced group of 42 collegiate athletes were assigned to an exercise (n=28) and a control (n=14) group using 2:1 block randomization. The exercise group completed a graded 4-stage exercise protocol on a stationary bicycle (100W × 5min; 150W × 5min; 200W × 5min; sprint × 2min) while the control group was tested at identical time periods without exercising. Mean RTclin was calculated over 8 trials as the fall time of a vertically-suspended rigid shaft after its release by the examiner before being caught by the athlete; RTclin was measured at baseline and after each of the 4 stages. Results As both heart rate and rate of perceived exertion significantly increased over the 4 stages in the exercise group (p<.001), mean RTclin showed a significant overall decline during repeated test administration (p<.008). However, there were no significant group (exercise vs. control, p=0.822) or group-by-stage interaction (p=0.169) effects on RTclin as assessed by repeated measures analysis of variance. Conclusion Exercise did not appear to affect RTclin performance in this study. This suggests that RTclin measured during a sideline concussion assessment does not need to be adjusted to account for the acute effects of exercise. PMID:24002343

  7. Acute Effects of Static and Dynamic Stretching on Balance, Agility, Reaction Time and Movement Time

    PubMed Central

    Chatzopoulos, Dimitris; Galazoulas, Christos; Patikas, Dimitrios; Kotzamanidis, Christos

    2014-01-01

    The purpose of this study was to compare the acute effects of three different stretching protocols on balance, agility, reaction time and movement time of the upper limbs. Participants were thirty one female high school athletes (age = 17.3 ± 0.5 yr.). All participants performed one of the following protocols on different days: (a) 3 min jogging followed by 7 min static stretching (SS), (b) 3 min jogging followed by 7 min dynamic stretching (DS), and (c) 3 min jogging followed by 7 min of rest (NS). After the protocols participants performed the following tests: dynamic balance, 505 agility test, reaction time (time between a sound stimulus and release of a button) and movement time (movement of the upper extremity over a 0.5 m distance). The order of stretching protocols and performance tests were counterbalanced to avoid carryover effects. Repeated measures analysis of variance revealed significant main effects for all variables except reaction time. The DS protocol compared to SS performed significantly better in balance, agility and movement time. Additionally, the DS protocol compared to NS performed significantly better in agility. According to the results of the study, a DS protocol is more appropriate than SS for activities that require balance, rapid change of running direction (agility) and movement time of the upper extremities. Key points Static stretching has a negative effect on balance and agility performance compared to dynamic stretching. There was no effect of the stretching protocols on reaction time. Dynamic stretching was more effective than static stretching for increasing movement time of the upper extremities. PMID:24790497

  8. Pathobiochemical mechanisms during the acute phase response.

    PubMed

    Kleesiek, K; Greiling, H

    1984-01-01

    The acute phase response is characterised by the following sequence of principle phenomena: (1) an early local inflammatory reaction, (2) formation of inflammatory humoral factors inducing a systemic reaction, (3) stimulation of glycoprotein synthesis predominantly in the hepatocytes, and (4) an increase in the plasma concentration of acute phase proteins, when the rate of biosynthesis exceeds the degradation rate. Inflammatory mediators (lysosomal enzymes, oxygen derived radicals, prostaglandins) are mainly released during phagocytosis by granulocytes and macrophages. The signal reaching the hepatocytes is not yet clearly identified. A leukocyte endogenous mediator (LEM) released by macrophages is described. There is evidence that prostaglandins and probably proteinase alpha 2-macroglobulin complexes are also involved. The hepatic acute phase protein synthesis is modulated by hormones (insulin, cortisol, somatotropin). The biochemical events in the hepatocyte include an increase in protein synthesis and the regulatory control of the glycosylation of polypeptide precursors. The secreted glycoproteins serve variously as inhibitors or mediators of the inflammatory processes. PMID:6208159

  9. Screening of an anti-inflammatory peptide from Hydrophis cyanocinctus and analysis of its activities and mechanism in DSS-induced acute colitis

    PubMed Central

    Zheng, Zengjie; Jiang, Hailong; Huang, Yan; Wang, Jie; Qiu, Lei; Hu, Zhenlin; Ma, Xingyuan; Lu, Yiming

    2016-01-01

    Snake has been used for centuries as a traditional Chinese medicine, especially for therapeutic treatment for inflammatory diseases; however, its mechanisms of action and active constituents remain controversial. In our study, a tumor necrosis factor receptor 1 (TNFR1) selective binding peptide, Hydrostatin-SN1 (H-SN1), which was screened from a Hydrophis cyanocinctus venom gland T7 phage display library, was shown to exhibit significant anti-inflammatory activity in vitro and in vivo. As a TNFR1 antagonist, it reduced cytotoxicity mediated by TNF-α in L929 fibroblasts and effectively inhibited the combination between TNF-α with TNFR1 in surface plasmon resonance analysis. H-SN1 was also shown to suppress TNFR1–associated signaling pathways as it minimized TNF-α-induced NF-кB and MAPK activation in HEK293 embryonic kidney and HT29 adenocarcinoma cell lines. We next determined the effect of H-SN1 in vivo using a murine model of acute colitis induced by dextran sodium sulfate, demonstrating that H-SN1 lowered the clinical parameters of acute colitis including the disease activity index and histologic scores. H-SN1 also inhibited TNF/TNFR1 downstream targets at both mRNA and protein levels. These results indicate that H-SN1 might represent a suitable candidate for use in the treatment of TNF-α-associated inflammatory diseases such as inflammatory bowel diseases. PMID:27158082

  10. Different types of inflammatory reactions in peri-implant soft tissues.

    PubMed

    Ericsson, I; Persson, L G; Berglundh, T; Marinello, C P; Lindhe, J; Klinge, B

    1995-03-01

    The aim of the present study was to analyze some features of the peri-implant mucosa at sites in the dog model which had been exposed to plaque accumulation for periods up to 9 months. The experiment was carried out in 5 labrador dogs. The mandibular right and left 2nd, 3rd and 4th premolars (2P2, 3P3, 4P4) and the 1st molars (1M1) were extracted. Following a 3-month healing period, 3 titanium fixtures (Nobelpharma AB, Göteborg, Sweden) were installed in the edentulous premolar/molar regions. Abutment connection was performed 3 months later and a meticulous plaque control period of 3 months was initiated. A clinical examination was performed at the end of this preparatory period and a main study period of 9 months continued. During this period, the plaque control regimen was maintained in the mesial and central (left: L1, 2 and right: R1, 2) implant segments, whereas plaque was allowed to accumulate on the distal implants, i.e.. L3 and R3. At the end of the main study period, i.e., 12 months after abutment connection, the clinical examination was repeated, the animals perfused and biopsies obtained. Semi-thin sections were produced for histometric and morphometric analyses. The peri-implant mucosa at implant sites exposed to daily and comprehensive plaque control at biopsy was clinically noninflamed and the connective tissue lateral to a junctional epithelium was devoid of accumulations of inflammatory cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7790533

  11. Acute and long-term effect of infliximab on humoral and echocardiographic parameters in patients with chronic inflammatory diseases.

    PubMed

    Tomáš, L'ubomír; Lazúrová, Ivica; Pundová, Lýdia; Oetterová, Mária; Zakuciová, Mária; Petrášová, Darina; Studenčan, Martin

    2013-01-01

    Tumor necrosis factor alpha (TNF-alpha) plays an important role in the pathogenesis of chronic inflammatory diseases, i.e., rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), and ulcerative colitis (UC). Anti-TNF-alpha strategies are successfully used in their treatment. However, their effect on heart function is still uncertain. The objectives of the study were to examine the acute and long-term effect of infliximab on the heart morphology and function in patients with chronic inflammatory disorders. Thirty-one patients (21 men and 10 women) were included. Ten percent of them were diagnosed with RA, 22.5 % with AS, 22.5 % with CD, and 45 % with UC, respectively. N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) was measured before and immediately after infliximab administration at the beginning of the study and in the sixth and 12th months. Echocardiography was performed at baseline and in the sixth and 12th months. There was a significant increase in NT-proBNP after the first infliximab infusion (88.40 ± 14.09 vs. 95.24 ± 14.28 pg/ml, p = 0.0046) and similar response was detected after each infusion in the sixth and 12th months. Plasma NT-proBNP slightly but not significantly decreased (88.40 ± 14.09 vs. 81.74 ± 23.14 pg/ml, p = 0.583, and 88.40 ± 14.09 vs. 56.83 ± 17.77 pg/ml, p = 0.0576, in the sixth and 12th months, respectively). There were no significant changes in echocardiographic structural and functional parameters of the left ventricle during follow-up. Plasma NT-proBNP mildly but significantly increases immediately after infliximab infusion. However, long-term infliximab administration does not deteriorate both cardiac morphology and function. PMID:23010850

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

    SciTech Connect

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

    2006-07-01

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

  13. Recurrent acute hemolytic transfusion reactions by antibodies against Doa antigens, not detected by cross-matching.

    PubMed

    Baumgarten, Ruben; van Gelder, Warry; van Wintershoven, Joyce; Maaskant-Van Wijk, Petra A; Beckers, Erik A M

    2006-02-01

    An 81-year-old male patient suffered from recurrent acute hemolytic transfusion reactions after transfusion with phenotyped cross-match-negative red blood cells (RBCs). Extensive posttransfusion workup eventually revealed Dombrock (a) (Do(a)) antibodies. Because commercially available cell panels do not allow for identification of anti-Do(a) and owing to the lack of Do(a) typing serum samples, selection of matched units of RBCs is dependent on negative cross-match results. In this case, selection of Do(a-) units by cross-matching failed, indicating that serologic methods were not reliable. A polymerase chain reaction with sequence-specific priming assay was used to detect DOA and DOB alleles, which encode Do(a) and Do(b) antigens, respectively. The patient was confirmed to be DOB/DOB by DNA sequencing. Furthermore, the involved mismatched units in each of the three hemolytic episodes were shown to be Do(a+). In the presenting case, DNA typing appeared to be superior to serologic methods in selecting matched RBC units in the presence of anti-Do(a). PMID:16441602

  14. Acute audiovestibular deficit with complete ocular tilt reaction and absent VEMPs.

    PubMed

    Goto, Fumiyuki; Ban, Yumiko; Tsutumi, Tomoko

    2011-07-01

    A patient presenting with vertical diplopia along with ocular tilt reaction (OTR) due to peripheral vestibular dysfunction is a rare occurrence. OTR is an eye-head postural reaction consisting of head tilt, skew deviation, conjugated eye cyclotorsion, and alteration of vertical perception, and is thought to occur with central lesions, mainly brainstem lesions. Here, we report a case of a patient who was suffering from left acute peripheral cochleovestibular loss. He had profound deafness and absence of caloric response on the left side. No central lesion was observed on magnetic resonance images. Neuro-ophthalmological examination showed OTR consisting of head tilt, skew deviation with left hypotropia, excyclotorsion, and tilt of the static visual vertical directed to the left side. Both utricular and saccular dysfunctions were identified by the absence of cervical vestibular evoked myogenic potential (cVEMP) and ocular VEMP (oVEMP) on the left side. Within a month, the OTR disappeared completely probably because of vestibular compensation. This is the first report to state that the peripheral otolith dysfunction causing reversible vertical diplopia was identified by objective examinations (VEMP). PMID:21431953

  15. Bone marrow transplantation in the rat. III. Structure of the liver inflammatory lesion in acute graft-versus-host disease

    SciTech Connect

    Leszczynski, D.; Renkonen, R.; Haeyry, P.

    1985-08-01

    The liver is a major parenchymal target organ of acute graft-versus-host disease (aGVHD) after bone marrow transplantation in the rat. The authors have analyzed the nature of cellular infiltrates in the liver using monoclonal antibodies against white cell subsets and investigated the anatomic distribution of the inflammatory cell subsets inside the liver parenchyma. Several types of white cells are present in a normal control liver: In the portal area the T-helper (Th) cells predominate, (surface) immunoglobulin-expressing B cells are present in ample numbers, and most of the phagocytes are Ia-positive. In the central vein area the T-suppressor/killer cells (Tsk) dominate, no B cells are present, and most of the phagocytes are Ia-negative. During aGVHD the number of T cells increases rapidly in the portal area; and after an initial strong increase, the Th/Tsk ratio decreases but remains still above 1. In the central vein area there is also an increase in the number of T cells, compared with that in the syngeneic recipient, but the Th/Tsk ratio rapidly decreases and remains uniformly below 1. During aGVHD the B cells entirely disappear from the portal area, whereas a small but distinct number of mature plasma cells with intracellular immunoglobulin appear in the central vein area. Following irradiation the Ia-positive phagocytic cells entirely disappear from the portal area and decrease distinctly in number in the central vein area. During aGVHD the number of Ia-positive phagocytes increases again in both locations. In the central vein area the positive phagocytes are seen over the background level, and, concomitantly, the Ia-negative phagocytes disappear.

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

    SciTech Connect

    Marín-Prida, Javier; Riva, Federica; Pentón-Arias, Eduardo

    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.

  17. Differential effects of naltrexone on cardiac, subjective and behavioural reactions to acute ethanol intoxication

    PubMed Central

    Peterson, Jordan B.; Conrod, Patricia; Vassileva, Jasmin; Gianoulakis, Christina; Pihl, Robert O.

    2006-01-01

    Objective Alcohol may have psychomotor stimulant properties during the rising limb of the blood alcohol curve at commonly self-administered doses. Increased heart rate (HR) immediately after alcohol consumption may serve as an indicator or marker of such properties, which appear to be potentially opiate-mediated and dopamine-dependent. Naltrexone, an opiate antagonist, has been used successfully in the treatment of alcoholism and may produce its therapeutic effects through its effects on alcohol metabolism or by blocking alcohol's rewarding effects. We hypothesized that, if naltrexone blocks the psychomotor stimulant properties of ethanol, then it would decrease or eliminate the HR increase associated with acute alcohol intoxication and that this would be independent of any effect on alcohol metabolism. Methods Twenty male subjects were administered placebo and alcohol (1.0 mL 95% USP ethanol/kg body weight) in a laboratory setting on one day and naltrexone (50 mg) and alcohol on another (counterbalanced). We assessed all subjects for a change in HR and for a subjective and behavioural response from 35 to 170 minutes after drug or alcohol administration. Results The placebo and alcohol mix produced a significant mean HR increase from baseline (F1,95 = 46.01, p < 0.0001, Cohen's d = 0.62), while naltrexone and alcohol did not (nonsignificant). The significant effects of naltrexone on blood alcohol level did not account for the effect of naltrexone on alcohol-induced HR change but did account for alterations in subjective and behavioural response to alcohol. Conclusions Naltrexone appears to substantially reduce the HR increase that is characteristic of alcohol intoxication. This finding appears to lend moderate support to the notions that, first, naltrexone has differential effects on alcohol reactions and, second, that it specifically blocks the acute psychomotor stimulant properties of alcohol. PMID:17136216

  18. Cortisol Awakening Response Prospectively Predicts Peritraumatic and Acute Stress Reactions in Police Officers

    PubMed Central

    Inslicht, Sabra S.; Otte, Christian; McCaslin, Shannon E.; Apfel, Brigitte A.; Henn-Haase, Clare; Metzler, Thomas; Yehuda, Rachel; Neylan, Thomas C.; Marmar, Charles R.

    2011-01-01

    Background The hypothalamic pituitary adrenal (HPA) axis is a major stress response system hypothesized to be involved in the pathogenesis of posttraumatic stress disorder (PTSD). However, few studies have prospectively examined the relationships among pre-exposure HPA activity, acute stress reactions and PTSD symptoms. Methods Two hundred and ninety-six police recruits were assessed during academy training prior to duty-related critical incident exposure and provided salivary cortisol at first awakening and after 30 minutes. A measure of cortisol awakening response (CAR) was computed as the change in cortisol level from the first to the second collection. At 12, 24, and 36 months following the start of active police service, officers were assessed for peritraumatic distress, peritraumatic dissociation, ASD symptoms, and PTSD symptoms to their self-identified worst duty-related critical incident. Mixed models for repeated measures were used to analyze the effects of CAR on the outcome variables pooled across the three follow-up assessments. Results Mixed model analyses indicated that after controlling for time of awakening, first awakening cortisol levels, and cumulative critical incident stress exposure, CAR during academy training was associated with greater peritraumatic dissociation, β=.14, z=3.49, p<.0001, and greater acute stress disorder (ASD) symptoms during police service assessed at 12, 24, and 36 months, β=.09, z=2.03, p<.05, but not with peritraumatic distress β=.03, z=.81, p=.42 or PTSD symptoms β=−.004, z=−.09, p=.93. Conclusions These findings suggest that greater cortisol response to awakening is a pre-exposure risk factor for peritraumatic dissociation and ASD symptoms during police service. PMID:21906725

  19. Decreased reaction time variability is associated with greater cardiovascular responses to acute stress.

    PubMed

    Wawrzyniak, Andrew J; Hamer, Mark; Steptoe, Andrew; Endrighi, Romano

    2016-05-01

    Cardiovascular (CV) responses to mental stress are prospectively associated with poor CV outcomes. The association between CV responses to mental stress and reaction times (RTs) in aging individuals may be important but warrants further investigation. The present study assessed RTs to examine associations with CV responses to mental stress in healthy, older individuals using robust regression techniques. Participants were 262 men and women (mean age = 63.3 ± 5.5 years) from the Whitehall II cohort who completed a RT task (Stroop) and underwent acute mental stress (mirror tracing) to elicit CV responses. Blood pressure, heart rate, and heart rate variability were measured at baseline, during acute stress, and through a 75-min recovery. RT measures were generated from an ex-Gaussian distribution that yielded three predictors: mu-RT, sigma-RT, and tau-RT, the mean, standard deviation, and mean of the exponential component of the normal distribution, respectively. Decreased intraindividual RT variability was marginally associated with greater systolic (B = -.009, SE = .005, p = .09) and diastolic (B = -.004, SE = .002, p = .08) blood pressure reactivity. Decreased intraindividual RT variability was associated with impaired systolic blood pressure recovery (B = -.007, SE = .003, p = .03) and impaired vagal tone (B = -.0047, SE = .0024, p = .045). Study findings offer tentative support for an association between RTs and CV responses. Despite small effect sizes and associations not consistent across predictors, these data may point to a link between intrinsic neuronal plasticity and CV responses. PMID:26894967

  20. Decreased reaction time variability is associated with greater cardiovascular responses to acute stress

    PubMed Central

    Hamer, Mark; Steptoe, Andrew; Endrighi, Romano

    2016-01-01

    Abstract Cardiovascular (CV) responses to mental stress are prospectively associated with poor CV outcomes. The association between CV responses to mental stress and reaction times (RTs) in aging individuals may be important but warrants further investigation. The present study assessed RTs to examine associations with CV responses to mental stress in healthy, older individuals using robust regression techniques. Participants were 262 men and women (mean age = 63.3 ± 5.5 years) from the Whitehall II cohort who completed a RT task (Stroop) and underwent acute mental stress (mirror tracing) to elicit CV responses. Blood pressure, heart rate, and heart rate variability were measured at baseline, during acute stress, and through a 75‐min recovery. RT measures were generated from an ex‐Gaussian distribution that yielded three predictors: mu‐RT, sigma‐RT, and tau‐RT, the mean, standard deviation, and mean of the exponential component of the normal distribution, respectively. Decreased intraindividual RT variability was marginally associated with greater systolic (B = −.009, SE = .005, p = .09) and diastolic (B = −.004, SE = .002, p = .08) blood pressure reactivity. Decreased intraindividual RT variability was associated with impaired systolic blood pressure recovery (B = −.007, SE = .003, p = .03) and impaired vagal tone (B = −.0047, SE = .0024, p = .045). Study findings offer tentative support for an association between RTs and CV responses. Despite small effect sizes and associations not consistent across predictors, these data may point to a link between intrinsic neuronal plasticity and CV responses. PMID:26894967

  1. Inflammatory eye reactions in patients treated with bisphosphonates and other osteoporosis medications: cohort analysis using a national prescription database.

    PubMed

    Pazianas, Michael; Clark, Emma M; Eiken, Pia A; Brixen, Kim; Abrahamsen, Bo

    2013-03-01

    Ocular inflammatory reactions have been described in patients on bisphosphonate treatment. We estimated the incidence rate of ocular inflammation at 3 and 12 months in patients treated for osteoporosis using a register-based cohort linked to prescription data (hospitals and private practice) and hospital data. From January 1, 1997 to December 31, 2007, a total of 88,202 patients beginning osteoporosis therapy were identified. Of those patients, 82,404 (93%) began oral bisphosphonates and 5798 (7%) nonbisphosphonates. Within the first year of treatment, 4769 (5.4%) of patients on osteoporosis therapy filled one or more prescriptions for topical eye steroids (TES). TES treatment rates (per 1000 patient-years) in the first year of osteoporosis treatment were 44 (95% confidence interval [CI] 42 to 46) for alendronate, 40 (95% CI 38 to 43) for etidronate, 45 (95% CI 35 to 57) for risedronate, 32 (95% CI 27 to 37) for raloxifene, and 64 (95% CI 49 to 83) for strontium ranelate. After adjustment for age, Charlson index, and the number of comedications, pulmonary disease in men was associated with an increased use of TES (odds ratio [OR] = 1.48; 95% CI 1.17 to 1.86; p = 0.001). In women, malignant disease (OR = 1.27; 95% CI 1.02 to 1.60; p = 0.04) and pulmonary disease (OR = 1.32; 95% CI 1.07 to 1.62; p = 0.01) were significant predictors at 3 months and rheumatic diseases at 12 months (OR = 1.20; 95% CI 1.10 to 1.31; p < 0.001). There was no significant difference between the different drug classes (bisphosphonates versus nonbisphosphonates, alendronate versus nonalendronate-bisphosphonates) for risk of ocular inflammation, with age and the number of comedications being the only significant predictors. Hospital-treated uveitis (48 patients, or 0.05%) showed a similar trend. In conclusion, after initiation of treatment for osteoporosis, the risk of inflammatory eye reactions requiring TES is relatively low and not significantly different

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

    PubMed

    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. PMID:24792436

  3. Upregulation of miR-146a contributes to the suppression of inflammatory responses in LPS-induced acute lung injury.

    PubMed

    Zeng, Zhenguo; Gong, Honghan; Li, Yong; Jie, Kemin; Ding, Chengzhi; Shao, Qiang; Liu, Fen; Zhan, Yian; Nie, Cheng; Zhu, Weifeng; Qian, Kejian

    2013-09-01

    Despite the critical role of microRNA in inflammatory response, little is known about its function in inflammation-induced Acute Lung Injury (ALI)/Acute Respiratory Distress Syndrome (ARDS). To investigate the potential role of microRNA146a (miR-146a) in ALI, we used lipopolysaccharide (LPS)-induced ALI rat model. Our data revealed that LPS-induced lung injury in rats resulted in significant upregulation of proinflammatory cytokine tumor necrosis factor-alpha (TNF-α), IL-6, IL-1β, and miR-146a expression. LPS treatment also leads to higher expression of miR-146a as well as increase in secretion of TNF-α, IL-6, and IL-1β in alveolar macrophage (AM) NR8383 cells in a time-dependent manner. Manipulation with miR146a mimic significantly suppressed LPS-mediated TNF-α, IL-6, and IL-1β induction in NR8383 cells by repressing expression of IRAK-1 and TRAF-6. These data clearly indicate that the upregulation of miR146a suppresses inflammatory mediators in LPS induced-ALI model. Therefore, miR-146a may be therapeutically targeted as a mean to repress inflammatory response following ALI. PMID:23848342

  4. Taurine and inflammatory diseases.

    PubMed

    Marcinkiewicz, Janusz; Kontny, Ewa

    2014-01-01

    Taurine (2-aminoethanesulfonic acid) is the most abundant free amino acid in humans and plays an important role in several essential biological processes such as bile acid conjugation, maintenance of calcium homeostasis, osmoregulation and membrane stabilization. Moreover, attenuation of apoptosis and its antioxidant activity seem to be crucial for the cytoprotective effects of taurine. Although these properties are not tissue specific, taurine reaches particularly high concentrations in tissues exposed to elevated levels of oxidants (e.g., inflammatory cells). It suggests that taurine may play an important role in inflammation associated with oxidative stress. Indeed, at the site of inflammation, taurine is known to react with and detoxify hypochlorous acid generated by the neutrophil myeloperoxidase (MPO)-halide system. This reaction results in the formation of less toxic taurine chloramine (TauCl). Both haloamines, TauCl and taurine bromamine (TauBr), the product of taurine reaction with hypobromous acid (HOBr), exert antimicrobial and anti-inflammatory properties. In contrast to a well-documented regulatory role of taurine and taurine haloamines (TauCl, TauBr) in acute inflammation, their role in the pathogenesis of inflammatory diseases is not clear. This review summarizes our current knowledge concerning the role of taurine, TauCl and TauBr in the pathogenesis of inflammatory diseases initiated or propagated by MPO-derived oxidants. The aim of this paper is to show links between inflammation, neutrophils, MPO, oxidative stress and taurine. We will discuss the possible contribution of taurine and taurine haloamines to the pathogenesis of inflammatory diseases, especially in the best studied example of rheumatoid arthritis. PMID:22810731

  5. Characterizing the Mechanistic Pathways of the Instant Blood-Mediated Inflammatory Reaction in Xenogeneic Neonatal Islet Cell Transplantation

    PubMed Central

    Liuwantara, David; Chew, Yi Vee; Favaloro, Emmanuel J.; Hawkes, Joanne M.; Burns, Heather L.; O'Connell, Philip J.; Hawthorne, Wayne J.

    2016-01-01

    Introduction The instant blood-mediated inflammatory reaction (IBMIR) causes major loss of islets after transplantation and consequently represents the initial barrier to survival of porcine neonatal islet cell clusters (NICC) after xenotransplantation. Methods This study used novel assays designed to characterize the various immunologic components responsible for xenogeneic IBMIR to identify initiators and investigate processes of IBMIR-associated coagulation, complement activation and neutrophil infiltration. The IBMIR was induced in vitro by exposing NICC to platelet-poor or platelet-rich human plasma or isolated neutrophils. Results We found that xenogeneic IBMIR was characterized by rapid, platelet-independent thrombin generation, with addition of platelets both accelerating and exacerbating this response. Platelet-independent complement activation was observed as early as 30 minutes after NICC exposure to plasma. However, membrane attack complex formation was not observed in NICC histopathology sections until after 60 minutes. We demonstrated for the first time that NICC-mediated complement activation was necessary for neutrophil activation in the xenogeneic IBMIR setting. Finally, using the Seahorse extracellular flux analyzer, we identified substantial loss of islet function (up to 40%) after IBMIR with surviving NICC showing evidence of mitochondrial damage. Conclusions This study used novel assays to describe multiple key pathways by which xenogeneic IBMIR causes islet destruction, allowing further refinement of future interventions aimed at resolving the issue of IBMIR in xenotransplantation. PMID:27500267

  6. Multicenter Orthopaedic Outcome Network Early Anti-inflammatory Treatment in Patients with Acute ACL Tear” (MOON-AAA) Clinical Trial

    PubMed Central

    Lattermann, Christian; Proffitt, Mary; Huston, Laura J.; Gammon, Lee; Johnson, Darren L.; Kraus, Virginia B.; Spindler, Kurt P.

    2016-01-01

    Objectives: We present the early results from the “Multicenter Orthopaedic Outcome Network Early Anti-inflammatory Treatment in Patients with Acute ACL Tear and Painful Effusions” (MOON-AAA) clinical trial (figure 1). This trial allows for a well controlled prospective cohort of patients with isolated ACL injury at risk for OA. We compared the effect of a single versus a repeated dosage of Kenalog within the first two weeks after ACL injury and its effect on chondral degradation in the first 4 weeks prior to surgical reconstruction of the ACL. Methods: 49 patients with isolated ACL tears were enrolled. Knee joints were aspirated and patients received an injection with 40 mg Kenalog either within 4 days, 10 days, both time points or not at all (saline injection control). Serum, synovial fluid and urine were collected at 3 time points. Permutated block randomization, triple blinding, independent monitoring and standardized x-ray was performed to comply with GCP standards. Patient reported outcomes were collected at 6 time points up to 6 months post-ACL reconstruction(IKDC, KOOS and Marx activity level). A standardized synovial fluid biomarker panel was analyzed according to OARSI guidelines. Statistical analysis were performed using SAS mixed models analysis. Results: Serum analysis shows significant change after injury. Chondrodegradatory markers such as CTX-II, MMP-1 and MMP-3 as well as COMP indicate a progressive destruction of chondral matrix and collagen breakdown . There is a dramatic (250%) increase of CTX-II in the first 4 weeks. Matrix proteins such as MMP-1 and 3 as well as COMP show an initial increase and then a steep decline (see figure 1). Inflammatory markers (IL-1 alpha, IL-1beta, IRAP) show a decline from the time of injury. IL-1 alpha, however shows a dramatic uptake after week 2. This longitudinal data confirms a dramatic onset of early osteoarthritic biomarker profiles immediately after ACL injury as measured in synovial fluid

  7. CT Findings of Foreign Body Reaction to a Retained Endoloop Ligature Plastic Tube Mimicking Acute Appendicitis: A Case Report.

    PubMed

    Ahn, Jae Hong; Kang, Chae Hoon; Choi, Soo-Jung; Park, Man Soo; Jung, Seung Mun; Ryu, Dae Shick; Shin, Dong Rock

    2016-01-01

    Many hospitals experience one or more retained surgical instrument events with risk of patient morbidity and medicolegal problems. Identification of retained surgical instrument is important. The radiologists should be familiar with imaging finding of retained surgical instrument. In a 62-year-old female with a retained plastic tube, localized peritoneal infiltration around air-containing tubular structure mimicked acute appendicitis on abdomen computed tomography (CT), one year after laparoscopic cholecystectomy. We reported CT findings of foreign body reaction related to retained Endoloop ligature plastic tube mimicking acute appendicitis. PMID:27390545

  8. CT Findings of Foreign Body Reaction to a Retained Endoloop Ligature Plastic Tube Mimicking Acute Appendicitis: A Case Report

    PubMed Central

    Kang, Chae Hoon; Choi, Soo-Jung; Park, Man Soo; Jung, Seung Mun; Ryu, Dae Shick; Shin, Dong Rock

    2016-01-01

    Many hospitals experience one or more retained surgical instrument events with risk of patient morbidity and medicolegal problems. Identification of retained surgical instrument is important. The radiologists should be familiar with imaging finding of retained surgical instrument. In a 62-year-old female with a retained plastic tube, localized peritoneal infiltration around air-containing tubular structure mimicked acute appendicitis on abdomen computed tomography (CT), one year after laparoscopic cholecystectomy. We reported CT findings of foreign body reaction related to retained Endoloop ligature plastic tube mimicking acute appendicitis. PMID:27390545

  9. Acute microbiologically negative hypoxic interstitial pneumonia on HAART: Immune Reconstitution Inflammatory Syndrome unmasking Pneumocystis Jiroveci infection with an atypical presentation

    PubMed Central

    Sovaila, S; de Raigniac, A; Picard, C; Taulera, O; Lascoux-Combe, C; Sereni, D; Bourgarit, A

    2012-01-01

    Highly active antiretroviral therapy for AIDS sometimes engenders inflammatory manifestations resulting from an inappropriate and unbalanced immune-system restoration, called Immune Reconstitution inflammatory Syndrome, which, in turn, can unmask a subclinical infection/pathology. Despite our patient’s evident syndrome, the atypical clinical, microbiologic and radiologic feature of Pneumocystis pneumonia made its diagnosis difficult. PMID:22802889

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

    PubMed

    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

    2013-10-01

    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 24h 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 H2O2 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. PMID:23732081

  11. Anti-inflammatory effects of a polyphenols-rich extract from tea (Camellia sinensis) flowers in acute and chronic mice models.

    PubMed

    Chen, Bang-Tian; Li, Wei-Xi; He, Rong-Rong; Li, Yi-Fang; Tsoi, Bun; Zhai, Yu-Jia; Kurihara, Hiroshi

    2012-01-01

    While beneficial health properties of tea leaves have been extensively studied, less attention is paid to the flowers of tea. In this study, the anti-inflammatory effects of hot water extract of tea (Camellia sinensis) flowers were investigated. Pharmacological studies found that administration of tea flowers extract (TFE) could effectively inhibit croton oil-induced ear edema and carrageenin-induced paw edema. Furthermore, administration of TFE also protected against Propionibacterium acnes (P. ances) plus lipopolysaccharide-(LPS-) induced liver inflammation by reversing the histologic damage and plasma alanine aminotransferase (ALT) increase. Moreover, the levels of nitric oxide (NO), tumor necrosis factor-(TNF)-α and interleukin-(IL-) 1β mRNA in mouse liver were markedly suppressed after treatment with TFE in mice with immunological liver inflammation. These results indicated that tea flowers had potent anti-inflammatory effects on acute and immunological inflammation in vivo, and may be used as a functional natural food. PMID:22900128

  12. Pattern Analysis of Acute Mucosal Reactions in Patients With Head and Neck Cancer Treated With Conventional and Accelerated Irradiation

    SciTech Connect

    Wygoda, Andrzej Maciejewski, Boguslaw; Skladowski, Krzysztof; Hutnik, Marcin; Pilecki, Boleslaw; Golen, Maria; Rutkowski, Tomasz

    2009-02-01

    Purpose: To evaluate severity of acute mucosal reactions (AMR) caused by conventional (CF) and accelerated fractionation (AF) regimens using a modified Dische system and to analyze differences in incidence and severity of AMR according to frequency and regularity of scoring. Methods and Materials: Sixty-six consecutive patients (33 CF, 33 AF) with head and neck cancer irradiated with 5 fractions in 5 days per week (CF) or with 7 fractions in 7 days (AF) to a total dose of 70 Gy. A modified Dische system was used for daily quantitation of AMR during radiotherapy until complete healing. Results: Confluent mucositis (CM) was noted in 79% of patients in the CF group and 85% in the AF group. In 24% of the CF group and 18% of the AF group the CM presented a wave-like pattern. In 55% of CF and 67% of AF a classic triphasic pattern was noted. In 12 patients acute reactions did not transgress the level of spotted mucositis. The present study clearly shows that quantitation of the incidence and severity of acute mucosal effects strongly depends on frequent and regular scoring. A significant difference in the incidence of CM between the CF and AF groups was noted, mainly in weeks 4-6 of irradiation. When once-weekly irregular instead of daily scoring was evaluated, the incidence of CM was underestimated by approximately 20-36%. Conclusions: Acute mucosal reactions occur as a complex of morphologic and functional disorders with individual intensity, even among patients treated with the same fractionation regimen. In some cases they present a 'wave-like' pattern during irradiation. Therefore, precise quantitation of acute effects requires regular and frequent scoring.

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

    PubMed Central

    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 < 0.05). In response to 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 < 0.05). The MSM group had higher IL-1β at baseline when compared to YSM, although IL-1ra was greater for YSM at baseline (P < 0.05). Finally, the post-exercise leukocyte response was greater in MSM compared to YSM and non-smokers (P < 0.05). In conclusion, smoker’s exhibit elevated MCP-1 and IL-1β that seem to be evident with a longer 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

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

    PubMed

    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 < 0.05). In response to 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 < 0.05). The MSM group had higher IL-1β at baseline when compared to YSM, although IL-1ra was greater for YSM at baseline (P < 0.05). Finally, the post-exercise leukocyte response was greater in MSM compared to YSM and non-smokers (P < 0.05). In conclusion, smoker's exhibit elevated MCP-1 and IL-1β that seem to be evident with a longer 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

  15. Alert cell strategy: mechanisms of inflammatory response and organ protection.

    PubMed

    Hatakeyama, Noboru; Matsuda, Naoyuki

    2014-01-01

    Systemic inflammatory response syndrome (SIRS) is triggered by various factors such as surgical operation, trauma, burn injury, ischemia, pancreatitis and bacterial translocation. Sepsis is a SIRS associated with bacterial infection. SIRS and sepsis tend to trigger excessive production of inflammatory cytokines and other inflammatory molecules and induce multiple organ failure, such as acute lung injury, acute kidney injury and inflammatory cardiac injury. Epithelial and endothelial cells in some major organs express inflammatory receptors on the plasma membrane and work as alert cells for inflammation, and regulation of these alert cells could have a relieving effect on the inflammatory response. In inflammatory conditions, initial cardiac dysfunction is mediated by decreased preload and adequate infusion therapy is required. Tachyarrhythmia is a complication of inflammatory conditions and early control of the inflammatory reaction would prevent the structural remodeling that is resistant to therapies. Furthermore, there seems to be crosstalk between major organs with a central focus on the kidneys in inflammatory conditions. As an alert cell strategy, volatile anesthetics, sevoflurane and isoflurane, seem to have anti-inflammatory effects, and both experimental and clinical studies have shown the beneficial effects of these drugs in various settings of inflammatory conditions. On the other hand, in terms of intravenous anesthetics, propofol and ketamine, their current status is still controversial as there is a lack of confirmatory evidence on whether they have an organ-protective effect in inflammatory conditions. The local anesthetic lidocaine suppressed inflammatory responses upon both systemic and local administration. For the control of inflammatory conditions, anesthetic agents may be a target of drug development in accordance with other treatments and drugs. PMID:25229471

  16. Parameters of immunity acute phase reaction in men in relation to exposure duration to mercury vapours.

    PubMed

    Moszczynski, P; Moszczynski, P; Słowinski, S; Bem, S; Bartus, R

    1991-01-01

    The study was carried out in 89 men aged 21 to 57 years with a history of exposure to mercury vapour from 2 to 26 years during occupational work involving chlorine production by the method of mercury electrolysis. The workers were divided into three groups depending on the duration of occupational exposure: 1) 32 workers with a short history of exposure 2-10 years, 2) 37 workers with medium-long exposure - 11-20 years, and 3) 20 workers with a history of long exposure - 21-26 years. The urinary concentrations of mercury in these individuals was 73 +/- 60 microliters x 1(-1), and in blood this concentration was not exceeding 50 microliters x 1(-1). The control group comprised 40 men aged 17 to 52 years. They had not had any occupational exposure to chemicals, or harmful physical factors. On the basis of clinical, haematological and biochemical studies 89 workers with occupational exposure to mercury vapour were regarded as clinically healthy. None of them had any symptoms and signs of the complete neurasthenic syndrome or organic brain injury. Increased nervous excitability was the complaint of 24 workers, 9 had headaches, sleep disturbances were reported by 5, and a feeling of tiredness and apathy was mentioned by 5 men. EEG recording demonstrated 81 normal tracings, and moderately pathological records in 8 men. The parameters of immunity and proteins acute phase reaction were determined, measuring the concentration of immunoglobulins, lysozyme, C3c, C4, alpha 1-acid glycoprotein, haptoglobin and ceruloplasmin in serum. A lower level of IgA, IgG and lysozyme was only noted in individuals with occupational exposure exceeding 20 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1725175

  17. Pharmacovigilance program to monitor adverse reactions of recombinant streptokinase in acute myocardial infarction

    PubMed Central

    Betancourt, Blas Y; Marrero-Miragaya, María A; Jiménez-López, Giset; Valenzuela-Silva, Carmen; García-Iglesias, Elizeth; Hernández-Bernal, Francisco; Debesa-García, Francisco; González-López, Tania; Alvarez-Falcón, Leovaldo; López-Saura, Pedro A

    2005-01-01

    Background Streptokinase (SK) is an effective fibrinolytic agent for the treatment of acute myocardial infarction (AMI). The objective of the present study was to assess the adverse drug reactions (ADRs) associated with intravenous recombinant SK in patients with AMI in routine clinical practice. Methods A national, prospective and spontaneous reporting-based pharmacovigilance program was conducted in Cuba. Patient demographics, suspected ADR description, elements to define causality, and outcomes were documented and analyzed. Results A total of 1496 suspected ADRs identified in 792 patients out of the 1660 (47.7 %) prescriptions reported in the program, were received from July 1995 to July 2002. Most of the patients (71.3%) were male, 67.2% were white and mean age was 61.6 ± 13.0 years. The mean time interval between the onset of symptoms and the start of the SK infusion was 4.9 ± 3.7 h. The most frequently reported ADRs were hypotension, arrhythmias, chills, tremors, vomiting, nauseas, allergy, bleeding and fever. ADR severity was 38% mild, 38% moderate, 10% severe, and 4% very severe. Only 3 patients with hemorrhagic stroke were reported. Seventy-two patients died in-hospital mainly because of cardiac causes associated with the patient's underlying clinical condition. Mortality was 3 times more likely in patients suffering arrhythmias than in those without this event (odds ratio 3.1, 95% CI: 1.8 to 5.1). Most of the reported ADRs were classified as possibly or probably associated with the study medication. Conclusion Recombinant SK was associated with a similar post-marketing safety profile to those suggested in previous clinical trials. PMID:16262910

  18. Guideline on the investigation and management of acute transfusion reactions. Prepared by the BCSH Blood Transfusion Task Force.

    PubMed

    Tinegate, Hazel; Birchall, Janet; Gray, Alexandra; Haggas, Richard; Massey, Edwin; Norfolk, Derek; Pinchon, Deborah; Sewell, Carrock; Wells, Angus; Allard, Shubha

    2012-10-01

    Although acute non-haemolytic febrile or allergic reactions (ATRs) are a common complication of transfusion and often result in little or no morbidity, prompt recognition and management are essential. The serious hazards of transfusion haemovigilance organisation (SHOT) receives 30-40 reports of anaphylactic reactions each year. Other serious complications of transfusion, such as acute haemolysis, bacterial contamination, transfusion-related acute lung injury (TRALI) or transfusion-associated circulatory overload (TACO) may present with similar clinical features to ATR. This guideline describes the approach to a patient developing adverse symptoms and signs related to transfusion, including initial recognition, establishing a likely cause, treatment, investigations, planning future transfusion and reporting within the hospital and to haemovigilance organisations. Key recommendations are that adrenaline should be used as first line treatment of anaphylaxis, and that transfusions should only be carried out where patients can be directly observed and where staff are trained in manging complications of transfusion, particularly anaphylaxis. Management of ATRs is not dependent on classification but should be guided by symptoms and signs. Patients who have experienced an anaphylactic reaction should be discussed with an allergist or immunologist, in keeping with UK resuscitation council guidelines. PMID:22928769

  19. The Incidence of Hypersensitivity Reactions to Pegylated Asparaginase in Children With Acute Lymphoblastic Leukemia: A City-wide Experience.

    PubMed

    Alrazzak, Muaz; Beaupin, Lynda K; Kinyoun, Peter; Barth, Matthew

    2016-01-01

    Asparaginase (ASNase) is an imperative component of pediatric acute lymphoblastic leukemia (ALL) therapy. Pegylating the ASNase extends its biological half-life in vivo and has become the only ASNase available in the United States for frontline therapy of ALL and lymphoblastic lymphoma. It is either infused intravenously (IV) or injected intramuscularly (IM), administrations of which are associated with hypersensitivity reaction ranging from localized skin reaction to severe anaphylaxis. A retrospective review of 96 medical records of pediatric ALL patients was performed. We compared the incidence of hypersensitivity reaction associated with IV versus IM administration of pegylated ASNase. Ninety-one patients were included in the final analysis; 31 having received pegylated ASNase IV and 60 receiving it IM. The incidence of any grade ≥ 2 hypersensitivity reaction in patients who received IV ASNase was 32.2% compared with 13.3% in the IM group (P=0.032). There was no difference in higher grade hypersensitivity reactions (19.4% vs. 11.7%). Most reactions tended to occur during periods of leukemia therapy that did not include concomitant steroid therapy. Our retrospective analysis indicates that IV administration of pegylated ASNase increases the incidence of low-grade, but not grade 3-4, hypersensitivity reactions compared with IM administration. PMID:26558809

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

    PubMed

    Worm, Jesper; Stenvang, Jan; Petri, Andreas; Frederiksen, Klaus Stensgaard; Obad, Susanna; Elmén, Joacim; Hedtjärn, Maj; Straarup, Ellen Marie; Hansen, Jens Bo; Kauppinen, Sakari

    2009-09-01

    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 and that the transcription factor c/ebp Beta is a direct target of miR-155. Interestingly, expression profiling of LPS-stimulated macrophages combined with overexpression and silencing of miR-155 in murine macrophages and human monocytic cells uncovered marked changes in the expression of granulocyte colony-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 in mouse splenocytes. Finally, we report for the first time on miR-155 silencing in vivo in a mouse inflammation model, which underscores the potential of miR-155 antagonists in the development of novel therapeutics for treatment of chronic inflammatory diseases. PMID:19596814

  1. Ginsenoside Rg1 improves lipopolysaccharide-induced acute lung injury by inhibiting inflammatory responses and modulating infiltration of M2 macrophages.

    PubMed

    Bao, Suhong; Zou, Yun; Wang, Bing; Li, Yinjiao; Zhu, Jiali; Luo, Yan; Li, Jinbao

    2015-09-01

    Ginsenoside Rg1 (Rg1), the major effective component of ginseng, has been reported to have potent anti-inflammatory properties. However, the effect of ginsenoside Rg1 on lipopolysaccharide (LPS) -induced acute lung injury (ALI) in mice was unknown. The present study was designed to investigate the protective role of Rg1 on LPS-induced ALI and explore the potential mechanisms. The mice were divided randomly into four groups: the sham group, the LPS group and the LPS+Rg1 (40 mg/kg or 200mg/kg) pretreatment groups. All mice received Rg1 or an equivalent volume of phosphate buffer saline (PBS) intraperitoneally 1h before LPS administration. Edema quantification, histology, and apoptosis were detected 6h after LPS administration. The number of inflammatory cells, the percentage of alternative activated (M2) macrophages and the exudate quantification in bronchoalveolar lavage fluid (BALF) were evaluated. The caspase 3 expression, and the levels of phosphorylated IκB-α and p65 were tested. The results showed that the Rg1 pretreatment group markedly improved lung damage, modulated the infiltration of neutrophils and M2 macrophages, prevented the production of protein and proinflammatory cytokines in BALF, and inhibited apoptosis in lung. We also found that Rg1 suppressed NF-κB and caspase 3 activation. These data suggest that Rg1 plays a protective role against LPS-induced ALI by ameliorating inflammatory responses, regulating the infiltration of M2 macrophages, and inhibiting pulmonary cell apoptosis. PMID:26122136

  2. Evaluation of chemical mediators and cellular response during acute and chronic gut inflammatory response induced by dextran sodium sulfate in mice.

    PubMed

    Bento, Allisson Freire; Leite, Daniela Ferraz Pereira; Marcon, Rodrigo; Claudino, Rafaela Franco; Dutra, Rafael Cypriano; Cola, Maíra; Martini, Alessandra Cadete; Calixto, João B

    2012-12-01

    Inflammatory bowel disease (IBD) affects millions of people worldwide but its pathophysiology remains unclear. Therefore, experimental models of colitis have contributed crucially for the understanding of IBD, and also in the investigations for effective therapies. Herein we investigated the kinetics of inflammatory mediator production and cell infiltration during acute and chronic dextran sodium sulfate (DSS)-induced colitis. The induction phases with DSS were characterized by severe disease activity with massive colonic polymorphonuclear infiltration and increased levels of tumor necrosis factor-α (TNF-α), keratinocyte-derived chemokine (CXCL1/KC), interleukin (IL)-17 and vascular adhesion molecule-1 (VCAM-1). Interestingly, in the recovery periods, we found marked increase of anti-inflammatory mediators IL-10, IL-4, transforming growth factor-β (TGF-β) and cyclooxygenase 2 (COX-2) that seems be essential for the resolution of intestinal inflammation. Furthermore, nuclear factor κB (NFκB) and regulatory T cell marker forkhead box P3 (FoxP3) were increased gradually during experimental colitis, demonstrating a discrepant profile response and evident immune disbalance in the chronic phase of intestinal mucosal inflammation. Taken together, these results provide valuable information for studies on DSS-induced colitis and especially for the identification of biomarkers that predict disease course and possible therapeutic interventions. PMID:23000912

  3. Rare allergic reaction of the kidney: sitagliptin-induced acute tubulointerstitial nephritis.

    PubMed

    Alsaad, Ali A; Dhannoon, Sarah M; Pantin, Sally-Ann L; Porter, Ivan E

    2016-01-01

    A 56-year-old man with a history of diabetes mellitus type-2 and stage-2 chronic kidney disease secondary to diabetic nephropathy presented with an acute deterioration of kidney function. Non-invasive work-up failed to reveal the underlying aetiology for the acute kidney failure. Kidney biopsy revealed acute tubulointerstitial nephritis (ATIN) which was attributed to sitagliptin use. Only few case reports have shown this correlation. Our aim is to alert physicians and other providers of the potential effect of sitagliptin to cause ATIN with this biopsy-proven case. PMID:27436034

  4. Biochemical and histological evaluations of anti-inflammatory and antioxidant p-chloro-selenosteroid actions in acute murine models of inflammation.

    PubMed

    Marcondes Sari, Marcel Henrique; Souza, Ana Cristina Guerra; Rosa, Suzan Gonçalves; Chagas, Pietro Maria; da Luz, Sônia Cristina Almeida; Rodrigues, Oscar Endrigo Dorneles; Nogueira, Cristina Wayne

    2016-06-15

    This study investigated the potential p-chloro-selenosteroid (PCS) anti-inflammatory effect in different animal models of acute inflammation. In order to determine a time- and a dose-curve response of action, female adult Swiss mice (25-35g) were divided in different groups and pretreated by the intragastric route (i.g.) with PCS (5-10mg/kg) and after the specific times (5, 30 and 60min) the ear inflammation was induced with croton oil (2.5%, 20μl). The ear edema, myeloperoxidase (MPO) activity and histological analyses were performed. In a second experiment, the pleurisy model was used to determine the PCS protective effect (10mg/kg, i.g., 30min before induction) in the inflammatory and oxidative alterations induced by an intrapleural injection of a 1% carrageenan solution (0.1ml) in exudate and lung samples. Dexamethasone (1mg/kg, i.g.) was used as positive control for both models. Statistical analysis was performed through a One-Way ANOVA test followed by the Newman-Keuls' test. Pretreatment of 30min with PCS, only at a dose of 10mg/kg, decreased ear edema and the MPO activity as well as the histological alterations induced by croton oil. In the pleurisy model, PCS (10mg/kg, i.g.; 30min) reduced the leukocyte counts, histological alterations, MPO and adenosine deaminase activities, oxidative damage and the non-enzymatic antioxidant defense imbalance. PCS had a similar anti-inflammatory profile to dexamethasone; however, it showed a better antioxidant effect. PCS had anti-inflammatory and antioxidant actions in two well established inflammation models in mice. PMID:27102337

  5. Study on local inflammatory reactions and other parameters during subcutaneous mistletoe application in HIV-positive patients and HIV-negative subjects over a period of 18 weeks.

    PubMed

    Stoss, M; van Wely, M; Musielsky, H; Gorter, R W

    1999-04-01

    Subcutaneous injections of fermented and unfermented aqueous extracts of Viscum album L. result in a local inflammatory reaction at the injection site. In this trial, the symptoms associated with this local reaction were investigated. Furthermore the occurrence of local reactions was tried to correlate with an increase in CD3/25- and CD8/38-positive lymphocyte counts, with eosinophilic granulocyte numbers, and with the formation of mistletoe lectin antibodies. Included in the trial were 30 HIV-antibody-positive patients and 17 healthy non-smokers, aged 24-51 years. The CD4 cell count in the HIV-negative subjects was > 800/microliter, compared with 200-600/microliter in the HIV-positive patients. All study participants had a Karnofsky score > or = 70. The trial subjects were observed over a period of 18 weeks. With escalation of the dose of a fermented and unfermented extract of Viscum album L. (Iscador Qu Spezial and Viscum album QuFrF), there was an increase in local reactions. Erythema at the injection site was the most frequently reported symptom. Between the doses and the symptoms induration, swelling and pruritus were marked correlations. Effects of the application of mistletoe extracts on the immune system were demonstrated by an increase in CD3/25-positive lymphocyte counts and antibodies against mistletoe-lectins. There were no changes in eosinophilic granulocytes or CD8/38-positive lymphocyte populations. For evaluation of the therapeutic applications of mistletoe extracts in HIV-positive patients it is advisable to assess primarily activation of CD3-positive lymphocytes and the patient response on the basis of the local reaction. The local inflammatory reaction at the injection site is desirable and well tolerated if the reaction is smaller than 5 cm in diameter. PMID:10337457

  6. Acute profound thrombocytopenia with second exposure to eptifibatide associated with a strong antibody reaction

    PubMed Central

    ATTAYA, SHARIFF; KANTHI, YOGENDRA; ASTER, RICHARD; MCCRAE, KEITH

    2015-01-01

    We present a case of eptifibatide-induced acute profound thrombocytopenia in a 64-year-old male receiving eptifibatide for the second time during percutaneous coronary intervention. Although rare, short and self-limited episodes of acute and profound thrombocytopenia have been associated with eptifibatide exposure. The thrombocytopenia is thought to be immune mediated, and assays are available to test for eptifibatide-induced platelet antibodies. PMID:19172524

  7. A comparative analysis of the activity of ligands acting at P2X and P2Y receptor subtypes in models of neuropathic, acute and inflammatory pain

    PubMed Central

    Andó, RD; Méhész, B; Gyires, K; Illes, P; Sperlágh, B

    2010-01-01

    Background and purpose: This study was undertaken to compare the analgesic activity of antagonists acting at P2X1, P2X7, and P2Y12 receptors and agonists acting at P2Y1, P2Y2, P2Y4, and P2Y6 receptors in neuropathic, acute, and inflammatory pain. Experimental approach: The effect of the wide spectrum P2 receptor antagonist PPADS, the selective P2X7 receptor antagonist Brilliant Blue G (BBG), the P2X1 receptor antagonist (4,4′,4″,4-[carbonylbis(imino-5,1,3-benzenetriyl-bis(carbonylimino))]tetrakis-1,3-benzenedisulfonic acid, octasodium salt (NF449) and (8,8′-[carbonylbis(imino-3,1-phenylenecarbonylimino)]bis-1,3,5-naphthalene-trisulphonic acid, hexasodium salt (NF023), the P2Y12 receptor antagonist (2,2-dimethyl-propionic acid 3-(2-chloro-6-methylaminopurin-9-yl)-2-(2,2-dimethyl-propionyloxymethyl)-propylester (MRS2395), the selective P2Y1 receptor agonist ([[(1R,2R,3S,4R,5S)-4-[6-amino-2-(methylthio)-9H-purin-9-yl]-2,3-dihydroxybicyclo[3.1.0]hex-1-yl]methyl] diphosphoric acid mono ester trisodium salt (MRS2365), the P2Y2/P2Y4 agonist uridine-5′-triphosphate (UTP), and the P2Y4/P2Y6 agonist uridine-5′-diphosphate (UDP) were examined on mechanical allodynia in the Seltzer model of neuropathic pain, on acute thermal nociception, and on the inflammatory pain and oedema induced by complete Freund's adjuvant (CFA). Key results: MRS2365, MRS2395 and UTP, but not the other compounds, significantly alleviated mechanical allodynia in the neuropathic pain model, with the following rank order of minimal effective dose (mED) values: MRS2365 > MRS2395 > UTP. All compounds had a dose-dependent analgesic action in acute pain except BBG, which elicited hyperalgesia at a single dose. The rank order of mED values in acute pain was the following: MRS2365 > MRS2395 > NF449 > NF023 > UDP = UTP > PPADS. MRS2365 and MRS2395 had a profound, while BBG had a mild effect on inflammatory pain, with a following rank order of mED values: MRS2395 > MRS2365 > BBG. None of the tested

  8. Inhibition of inflammatory reactions in 2,4-Dinitrochlorobenzene induced Nc/Nga atopic dermatitis mice by non-thermal plasma.

    PubMed

    Choi, Jeong-Hae; Song, Yeon-Suk; Lee, Hae-June; Hong, Jin-Woo; Kim, Gyoo-Cheon

    2016-01-01

    Non-thermal plasma (NTP) has recently been introduced and reported as a novel tool with a range of medicinal and biological roles. Although many studies using NTP have been performed, none has investigated the direct relationship between NTP and immune responses yet. Especially, the effects of NTP on atopic dermatitis (AD) were not been explored. Here, NTP was tested whether it controls immune reactions of AD. NTP treatment was administered to pro-inflammatory cytokine-stimulated keratinocytes and DNCB (2,4-Dinitrochlorobenzene)-induced atopic dermatitis mice, then the immune reactions of cells and skin tissues were monitored. Cells treated with NTP showed decreased expression levels of CCL11, CCL13, and CCL17 along with down-regulation of NF-κB activity. Repeated administration of NTP to AD-induced mice reduced the numbers of mast cells and eosinophils, IgE, CCL17, IFNγ levels, and inhibited NF-κB activity in the skin lesion. Furthermore, combined treatment with NTP and 1% hydrocortisone cream significantly decreased the immune responses of AD than that with either of these two treatments individually. Overall, this study revealed that NTP significantly inhibits several immune reactions of AD by regulating NF-κB activity. Therefore, NTP could be useful to suppress the exaggerated immune reactions in severe skin inflammatory diseases such as AD. PMID:27271011

  9. Inhibition of inflammatory reactions in 2,4-Dinitrochlorobenzene induced Nc/Nga atopic dermatitis mice by non-thermal plasma

    PubMed Central

    Choi, Jeong-Hae; Song, Yeon-Suk; Lee, Hae-June; Hong, Jin-Woo; Kim, Gyoo-Cheon

    2016-01-01

    Non-thermal plasma (NTP) has recently been introduced and reported as a novel tool with a range of medicinal and biological roles. Although many studies using NTP have been performed, none has investigated the direct relationship between NTP and immune responses yet. Especially, the effects of NTP on atopic dermatitis (AD) were not been explored. Here, NTP was tested whether it controls immune reactions of AD. NTP treatment was administered to pro-inflammatory cytokine-stimulated keratinocytes and DNCB (2,4-Dinitrochlorobenzene)-induced atopic dermatitis mice, then the immune reactions of cells and skin tissues were monitored. Cells treated with NTP showed decreased expression levels of CCL11, CCL13, and CCL17 along with down-regulation of NF-κB activity. Repeated administration of NTP to AD-induced mice reduced the numbers of mast cells and eosinophils, IgE, CCL17, IFNγ levels, and inhibited NF-κB activity in the skin lesion. Furthermore, combined treatment with NTP and 1% hydrocortisone cream significantly decreased the immune responses of AD than that with either of these two treatments individually. Overall, this study revealed that NTP significantly inhibits several immune reactions of AD by regulating NF-κB activity. Therefore, NTP could be useful to suppress the exaggerated immune reactions in severe skin inflammatory diseases such as AD. PMID:27271011

  10. Inhibition of inflammatory reactions in 2,4-Dinitrochlorobenzene induced Nc/Nga atopic dermatitis mice by non-thermal plasma

    NASA Astrophysics Data System (ADS)

    Choi, Jeong-Hae; Song, Yeon-Suk; Lee, Hae-June; Hong, Jin-Woo; Kim, Gyoo-Cheon

    2016-06-01

    Non-thermal plasma (NTP) has recently been introduced and reported as a novel tool with a range of medicinal and biological roles. Although many studies using NTP have been performed, none has investigated the direct relationship between NTP and immune responses yet. Especially, the effects of NTP on atopic dermatitis (AD) were not been explored. Here, NTP was tested whether it controls immune reactions of AD. NTP treatment was administered to pro-inflammatory cytokine-stimulated keratinocytes and DNCB (2,4-Dinitrochlorobenzene)-induced atopic dermatitis mice, then the immune reactions of cells and skin tissues were monitored. Cells treated with NTP showed decreased expression levels of CCL11, CCL13, and CCL17 along with down-regulation of NF-κB activity. Repeated administration of NTP to AD-induced mice reduced the numbers of mast cells and eosinophils, IgE, CCL17, IFNγ levels, and inhibited NF-κB activity in the skin lesion. Furthermore, combined treatment with NTP and 1% hydrocortisone cream significantly decreased the immune responses of AD than that with either of these two treatments individually. Overall, this study revealed that NTP significantly inhibits several immune reactions of AD by regulating NF-κB activity. Therefore, NTP could be useful to suppress the exaggerated immune reactions in severe skin inflammatory diseases such as AD.

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

    PubMed

    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. PMID:26375251

  12. The CD14+CD16+ Inflammatory Monocyte Subset Displays Increased Mitochondrial Activity and Effector Function During Acute Plasmodium vivax Malaria

    PubMed Central

    Antonelli, Lis R. V.; Leoratti, Fabiana M. S.; Costa, Pedro A. C.; Rocha, Bruno C.; Diniz, Suelen Q.; Tada, Mauro S.; Pereira, Dhelio B.; Teixeira-Carvalho, Andrea; Golenbock, Douglas T.; Gonçalves, Ricardo; Gazzinelli, Ricardo T.

    2014-01-01

    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. PMID:25233271

  13. The CD14+CD16+ inflammatory monocyte subset displays increased mitochondrial activity and effector function during acute Plasmodium vivax malaria.

    PubMed

    Antonelli, Lis R V; Leoratti, Fabiana M S; Costa, Pedro A C; Rocha, Bruno C; Diniz, Suelen Q; Tada, Mauro S; Pereira, Dhelio B; Teixeira-Carvalho, Andrea; Golenbock, Douglas T; Gonçalves, Ricardo; Gazzinelli, Ricardo T

    2014-09-01

    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. PMID:25233271

  14. Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 Pathway

    PubMed Central

    Zhang, Xiang-Sheng; Li, Wei; Wu, Qi; Wu, Ling-Yun; Ye, Zhen-Nan; Liu, Jing-Peng; Zhuang, Zong; Zhou, Meng-Liang; Zhang, Xin; Hang, Chun-Hua

    2016-01-01

    Toll-like receptor 4 (TLR4) has been proven to play a critical role in neuroinflammation and to represent an important therapeutic target following subarachnoid hemorrhage (SAH). Resveratrol (RSV), a natural occurring polyphenolic compound, has a powerful anti-inflammatory property. However, the underlying molecular mechanisms of RSV in protecting against early brain injury (EBI) after SAH remain obscure. The purpose of this study was to investigate the effects of RSV on the TLR4-related inflammatory signaling pathway and EBI in rats after SAH. A prechiasmatic cistern SAH model was used in our experiment. The expressions of TLR4, high-mobility group box 1 (HMGB1), myeloid differentiation factor 88 (MyD88), and nuclear factor-κB (NF-κB) were evaluated by Western blot and immunohistochemistry. The expressions of Iba-1 and pro-inflammatory cytokines in brain cortex were determined by Western blot, immunofluorescence staining, or enzyme-linked immunosorbent assay. Neural apoptosis, brain edema, and neurological function were further evaluated to investigate the development of EBI. We found that post-SAH treatment with RSV could markedly inhibit the expressions of TLR4, HMGB1, MyD88, and NF-κB. Meanwhile, RSV significantly reduced microglia activation, as well as inflammatory cytokines leading to the amelioration of neural apoptosis, brain edema, and neurological behavior impairment at 24 h after SAH. However, RSV treatment failed to alleviate brain edema and neurological deficits at 72 h after SAH. These results indicated that RSV treatment could alleviate EBI after SAH, at least in part, via inhibition of TLR4-mediated inflammatory signaling pathway. PMID:27529233

  15. Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 Pathway.

    PubMed

    Zhang, Xiang-Sheng; Li, Wei; Wu, Qi; Wu, Ling-Yun; Ye, Zhen-Nan; Liu, Jing-Peng; Zhuang, Zong; Zhou, Meng-Liang; Zhang, Xin; Hang, Chun-Hua

    2016-01-01

    Toll-like receptor 4 (TLR4) has been proven to play a critical role in neuroinflammation and to represent an important therapeutic target following subarachnoid hemorrhage (SAH). Resveratrol (RSV), a natural occurring polyphenolic compound, has a powerful anti-inflammatory property. However, the underlying molecular mechanisms of RSV in protecting against early brain injury (EBI) after SAH remain obscure. The purpose of this study was to investigate the effects of RSV on the TLR4-related inflammatory signaling pathway and EBI in rats after SAH. A prechiasmatic cistern SAH model was used in our experiment. The expressions of TLR4, high-mobility group box 1 (HMGB1), myeloid differentiation factor 88 (MyD88), and nuclear factor-κB (NF-κB) were evaluated by Western blot and immunohistochemistry. The expressions of Iba-1 and pro-inflammatory cytokines in brain cortex were determined by Western blot, immunofluorescence staining, or enzyme-linked immunosorbent assay. Neural apoptosis, brain edema, and neurological function were further evaluated to investigate the development of EBI. We found that post-SAH treatment with RSV could markedly inhibit the expressions of TLR4, HMGB1, MyD88, and NF-κB. Meanwhile, RSV significantly reduced microglia activation, as well as inflammatory cytokines leading to the amelioration of neural apoptosis, brain edema, and neurological behavior impairment at 24 h after SAH. However, RSV treatment failed to alleviate brain edema and neurological deficits at 72 h after SAH. These results indicated that RSV treatment could alleviate EBI after SAH, at least in part, via inhibition of TLR4-mediated inflammatory signaling pathway. PMID:27529233

  16. Acute Phase Proteins and Their Role in Periodontitis: A Review.

    PubMed

    Polepalle, Tejaswin; Moogala, Srinivas; Boggarapu, Shalini; Pesala, Divya Sai; Palagi, Firoz Babu

    2015-11-01

    Acute phase proteins are a class of proteins whose plasma concentration increase (positive acute phase proteins) or decrease (negative acute phase proteins) in response to inflammation. This response is called as the acute phase reaction, also called as acute phase response, which occurs approximately 90 minutes after the onset of a systemic inflammatory reaction. In Periodontitis endotoxins released from gram negative organisms present in the sub gingival plaque samples interact with Toll- like receptors (TLR) that are expressed on the surface of Polymorphonuclear leucocytes (PMNs) and monocytes which are in abundance in periodontal inflammation. The complex formed due to interaction of Endotoxins and TLR activates the Signal transduction pathway in both innate and adaptive immunity resulting in production of Cytokines that co- ordinate the local and systemic inflammatory response. The pro inflammatory cytokines originating at the diseased site activates the liver cells to produce acute phase proteins as a part of non specific response. The production of Acute phase proteins is regulated to a great extent by Cytokines such as IL-1, IL-6, IL-8, TNF-α and to a lesser extent by Glucocorticoid hormones. These proteins bind to bacteria leading to activation of complement proteins that destroys pathogenic organisms. Studies have shown that levels of acute phase proteins are increased in otherwise healthy adults with poor periodontal status. This article highlights about the synthesis, structure, types and function of acute phase proteins and the associated relation of acute phase proteins in Periodontitis. PMID:26674303

  17. Acute Phase Proteins and Their Role in Periodontitis: A Review

    PubMed Central

    Moogala, Srinivas; Boggarapu, Shalini; Pesala, Divya Sai; Palagi, Firoz Babu

    2015-01-01

    Acute phase proteins are a class of proteins whose plasma concentration increase (positive acute phase proteins) or decrease (negative acute phase proteins) in response to inflammation. This response is called as the acute phase reaction, also called as acute phase response, which occurs approximately 90 minutes after the onset of a systemic inflammatory reaction. In Periodontitis endotoxins released from gram negative organisms present in the sub gingival plaque samples interact with Toll- like receptors (TLR) that are expressed on the surface of Polymorphonuclear leucocytes (PMNs) and monocytes which are in abundance in periodontal inflammation. The complex formed due to interaction of Endotoxins and TLR activates the Signal transduction pathway in both innate and adaptive immunity resulting in production of Cytokines that co- ordinate the local and systemic inflammatory response. The pro inflammatory cytokines originating at the diseased site activates the liver cells to produce acute phase proteins as a part of non specific response. The production of Acute phase proteins is regulated to a great extent by Cytokines such as IL-1, IL-6, IL-8, TNF-α and to a lesser extent by Glucocorticoid hormones. These proteins bind to bacteria leading to activation of complement proteins that destroys pathogenic organisms. Studies have shown that levels of acute phase proteins are increased in otherwise healthy adults with poor periodontal status. This article highlights about the synthesis, structure, types and function of acute phase proteins and the associated relation of acute phase proteins in Periodontitis. PMID:26674303

  18. Improved early diagnosis of acute inflammatory skeletal-articular diseases in children: A two-radiopharmaceutical approach

    SciTech Connect

    Handmaker, H.; Giammona, S.T.

    1984-05-01

    The febrile child with a painful bone or joint still presents a difficult pediatric diagnostic problem. Acute hematogenous osteomyelitis, septic arthritis, and cellulitis are the most common causes of this symptom. Thirty-seven patients with these disorders were studied. Because findings from technetium-99m phosphate bone scans and roentgenograms are often normal in patients in the early stages of acute hematogenous osteomyelitis, children suspected of having this disorder were tested using gallium-67 citrate scans in addition to the other diagnostic procedures. The increased diagnostic accuracy of this approach over that of bone scan and roentgenogram studies alone was observed in the children with fever and bone or joint pain.

  19. Enhancement of delayed hypersensitivity inflammatory reactions in guinea pig skin by 12(R)-hydroxy-5,8,14-eicosatrienoic acid.

    PubMed

    Conners, M S; Schwartzman, M L; Quan, X; Heilman, E; Chauhan, K; Falck, J R; Godfrey, H P

    1995-01-01

    Delayed-type hypersensitivity (DTH) reactions are initiated by sensitized T cells. Their progression is dependent upon the local release of various autacoids, including cytokines and eicosanoids, by T cells, infiltrating inflammatory cells, and resident tissue cells. 12(R)-hydroxy-5,8,14-eicosatrienoic acid [12(R)-HETrE], an eicosanoid produced by skin and cornea, possesses potent proinflammatory properties at picomolar concentrations including vasodilation, increase in membrane permeability, neutrophil chemotaxis, and angiogenesis. Because DTH reactions are associated with many of these same phenomena, we examined the effect of 12(R)-HETrE and related 12-hydroxyeicosanoids on the expression of DTH to purified protein derivative of tuberculin in sensitized guinea pigs. In the absence of purified protein derivative of tuberculin, none of the eicosanoids evoked erythema or edema after intradermal injection at doses up to 100 pmol. When injected together with purified protein derivative of tuberculin, 12(R)-hydroxy-5,8,10,14-eicosatetraenoic acid [12(R)-HETE], but not its enantiomer 12(S)-HETE, significantly inhibited macroscopic expression of delayed reactivity (erythema) only at the highest dose tested, 10 pmol. In contrast, 12(R)-HETrE significantly enhanced expression of DTH at doses between 1 fmol and 1 pmol (50% and 30% increases above control, respectively). Its stereoisomer, 12(S)-HETrE, did not enhance DTH at any tested dose, but was able to block the activity of 12(R)-HETrE when injected simultaneously. Enhancement or inhibition of visible skin responses was not associated with qualitative or quantitative changes in cellular infiltrates at the reaction site. 12(R)-HETrE had no effect on the nonimmunologic inflammatory skin reaction induced by phorbol myristate acetate, suggesting selectivity toward DTH. We conclude that 12(R)-HETrE enhances DTH via a yet to be determined mechanism and that its stereoisomer, 12(S)-HETrE, may be a useful antagonist for

  20. Rapid cooling after acute hyperthermia alters intestinal tissue morphology and increases the systemic inflammatory response in pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acute hyperthermia can result in mortality if recovery is not appropriately managed. The study objective was to determine the effects of heatstroke recovery methods on the physiological response in pigs. In four repetitions, 36 male pigs (88.7 ± 1.6 kg BW) were exposed to thermoneutral conditions (T...

  1. Comprehensive Evaluation of Personal, Clinical, and Radiation Dosimetric Parameters for Acute Skin Reaction during Whole Breast Radiotherapy

    PubMed Central

    Yang, Dae Sik; Lee, Jung Ae; Lee, Nam Kwon; Park, Young Je; Lee, Suk; Kim, Chul Yong; Son, Gil Soo

    2016-01-01

    Skin reaction is major problem during whole breast radiotherapy. To identify factors related to skin reactions during whole breast radiotherapy, various personal, clinical, and radiation dosimetric parameters were evaluated. From January 2012 to December 2013, a total of 125 patients who underwent breast conserving surgery and adjuvant whole breast irradiation were retrospectively reviewed. All patients had both whole breast irradiation and boost to the tumour bed. Skin reaction was measured on the first day of boost therapy based on photography of the radiation field and medical records. For each area of axilla and inferior fold, the intensity score of erythema (score 1 to 5) and extent (score 0 to 1) were summed. The relationship of various parameters to skin reaction was evaluated using chi-square and linear regression tests. The V100 (volume receiving 100% of prescribed radiation dose, p < 0.001, both axilla and inferior fold) and age (p = 0.039 for axilla and 0.026 for inferior fold) were significant parameters in multivariate analyses. The calculated axilla dose (p = 0.003) and breast separation (p = 0.036) were also risk factors for axilla and inferior fold, respectively. Young age and large V100 are significant factors for acute skin reaction that can be simply and cost-effectively measured. PMID:27579310

  2. Comprehensive Evaluation of Personal, Clinical, and Radiation Dosimetric Parameters for Acute Skin Reaction during Whole Breast Radiotherapy.

    PubMed

    Yang, Dae Sik; Lee, Jung Ae; Yoon, Won Sup; Lee, Nam Kwon; Park, Young Je; Lee, Suk; Kim, Chul Yong; Son, Gil Soo

    2016-01-01

    Skin reaction is major problem during whole breast radiotherapy. To identify factors related to skin reactions during whole breast radiotherapy, various personal, clinical, and radiation dosimetric parameters were evaluated. From January 2012 to December 2013, a total of 125 patients who underwent breast conserving surgery and adjuvant whole breast irradiation were retrospectively reviewed. All patients had both whole breast irradiation and boost to the tumour bed. Skin reaction was measured on the first day of boost therapy based on photography of the radiation field and medical records. For each area of axilla and inferior fold, the intensity score of erythema (score 1 to 5) and extent (score 0 to 1) were summed. The relationship of various parameters to skin reaction was evaluated using chi-square and linear regression tests. The V 100 (volume receiving 100% of prescribed radiation dose, p < 0.001, both axilla and inferior fold) and age (p = 0.039 for axilla and 0.026 for inferior fold) were significant parameters in multivariate analyses. The calculated axilla dose (p = 0.003) and breast separation (p = 0.036) were also risk factors for axilla and inferior fold, respectively. Young age and large V 100 are significant factors for acute skin reaction that can be simply and cost-effectively measured. PMID:27579310

  3. Letter: Localized cutaneous reaction to intramuscular vitamin K in a patient with acute fatty liver of pregnancy.

    PubMed

    Sousa, Tatiana; Hunter, Lindsey; Petitt, Matthew; Wilkerson, Michael George

    2010-01-01

    Vitamin K1 is frequently used in the treatment and prevention of hypoprothrombinemia and hemorrhagic disease of the newborn. It also serves as an antidote to anticoagulants. Erythematous, indurated, pruritic plaques uncommonly occur in adults after intramuscular injection with vitamin K1. We present a case of a localized cutaneous reaction to intramuscular vitamin K1 in a peripartum patient with acute fatty liver of pregnancy. The history and clinical presentation of our case is presented with a discussion of the pathogenesis pathogenesis of vitamin K1 and available treatment for this condition. PMID:21199642

  4. Acute exposure to Buenos Aires air particles (UAP-BA) induces local and systemic inflammatory response in middle-aged mice: A time course study.

    PubMed

    Orona, Nadia S; Ferraro, Sebastián A; Astort, Francisco; Morales, Celina; Brites, Fernando; Boero, Laura; Tiscornia, Gisela; Maglione, Guillermo A; Saldiva, Paulo H N; Yakisich, Sebastian; Tasat, Deborah R

    2016-01-01

    Exposure to air particulate matter (PM) is associated with increased cardiovascular morbimortality. However, PM doesn't affect equally to all people, being the old cohort the most susceptible and studied. We hypothesized that another specific life phase, the middle-aged subpopulation, may be negatively affected. Therefore, the aim of this study was to analyze in vivo the acute biological impact of two environmental particles, Urban Air Particles from Buenos Aires and Residual Oil Fly Ash, on the cardiorespiratory system of middle-aged mice, evaluating oxidative metabolism and inflammation. Both PM provoked a local and systemic inflammatory response, leading to a reduced alveolar area in the lung, an epicard inflammation in the heart, an increment of IL-6, and a reduction on PON 1 activity in serum of middle-aged animals. The positive correlation of local parameters with systemic markers of oxidative stress and inflammation could be responsible for associations of cardiovascular morbimortality in this subpopulation. PMID:26255684

  5. Accuracy of the new radiographic sign of fecal loading in the cecum for differential diagnosis of acute appendicitis in comparison with other inflammatory diseases of right abdomen: a prospective study

    PubMed Central

    Petroianu, A; Alberti, LR

    2012-01-01

    Rationale: To assess the importance of the new radiographic sign of faecal loading in the cecum for the diagnosis of acute appendicitis, in comparison with other inflammatory diseases, and to verify the maintenance of this radiographic sign after surgical treatment of appendicitis. Methods: 470 consecutive patients admitted to the hospital due to acute abdomen were prospectively studied: Group 1 [n=170] – diagnosed with acute appendicitis, subdivided into: Subgroup 1A – [n=100] – submitted to an abdominal radiographic study before surgical treatment, Subgroup 1B – [n=70] – patients who had plain abdominal X-rays done before the surgical procedure and also the following day; Group 2 [n=100] – right nephrolithiasis; Group 3 [n=100] – right acute inflammatory pelvic disease; Group 4 [n=100] – acute cholecystitis. The patients of Groups 2,3 and 4 were submitted to abdominal radiography during the pain episode. Results: The sign of faecal loading in the cecum, characterized by hypo transparency interspersed with multiple small foci of hyper transparent images, was present in 97 patients of Subgroup 1A, in 68 patients of Subgroup 1B, in 19 patients of Group 2, in 12 patients of Group 3 and in 13 patients of Group 4. During the postoperative period the radiographic sign disappeared in 66 of the 68 cases that had presented with the sign. The sensitivity of the radiographic sign for acute appendicitis was 97.05% and its specificity was 85.33%. The positive predictive value for acute appendicitis was 78.94% and its negative predictive value was 98. 08%. Discussion: The radiographic image of faecal loading in the cecum is associated with acute appendicitis and disappears after appendectomy. This sign is uncommon in other acute inflammatory diseases of the right side of the abdomen. PMID:22574093

  6. Ethanol Extract of Antrodia camphorata Grown on Germinated Brown Rice Suppresses Inflammatory Responses in Mice with Acute DSS-Induced Colitis

    PubMed Central

    Park, Dong Ki; Park, Hye-Jin

    2013-01-01

    The anti-inflammatory activity of Antrodia camphorata (AC) grown on germinated brown rice (CBR) extract was evaluated in vitro and in vivo. CBR suppressed the release of nitric oxide (NO) and prostaglandin (PG) E2 from lipopolysaccharide-(LPS-)stimulated RAW264.7 cells. CBR inhibited the level of inducible nitric oxide synthase (iNOS) and cyclooxygenase-(COX-)2 proteins, and it activated p38-MAPK, extracellular signal-related kinases (ERK), and NF-κB in LPS-stimulated RAW264.7 macrophages. LPS-induced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA expression was reduced in CBR-treated RAW264.7 cells. In concert with in vitro data, CBR suppressed the levels of dextran-sulfate-sodium-(DSS-)induced iNOS and COX-2 proteins in the colon tissue. CBR treatment inhibited activated p38-MAPK, ERK, and NF-κB proteins in the colon tissue of DSS-induced mice. TNF-α and IL-6 mRNA expression was reduced in DSS+CBR-treated mice. The disease activity index and histological scores were significantly lower in CBR-treated mice (500 mg/kg/day) than in DSS-treated mice (P < 0.05 versus DSS). This is the first report of anti-inflammatory activity of CBR in DSS-induced acute colitis. These results suggest that CBR is a promising, potential agent for preventing acute colitis through the inhibition of NF-κB signaling and its upstream signaling molecules, including MAPKs. PMID:23818935

  7. CaM Kinase II mediates maladaptive post-infarct remodeling and pro-inflammatory chemoattractant signaling but not acute myocardial ischemia/reperfusion injury

    PubMed Central

    Weinreuter, Martin; Kreusser, Michael M; Beckendorf, Jan; Schreiter, Friederike C; Leuschner, Florian; Lehmann, Lorenz H; Hofmann, Kai P; Rostosky, Julia S; Diemert, Nathalie; Xu, Chang; Volz, Hans Christian; Jungmann, Andreas; Nickel, Alexander; Sticht, Carsten; Gretz, Norbert; Maack, Christoph; Schneider, Michael D; Gröne, Hermann-Josef; Müller, Oliver J; Katus, Hugo A; Backs, Johannes

    2014-01-01

    CaMKII was suggested to mediate ischemic myocardial injury and adverse cardiac remodeling. Here, we investigated the roles of different CaMKII isoforms and splice variants in ischemia/reperfusion (I/R) injury by the use of new genetic CaMKII mouse models. Although CaMKIIδC was upregulated 1 day after I/R injury, cardiac damage 1 day after I/R was neither affected in CaMKIIδ-deficient mice, CaMKIIδ-deficient mice in which the splice variants CaMKIIδB and C were re-expressed, nor in cardiomyocyte-specific CaMKIIδ/γ double knockout mice (DKO). In contrast, 5 weeks after I/R, DKO mice were protected against extensive scar formation and cardiac dysfunction, which was associated with reduced leukocyte infiltration and attenuated expression of members of the chemokine (C-C motif) ligand family, in particular CCL3 (macrophage inflammatory protein-1α, MIP-1α). Intriguingly, CaMKII was sufficient and required to induce CCL3 expression in isolated cardiomyocytes, indicating a cardiomyocyte autonomous effect. We propose that CaMKII-dependent chemoattractant signaling explains the effects on post-I/R remodeling. Taken together, we demonstrate that CaMKII is not critically involved in acute I/R-induced damage but in the process of post-infarct remodeling and inflammatory processes. PMID:25193973

  8. Heat-Processed Scutellariae Radix Enhances Anti-Inflammatory Effect against Lipopolysaccharide-Induced Acute Lung Injury in Mice via NF-κB Signaling

    PubMed Central

    Shin, Yu Ock; Park, Chan Hum; Lee, Gyeong-Hwan; Yokozawa, Takako; Roh, Seong-Soo; Rhee, Man Hee

    2015-01-01

    The present study was conducted to examine whether heat-processed Scutellariae Radix has an ameliorative effect on lipopolysaccharide- (LPS-) induced acute lung injury in mice. The effects of Scutellariae Radix heat-processed at 160°C (HSR) were compared with those of nonheat-processed Scutellariae Radix (NSR). The LPS-treated group displayed a markedly decreased body weight and significantly increased lung weight; however, the administration of NSR or HSR improved both the body and lung weights. The increased oxidative stress and inflammatory biomarker levels in the serum and lung were reduced significantly with HSR. The reduced superoxide dismutase and catalase increased significantly by both NSR and HSR. Also, the dysregulated oxidative stress and inflammation were significantly ameliorated by NSR and HSR. The expression of inflammatory mediators and cytokines by nuclear factor-kappa B activation was modulated through inhibition of a nuclear factor kappa Bα degradation. Also, lung histological change was markedly suppressed by HSR rather than NSR. Overall, the ameliorative effects of HSR were superior to those when being nonheat-processed. The representative flavonoid contents of Scutellariae Radix that include baicalin, baicalein, and wogonin were greater by heat process. These data reveal heat-processed Scutellariae Radix may be a critical factor involved in the improvement of lung disorders caused by LPS. PMID:26167192

  9. Metabolic Syndrome Augments the Risk of Early Neurological Deterioration in Acute Ischemic Stroke Patients Independent of Inflammatory Mediators: A Hospital-Based Prospective Study

    PubMed Central

    Zhang, Xiaohao; Sun, Zhiguang; Ding, Caixia; Tang, Yinyan; Jiang, Xuemei; Xie, Yi; Li, Chuanyou; Zhang, Lankun; Hu, Dan; Li, Tingting; Xu, Gelin; Sheng, Lei

    2016-01-01

    Background and Aims. Metabolic syndrome (MetS) has been associated with occurrence and prognosis of ischemic stroke. This study aimed to evaluate whether an association exists between MetS and early neurological deterioration (END) following acute ischemic stroke and the possible role inflammatory biomarkers play. Methods and Results. We conducted a prospective cohort investigation that involved 208 stroke patients within 48 hours from symptom onset. MetS was determined by the modified National Cholesterol Education Program/Adult Treatment Panel III criteria. END was defined as an increase of ⩾1 point in motor power or ⩾2 points in the total National Institutes of Health Stroke Scale (NIHSS) score within 7 days. Univariate logistic regression analysis showed that patients with MetS had a 125% increased risk of END (OR 2.25; 95% CI 1.71–4.86, P = 0.005). After adjustment for fibrinogen and high-sensitivity C-reactive protein, MetS remained significantly correlated to END (OR 2.20; 95% CI 1.10–4.04, P = 0.026) with a 77% elevated risk per additional MetS trait (OR 1.77; 95% CI 1.23–2.58, P = 0.002). Conclusions. This study demonstrated that MetS may be a potential predictor for END after ischemic stroke, which was independent of raised inflammatory mediators. PMID:27119010

  10. Artesunate ameliorates severe acute pancreatitis (SAP) in rats by inhibiting expression of pro-inflammatory cytokines and Toll-like receptor 4.

    PubMed

    Cen, Yanyan; Liu, Chao; Li, Xiaoli; Yan, Zifei; Kuang, Mei; Su, Yujie; Pan, Xichun; Qin, Rongxin; Liu, Xin; Zheng, Jiang; Zhou, Hong

    2016-09-01

    Severe acute pancreatitis (SAP) is a severe clinical condition with significant morbidity and mortality. Multiple organs dysfunction (MOD) is the leading cause of SAP-related death. The over-release of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α is the underlying mechanism of MOD; however, there is no effective agent against the inflammation. Herein, artesunate (AS) was found to increase the survival of SAP rats significantly when injected with 3.5% sodium taurocholate into the biliopancreatic duct in a retrograde direction, improving their pancreatic pathology and decreasing serum amylase and pancreatic lipase activities along with substantially reduced pancreatic IL-1β and IL-6 release. In vitro, AS-pretreatment strongly inhibited IL-1β and IL-6 release and their mRNA expressions in the pancreatic acinar cells treated with lipopolysaccharide (LPS) but exerted little effect on TNF-α release. Additionally, AS reduced the mRNA expressions of Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) p65 as well as their protein expressions in the pancreatic acinar cells. In conclusion, our results demonstrated that AS could significantly protect SAP rats, and this protection was related to the reduction of digestive enzyme activities and pro-inflammatory cytokine expressions via inhibition of TLR4/NF-κB signaling pathway. Therefore, AS may be considered as a potential therapeutic agent against SAP. PMID:27318790

  11. Peroxisome proliferator-activated receptor α activation attenuates the inflammatory response to protect the liver from acute failure by promoting the autophagy pathway.

    PubMed

    Jiao, M; Ren, F; Zhou, L; Zhang, X; Zhang, L; Wen, T; Wei, L; Wang, X; Shi, H; Bai, L; Zhang, X; Zheng, S; Zhang, J; Chen, Y; Han, Y; Zhao, C; Duan, Z

    2014-01-01

    Peroxisome proliferator-activated receptor α (PPARα) has been reported to induce a potent anti-inflammatory response. Autophagy is a recently recognized rudimentary cellular response to inflammation and injury. The aim of the present study was to test the hypothesis that PPARα activation mediates autophagy to inhibit liver inflammation and protect against acute liver failure (ALF). PPARα expression during ALF and the impact of PPARα activation by Wy-14 643 on the hepatic immune response were studied in a D-galactosamine/lipopolysaccharide-induced mouse model. Autophagy was inhibited by 3-methyladenine or small interfering RNA (siRNA) against Atg7. In both the mouse model and human ALF subjects, PPARα was significantly downregulated in the injured liver. PPARα activation by pretreatment with Wy-14 643 protected against liver injury in mice. The protective effect of PPARα activation relied on the suppression of inflammatory mechanisms through the induction of autophagy. This hypothesis is supported by the following evidence: first, PPARα activation suppressed proinflammatory responses and inhibited phosphorylated NF-κBp65, phosphorylated JNK and phosphorylated ERK pathways in vivo. Second, protection by PPARα activation was due to the induction of autophagy because inhibition of autophagy by 3-methyladenine or Atg7 siRNA reversed liver protection and inflammation. Third, PPARα activation directly induced autophagy in primary macrophages in vitro, which protected cells from a lipopolysaccharide-induced proinflammatory response. Here, for the first time, we have demonstrated that PPARα-mediated induction of autophagy ameliorated liver injury in cases of ALF by attenuating inflammatory responses, indicating a potential therapeutic application for ALF treatment. PMID:25165883

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

    PubMed

    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. PMID:24190328

  13. Angiogenic and inflammatory markers in acute respiratory distress syndrome and renal injury associated to A/H1N1 virus infection.

    PubMed

    Bautista, Edgar; Arcos, Magali; Jimenez-Alvarez, Luís; García-Sancho, Ma Cecilia; Vázquez, María E; Peña, Erika; Higuera, Anjarath; Ramírez, Gustavo; Fernández-Plata, Rosario; Cruz-Lagunas, Alfredo; García-Moreno, Sara A; Urrea, Francisco; Ramírez, Remedios; Correa-Rotter, Ricardo; Pérez-Padilla, José Rogelio; Zúñiga, Joaquín

    2013-06-01

    Acute kidney injury (AKI) is often associated to acute respiratory distress syndrome (ARDS) due to influenza A/H1N1 virus infection. The profile of angiogenic and inflammatory factors in ARDS patients may be relevant for AKI. We analyzed the serum levels of several angiogenic factors, cytokines, and chemokines in 32 patients with A/H1N1 virus infection (17 with ARDS/AKI and 15 ARDS patients who did not developed AKI) and in 18 healthy controls. Significantly higher levels of VEGF, MCP-1, IL-6, IL-8 and IP-10 in ARDS/AKI patients were detected. Adjusting by confusing variables, levels of MCP-1 ≥150 pg/mL (OR=12.0, p=0.04) and VEGF ≥225 pg/mL (OR=6.4, p=0.03) were associated with the development of AKI in ARDS patients. Higher levels of MCP-1 and IP-10 were significantly associated with a higher risk of death in patients with ARDS (hazard ratio (HR)=10.0, p=0.02; HR=25.5, p=0.03, respectively) even taking into account AKI. Patients with influenza A/H1N1 infection and ARDS/AKI have an over-production of MCP-1, VEGF and IP-10 possibly contributing to kidney injury and are associated to a higher risk of death. PMID:23542734

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

    PubMed Central

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

    2015-01-01

    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), but HIIE promoted higher values than SSE (p < 0.05); the NEFA levels were higher immediately post-exercise than at rest only in the SSE condition (0.71 ± 0.04 to 0.82±0.09 mEq/L, respectively, p < 0.05), yet, SSE promoted higher values than HIIE immediately after exercise (HIIE 0.72±0.03 vs SSE 0.82±0.09 mEq·L-1, p < 0.05). Glucose and uric acid levels did not show changes under the different conditions (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. Key points Metabolic contribution of both exercise, HIIE and SSE, was different. Both protocols leading to an anti-inflammatory status. HIIE induce a higher energy expenditure take

  15. The acute inflammatory response to intranigral α-synuclein differs significantly from intranigral lipopolysaccharide and is exacerbated by peripheral inflammation

    PubMed Central

    2011-01-01

    Background Activated microglia are a feature of the host response to neurodegeneration in Parkinson's disease (PD) and are thought to contribute to disease progression. Recent evidence suggests that extracellular α-synuclein (eSNCA) may play an important role in the pathogenesis of PD and that this may be mediated by a microglial response. Methods We wished to discover whether the host response to eSNCA would be sufficient to induce significant cytokine production. In vitro cultured BV-2 microglia were used to determine the basic inflammatory response to eSNCA. In vivo, 8-week old Biozzi mice were subjected to a single intranigral injection of either 3 μg SNCA, lipopolysaccharide (LPS) or serum protein (BSA) and allowed to recover for 24 hours. A second cohort of animals were peripherally challenged with LPS (0.5 mg/kg) 6 hours prior to tissue collection. Inflammation was studied by quantitative real-time PCR for a number of pro-inflammatory genes and immunohistochemistry for microglial activation, endothelial activation and cell death. Results In vitro data showed a robust microglial response to SNCA, including a positive NFĸB response and the production of pro-inflammatory cytokines. Direct injection of SNCA into the substantia nigra resulted in the upregulation of mRNA expression of proinflammatory cytokines, the expression of endothelial markers of inflammation and microglial activation. However, these results were significantly different to those obtained after direct injection of LPS. By contrast, when the animals were injected intracerebrally with SNCA and subsequently challenged with systemic LPS, the level of production of IL-1β in the substantia nigra became comparable to that induced by the direct injection of LPS into the brain. The injection of albumin into the nigra with a peripheral LPS challenge did not provoke the production of a significant inflammatory response. Direct injection of LPS into the substantia nigra also induces cell death in a

  16. Comparison of acute non-haemolytic transfusion reactions in female and male patients receiving female or male blood components

    PubMed Central

    Imoto, S; Araki, N; Shimada, E; Saigo, K; Nishimura, K; Nose, Y; Bouike, Y; Hashimoto, M; Mito, H; Okazaki, H

    2007-01-01

    To study the relationship between antibodies detected in patients’ and/or donors’ sera and the clinical features of acute non-haemolytic transfusion reactions (ANHTRs), and to determine any gender-related difference. ANHTRs range from urticaria to transfusion-related acute lung injury (TRALI). Antibodies to human leukocyte antigen (HLA), granulocytes, platelets, and/or plasma proteins are implicated in some of the ANHTRs. A higher antibody positivity is expected for females than for males. A comparative study of ANHTRs for antibody positivity and their clinical features between females and males for both patients and donors is helpful for characterizing ANHTRs including TRALI more clearly, but such studies are few and outdated. Two hundred and twenty-three ANHTR cases reported by 45 hospitals between October 2000 and July 2005 were analysed. The patients and 196 donors of suspect blood products were screened for antibodies to HLA Class I, HLA Class II, granulocytes, and platelets. The patients were also screened for anti-plasma protein antibodies. The types and severity of ANHTR did not differ significantly between female and male patients. The frequency of the anti-HLA antibodies, but not that of the non-HLA antibodies, was significantly higher in females. Non-HLA antibodies were significantly associated with severe reactions in females. All the TRALI cases had predisposing risk factors for acute lung injury, and 60% of the cases showed anti-leucocyte antibodies. Although the anti-HLA antibodies were detected more frequently in females than males, no significant association of ANHTRs including TRALI with gender, not only for patients, but also for donors, could be shown in this study. PMID:18067650

  17. Inflammatory glaucoma

    PubMed Central

    Bodh, Sonam A.; Kumar, Vasu; Raina, Usha K.; Ghosh, B.; Thakar, Meenakshi

    2011-01-01

    Glaucoma is seen in about 20% of the patients with uveitis. Anterior uveitis may be acute, subacute, or chronic. The mechanisms by which iridocyclitis leads to obstruction of aqueous outflow include acute, usually reversible forms (e.g., accumulation of inflammatory elements in the intertrabecular spaces, edema of the trabecular lamellae, or angle closure due to ciliary body swelling) and chronic forms (e.g., scar formation or membrane overgrowth in the anterior chamber angle). Careful history and follow-up helps distinguish steroid-induced glaucoma from uveitic glaucoma. Treatment of combined iridocyclitis and glaucoma involves steroidal and nonsteroidal antiinflammatory agents and antiglaucoma drugs. However, glaucoma drugs can often have an unpredictable effect on intraocular pressure (IOP) in the setting of uveitis. Surgical intervention is required in case of medical failure. Method of Literature Search: Literature on the Medline database was searched using the PubMed interface. PMID:21713239

  18. Alpinetin attenuates inflammatory responses by suppressing TLR4 and NLRP3 signaling pathways in DSS-induced acute colitis.

    PubMed

    He, Xuexiu; Wei, Zhengkai; Wang, Jingjing; Kou, Jinhua; Liu, Weijian; Fu, Yunhe; Yang, Zhengtao

    2016-01-01

    Alpinetin, a composition of Alpinia katsumadai Hayata, has been reported to have a number of biological properties, such as antibacterial, antitumor and other important therapeutic activities. However, the effect of alpinetin on inflammatory bowel disease (IBD) has not yet been reported. The purpose of this study was to investigate the anti-inflammatory effect and mechanism of alpinetin on dextran sulfate sodium (DSS)-induced colitis in mice. In vivo, DSS-induced mice colitis model was established by giving mice drinking water containing 5% (w/v) DSS for 7 days. Alpinetin (25, 50 and 100 mg/kg) were administered once a day by intraperitoneal injection 3 days before DSS treatment. In vitro, phorbol myristate acetate (PMA)-differentiated monocytic THP-1 macrophages were treated with alpinetin and stimulated by lipopolysaccharide (LPS). The results showed that alpinetin significantly attenuated diarrhea, colonic shortening, histological injury, myeloperoxidase (MPO) activity and the expressions of tumor necrosis factor (TNF-α) and interleukin (IL-1β) production in mice. In vitro, alpinetin markedly inhibited LPS-induced TNF-α and IL-1β production, as well as Toll-like receptor 4 (TLR4) mediated nuclear transcription factor-kappaB (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome activation. In conclusion, this study demonstrated that alpinetin had protective effects on DSS-induced colitis and may be a promising therapeutic reagent for colitis treatment. PMID:27321991

  19. Alpinetin attenuates inflammatory responses by suppressing TLR4 and NLRP3 signaling pathways in DSS-induced acute colitis

    PubMed Central

    He, Xuexiu; Wei, Zhengkai; Wang, Jingjing; Kou, Jinhua; Liu, Weijian; Fu, Yunhe; Yang, Zhengtao

    2016-01-01

    Alpinetin, a composition of Alpinia katsumadai Hayata, has been reported to have a number of biological properties, such as antibacterial, antitumor and other important therapeutic activities. However, the effect of alpinetin on inflammatory bowel disease (IBD) has not yet been reported. The purpose of this study was to investigate the anti-inflammatory effect and mechanism of alpinetin on dextran sulfate sodium (DSS)-induced colitis in mice. In vivo, DSS-induced mice colitis model was established by giving mice drinking water containing 5% (w/v) DSS for 7 days. Alpinetin (25, 50 and 100 mg/kg) were administered once a day by intraperitoneal injection 3 days before DSS treatment. In vitro, phorbol myristate acetate (PMA)-differentiated monocytic THP-1 macrophages were treated with alpinetin and stimulated by lipopolysaccharide (LPS). The results showed that alpinetin significantly attenuated diarrhea, colonic shortening, histological injury, myeloperoxidase (MPO) activity and the expressions of tumor necrosis factor (TNF-α) and interleukin (IL-1β) production in mice. In vitro, alpinetin markedly inhibited LPS-induced TNF-α and IL-1β production, as well as Toll-like receptor 4 (TLR4) mediated nuclear transcription factor-kappaB (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome activation. In conclusion, this study demonstrated that alpinetin had protective effects on DSS-induced colitis and may be a promising therapeutic reagent for colitis treatment. PMID:27321991

  20. INFLUENCE OF NMDA AND NON-NMDA ANTAGONISTS ON ACUTE AND INFLAMMATORY PAIN IN THE TRIGEMINAL TERRITORY

    PubMed Central

    Piovesan, Elcio Juliato; Randunz, Vitor; Utiumi, Marco; Lange, Marcos Cristiano; Kowacs, Pedro André; Mulinari, Rogério Andrade; Oshinsky, Michael; Vital, Maria; Sereniki, Adriana; Fernandes, Artur Furlaneto; Silva, Lucas Leite e; Werneck, Lineu César

    2016-01-01

    NMDA and non-NMDA receptors are involved in spinal transmission of nociceptive information in physiological and pathological conditions. Our objective was to study the influence of NMDA and non-NMDA receptor antagonists on pain control in the trigeminal system using a formalin-induced orofacial pain model. Motor performance was also evaluated. Male Rattus norvegicus were pre-treated with topiramate (T) (n=8), memantine (M) (n=8), divalproex (D) (n=8) or isotonic saline solution (ISS) (n=10) intraperitoneally 30 minutes before the formalin test. Formalin 2.5% was injected into the right upper lip (V2 branch) and induced two phases: phase I (early or neurogenic) (0–3 min) and phase II (late or inflammatory) (12–30 min). For motor behavior performance we used the open-field test and measured latency to movement onset, locomotion and rearing frequencies, and immobility time. Pre-treatment of animals with M and D only attenuated nociceptive formalin behavior for phase II. T increased locomotion and rearing frequencies and reduced immobility time. Treatment with M increased immobility time and with D reduced locomotion frequency. Our results showed that the NMDA antagonist (M) is more potent than the non-NMDA antagonists (D and T) in the control of pain in the inflammatory phase. The non-NMDA topiramate improved motor performance more than did D and M, probably because T has more anxiolytic properties. PMID:19099122

  1. Roles of MAS-related G protein coupled receptor-X2 (MRGPRX2) on mast cell-mediated host defense, pseudoallergic drug reactions and chronic inflammatory diseases

    PubMed Central

    Subramanian, Hariharan; Gupta, Kshitij; Ali, Hydar

    2016-01-01

    Mast cells (MCs), which are granulated tissue-resident cells of hematopoietic lineage, contribute to vascular homeostasis, innate/adaptive immunity and wound healing. MCs are, however, best known for their roles in allergic and inflammatory diseases such as anaphylaxis, food allergy, rhinitis, itch, urticaria, atopic dermatitis and asthma. In addition to the high affinity IgE receptor (FcεRI), MCs express numerous G protein coupled receptors (GPCRs), which are the largest group of membrane receptor proteins and are the most common targets of drug therapy. Antimicrobial host defense peptides (HDPs), neuropeptides (NPs), major basic protein (MBP), eosinophil peroxidase (EPO) and many FDA approved peptidergic drugs activate human MCs via a novel GPCR known as MAS-related G protein coupled receptor-X2 (MRGPRX2; formerly known as MrgX2). Unique features of MRGPRX2 that distinguish it from other GPCRs include their presence both on plasma membrane and intracellular sites and their selective expression in MCs. In this article, we review the possible roles of MRGPRX2 on host defense, drug-induced anaphylactoid reactions, neurogenic inflammation, pain, itch and chronic inflammatory diseases such as urticaria and asthma. We propose that HDPs that kill microbes directly and activate MCs via MRGPRX2 could serve as novel GPCR targets to modulate host defense against microbial infection. Furthermore, monoclonal antibodies or small molecule inhibitors of MRGPRX2 could be developed for the treatment of MC-dependent allergic and inflammatory disorders. PMID:27448446

  2. Involvement of mitogen-activated protein kinase and NF-κB signaling pathways in perfluorooctane sulfonic acid-induced inflammatory reaction in BV2 microglial cells.

    PubMed

    Zhu, Jingying; Qian, Wenyi; Wang, Yixin; Gao, Rong; Wang, Jun; Xiao, Hang

    2015-12-01

    Microglial activation is closely related to the pathogenesis of neurodegenerative diseases by producing proinflammatory cytokines. Perfluorooctane sulfonic acid (PFOS), known as an emerging persistent organic pollutant, is reported to disturb human immune homeostasis; however, whether it affects cytokine production or the immune response in the central nervous system remains unclear. The present study was aimed to explore whether PFOS contributed to inflammatory action and to investigate the corresponding mechanisms in BV2 microglia. PFOS-mediated morphologic changes, cytokine responses and signaling events were examined by light microscopy, real-time polymerase chain reaction, enzyme-linked immunosorbent assay and Western blot assays. Our results indicated that PFOS increased BV2 cells activation and simultaneously increased tumor necrosis factor alpha and interleukin-6 expression. In addition, the c-Jun N-terminal protein kinase inhibitor (SP600125), as well as ERK1/2 blocker (PD98059), transcriptionally at least, displayed anti-inflammatory properties on PFOS-elicited cytokine responses. Moreover, the inflammatory transcription factor NF-κB was specifically activated by PFOS as well. These results, taken together, suggested that PFOS exerts its functional effects on the response of microglial cell activation via, in part, the c-Jun N-terminal protein kinase, ERK and NF-κB signaling pathways with its subsequent influence on proinflammatory action. PMID:25677194

  3. Comparison between qualitative and real-time polymerase chain reaction to evaluate minimal residual disease in children with acute lymphoblastic leukemia

    PubMed Central

    Paula, Francisco Danilo Ferreira; Elói-Santos, Silvana Maria; Xavier, Sandra Guerra; Ganazza, Mônica Aparecida; Jotta, Patricia Yoshioka; Yunes, José Andrés; Viana, Marcos Borato; Assumpção, Juliana Godoy

    2015-01-01

    Introduction Minimal residual disease is an important independent prognostic factor that can identify poor responders among patients with acute lymphoblastic leukemia. Objective The aim of this study was to analyze minimal residual disease using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements by conventional polymerase chain reaction followed by homo-heteroduplex analysis and to compare this with real-time polymerase chain reaction at the end of the induction period in children with acute lymphoblastic leukemia. Methods Seventy-four patients diagnosed with acute lymphoblastic leukemia were enrolled. Minimal residual disease was evaluated by qualitative polymerase chain reaction in 57 and by both tests in 44. The Kaplan–Meier and multivariate Cox methods and the log-rank test were used for statistical analysis. Results Nine patients (15.8%) were positive for minimal residual disease by qualitative polymerase chain reaction and 11 (25%) by real-time polymerase chain reaction considering a cut-off point of 1 × 10−3 for precursor B-cell acute lymphoblastic leukemia and 1 × 10−2 for T-cell acute lymphoblastic leukemia. Using the qualitative method, the 3.5-year leukemia-free survival was significantly higher in children negative for minimal residual disease compared to those with positive results (84.1% ± 5.6% versus 41.7% ± 17.3%, respectively; p-value = 0.004). There was no significant association between leukemia-free survival and minimal residual disease by real-time polymerase chain reaction. Minimal residual disease by qualitative polymerase chain reaction was the only variable significantly correlated to leukemia-free survival. Conclusion Given the difficulties in the implementation of minimal residual disease monitoring by real-time polymerase chain reaction in most treatment centers in Brazil, the qualitative polymerase chain reaction strategy may be a cost-effective alternative. PMID:26670399

  4. Annexin A1 reduces inflammatory reaction and tissue damage through inhibition of phospholipase A2 activation in adult rats following spinal cord injury.

    PubMed

    Liu, Nai-Kui; Zhang, Yi Ping; Han, Shu; Pei, Jiong; Xu, Lisa Y; Lu, Pei-Hua; Shields, Christopher B; Xu, Xiao-Ming

    2007-10-01

    Annexin A1 (ANXA1) has been suggested to be a mediator of the anti-inflammatory actions of glucocorticoids and more recently an endogenous neuroprotective agent. In the present study, we investigated the anti-inflammatory and neuroprotective effects of ANXA1 in a model of contusive spinal cord injury (SCI). Here we report that injections of ANXA1 (Ac 2-26) into the acutely injured spinal cord at 2 concentrations (5 and 20 microg) inhibited SCI-induced increases in phospholipase A2 and myeloperoxidase activities. In addition, ANXA1 administration reduced the expression of interleukin-1beta and activated caspase-3 at 24 hours, and glial fibrillary acidic protein at 4 weeks postinjury. Furthermore, ANXA1 administration significantly reversed phospholipase A2-induced spinal cord neuronal death in vitro and reduced tissue damage and increased white matter sparing in vivo, compared to the vehicle-treated controls. Fluorogold retrograde tracing showed that ANXA1 administration protected axons of long descending pathways at 6 weeks post-SCI. ANXA1 administration also significantly increased the number of animals that responded to transcranial magnetic motor-evoked potentials. However, no measurable behavioral improvement was found after these treatments. These results, particularly the improvements obtained in tissue sparing and electrophysiologic measures, suggest a neuroprotective effect of ANXA1. PMID:17917587

  5. Effects of bone marrow MSCs transfected with sRAGE on the intervention of HMGB1 induced immuno-inflammatory reaction

    PubMed Central

    Wang, Jun; Wang, Hao; Shi, Jiong; Ding, Yitao

    2015-01-01

    Background: High mobility group box chromosomal protein 1 (HMGB1) is an important proinflammatory molecule in many inflammatory disorders, but little is known about its role in acute liver failure (ALF). In this study, we determined the plasma and hepatic tissue levels of HMGB1 in a d-galactosamine-induced rat ALF model and investigated the effect of soluble receptor for advanced glycation end products (sRAGE) on ALF successfully. Methods: Male Sprague-Dawley rats were divided into five groups randomly. Group A (Control group, n=20) received administrated saline via peritoneal cavity. Group B (ALF group, n=20) induced by d-galactosamine (0.6 g/kg) via peritoneal cavity. Group C (HMGB1 group, n=20) were treated with HMGB1 recombination protein (200 μg/kg) via penile vein after ALF model induced. Group D (sRAGE group, n=20) received administrated sRAGE recombination protein (400 μg/kg) via penile vein after ALF model induced. Group E (sRAGE-MSC group, n=20) received 3×106 MSC transplantation which could maintain a stable expression of sRAGE via penile vein after ALF model induced. Liver function, level of cytokines and liver pathological changes were measured. Results: We determined that the plasma levels and hepatic tissue levels of HMGB1 were significant increased in ALF model (P<0.05). SRAGE group and sRAGE-MSC group could significantly prolong ALF rat survival time, as well as improve its liver functions, inflammatory cytokines level and hepatocytes necrosis. Conclusion: SRAGE as a ligand decoy has illustrated largely beneficial effects on reducing immuno-inflammatory response, which holds promise for the identification of potential therapeutic targets and/or biomarkers of RAGE activity in ALF. PMID:26722388

  6. Inhibition of acute lung injury by rubriflordilactone in LPS-induced rat model through suppression of inflammatory factor expression

    PubMed Central

    Wang, Yan-Ying; Qiu, Xin-Guang; Ren, Hong-Liang

    2015-01-01

    The present study demonstrates the effect of rubriflordilactone on lipopolysaccharide (LPS)-induced acute kidney injury in rats and MLE-15 cells. LPS administration in rats resulted in formation of edema which was inhibited by pretreatment with rubriflordilactone. The pulmonary tissues of LPS administered rats and MLE-15 cells showed a significant increase in the expression of matrix metalloproteinase-9, interleukin-6 and inducible nitric oxide synthase. However, rubriflordilactone treatment prior to LPS administration caused a significant reduction in the expression of these factors at a concentration of 10 nm/kg. Analysis of the Sirtuin 1 (Sirt1) expression revealed significant (P=0.002) reduction on exposure to LPS in MLE-15 cells. However, rubriflordilactone treatment at 10 nm/ml concentration before LPS exposure caused inhibition of LPS induced reduction in Sirt1 expression. Silencing of Sirt1 by siRNA in MLE-15 cells led to inhibition of increased Sirt1 expression by rubriflordilactone in LPS administered rats. These findings suggest that rubriflordilactone inhibits LPS induced acute lung injury in rats and MLE-15 cells through promotion of Sirt1 expression. PMID:26884869

  7. Inhibition of acute lung injury by rubriflordilactone in LPS-induced rat model through suppression of inflammatory factor expression.

    PubMed

    Wang, Yan-Ying; Qiu, Xin-Guang; Ren, Hong-Liang

    2015-01-01

    The present study demonstrates the effect of rubriflordilactone on lipopolysaccharide (LPS)-induced acute kidney injury in rats and MLE-15 cells. LPS administration in rats resulted in formation of edema which was inhibited by pretreatment with rubriflordilactone. The pulmonary tissues of LPS administered rats and MLE-15 cells showed a significant increase in the expression of matrix metalloproteinase-9, interleukin-6 and inducible nitric oxide synthase. However, rubriflordilactone treatment prior to LPS administration caused a significant reduction in the expression of these factors at a concentration of 10 nm/kg. Analysis of the Sirtuin 1 (Sirt1) expression revealed significant (P=0.002) reduction on exposure to LPS in MLE-15 cells. However, rubriflordilactone treatment at 10 nm/ml concentration before LPS exposure caused inhibition of LPS induced reduction in Sirt1 expression. Silencing of Sirt1 by siRNA in MLE-15 cells led to inhibition of increased Sirt1 expression by rubriflordilactone in LPS administered rats. These findings suggest that rubriflordilactone inhibits LPS induced acute lung injury in rats and MLE-15 cells through promotion of Sirt1 expression. PMID:26884869

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

    PubMed

    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 < 0.05 versus normoxia). Despite an 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. PMID:25344270

  9. Anti-inflammatory effects of locally applied enzyme-loaded ultradeformable vesicles on an acute cutaneous model.

    PubMed

    Simões, Sandra; Marques, Cláudia; Cruz, Maria Eugénia; Martins, Maria Bárbara Figueira

    2009-11-01

    Superoxide dismutase (SOD) and catalase (CAT) are active scavengers of reactive oxygen species and were incorporated into ultradeformable vesicles with the aim of increasing enzyme bioavailability (skin delivery). These special very adaptable vesicles have been formulated and optimized for enzyme transport in order to penetrate into or across the intact skin barrier. Anti-inflammatory activity of SOD-loaded, CAT-loaded and of SOD- and CAT-loaded ultradeformable vesicles applied epicutaneously was measured using different protein doses on the skin, on an arachidonic acid-induced mouse ear oedema. The biological anti-oedema activity is a measurement of drug-targeting potentiation in the organ. Delivery by means of deformable vesicles was compared to conventional vesicles or the absence of an enzyme carrier mediated transport. This was done at various times following prophylactic application of the test formulations. Positive reference groups were treated epicutaneously with several low molecular weight non-steroidal anti-inflammatory drugs (NSAIDs). The latter included indomethacin (3 mg kg(-1)), etofenamate (30 mg kg(-1)) and piroxicam (1 mg kg(-1)) and reduced the oedema by 94 +/- 4%, 81 +/- 4% and 42 +/- 5%, respectively, if measured 30 min after ear treatment with a NSAID. Of the enzyme-loaded carriers tested, only the enzyme-loaded ultradeformable vesicles reduced the swelling of ears significantly: SOD (90 microg kg(-1)), CAT (250 microg kg(-1)) and SOD (90 microg kg(-1)) plus CAT (250 microg kg(-1)) reduced the oedema by 70 +/- 12%, 65 +/- 10% and 61 +/- 19%, respectively, at t = 30 min. Aqueous enzyme solutions and empty carriers had no such effect. The combination of two enzymes resulted in no increased therapeutic effect, but the results are inconclusive since only two dose combinations were tested. The results presented in this study suggest that antioxidant enzymes delivered by means of ultradeformable lipid vesicles can serve as a novel region

  10. Increase in cholinergic modulation with pyridostigmine induces anti-inflammatory cell recruitment soon after acute myocardial infarction in rats.

    PubMed

    Rocha, Juraci Aparecida; Ribeiro, Susan Pereira; França, Cristiane Miranda; Coelho, Otávio; Alves, Gisele; Lacchini, Silvia; Kallás, Esper Georges; Irigoyen, Maria Cláudia; Consolim-Colombo, Fernanda M

    2016-04-15

    We tested the hypothesis that an increase in the anti-inflammatory cholinergic pathway, when induced by pyridostigmine (PY), may modulate subtypes of lymphocytes (CD4+, CD8+, FOXP3+) and macrophages (M1/M2) soon after myocardial infarction (MI) in rats. Wistar rats, randomly allocated to receive PY (40 mg·kg(-1)·day(-1)) in drinking water or to stay without treatment, were followed for 4 days and then were subjected to ligation of the left coronary artery. The groups-denominated as the pyridostigmine-treated infarcted (IP) and infarcted control (I) groups-were submitted to euthanasia 3 days after MI; the heart was removed for immunohistochemistry, and the peripheral blood and spleen were collected for flow cytometry analysis. Noninfarcted and untreated rats were used as controls (C Group). Echocardiographic measurements were registered on the second day after MI, and heart rate variability was measured on the third day after MI. The infarcted groups had similar MI areas, degrees of systolic dysfunction, blood pressures, and heart rates. Compared with the I Group, the IP Group showed a significant higher parasympathetic modulation and a lower sympathetic modulation, which were associated with a small, but significant, increase in diastolic function. The IP Group showed a significant increase in M2 macrophages and FOXP3(+)cells in the infarcted and peri-infarcted areas, a significantly higher frequency of circulating Treg cells (CD4(+)CD25(+)FOXP3(+)), and a less extreme decrease in conventional T cells (CD25(+)FOXP3(-)) compared with the I Group. Therefore, increasing cholinergic modulation with PY induces greater anti-inflammatory cell recruitment soon after MY in rats. PMID:26791829

  11. Acute Psychophysiological Relationships Between Mood, Inflammatory and Cortisol Changes in Response to Simulated Physical Firefighting Work and Sleep Restriction.

    PubMed

    Wolkow, Alexander; Aisbett, Brad; Reynolds, John; Ferguson, Sally A; Main, Luana C

    2016-06-01

    This study examined how changes in wildland firefighters' mood relate to cytokine and cortisol levels in response to simulated physical firefighting work and sleep restriction. Firefighters completed 3 days of simulated wildfire suppression work separated by an 8-h (control condition; n = 18) or 4-h sleep opportunity (sleep restriction condition; n = 17) each night. Firefighters' mood was assessed daily using the Mood Scale II and Samn-Perelli fatigue scale. Participants also provided samples for the determination of salivary cortisol and pro- (IL-6, IL-8, IL-1β, TNF-α) and anti-inflammatory (IL-4, IL-10) cytokine levels. An increase in the positive mood dimension Happiness was related to a rise in IL-8 and TNF-α in the sleep restriction condition. A rise in the positive mood dimension Activation among sleep restricted firefighters was also related to higher IL-6 levels. An increase in the negative mood dimension Fatigue in the sleep restriction condition was associated with increased IL-6, TNF-α, IL-10 and cortisol levels. In addition, an increase in Fear among sleep restricted firefighters was associated with a rise in TNF-α. Elevated positive mood and immune activation may reflect an appropriate response by the firefighters to these stressors. To further understand this relationship, subsequent firefighting-based research is needed that investigates whether immune changes are a function of affective arousal linked to the expression of positive moods. Positive associations between negative mood and inflammatory and cortisol levels to physical work and restricted sleep provide useful information to fire agencies about subjective fire-ground indicators of physiological changes. PMID:26698865

  12. Mice Deficient in Interferon-Gamma or Interferon-Gamma Receptor 1 Have Distinct Inflammatory Responses to Acute Viral Encephalomyelitis

    PubMed Central

    Lee, Eun-Young; Schultz, Kimberly L. W.; Griffin, Diane E.

    2013-01-01

    Interferon (IFN)-gamma is an important component of the immune response to viral infections that can have a role both in controlling virus replication and inducing inflammatory damage. To determine the role of IFN-gamma in fatal alphavirus encephalitis, we have compared the responses of wild type C57BL/6 (WTB6) mice with mice deficient in either IFN-gamma (GKO) or the alpha-chain of the IFN-gamma receptor (GRKO) after intranasal infection with a neuroadapted strain of sindbis virus. Mortalities of GKO and GRKO mice were similar to WTB6 mice. Both GKO and GRKO mice had delayed virus clearance from the brain and spinal cord, more infiltrating perforin+ cells and lower levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 mRNAs than WTB6 mice. However, inflammation was more intense in GRKO mice than WTB6 or GKO mice with more infiltrating CD3+ T cells, greater expression of major histocompatibility complex-II and higher levels of interleukin-17A mRNA. Fibroblasts from GRKO embryos did not develop an antiviral response after treatment with IFN-gamma, but showed increases in TNF-alpha, IL-6, CXCL9 and CXCL10 mRNAs although these increases developed more slowly and were less intense than those of WTB6 fibroblasts. These data indicate that both GKO and GRKO mice fail to develop an IFN-gamma-mediated antiviral response, but differ in regulation of the inflammatory response to infection. Therefore, GKO and GRKO cannot be considered equivalent when assessing the role of IFN-gamma in CNS viral infections. PMID:24204622

  13. A selected reaction monitoring-based analysis of acute phase proteins in interstitial fluids from experimental equine wounds healing by secondary intention.

    PubMed

    Bundgaard, Louise; Bendixen, Emøke; Sørensen, Mette Aa; Harman, Victoria M; Beynon, Robert J; Petersen, Lars J; Jacobsen, Stine

    2016-05-01

    In horses, pathological healing with formation of exuberant granulation tissue (EGT) is a particular problem in limb wounds, whereas body wounds tend to heal without complications. Chronic inflammation has been proposed to be central to the pathogenesis of EGT. This study aimed to investigate levels of inflammatory acute phase proteins (APPs) in interstitial fluid from wounds in horses. A novel approach for absolute quantification of proteins, selected reaction monitoring (SRM)-based mass spectrometry in combination with a quantification concatamer (QconCAT), was used for the quantification of five established equine APPs (fibrinogen, serum amyloid A, ceruloplasmin, haptoglobin, and plasminogen) and three proposed equine APPs (prothrombin, α-2-macroglobulin, and α-1-antitrypsin). Wound interstitial fluid was recovered by large pore microdialysis from experimental body and limb wounds from five horses at days 1, 2, 7, and 14 after wounding and healing without (body) and with (limb) the formation of EGT. The QconCAT included proteotypic peptides representing each of the protein targets and was used to direct the design of a gene, which was expressed in Escherichia coli in a media supplemented with stable isotopes for metabolically labeling of standard peptides. Co-analysis of wound interstitial fluid samples with the stable isotope-labeled QconCAT tryptic peptides in known amounts enabled quantification of the APPs in absolute terms. The concentrations of fibrinogen, haptoglobin, ceruloplasmin, prothrombin, and α-1-antitrypsin in dialysate from limb wounds were significantly higher than in dialysate from body wounds. This is the first report of simultaneous analysis of a panel of APPs using the QconCAT-SRM technology. The microdialysis technique in combination with the QconCAT-SRM-based approach proved useful for quantification of the investigated proteins in the wound interstitial fluid, and the results indicated that there is a state of sustained inflammation in

  14. Cellular and humoral immune reactions in chronic active liver disease. II. Lymphocyte subsets and viral antigens in liver biopsies of patients with acute and chronic hepatitis B.

    PubMed Central

    Eggink, H F; Houthoff, H J; Huitema, S; Wolters, G; Poppema, S; Gips, C H

    1984-01-01

    The characteristics and distribution of the inflammatory infiltrate in liver biopsies of 25 patients with hepatitis B viral (HBV) infection were studied in relation to the distribution and expression of HBV antigens. Mononuclear subsets were characterized with monoclonal (OKT, OKM, Leu) antibodies to surface antigens. For the demonstration of viral antigens directly conjugated antibodies to surface (HBsAg), core (HBcAg) and 'e' (HBeAg) antigen were used. For the study of mutual relations all methods were performed on serial cut tissue sections. In chronic active hepatitis B (CAH-B, n = 12) OKT8+ lymphocytes of T cell origin were the only cell type present in areas with liver cell degeneration and T cell cytotoxicity appears to be the only immune mechanism. In chronic persistent hepatitis B (CPH-B, n = 7) the only conspicuous feature was the presence of many Leu 3+ lymphocytes of the helper/inducer population in the portal tracts. In acute hepatitis B (AHB, n = 6) OKT8+ cells of non-T origin (OKT1-,3-) and Leu 7+ cells of presumed natural killer (NK) potential predominated in the areas with liver cell necrosis, and non-T cell cytotoxicity appears to be the predominant immune mechanism. In none of these disease entities a positive spatial relation could be established between the cytotoxic cells and the demonstrable expression of HBV antigens in hepatocytes. It is concluded that differences in immunological reaction pattern may explain the different course in the three forms of HBV infection studied. Images Fig. 1 Fig. 2 PMID:6713726

  15. Demonstration of correlations between the 8 and 10 kHz atmospherics and the inflammatory reaction of rats after carrageenan injection

    NASA Astrophysics Data System (ADS)

    Ruhenstroth-Bauer, Gerhard; Rösing, Olga; Baumer, Hans; Sönning, Walter; Lehmacher, Walter

    1988-09-01

    Between the mean daily density of 28 kHz atmospherics and the onset of epileptic fits there is a highly significant correlation coefficient ( r) of 0.30; there is a negative coefficient of -0.20 between the fits and the mean daily density of 10 kHz atmospherics. The onset of heart infarction is correlated with 28 kHz atmospherics ( r=0.15). Furthermore, we have discovered that sudden deafness is also correlated with certain configurations of atmospherics. In this paper we report the following correlation coefficients between the inflammatory reaction of rats to a carrageenan injection (rci) into a hind paw and the mean daily pulse rate of atmospherics of the same day: r=0.49 for the 8 kHz atmospherics ( P<0.02) and r=0.44 for the 10 kHz atmospherics ( P<0.04). The correlations between rci reaction and other atmospherics (12 and 28 kHz) are smaller and not significant. By the method of multiple linear regression we found a multiple R=0.54 between rci reaction and the 8 and 10 kHz atmospherics (the regression function for the rci reaction is 0.15+0.004×8 kHz+0.002×10 kHz, P<0.05).

  16. Effects of arachidonic acid intake on inflammatory reactions in dextran sodium sulphate-induced colitis in rats.

    PubMed

    Naito, Yukiko; Ji, Xu; Tachibana, Shigehiro; Aoki, Satoko; Furuya, Mami; Tazura, Yoshiyuki; Miyazawa, Daisuke; Harauma, Akiko; Moriguchi, Toru; Nagata, Tomoko; Iwai, Naoharu; Ohara, Naoki

    2015-09-14

    The aim of this study was to investigate the effects of the administration of oral arachidonic acid (AA) in rats with or without dextran sulphate sodium (DSS)-induced inflammatory bowel disease. Male Wistar rats were administered AA at 0, 5, 35 or 240 mg/kg daily by gavage for 8 weeks. Inflammatory bowel disease was induced by replacing drinking water with 3 % DSS solution during the last 7 d of the AA dosing period. These animals passed loose stools, diarrhoea and red-stained faeces. Cyclo-oxygenase-2 concentration and myeloperoxidase activity in the colonic tissue were significantly increased in the animals given AA at 240 mg/kg compared with the animals given AA at 0 mg/kg. Thromboxane B2 concentration in the medium of cultured colonic mucosae isolated from these groups was found to be dose-dependently increased by AA, and the increase was significant at 35 and 240 mg/kg. Leukotriene B4 concentration was also significantly increased and saturated at 5 mg/kg. In addition, AA at 240 mg/kg promoted DSS-induced colonic mucosal oedema with macrophage infiltration. In contrast, administration of AA for 8 weeks, even at 240 mg/kg, showed no effects on the normal rats. These results suggest that in rats with bowel disease AA metabolism is affected by oral AA, even at 5 mg/kg per d, and that excessive AA may aggravate inflammation, whereas AA shows no effects in rats without inflammatory bowel disease. PMID:26234346

  17. Anti-inflammatory mechanisms of apolipoprotein A-I mimetic peptide in acute respiratory distress syndrome secondary to sepsis.

    PubMed

    Sharifov, Oleg F; Xu, Xin; Gaggar, Amit; Grizzle, William E; Mishra, Vinod K; Honavar, Jaideep; Litovsky, Silvio H; Palgunachari, Mayakonda N; White, C Roger; Anantharamaiah, G M; Gupta, Himanshu

    2013-01-01

    Acute respiratory distress syndrome (ARDS) due to sepsis has a high mortality rate with limited treatment options. High density lipoprotein (HDL) exerts innate protective effects in systemic inflammation. However, its role in ARDS has not been well studied. Peptides such as L-4F mimic the secondary structural features and functions of apolipoprotein (apo)A-I, the major protein component of HDL. We set out to measure changes in HDL in sepsis-mediated ARDS patients, and to study the potential of L-4F to prevent sepsis-mediated ARDS in a rodent model of lipopolysaccharide (LPS)-mediated acute lung injury, and a combination of primary human leukocytes and human ARDS serum. We also analyzed serum from non-lung disease intubated patients (controls) and sepsis-mediated ARDS patients. Compared to controls, ARDS demonstrates increased serum endotoxin and IL-6 levels, and decreased HDL, apoA-I and activity of anti-oxidant HDL-associated paraoxanase-1. L-4F inhibits the activation of isolated human leukocytes and neutrophils by ARDS serum and LPS in vitro. Further, L-4F decreased endotoxin activity and preserved anti-oxidant properties of HDL both in vitro and in vivo. In a rat model of severe endotoxemia, L-4F significantly decreased mortality and reduces lung and liver injury, even when administered 1 hour post LPS. Our study suggests the protective role of the apoA-I mimetic peptide L-4F in ARDS and gram-negative endotoxemia and warrant further clinical evaluation. The main protective mechanisms of L-4F are due to direct inhibition of endotoxin activity and preservation of HDL anti-oxidant activity. PMID:23691230

  18. Acute Effects of Dietary Fat on Inflammatory Markers and Gene Expression in First-Degree Relatives of Type 2 Diabetes Patients

    PubMed Central

    Pietraszek, Anna; Gregersen, Søren; Hermansen, Kjeld

    2011-01-01

    BACKGROUND: Subjects with type 2 diabetes (T2D) and their relatives (REL) carry an increased risk of cardiovascular disease (CVD). Low-grade inflammation, an independent risk factor for CVD, is modifiable by diet. Subjects with T2D show elevated postprandial inflammatory responses to fat-rich meals, while information on postprandial inflammation in REL is sparse. AIM: To clarify whether medium-chain saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) have differential acute effects on low-grade inflammation in REL compared to controls (CON). METHODS: In randomized order, 17 REL and 17 CON ingested two fat-rich meals, with 72 energy percent from MUFA and 79 energy percent from mainly medium-chain SFA, respectively. Plasma high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), adiponectin, and leptin were measured at baseline, 15 min, 60 min, and 240 min postprandially. Muscle and adipose tissue biopsies were taken at baseline and 210 min after the test meal, and expression of selected genes was analyzed. RESULTS: Plasma IL-6 increased (p < 0.001) without difference between REL and CON and between the meals, whereas plasma adiponectin and plasma hs-CRP were unchanged during the 240 min observation period. Plasma leptin decreased slightly in response to medium-chain SFA in both groups, and to MUFA in REL. Several genes were differentially regulated in muscle and adipose tissue of REL and CON. CONCLUSIONS: MUFA and medium-chain SFA elicit similar postprandial circulating inflammatory responses in REL and CON. Medium-chain SFA seems more proinflammatory than MUFA, judged by the gene expression in muscle and adipose tissue of REL and CON. PMID:22580729

  19. Plant Derived Aporphinic Alkaloid S-(+)-Dicentrine Induces Antinociceptive Effect in Both Acute and Chronic Inflammatory Pain Models: Evidence for a Role of TRPA1 Channels

    PubMed Central

    Montrucchio, Deise Prehs; Córdova, Marina Machado; Soares Santos, Adair Roberto

    2013-01-01

    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. PMID:23861794

  20. Extracellular membrane vesicles from umbilical cord blood-derived MSC protect against ischemic acute kidney injury, a feature that is lost after inflammatory conditioning

    PubMed Central

    Kilpinen, Lotta; Impola, Ulla; Sankkila, Lotta; Ritamo, Ilja; Aatonen, Maria; Kilpinen, Sami; Tuimala, Jarno; Valmu, Leena; Levijoki, Jouko; Finckenberg, Piet; Siljander, Pia; Kankuri, Esko; Mervaala, Eero; Laitinen, Saara

    2013-01-01

    Background Mesenchymal stromal cells (MSC) are shown to have a great therapeutic potential in many immunological disorders. Currently the therapeutic effect of MSCs is considered to be mediated via paracrine interactions with immune cells. Umbilical cord blood is an attractive but still less studied source of MSCs. We investigated the production of extracellular membrane vesicles (MVs) from human umbilical cord blood derived MSCs (hUCBMSC) in the presence (MVstim) or absence (MVctrl) of inflammatory stimulus. Methods hUCBMSCs were cultured in serum free media with or without IFN-γ and MVs were collected from conditioned media by ultracentrifugation. The protein content of MVs were analyzed by mass spectrometry. Hypoxia induced acute kidney injury rat model was used to analyze the in vivo therapeutic potential of MVs and T-cell proliferation and induction of regulatory T cells were analyzed by co-culture assays. Results Both MVstim and MVctrl showed similar T-cell modulation activity in vitro, but only MVctrls were able to protect rat kidneys from reperfusion injury in vivo. To clarify this difference in functionality we made a comparative mass spectrometric analysis of the MV protein contents. The IFN-γ stimulation induced dramatic changes in the protein content of the MVs. Complement factors (C3, C4A, C5) and lipid binding proteins (i.e apolipoproteins) were only found in the MVctrls, whereas the MVstim contained tetraspanins (CD9, CD63, CD81) and more complete proteasome complex accompanied with MHCI. We further discovered that differently produced MV pools contained specific Rab proteins suggesting that same cells, depending on external signals, produce vesicles originating from different intracellular locations. Conclusions We demonstrate by both in vitro and in vivo models accompanied with a detailed analysis of molecular characteristics that inflammatory conditioning of MSCs influence on the protein content and functional properties of MVs revealing the

  1. Acute hemolytic transfusion reactions due to multiple alloantibodies including anti-E, anti-c and anti-Jkb.

    PubMed

    Park, Tae Sung; Kim, Ki Uk; Jeong, Woo Jin; Kim, Hyung Hoi; Chang, Chulhun L; Chung, Joo Seop; Cho, Goon Jae; Lee, Eun Yup; Son, Han Chul

    2003-12-01

    We report a case of two consecutive episodes of acute hemolytic transfusion reactions (HTRs) due to multiple alloantibodies in a 34-yr-old man who suffered from avascular necrosis of left femoral head. He received five units of packed red blood cells (RBCs) during surgery. Then the transfusion of packed RBCs was required nine days after the surgery because of the unexplained drop in hemoglobin level. The transfusion of the first two units resulted in fever and brown-colored urine, but he received the transfusion of another packed RBCs the next day. He experienced even more severe symptoms during the transfusion of the first unit. We performed antibody screening test, and it showed positive results. Multiple alloantibodies including anti-E, anti-c and anti-Jkb were detected by antibody identification study. Acute HTRs due to multiple alloantibodies were diagnosed, and the supportive cares were done for 6 days. We suggest the antibody screening test should be included in the panel of pretransfusion tests for safer transfusion, and it is particularly mandatory for the patients with multiple transfusions, pregnant women, and preoperative patients. PMID:14676451

  2. [Effect of training on treadmill performance, aerobic capacity and body reactions to acute cold exposure].

    PubMed

    Iakushkin, A V; Akimov, E B; Andreev, R S; Kalenov, Iu N; Kozlov, A V; Kuznetsova, O V; Son'kin, V D

    2014-01-01

    An attempt was made to test the hypothesis that regular physical activity at the anaerobic threshold is able to stimulate an increase in the amount of body fat brown or beige, which can manifest itself in increasing lactate utilization during exercise and increase the reactivity in response to acute regional cooling. The methods used are: ramp test, regional acute cold exposure, measurement of gas exchange, lactate and glucose in the blood, heart rate, and heart rate variability, blood pressure and respiration variability at rest and during standard functional tests; infrared thermal imaging, statistical methods of results analysis. Workout 10 physically active volunteers (7 males and 3 females) on a treadmill at a speed corresponding to 75-80% of the persona VO2max for 30 minutes 3 times per week at a fixed ambient temperature 21-22°C for 6 weeks resulted in a significant (from 19 to 39%) increase in test work duration but VO2max on average changed little. The increase in power of anaerobic threshold was associated with a sharp slowdown in the accumulation of lactate in progress of ramp test. Lactate utilization rate during the recovery period, on the contrary, increased. In general, significantly increased work efficiency at a test load. Not revealed noticeable changes in the condition and response to a standard functional tests of autonomic systems, as judged by heart rate variability, blood pressure and respiration variability at rest and during orthostatic tests and imposed breathing rhythm. The functional response of the body to acute cold exposure (1 minute cooling of the feet in ice water) is not changed after a cycle of training--either in terms of metabolism (oxygen consumption, etc.), or the dynamics of the skin temperature in areas of most probable location of brown adipose tissue (BAT). These data do not confirm the previously expressed (2010) hypothesis about the function of BAT as a universal homeostatic instrument in the body. Probably, if under

  3. Analgesic effect of percutaneously absorbed non-steroidal anti-inflammatory drugs: an experimental study in a rat acute inflammation model

    PubMed Central

    Sekiguchi, Miho; Shirasaka, Masayoshi; Konno, Shin-ichi; Kikuchi, Shin-ichi

    2008-01-01

    Background External medication that is absorbed percutaneously may be used to reduce inflammation and relieve pain from acute injuries such as ankle sprains and bruises. The plaster method of percutaneous absorption for non-steroidal anti-inflammatory drugs (NSAIDs) was established in Japan in 1988. However, due to the possibility of a placebo effect, the efficacy of this method remains unclear. This experimental study was conducted to control for the placebo effect and to study the efficacy of the plaster method in relieving pain by using a rat model of inflammation. Methods Male Wistar-Imamichi rats were used. A yeast suspension was injected into the right hind paw to induce inflammation. A sheet (2.0 × 1.75 cm) containing the drug was adhered to the inflamed paw. Five treatment groups were used, and each sheet contained a single drug: loxoprofen sodium (loxoprofen-Na) (2.5 mg); felbinac (1.75 mg); indomethacin (1.75 mg); ketoprofen (0.75 mg); or base only (control, 0 mg). Mechanical pain threshold, expression of c-Fos in the dorsal horn, and amount of prostaglandin (PG) E2 in the inflamed paw were evaluated. Results Pain threshold increased after treatment, and was significantly increased in the loxoprofen-Na group compared with the control group (p < 0.05). Amounts of PGE2 were significantly decreased in the loxoprofen-Na and indomethacin groups compared with the control group (p < 0.05). Expression of c-Fos was significantly decreased in the loxoprofen-Na group compared with the control group (p < 0.05). Conclusion Percutaneously absorbed NSAIDs have an analgesic effect, inhibit expression of c-Fos in the dorsal horn, and reduce PGE2 in inflamed tissue, indicating the efficacy of this method of administration for acute inflammation and localized pain. PMID:18234123

  4. Reduction of Acute Inflammatory Effects of Fumed Silica Nanoparticles in the Lung by Adjusting Silanol Display through Calcination and Metal Doping.

    PubMed

    Sun, Bingbing; Pokhrel, Suman; Dunphy, Darren R; Zhang, Haiyuan; Ji, Zhaoxia; Wang, Xiang; Wang, Meiying; Liao, Yu-Pei; Chang, Chong Hyun; Dong, Juyao; Li, Ruibin; Mädler, Lutz; Brinker, C Jeffrey; Nel, André E; Xia, Tian

    2015-09-22

    The production of pyrogenic (fumed) silica is increasing worldwide at a 7% annual growth rate, including expanded use in food, pharmaceuticals, and other industrial products. Synthetic amorphous silica, including fumed silica, has been generally recognized as safe for use in food products by the Food and Drug Administration. However, emerging evidence from experimental studies now suggests that fumed silica could be hazardous due to its siloxane ring structure, high silanol density, and "string-of-pearl-like" aggregate structure, which could combine to cause membrane disruption, generation of reactive oxygen species, pro-inflammatory effects, and liver fibrosis. Based on this structure-activity analysis (SAA), we investigated whether calcination and rehydration of fumed silica changes its hazard potential in the lung due to an effect on silanol density display. This analysis demonstrated that the accompanying change in surface reactivity could indeed impact cytokine production in macrophages and acute inflammation in the lung, in a manner that is dependent on siloxane ring reconstruction. Confirmation of this SAA in vivo, prompted us to consider safer design of fumed silica properties by titanium and aluminum doping (0-7%), using flame spray pyrolysis. Detailed characterization revealed that increased Ti and Al doping could reduce surface silanol density and expression of three-membered siloxane rings, leading to dose-dependent reduction in hydroxyl radical generation, membrane perturbation, potassium efflux, NLRP3 inflammasome activation, and cytotoxicity in THP-1 cells. The reduction of NLRP3 inflammasome activation was also confirmed in bone-marrow-derived macrophages. Ti doping, and to a lesser extent Al doping, also ameliorated acute pulmonary inflammation, demonstrating the possibility of a safer design approach for fumed silica, should that be required for specific use circumstances. PMID:26200133

  5. Sevoflurane Inhibits Nuclear Factor-κB Activation in Lipopolysaccharide-Induced Acute Inflammatory Lung Injury via Toll-Like Receptor 4 Signaling

    PubMed Central

    Sun, Xi Jia; Li, Xiao Qian; Wang, Xiao Long; Tan, Wen Fei; Wang, Jun Ke

    2015-01-01

    Background Infection is a common cause of acute lung injury (ALI). This study was aimed to explore whether Toll-like receptors 4 (TLR4) of airway smooth muscle cells (ASMCs) play a role in lipopolysaccharide (LPS)-induced airway hyperresponsiveness and potential mechanisms. Methods In vivo: A sensitizing dose of LPS (50 µg) was administered i.p. to female mice before anesthesia with either 3% sevoflurane or phenobarbital i.p. After stabilization, the mice were challenged with 5 µg of intratracheal LPS to mimic inflammatory attack. The effects of sevoflurane were assessed by measurement of airway responsiveness to methacholine, histological examination, and IL-1, IL-6, TNF-α levels in bronchoalveolar lavage fluid (BALF). Protein and gene expression of TLR4 and NF-κB were also assessed. In vitro: After pre-sensitization of ASMCs and ASM segments for 24h, levels of TLR4 and NF-κB proteins in cultured ASMCs were measured after continuous LPS exposure for 1, 3, 5, 12 and 24h in presence or absence of sevoflurane. Constrictor and relaxant responsiveness of ASM was measured 24 h afterwards. Results The mRNA and protein levels of NF-κB and TLR4 in ASM were increased and maintained at high level after LPS challenge throughout 24h observation period, both in vivo and in vitro. Sevoflurane reduced LPS-induced airway hyperresponsiveness, lung inflammatory cell infiltration and proinflammatory cytokines release in BALF as well as maximal isometric contractile force of ASM segments to acetylcholine, but it increased maximal relaxation response to isoproterenol. Treatment with specific NF-κB inhibitor produced similar protections as sevoflurane, including decreased expressions of TLR4 and NF-κB in cultured ASMCs and improved pharmacodynamic responsiveness of ASM to ACh and isoproterenol. Conclusions This study demonstrates the crucial role of TLR4 activation in ASMCs during ALI in response to LPS. Sevoflurane exerts direct relaxant and anti-inflammatory effects in vivo

  6. Acute and long-term effect of percutaneous coronary intervention on serially-measured oxidative, inflammatory, and coagulation biomarkers in patients with stable angina.

    PubMed

    Leibundgut, Gregor; Lee, Jun-Hee; Strauss, Bradley H; Segev, Amit; Tsimikas, Sotirios

    2016-05-01

    To derive insights into the temporal changes in oxidative, inflammatory and coagulation biomarkers in patients with stable angina undergoing percutaneous coronary intervention (PCI). PCI is associated with a variety of biochemical and mechanical stresses to the vessel wall. Oxidized phospholipids are present on plasminogen (OxPL-PLG) and potentiate fibrinolysis in vitro. We recently showed that OxPL-PLG increase following acute myocardial infarction, suggesting that they are involved in atherothrombosis. Plasma samples were collected before, immediately after, 6 and 24 h, 3 and 7 days, and 1, 3, and 6 months after PCI in 125 patients with stable angina undergoing uncomplicated PCI. Plasminogen levels, OxPL-PLG, and an array of 16 oxidative, inflammatory and coagulation biomarkers were measured with established assays. OxPL-PLG and plasminogen declined significantly immediately post-PCI, rebounded to baseline, peaked at 3 days and slowly returned to baseline by 6 months (p < 0.0001 by ANOVA). The temporal trends to maximal peak in biomarkers were as follows: immediately post PCI: OxPL-apoB and lipoprotein (a); Day 1-the inflammatory biomarker IL-6; Day 3-CRP and coagulation biomarkers OxPL-PLG, plasminogen and tissue plasminogen activity; Day 3 to 7-plasminogen activator inhibitor activity, and complement factor H binding to malondialdehyde-LDL and MDA-LDL IgG; Day 7-30 MDA-LDL IgM, CuOxLDL IgM, and ApoB-IC IgM and IgG; >30 days uPA activity, uPA antigen, CuOxLDL IgG and peptide mimotope to MDA-LDL. Most of the biomarkers trended to baseline by 6 months. PCI results in a specific, temporal sequence of changes in plasma biomarkers. These observations provide insights into the effects of iatrogenic barotrauma and plaque disruption during PCI and suggest avenues of investigation to explain complications of PCI and development of targeted therapies to enhance procedural success. PMID:26964999

  7. Effect of low-level laser therapy on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation

    PubMed Central

    2013-01-01

    Introduction Inflammation of the synovial membrane plays an important role in the pathophysiology of osteoarthritis (OA). The synovial tissue of patients with initial OA is characterized by infiltration of mononuclear cells and production of proinflammatory cytokines and other mediators of joint injury. The objective was to evaluate the effect of low-level laser therapy (LLLT) operating at 50 mW and 100 mW on joint inflammation in rats induced by papain, through histopathological analysis, differential counts of inflammatory cells (macrophages and neutrophils), as well as gene expression of interleukin 1-beta and 6 (IL-1β and IL-6), and protein expression of tumor necrosis factor alpha (TNFα). Methods Male Wistar rats (n = 60) were randomly divided into four groups of 15 animals, namely: a negative control group; an inflammation injury positive control group; a 50 mW LLLT group, subjected to injury and treated with 50 mW LLLT; and a 100 mW LLLT group, subjected to injury and treated with 100 mW LLLT. The animals were subject to joint inflammation (papain solution, 4%) and then treated with LLLT (808 nm, 4 J, 142.4 J/cm2, spot size 0.028 for both groups). On the day of euthanasia, articular lavage was collected and immediately centrifuged; the supernatant was saved for analysis of expression of TNFα protein by enzyme-linked immunosorbent assay and expression of IL-1β and IL-6 mRNA by real-time polymerase chain reaction. A histologic examination of joint tissue was also performed. For the statistical analysis, analysis of variance with Tukey's post-hoc test was used for comparisons between each group. All data are expressed as mean values and standard deviation, with P < 0.05. Results Laser treatment with 50 mW was more efficient than 100 mW in reducing cellular inflammation, and decreased the expression of IL-1β and IL-6. However, the 100 mW treatment led to a higher reduction of TNFα compared with the 50 mW treatment. Conclusions LLLT with 50 mW was more

  8. Suspected acute hemolytic transfusion reaction mediated by anti-Di(a).

    PubMed

    Bennett, Ashwini; Boyapati, Ray K; Hong, Frank S

    2015-01-01

    Anti-Di(a) can mediate hemolytic disease of the fetus and newborn, but it is unclear if it can cause hemolytic transfusion reactions (HTRs). To date, there has only been one report of a possible immediate HTR attributed to anti-Di(a). Our case report details an immediate HTR due to anti-Di(a) in a patient with pre-existing liver failure. This reaction triggered multi-organ failure, and the patient subsequently died. This case also highlights the importance of considering HTRs even when routine antibody screening has been unremarkable, particularly when electronic crossmatch is used, because of the potential for an alloantibody against a low-prevalence antigen. PMID:27187197

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

    PubMed Central

    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

  10. Anti‑inflammatory effects of Panax notoginseng saponins ameliorate acute lung injury induced by oleic acid and lipopolysaccharide in rats.

    PubMed

    Chen, Yu-Qing; Rong, Ling; Qiao, Jian-Ou

    2014-09-01

    This study investigated the effect of Panax notoginseng saponins (PNS) on acute lung injury (ALI) induced by oleic acid (OA) and lipopolysaccharide (LPS). A total of 28 Wistar rats were divided into four groups: sham; sham + PNS; OA‑LPS‑induced ALI and ALI + PNS. Lung tissue histology, lung wet‑to‑dry (W/D) weight ratio, extravascular lung water (EVLW) and epithelial sodium channel α (αENaC) mRNA and protein expression were examined. In addition, levels of inflammatory cytokines, including tumor necrosis factor α (TNF‑α), interleukin (IL)‑6 and IL‑10, as well as total leukocyte and neutrophil counts, were analyzed in rat bronchoalveolar lavage fluid (BALF) and serum. ALI + PNS rats were observed to exhibit significantly lower pulmonary parenchymal damage and EVLW compared with ALI rats. Furthermore, total leukocyte and neutrophil counts, and levels of inflammatory cytokines were significantly decreased following PNS administration in ALI rats. In addition, the decrease in αENaC mRNA and protein expression observed in the lung tissue of ALI rats was partially restored following PNS treatment. PNS treatment was demonstrated to ameliorate OA‑LPS‑induced ALI, potentially through restoration of αENaC mRNA and protein expression and through PNS‑induced anti‑inflammatory effects. PMID:24938646

  11. Acute exposure to waterpipe tobacco smoke induces changes in the oxidative and inflammatory markers in mouse lung

    PubMed Central

    Khabour, Omar F.; Alzoubi, Karem H.; Bani-Ahmad, Mohammed; Dodin, Arwa; Eissenberg, Thomas; Shihadeh, Alan

    2013-01-01

    Context Tobacco smoking represents a global public health threat, claiming approximately 5 million lives a year. Waterpipe tobacco use has become popular particularly among youth in the past decade, buttressed by the perception that the waterpipe “filters” the smoke, rendering it less harmful than cigarette smoke. Objective In this study, we examined the acute exposure of waterpipe smoking on lung inflammation and oxidative stress in mice, and compared that to cigarette smoking. Materials and methods Mice were divided into three groups; fresh air control, cigarette and waterpipe. Animals were exposed to fresh air, cigarette, or waterpipe smoke using whole body exposure system one hour daily for 7 days. Results Both cigarette and waterpipe smoke exposure resulted in elevation of total white blood cell count, as well as absolute count of neutrophils, macrophages, and lymphocytes (P < 0.01). Both exposures also elevated proinflammatory markers such as TNF-α and IL-6 in BALF (P < 0.05), and oxidative stress markers including GPx activity in lungs (P < 0.05). Moreover, waterpipe smoke increased catalase activity in the lung (P < 0.05). However, none of the treatments altered IL-10 levels. Discussion and conclusion Results of cigarette smoking confirmed previous finding. Waterpipe results indicate that, similar to cigarettes, exposure to waterpipe tobacco smoke is harmful to the lungs. PMID:22906173

  12. Intense Inflammatory Reaction to Heparin Polymer Coated Intravascular Palmaz Stents in Porcine Arteries Compared to Uncoated Palmaz Stents

    SciTech Connect

    Goodwin, Scott C.; Yoon, Hyo-Chun; Chen, Gary; Abdel-Sayed, Peter; Costantino, Mary M.; Bonilla, Sheila M.; Nishimura, Earl

    2003-04-15

    The objective of this study was to evaluate the efficacy of heparin-polymer-coated intravascular stents in the reduction of vessel stenosis. Three types of coatings for Palmaz stents were tested: 1) heparin covalently bound to a polyethylene oxide(Hp-PEO) tether; 2) heparin copolymerized with ethylene vinyl acetate(Hp-Elvax) and 3) Elvax alone. Polymer-coated stents and uncoated controls were deployed in the external iliac arteries following endothelial injury in 18 swine. The animals were maintained on anatherogenic diet and examined by angiography at 6 and 12 weeks. The stented segments were then harvested for histopathologic analysis. Both types of heparin-coated stents resulted in increased luminal narrowing as compared to the contralateral uncoated stents. At 6 weeks, average luminal stenosis was 48% for Hp-PEO stents vs 35% for uncoated stents (p < 0.05). At 12 weeks, average luminal stenosis was 36% for Hp-PEO stents vs 26% for uncoated stents(p = NS). For Hp-Elvax stents, the average stenosis was 58% vs 33% for uncoated controls (p <0.05) at 6 weeks and 47% vs 19% for uncoated controls(p < 0.05) at 12 weeks. There was no significant difference between Hp-Elvax stents and Elvax stents(p = NS). Increased luminal narrowing in coated stents was primarily secondary to a marked inflammatory response.Heparin-polyethylene oxide and heparin-ethylene vinyl acetate-coated stents resulted in increased luminal narrowing as compared with uncoated stents, due to a marked inflammatory response.

  13. Dystonia as acute adverse reaction to cough suppressant in a 3-year-old girl.

    PubMed

    Polizzi, A; Incorpora, G; Ruggieri, M

    2001-01-01

    Cough suppressant preparations containing mixtures of dextromethorphan or codeine with antihistamines, decongestants (sympathomimetic), expectorants and antipyretics with either sedative or anticholinergic activity have been associated with dystonic reactions in children. We report on a 3-year-old girl who presented with episodic stiffness and abnormal posturing with rigidity after arbitrary maternal administration of a mixture of methylcodeine and extract from Hedera plant. PMID:11587381

  14. Non-Steroidal Anti-Inflammatory Drugs and Aspirin Therapy for the Treatment of Acute and Recurrent Idiopathic Pericarditis

    PubMed Central

    Schwier, Nicholas; Tran, Nicole

    2016-01-01

    Aspirin (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) are a mainstay of therapy for the treatment of idiopathic pericarditis (IP). A comprehensive review consisting of pertinent clinical literature, pharmacokinetic, and pharmacodynamic considerations, has not been released in recent years. This review will facilitate the clinician’s understanding of pharmacotherapeutic considerations for using ASA/NSAIDs to treat IP. Data were compiled using clinical literature consisting of case reports, cohort data, retrospective and prospective studies, and manufacturer package inserts. ASA, ibuprofen, indometacin, and ketorolac relatively have the most evidence in the treatment of IP, provide symptomatic relief of IP, and should be tapered accordingly. ASA is the drug of choice in patients with coronary artery disease (CAD), heart failure (HF), or renal disease, but should be avoided in patients with asthma and nasal polyps, who are naïve to ASA therapy. Ibuprofen is an inexpensive and relatively accessible option in patients who do not have concomitant CAD, HF, or renal disease. Indometacin is not available over-the-counter in the USA, and has a relatively higher incidence of central nervous system (CNS) adverse effects. Ketorolac is an intravenous option; however, clinicians must be mindful of the maximum dose that can be administered. While ASA/NSAIDs do not ameliorate the disease process of IP, they are part of first-line therapy (along with colchicine), for preventing recurrence of IP. ASA/NSAID choice should be dictated by comorbid conditions, tolerability, and adverse effects. Additionally, the clinician should be mindful of considerations such as tapering, high-sensitivity CRP monitoring, bleeding risk, and contraindications to ASA/NSAID therapy. PMID:27023565

  15. Non-Steroidal Anti-Inflammatory Drugs and Aspirin Therapy for the Treatment of Acute and Recurrent Idiopathic Pericarditis.

    PubMed

    Schwier, Nicholas; Tran, Nicole

    2016-01-01

    Aspirin (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) are a mainstay of therapy for the treatment of idiopathic pericarditis (IP). A comprehensive review consisting of pertinent clinical literature, pharmacokinetic, and pharmacodynamic considerations, has not been released in recent years. This review will facilitate the clinician's understanding of pharmacotherapeutic considerations for using ASA/NSAIDs to treat IP. Data were compiled using clinical literature consisting of case reports, cohort data, retrospective and prospective studies, and manufacturer package inserts. ASA, ibuprofen, indometacin, and ketorolac relatively have the most evidence in the treatment of IP, provide symptomatic relief of IP, and should be tapered accordingly. ASA is the drug of choice in patients with coronary artery disease (CAD), heart failure (HF), or renal disease, but should be avoided in patients with asthma and nasal polyps, who are naïve to ASA therapy. Ibuprofen is an inexpensive and relatively accessible option in patients who do not have concomitant CAD, HF, or renal disease. Indometacin is not available over-the-counter in the USA, and has a relatively higher incidence of central nervous system (CNS) adverse effects. Ketorolac is an intravenous option; however, clinicians must be mindful of the maximum dose that can be administered. While ASA/NSAIDs do not ameliorate the disease process of IP, they are part of first-line therapy (along with colchicine), for preventing recurrence of IP. ASA/NSAID choice should be dictated by comorbid conditions, tolerability, and adverse effects. Additionally, the clinician should be mindful of considerations such as tapering, high-sensitivity CRP monitoring, bleeding risk, and contraindications to ASA/NSAID therapy. PMID:27023565

  16. Anti-inflammatory effect of Moringa oleifera Lam. seeds on acetic acid-induced acute colitis in rats

    PubMed Central

    Minaiyan, Mohsen; Asghari, Gholamreza; Taheri, Diana; Saeidi, Mozhgan; Nasr-Esfahani, Salar

    2014-01-01

    Objective: Anti-inflammatory, immuno-modulatory, and antioxidant properties of Moringa oleifera Lam. suggest that it might have beneficial effects on colitis. The present study was performed to investigate the anticolitis effect of Moringa oleifera seeds hydro-alcoholic extract (MSHE) and its chloroform fraction (MCF) on acetic acid-induced colitis in rats. Materials and Methods: Both MSHE and MCF with three increasing doses (50, 100, and 200 mg/kg) were administered orally to separate groups of male Wistar rats, 2 h before ulcer induction (using acetic acid 4%) and continued for 5 days. Prednisolone (4 mg/kg) and normal saline (1 ml/kg) were used in reference and control groups, respectively. All rats were sacrificed 24 h after the last dose (at day 6) and tissue injuries were assessed macroscopically and pathologically. Results: Extracts with three doses mentioned before were effective to reduce weight of distal colon (8 cm) as a marker for inflammation and tissue edema. Three doses of MSHE and two greater doses of MCF (100 and 200 mg/kg) were effective to reduce ulcer severity, area, and index as well as mucosal inflammation severity and extent, crypt damage, invasion involvement, total colitis index, and MPO activity compared with controls. MCF (50 mg/kg) was not significantly effective in reducing evaluated parameters of colitis compared with controls. Conclusion: It is concluded that MSHE and MCF were both effective to treat experimental colitis and this might be attributed to their similar major components, biophenols and flavonoids. Since the efficacy was evident even in low doses of MSHE, presence of active constituents with high potency in seeds is persuasive. PMID:25050310

  17. Evaluating the consistency of location of the most severe acute skin reaction and highest skin dose measured by thermoluminescent dosimeter during radiotherapy for breast cancer.

    PubMed

    Sun, Li-Min; Huang, Chih-Jen; Chen, Hsiao-Yun; Chang, Gia-Hsin; Tsao, Min-Jen

    2016-01-01

    We conducted this prospective study to evaluate whether the location of the most severe acute skin reaction matches the highest skin dose measured by thermoluminescent dosimeter (TLD) during adjuvant radiotherapy (RT) for patients with breast cancer after breast conservative surgery. To determine whether TLD measurement can reflect the location of the most severe acute skin reaction, 80 consecutive patients were enrolled in this prospective study. We divided the irradiated field into breast, axillary, inframammary fold, and areola/nipple areas. In 1 treatment session when obvious skin reaction occurred, we placed the TLD chips onto the 4 areas and measured the skin dose. We determined whether the highest measured skin dose area is consistent with the location of the most severe skin reaction. The McNemar test revealed that the clinical skin reaction and TLD measurement are more consistent when the most severe skin reaction occurred at the axillary area, and the p = 0.0108. On the contrary, TLD measurement of skin dose is less likely consistent with clinical observation when the most severe skin reaction occurred at the inframammary fold, breast, and areola/nipple areas (all the p > 0.05). Considering the common site of severe skin reaction over the axillary area, TLD measurement may be an appropriate way to predict skin reaction during RT. PMID:27158022

  18. Histocompatibility reaction in tissue and cells of the marine sponge Suberites domuncula in vitro and in vivo: central role of the allograft inflammatory factor 1.

    PubMed

    Müller, Werner E G; Krasko, Anatoli; Skorokhod, Alexander; Bünz, Christina; Grebenjuk, Vladislav A; Steffen, Renate; Batel, Renato; Schröder, Heinz C

    2002-04-01

    Sponges (Porifera) are the phylogenetically oldest still extant metazoan phylum. Recently elements of their immune system have been cloned and analyzed, primarily from the demosponges Suberites domuncula and Geodia cydonium. By differential display, two genes were identified in S. domuncula, whose translation products are involved in graft rejection/fusion: the allograft inflammatory factor (AIF-1) and the Tcf-like transcription factor (TCF). Since the AIF-1 and TCF genes are upregulated in vivo after tissue transplantation, especially in allografts, we investigated whether this reaction can be monitored in vitro. Therefore, the autogeneic and the allogeneic mixed sponge cell reaction (MSCR) system was applied for the first time to identify distinct factors in sponges in vitro. The results confirm that the two AIF-1 and TCF genes are induced during allogeneic MSCR. Furthermore, the recombinant sponge AIF-1 causes an upregulation of the expression of the TCF. We conclude that the AIF-1 and TCF genes are upregulated in sponges during histoincompatibility reactions; the data support the view that sponges have immune systems composed of highly complex elements related to those found in mammalian systems. PMID:11976791

  19. 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

    SciTech Connect

    Khalid, Usman; McGough, Camilla; Hackett, Claire; Blake, Peter; Harrington, Kevin J.; Khoo, Vincent S.; Tait, Diana; Norman, Andrew R.; Andreyev, H. Jervoise N. . E-mail: j@andreyev.demon.co.uk

    2006-04-01

    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.

  20. Inflammatory cytokine and acute phase protein concentrations in the peripheral blood and uterine washings of cows with subclinical endometritis in the late postpartum period.

    PubMed

    Brodzki, Piotr; Kostro, Krzysztof; Krakowski, Leszek; Marczuk, Jan

    2015-06-01

    The aim of the study was to evaluate the concentrations of proinflammatory cytokines: tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), anti-inflammatory cytokine interleukin-10 (IL-10), and acute phase proteins (APPs)--haptoglobin (Hp) and serum amyloid A (SAA) in serum and uterine washings of cows with subclinical endometritis, and compare them to healthy animals. The study was performed on 24 cows on day 60 after delivery. The cows were divided into two groups based on the results of cytological tests: 12 cows with subclinical endometritis and 12 healthy cows. Experimental material consisted of blood serum and uterine washings. The levels of the following cytokines in the study material were determined with ELISA: TNF-α, IL-6, IL-10 and APPs - Hp and SAA. The results show that the levels of TNF-α (p < 0.01), IL-6, IL-10 as well as SAA and Hp were significantly higher in the serum of cows with subclinical endometritis compared to the controls (p < 0.001). Uterine washings had significantly higher levels of IL-6, IL-10, and Hp in the experimental cows compared to the controls (p < 0.001). The demonstrated differences in the concentration of cytokines and APP between cows with subclinical endometritis and healthy cows, in both the serum and uterine washings, may suggest the usefulness of these parameters in the diagnosis of subclinical endometritis in cows in the late postpartum period. PMID:25846950

  1. Fish Oil-Based Fat Emulsion Reduces Acute Kidney Injury and Inflammatory Response in Antibiotic-Treated Polymicrobial Septic Mice

    PubMed Central

    Shih, Juey-Ming; Shih, Yao-Ming; Pai, Man-Hui; Hou, Yu-Chen; Yeh, Chiu-Li; Yeh, Sung-Ling

    2016-01-01

    Acute kidney injury (AKI) is a common complication in sepsis. This study compared the effects of a fish oil-based with a mixed oil fat emulsion on remote renal injury in an antibiotic-treated septic murine model. Mice were randomly assigned to a normal control (NC) group and three septic groups. Sepsis was induced by cecal ligation and puncture (CLP). The antibiotic was injected intraperitoneally (IP) after CLP and then daily till the time of sacrifice. Three hours after antibiotic treatment, one of the septic groups was injected IP with a fish oil-based emulsion (FO), while the other two groups were given either a mixed oil emulsion (MO) or saline (SC). The septic groups were further divided into two separate time groups, with blood and kidneys samples collected at 24 h or 72 h post-CLP. The results showed that sepsis leads to the activation of neutrophils, T helper (Th)1/Th-2/Th-17 and Treg cells (p < 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. PMID:26999192

  2. Low molecular weight heparin prevents CLP-induced acute lung injury in rats by anti-inflammatory coagulation.

    PubMed

    Lu, Xiao; Zhao, Liang; Xu, Yong-Hua

    2013-02-01

    The aim of our study was to observe the influence of low molecular Weight heparin (LMWH) on systemic inflammation, including high mobility group box 1 protein (HMGB1) and protective effect on acute lung injury induced by cecal ligation and puncture(CLP). Discuss the mechanism of this effect. 144 male SD rats were randomly divided into sham operation group (A), normal treatment group (B), the LMWH treatment group (C), n=48.Group A received a sham operation and the other groups were underwent CLP operation. Groups A and B accepted intraperitoneal injection (i.p.) of normal saline (NS) at a dose of 2.0 ml/kg and ceftriaxone (30 mg/kg), Group C were intraperitoneal injection additional LMWH (150 U/kg) except saline and ceftriaxone. Observe points were made at 3, 6, 12, 18, 24, 48 h, the rats were anesthetized and killed, mortality, lungs wet/dry ratio and Pathology change were determined. HMGB-1 mRNA, protein of lung tissues was calculated by RT-PCR and Western blot. TNF-α and IL-6 of blood plasma calculated by ELSIA. There was significantly different in each index between A and B group (p<0.05).Compared with CLP group, there was a significant decrease in the lung injury, the mortality, HMGB1 mRNA and protein expression on lung tissues (p<0.05). LMWH can decreases cytokine, HMGB1 levels of lung tissue during CLP-induced inflammation. As a result, LMWH ameliorated lung pathology and reduces mortality in CLP-induced systemic inflammation in a rat model. This effect may be mediated through the inhibition of axis of inflammation and coagulation. PMID:23448611

  3. Fish Oil-Based Fat Emulsion Reduces Acute Kidney Injury and Inflammatory Response in Antibiotic-Treated Polymicrobial Septic Mice.

    PubMed

    Shih, Juey-Ming; Shih, Yao-Ming; Pai, Man-Hui; Hou, Yu-Chen; Yeh, Chiu-Li; Yeh, Sung-Ling

    2016-03-01

    Acute kidney injury (AKI) is a common complication in sepsis. This study compared the effects of a fish oil-based with a mixed oil fat emulsion on remote renal injury in an antibiotic-treated septic murine model. Mice were randomly assigned to a normal control (NC) group and three septic groups. Sepsis was induced by cecal ligation and puncture (CLP). The antibiotic was injected intraperitoneally (IP) after CLP and then daily till the time of sacrifice. Three hours after antibiotic treatment, one of the septic groups was injected IP with a fish oil-based emulsion (FO), while the other two groups were given either a mixed oil emulsion (MO) or saline (SC). The septic groups were further divided into two separate time groups, with blood and kidneys samples collected at 24 h or 72 h post-CLP. The results showed that sepsis leads to the activation of neutrophils, T helper (Th)1/Th-2/Th-17 and Treg cells (p < 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. PMID:26999192

  4. Antioxidant and anti-inflammatory potential of pomegranate rind extract to ameliorate cisplatin-induced acute kidney injury.

    PubMed

    Karwasra, Ritu; Kalra, Prerna; Gupta, Yogendra Kumar; Saini, Deepika; Kumar, Ajay; Singh, Surender

    2016-07-13

    Cisplatin is a chemotherapeutic agent, but the therapeutic utility is limited due to its dose dependent nephrotoxicity. The aim of the present study was to evaluate the nephroprotective effect of pomegranate in cisplatin-induced acute kidney injury. Wistar rats were allocated into six groups as follows: the normal control, cisplatin-induced, pomegranate rind extract treatment (50, 100 and 200 mg kg(-1)) and pomegranate rind extract per se group. All the experimental test drugs/vehicle were administered orally for a period of ten days. Intraperitoneal injection of cisplatin (8 mg kg(-1)) was administered on day 7 to all the groups except the normal control and pomegranate per se group. On day 10, cisplatin resulted in significant nephrotoxicity in Wistar rats with a drastic elevation of serum creatinine and BUN, a decline in the concentrations of GSH, MDA and superoxide dismutase (SOD), and an elevation in the TNF-α level in renal tissues. Pathological changes in renal tissues were examined by histopathology and dysfunction in mitochondria and proximal tubule cells was detected by transmission electron microscopy. The rate of apoptosis and the expression of caspase-3, Il-1β and IL-6 in rat renal tissues were detected by immunohistochemistry. The administration of pomegranate at a dose of 200 mg per kg body weight significantly (p < 0.001) ameliorates increased serum creatinine and BUN. In parallel to this, pomegranate also exhibits anti-apoptotic activity through the reduction of active caspase-3 expression in kidneys. Additionally, in-silico studies also confirmed a renoprotective effect of pomegranate. The above findings suggest that pomegranate can be used as a dietary supplement in the treatment of cisplatin-induced kidney injury by reducing apoptosis, oxidative stress and inflammation. PMID:27273121

  5. Selenium Pretreatment for Mitigation of Ischemia/Reperfusion Injury in Cardiovascular Surgery: Influence on Acute Organ Damage and Inflammatory Response.

    PubMed

    Steinbrenner, Holger; Bilgic, Esra; Pinto, Antonio; Engels, Melanie; Wollschläger, Lena; Döhrn, Laura; Kellermann, Kristine; Boeken, Udo; Akhyari, Payam; Lichtenberg, Artur

    2016-08-01

    Ischemia/reperfusion injury (IRI) contributes to morbidity and mortality after cardiovascular surgery requiring cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Multi-organ damage is associated with substantial decreases of blood selenium (Se) levels in patients undergoing cardiac surgery with CPB. We compared the influence of a dietary surplus of Se and pretreatment with ebselen, a mimic of the selenoenzyme glutathione peroxidase, on IRI-induced tissue damage and inflammation. Male Wistar rats were fed either a Se-adequate diet containing 0.3 ppm Se or supplemented with 1 ppm Se (as sodium selenite) for 5 weeks. Two other groups of Se-adequate rats received intraperitoneal injection of ebselen (30 mg/kg) or DMSO (solvent control) before surgery. The animals were connected to a heart-lung-machine and underwent 45 min of global ischemia during circulatory arrest at 16 °C, followed by re-warming and reperfusion. Selenite and ebselen suppressed IRI-induced leukocytosis and the increase in plasma levels of tissue damage markers (AST, ALT, LDH, troponin) during surgery but did not prevent the induction of proinflammatory cytokines (IL-6, TNF-α). Both Se compounds affected phosphorylation and expression of proteins related to stress response and inflammation: Ebselen increased phosphorylation of STAT3 transcription factor in the heart and decreased phosphorylation of ERK1/2 MAP kinases in the lungs. Selenite decreased ERK1/2 phosphorylation and HSP-70 expression in the heart. Pretreatment with selenite or ebselen protected against acute IRI-induced tissue damage during CPB and DHCA. Potential implications of their different actions with regard to molecular stress markers on the recovery after surgery represent promising targets for further investigation. PMID:27192987

  6. Preliminary evidence that exercise dependence is associated with blunted cardiac and cortisol reactions to acute psychological stress.

    PubMed

    Heaney, Jennifer L J; Ginty, Annie T; Carroll, Douglas; Phillips, Anna C

    2011-02-01

    Low or blunted cardiovascular and cortisol reactions to acute psychological stress have been shown to characterise those with a tobacco or alcohol dependency. The present study tested the hypothesis that exercise dependency would be similarly associated with blunted reactivity. Young female exercisers (N=219) were screened by questionnaire for exercise dependence. Ten women with probable exercise dependence and 10 non dependent controls were selected for laboratory stress testing. Cardiovascular activity and salivary cortisol were measured at rest and in response to a 10-min mental arithmetic stress task. The exercise dependent women showed blunted cardiac reactions to the stress task and blunted cortisol at 10, 20, and 30 minute post stress exposure. These effects could not be accounted for in terms of group differences in stress task performance, nor could the cardiac effects be attributed to group differences in cardio-respiratory fitness. It would seem that low stress reactivity is characteristic of a wide range of dependencies, and is not confined to substance dependence. Our results offer further support for the hypothesis that blunted stress reactivity may be a peripheral marker of a central motivational dysregulation. PMID:21145361

  7. Selective Blockade of Herpesvirus Entry Mediator–B and T Lymphocyte Attenuator Pathway Ameliorates Acute Graft-versus-Host Reaction

    PubMed Central

    del Rio, Maria-Luisa; Jones, Nick D.; Buhler, Leo; Norris, Paula; Shintani, Yasushi; Ware, Carl F.; Rodriguez-Barbosa, Jose-Ignacio

    2013-01-01

    The cosignaling network mediated by the herpesvirus entry mediator (HVEM; TNFRSF14) functions as a dual directional system that involves proinflammatory ligand, lymphotoxin that exhibits inducible expression and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes (LIGHT; TNFSF14), and the inhibitory Ig family member B and T lymphocyte attenuator (BTLA). To dissect the differential contributions of HVEM/BTLA and HVEM/LIGHT interactions, topographically-specific, competitive, and nonblocking anti-HVEM Abs that inhibit BTLA binding, but not LIGHT, were developed. We demonstrate that a BTLA-specific competitor attenuated the course of acute graft-versus-host reaction in a murine F1 transfer semiallogeneic model. Selective HVEM/BTLA blockade did not inhibit donor T cell infiltration into graft-versus-host reaction target organs, but decreased the functional activity of the alloreactive T cells. These results highlight the critical role of HVEM/BTLA pathway in the control of the allogeneic immune response and identify a new therapeutic target for transplantation and autoimmune diseases. PMID:22490863

  8. Mortality due to acute adverse drug reactions in Galicia: 1997-2011.

    PubMed

    Miguel-Arias, Domingo; Pereiro Gómez, César; Bermejo Barrera, Ana M; López de Abajo Rodríguez, Benito; Sobrido Prieto, María

    2016-01-01

    The aim of this research is to study all people who died in the Autonomous Community of Galicia from acute death after drugconsumption (ADR) in which there was judicial intervention during the period from 1997 to 2011, according to inclusion and exclusión criteria established by the National Drug Plan for the entire national territory. Sociodemographic and clinical characteristics of deceased subjects were studied, in order to identify key risk factors and/or vulnerable populations.A total of 805 deaths were recorded. The distribution by provinces and municipalities corresponds to the areas of greatest population, incidence of consumption and proximity to the coast. The average age of these patients was 34.34 years, with a gradual increase over years. Most of them were male (91.2%) and single (47.7). 43.5% of the deceased habitually used the parenteral route of administration and 36.4% had positive HIV serology. The most frequently-detected substances corresponded to opiates (heroin: 61.3%, methadone: 35.6%), followed by cocaine (53.7%), although the most common pattern was that of poly-consumption. ADR mortality figures remain relatively stable throughout the study period. The predominant pattern is that of males, opiates and a long history of consumption. PMID:26990265

  9. Gene expression profiling of inflammatory bladder disorders.

    PubMed

    Saban, Marcia R; Nguyen, Ngoc-Bich; Hurst, Robert E; Saban, Ricardo

    2003-03-01

    Inflammation underlies all major bladder pathologies including malignancy and represents a defense reaction to injury caused by physical damage, chemical substances, micro-organisms or other agents. During acute inflammation, activation of specific molecular pathways leads to an increased expression of selected genes whose products attack the insult, but ultimately should protect the tissue from the noxious stimulus. However, once the stimulus ceases, gene-expression should return to basal levels to avoid tissue damage, fibrosis, loss of function, and chronic inflammation. If this down-regulation does not occur, tissue fibrosis occurs as a serious complication of chronic inflammation. Although sensory nerve and most cells products are known to be key parts of the inflammatory puzzle, other key molecules are constantly being described that have a role in bladder inflammation. Therefore, as the database describing the repertoire of inflammatory mediators implicated in bladder inflammation increases, the central mechanisms by which injury can induce inflammation, cell damage, and repair often becomes less rather than more clear. To make sense of the vast knowledge of the genes involved in the inflammatory response may require analysis of the patterns of change and the elucidation of gene networks far more than definition of additional members of inflammatory cascades. This review discuss the appropriate use of microarray technology, which promises to solve both of these problems as well as identifying key molecules and mechanisms involved in the transition between acute and chronic inflammation. PMID:12647997

  10. Hypothermic Machine Perfusion Reduced Inflammatory Reaction by Downregulating the Expression of Matrix Metalloproteinase 9 in a Reperfusion Model of Donation After Cardiac Death.

    PubMed

    Fu, Zhen; Ye, Qifa; Zhang, Yang; Zhong, Zibiao; Xiong, Yan; Wang, Yanfeng; Hu, Long; Wang, Wei; Huang, Wei; Ko, Dicken Shiu-Chung

    2016-06-01

    The exact mechanism by which hypothermic machine perfusion (HMP) improves the graft quality in kidney transplantation of donation after cardiac death (DCD) remains unclear. The aim of this study was to investigate the correlation between the expression of matrix metalloproteinase 9 (MMP-9) and inflammatory reaction in kidney ischemia-reperfusion (I/R) injury injury followed by cold storage (CS) or HMP model of DCD. New Zealand white rabbit kidneys were subjected to 35 min of warm ischemia and 1 h reperfusion, then preserved by either 1 h reperfusion (sham-operated group), 4 h CS or 4 h HMP in vivo. Kidneys were reperfused 24 h followed by further analysis. No treatment was given to rabbits in the normal control group. The expression of MMP-9, nuclear factor-κB (NF-κB), and MMP-2 mRNA were detected by real-time PCR (RT-PCR). MMP-9 was located by immunohistochemistry and immunofluorescence methods. Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), myeloperoxidase (MPO), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured by kits for each groups. Compared with the CS group, the expression of MMP-9 and NF-κB mRNA were downregulated in HMP group (P < 0.05). In contrast, expression of MMP-2 mRNA had no statistical significance between CS group and HMP group (P > 0.05). In normal control and sham-operated groups, a low level of MMP-9 expression was detected in glomeruli. However, positive signals of MMP-9 were mostly located in the tubulointerstitium and the vascular wall of CS and HMP groups. Expression of TNF-α, IL-6, MDA, and activity of MPO decreased while activity of SOD in the HMP group increased in contrast to the CS group (P < 0.05). In conclusion, inflammatory cytokines mediated MMP-9 expression through NF-κB band to MMP-9 promoter region, resulting in renal injury. Therefore, HMP reduced inflammatory reaction by downregulating the expression of MMP-9, which may be the mechanism of kidney protection in I

  11. Opiates or cocaine: mortality from acute reactions in six major Spanish cities. State Information System on Drug Abuse (SEIT) Working Group.

    PubMed Central

    Sánchez, J; Rodríguez, B; de la Fuente, L; Barrio, G; Vicente, J; Roca, J; Royuela, L

    1995-01-01

    STUDY OBJECTIVE--To describe temporal and geographical variations in mortality from acute reactions to opiates or cocaine and the demographic and toxicological characteristics of persons who died from these in major Spanish cities between 1983 and 1991. DESIGN--Descriptive study. Data were obtained retrospectively from pathologists' reports. SETTING--Cities of Madrid, Barcelona, Valencia, Seville, Zaragoza, and Bilbao. SUBJECTS--Deaths from acute reactions to opiates or cocaine were defined as those in which pathologists' reports did not indicate any other cause of death and in which evidence was found of recent consumption of these drugs. MAIN RESULTS--The mortality rate from acute reactions to opiate/cocaine per 100,000 population in the six cities as a whole rose from 1.2 in 1983 to 8.2 in 1991. Average annual rates for the whole period ranged from 1.7 in Seville to 4.9 in Barcelona. The male/female rates ratio was 5.9:1. The mean age of persons who died rose from 25.1 years in 1983 to 28 years in 1991. In more than 90% of the cases in whom toxicological tests were undertaken opiates were detected, and the proportion in which benzodiazepines or cocaine were detected increased during the period studied. CONCLUSIONS--Between 1983 and 1991 mortality from acute reactions to opiates/cocaine rose dramatically in major Spanish cities and significant differences in mortality between cities were found. Deaths were concentrated among men and young people. Acute drug reactions became one of the leading causes of death in persons 15-39 years of age, representing 11.1% of mortality from all causes in 1988 for this age group. Future studies should examine the relationship between the temporal and geographical variations in this type of mortality and various personal, environmental and social factors. PMID:7707007

  12. Vitamin D and inflammatory diseases

    PubMed Central

    Yin, Kai; Agrawal, Devendra K

    2014-01-01

    Beyond its critical function in calcium homeostasis, vitamin D has recently been found to play an important role in the modulation of the immune/inflammation system via regulating the production of inflammatory cytokines and inhibiting the proliferation of proinflammatory cells, both of which are crucial for the pathogenesis of inflammatory diseases. Several studies have associated lower vitamin D status with increased risk and unfavorable outcome of acute infections. Vitamin D supplementation bolsters clinical responses to acute infection. Moreover, chronic inflammatory diseases, such as atherosclerosis-related cardiovascular disease, asthma, inflammatory bowel disease, chronic kidney disease, nonalcoholic fatty liver disease, and others, tend to have lower vitamin D status, which may play a pleiotropic role in the pathogenesis of the diseases. In this article, we review recent epidemiological and interventional studies of vitamin D in various inflammatory diseases. The potential mechanisms of vitamin D in regulating immune/inflammatory responses in inflammatory diseases are also discussed. PMID:24971027

  13. Early weaning alters the acute-phase reaction to an endotoxin challenge in beef calves.

    PubMed

    Carroll, J A; Arthington, J D; Chase, C C

    2009-12-01

    Previous research indicates that early weaning before shipment can reduce transportation-induced increases in acute-phase proteins (APP) and can increase feedlot performance in beef calves. These data suggest that the combination of weaning and transport stress may compromise the immune system of calves, thus hindering subsequent performance and health. Therefore, our objective was to determine if the innate immune response of early weaned calves (EW; 80 d of age) differed from normal-weaned calves (NW; 250 d of age) in response to an endotoxin challenge. Eighteen Brahman x Angus calves (8 and 10 EW and NW, respectively; 233 +/- 5 kg of BW) were used. Calves were maintained on pasture with supplement and then moved into individual pens for 1 wk of acclimation before the start of the study. Calves were fitted with an indwelling jugular catheter 1 d before LPS challenge (0 h; 1.0 microg/kg of BW, intravenously). Blood samples were collected at 30-min intervals from -2 to 8 h. Serum samples were stored at -80 degrees C until analyzed for cortisol, tumor necrosis factor-alpha (TNF), IL-1 beta, IL-6, interferon-gamma (IFN), ceruloplasmin, and haptoglobin. Whereas LPS increased serum cortisol (P or= 0.15) was observed. A weaning age x time interaction (P

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

    PubMed Central

    2010-01-01

    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 < 0.0001) with microarray results. Conclusions Many of the genes differentially expressed in this study, in parallel with the hypothermia, figure prominently in protection against

  15. Evaluation through in vivo reflectance confocal microscopy of the cutaneous neurogenic inflammatory reaction induced by capsaicin in human subjects

    NASA Astrophysics Data System (ADS)

    Căruntu, Constantin; Boda, Daniel

    2012-08-01

    We perform an in vivo analysis of the effects of capsaicin on cutaneous microvascularization. A total of 29 healthy subjects are administered a solution of capsaicin (CAP group) or a vehicle solution (nonCAP group) on the dorsal side of the nondominant hand. The evaluation is performed using in vivo reflectance confocal microscopy (RCM). Ten minutes after administration, the area of the section, the perimeter, and the Feret's diameter of the capillaries in the dermal papillae become significantly larger in the CAP group as against the nonCAP group, and this difference is maintained until the conclusion of the experiment. In vivo RCM allows the investigation of cutaneous vascular reactions induced by capsaicin. As such, this method may constitute an useful technique both for research and clinical practice.

  16. Kinetics of pro-inflammatory cytokines, interleukin-10, and virus neutralising antibodies during acute ephemeral fever virus infections in Brahman cattle.

    PubMed

    Barigye, R; Melville, L F; Davis, S; Walsh, S; Hunt, N; Hunt, R; Elliot, N

    2015-12-15

    While fever and inflammation are hallmark features of bovine ephemeral fever (BEF), the cytokine networks that underlie the acute phase of the disease have not been empirically defined in cattle. This study characterised the plasma kinetics of proinflammatory cytokines (IL-1β, IL-6, TNF-α) and IL-10 during acute BEF and elucidated on the relationship between the onset of the virus neutralizing antibody response and resolution of viraemia in natural BEF virus (BEFV) infections in cattle. Plasma from three BEFV-infected and three uninfected cattle was tested for the study cytokines by a cELISA, viraemia monitored by qRT-PCR, and virus neutralizing antibody titres determined using a standard protocol. Unlike the negative controls, plasma concentrations of IL-1β, TNF-α, IL-6, and IL-10 were consistently increased in the three virus-infected animals. Two of the infected heifers were recumbent and pyrexic on the first day of monitoring and increased cytokine production was already in progress by the time viraemia was detected in all the three infected animals. In all the virus-infected heifers, IL-1β was the most strongly expressed cytokine, IL-6 and IL-10 manifested intermediate plasma concentrations while TNF-α was the least expressed and demonstrated bi-phasic peaks three and five days after the onset of pyrexia. In two of the BEFV-infected heifers, viraemia resolved on the day of seroconversion while in the other infected animal, viral RNA was detectable up to three days after seroconversion. The present data document variable increase in plasma IL-1β, IL-6, TNF-α, and IL-10 during natural BEFV infections and the fact that upregulation of all but TNF-α precedes seroconversion. In addition to virus neutralising antibodies, it is likely that cytokine-mediated cellular mechanisms may be required for resolution of viraemia in BEF. Considering the anti-inflammatory properties of IL-10, its upregulation may potentially antagonise the fever response in BEFV

  17. Effect of the Diagnosis of Inflammatory Bowel Disease on Risk-Adjusted Mortality in Hospitalized Patients with Acute Myocardial Infarction, Congestive Heart Failure and Pneumonia

    PubMed Central

    Ehrenpreis, Eli D.; Zhou, Ying; Alexoff, Aimee; Melitas, Constantine

    2016-01-01

    Introduction Measurement of mortality in patients with acute myocardial infarction (AMI), congestive heart failure (CHF) and pneumonia (PN) is a high priority since these are common reasons for hospitalization. However, mortality in patients with inflammatory bowel disease (IBD) that are hospitalized for these common medical conditions is unknown. Methods A retrospective review of the 2005–2011 National Inpatient Sample (NIS), (approximately a 20% sample of discharges from community hospitals) was performed. A dataset for all patients with ICD-9-CM codes for primary diagnosis of acute myocardial infarction, pneumonia or congestive heart failure with a co-diagnosis of IBD, Crohn’s disease (CD) or ulcerative colitis (UC). 1:3 propensity score matching between patients with co-diagnosed disease vs. controls was performed. Continuous variables were compared between IBD and controls. Categorical variables were reported as frequency (percentage) and analyzed by Chi-square tests or Fisher’s exact test for co-diagnosed disease vs. control comparisons. Propensity scores were computed through multivariable logistic regression accounting for demographic and hospital factors. In-hospital mortality between the groups was compared. Results Patients with IBD, CD and UC had improved survival after AMI compared to controls. 94/2280 (4.1%) of patients with IBD and AMI died, compared to 251/5460 (5.5%) of controls, p = 0.01. This represents a 25% improved survival in IBD patients that were hospitalized with AMI. There was a 34% improved survival in patients with CD and AMI. There was a trend toward worsening survival in patients with IBD and CHF. Patients with CD and PN had improved survival compared to controls. 87/3362 (2.59%) patients with CD and PN died, compared to 428/10076 (4.25%) of controls, p < .0001. This represents a 39% improved survival in patients with CD that are hospitalized for PN. Conclusion IBD confers a survival benefit for patients hospitalized with AMI. A

  18. Inflammatory cytokines and acute-phase proteins concentrations in the peripheral blood and uterus of cows that developed endometritis during early postpartum.

    PubMed

    Brodzki, P; Kostro, K; Brodzki, A; Wawron, W; Marczuk, J; Kurek, Ł

    2015-07-01

    The aim of the study was to evaluate the level of proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6]), anti-inflammatory cytokine (interleukin-10 [IL-10]), and acute-phase proteins (haptoglobin [Hp] and serum amyloid A [SAA]) in serum and uterine washings in cows that developed endometritis during the early postpartum period. The study was carried out on 40 cows. The experimental group consisted of 20 cows with subclinical endometritis and the control group of 20 cows without endometritis. Analyses in both groups of cows were carried out at 5, 22, and 40 days postpartum (DPP). Experimental material consisted of the blood serum and uterine washings. The levels of the following cytokines: TNF-α, IL-6, IL-10 and acute-phase proteins: Hp and SAA were determined using ELISA. Our study reported that the levels of TNF-α, IL-6, IL-10, Hp, and SAA at 22 DPP were higher in cows with subclinical endometritis (P < 0.001). The levels of TNF-α (P = 0.01), IL-6 and IL-10 (P = 0.001), and Hp (P < 0.001) at 40 DPP were higher in cows with subclinical endometritis compared to healthy cows. The level of IL-10 in uterine washings at 5 DPP was higher (P = 0.001), whereas of SAA was lower (P = 0.01) in cows with subclinical endometritis. At 22 DPP, the levels of IL-6, IL-10, and Hp were higher (P < 0.001) in cows with endometritis. At 40 DPP, the level of TNF-α was lower, whereas these of IL-10 and Hp were elevated (P < 0.001) in cows with endometritis compared to healthy cows. The results indicate that the evaluation of the levels of cytokines and Hp in serum, but primarily in uterine washings, can be an important diagnostic indicator in cows that developed subclinical endometritis. High levels of IL-10 in cows with subclinical endometritis may contribute to the weakening of local resistance mechanisms of the uterus and lead to the persistence of the inflammation in the postpartum period. The present study also shows that the simultaneous examination

  19. Efficacy of anti-inflammatory or antibiotic treatment in patients with non-complicated acute bronchitis and discoloured sputum: randomised placebo controlled trial

    PubMed Central

    Moragas, Ana; Bayona, Carolina; Morros, Rosa; Pera, Helena; Plana-Ripoll, Oleguer; Cots, Josep M; Miravitlles, Marc

    2013-01-01

    Objective To evaluate the efficacy of oral anti-inflammatory or antibiotic treatment compared with placebo in the resolution of cough in patients with uncomplicated acute bronchitis and discoloured sputum. Design Multicentre, parallel, single blinded placebo controlled, randomised clinical trial. Setting Nine primary care centres in Spain. Participants Adults aged 18 to 70 presenting symptoms associated with respiratory tract infection of less than one week’s duration, with cough as the predominant symptom, the presence of discoloured sputum, and at least one other symptom of lower respiratory tract infection (dyspnoea, wheezing, chest discomfort, or chest pain). Interventions Patients were randomised to receive either ibuprofen 600 mg three times daily, amoxicillin-clavulanic acid 500 mg/125 mg three times daily, or placebo three times daily for 10 days. The duration of symptoms was measured with a diary card. Main outcome measure Number of days with frequent cough after the randomisation visit. Results 416 participants were randomised (136 to ibuprofen, 137 to antibiotic, and 143 to placebo) and 390 returned their symptom diaries fully completed. The median number of days with frequent cough was slightly lower among patients assigned to ibuprofen (9 days, 95% confidence interval 8 to 10 days) compared with those receiving amoxicillin-clavulanic acid (11 days, 10 to 12 days) or placebo (11 days, 8 to 14 days), albeit without statistically significant differences. Neither amoxicillin-clavulanic acid nor ibuprofen increased the probability of cough resolution (hazard ratio 1.03, 95% confidence interval 0.78 to 1.35 and 1.23, 0.93 to 1.61, respectively) compared with placebo. Adverse events were observed in 27 patients, and were more common in the antibiotic arm (12%) than ibuprofen or placebo arms (5% and 3%, respectively; P<0.01). Conclusion No significant differences were observed in the number of days with cough between patients with uncomplicated acute

  20. Interleukin-6 Induced "Acute" Phenotypic Microenvironment Promotes Th1 Anti-Tumor Immunity in Cryo-Thermal Therapy Revealed By Shotgun and Parallel Reaction Monitoring Proteomics.

    PubMed

    Xue, Ting; Liu, Ping; Zhou, Yong; Liu, Kun; Yang, Li; Moritz, Robert L; Yan, Wei; Xu, Lisa X

    2016-01-01

    Cryo-thermal therapy has been emerged as a promising novel therapeutic strategy for advanced breast cancer, triggering higher incidence of tumor regression and enhanced remission of metastasis than routine treatments. To better understand its anti-tumor mechanism, we utilized a spontaneous metastatic mouse model and quantitative proteomics to compare N-glycoproteome changes in 94 serum samples with and without treatment. We quantified 231 highly confident N-glycosylated proteins using iTRAQ shotgun proteomics. Among them, 53 showed significantly discriminated regulatory patterns over the time course, in which the acute phase response emerged as the most enhanced pathway. The anti-tumor feature of the acute response was further investigated using parallel reaction monitoring target proteomics and flow cytometry on 23 of the 53 significant proteins. We found that cryo-thermal therapy reset the tumor chronic inflammation to an "acute" phenotype, with up-regulation of acute phase proteins including IL-6 as a key regulator. The IL-6 mediated "acute" phenotype transformed IL-4 and Treg-promoting ICOSL expression to Th1-promoting IFN-γ and IL-12 production, augmented complement system activation and CD86(+)MHCII(+) dendritic cells maturation and enhanced the proliferation of Th1 memory cells. In addition, we found an increased production of tumor progression and metastatic inhibitory proteins under such "acute" environment, favoring the anti-metastatic effect. Moreover, cryo-thermal on tumors induced the strongest "acute" response compared to cryo/hyperthermia alone or cryo-thermal on healthy tissues, accompanying by the most pronounced anti-tumor immunological effect. In summary, we demonstrated that cryo-thermal therapy induced, IL-6 mediated "acute" microenvironment shifted the tumor chronic microenvironment from Th2 immunosuppressive and pro-tumorigenic to Th1 immunostimulatory and tumoricidal state. Moreover, the magnitude of "acute" and "danger" signals play a key

  1. Acute tubulointerstitial nephritis.

    PubMed

    Ulinski, Tim; Sellier-Leclerc, Anne-Laure; Tudorache, Elena; Bensman, Albert; Aoun, Bilal

    2012-07-01

    Acute tubulointerstitial nephritis (TIN) is a frequent cause of acute renal failure, characterised by the presence of inflammatory cell infiltrate in the interstitium of the kidney. Immuno-allergic reaction to certain medications, mainly non-steroidal anti-inflammatory drugs and antibiotics are by far the most important etiology for TIN today, but other situations such as infections, toxins, and vasculitis are known to induce TIN. Incidence of TIN is increasing, probably due to prescription habits and NSAID overuse, representing 3-7% of acute kidney injury in biopsies in children. Avoidance of the causal substance and rapid steroid therapy are hallmarks for patient care, but spontaneous initial recovery is very frequent and the general prognosis seems satisfactory. However, development of chronic TIN, without response to steroid or other immunosuppressive treatment, is possible. As the largest part of TIN is secondary to certain drugs, clear indications in particular for NSAID or antibiotics should be respected to reduce the number of TIN cases. PMID:21638156

  2. Intranasal Immunization with a Colloid-Formulated Bacterial Extract Induces an Acute Inflammatory Response in the Lungs and Elicits Specific Immune Responses

    PubMed Central

    Rial, A.; Lens, D.; Betancor, L.; Benkiel, H.; Silva, J. S.; Chabalgoity, J. A.

    2004-01-01

    Nonspecific stimulation of lung defenses by repeated oral administration of immunomodulators, such as bacterial extracts, has shown potential for the prevention of respiratory tract infections. Here, we show that intranasal (i.n.) immunization with a bacterial extract formulated as a colloid induces an acute inflammatory response in the lungs characterized by increased production of CCL and CXCL chemokines and a major influx of dendritic cells (DCs) and neutrophils, with a higher proportion of DCs showing an activated phenotype (high CD80/CD86 expression). Cytokine levels measured in bronchoalveolar-lavage samples showed a small increase in the production of tumor necrosis factor alpha and similar levels of the other cytokines measured (interleukin 10 [IL-10], IL-12, and gamma interferon [IFN-γ]) in immunized mice compared with control mice. However, the recall response of primed animals after antigenic challenge induced increased expression of IL-12 and IFN-γ mRNAs in lung homogenates. Overall, all these effects were not due to the lipopolysaccharide content in the bacterial extract. Furthermore, we found that three i.n. doses administered 2 to 3 weeks apart were enough to elicit long-lasting specific serum immunoglobulin G (IgG) and secretory IgA antibody responses. Assessment of IgG subclasses showed a balanced pattern of IgG1-IgG2a responses. The serum total IgE concentrations were also elevated in immunized mice 2 weeks after the third dose, but they significantly decreased soon afterwards. Our results suggest that simple formulations of bacterial extracts administered i.n. are highly immunogenic, eliciting local and systemic immune responses, and may serve as the basis for cost-effective immunotherapies for the prevention and treatment of respiratory infections. PMID:15102776

  3. Intranasal immunization with a colloid-formulated bacterial extract induces an acute inflammatory response in the lungs and elicits specific immune responses.

    PubMed

    Rial, A; Lens, D; Betancor, L; Benkiel, H; Silva, J S; Chabalgoity, J A

    2004-05-01

    Nonspecific stimulation of lung defenses by repeated oral administration of immunomodulators, such as bacterial extracts, has shown potential for the prevention of respiratory tract infections. Here, we show that intranasal (i.n.) immunization with a bacterial extract formulated as a colloid induces an acute inflammatory response in the lungs characterized by increased production of CCL and CXCL chemokines and a major influx of dendritic cells (DCs) and neutrophils, with a higher proportion of DCs showing an activated phenotype (high CD80/CD86 expression). Cytokine levels measured in bronchoalveolar-lavage samples showed a small increase in the production of tumor necrosis factor alpha and similar levels of the other cytokines measured (interleukin 10 [IL-10], IL-12, and gamma interferon [IFN-gamma]) in immunized mice compared with control mice. However, the recall response of primed animals after antigenic challenge induced increased expression of IL-12 and IFN-gamma mRNAs in lung homogenates. Overall, all these effects were not due to the lipopolysaccharide content in the bacterial extract. Furthermore, we found that three i.n. doses administered 2 to 3 weeks apart were enough to elicit long-lasting specific serum immunoglobulin G (IgG) and secretory IgA antibody responses. Assessment of IgG subclasses showed a balanced pattern of IgG1-IgG2a responses. The serum total IgE concentrations were also elevated in immunized mice 2 weeks after the third dose, but they significantly decreased soon afterwards. Our results suggest that simple formulations of bacterial extracts administered i.n. are highly immunogenic, eliciting local and systemic immune responses, and may serve as the basis for cost-effective immunotherapies for the prevention and treatment of respiratory infections. PMID:15102776

  4. Gastroprotective Effect of Cochinchina momordica Seed Extract in Nonsteroidal Anti-Inflammatory Drug-Induced Acute Gastric Damage in a Rat Model

    PubMed Central

    Lim, Ji Hwan; Kim, Joo-Hyun; Lee, Byoung Hwan; Seo, Pyoung Ju; Kang, Jung Mook; Jo, So Young; Park, Ji Hyun; Nam, Ryoung Hee; Chang, Hyun; Kwon, Jin-Won; Lee, Dong Ho

    2014-01-01

    Background/Aims The major compounds of Cochinchina momordica seed extract (SK-MS10) include momordica saponins. We report that the gastroprotective effect of SK-MS10 in an ethanol-induced gastric damage rat model is mediated by suppressing proinflammatory cytokines and downregulating cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LOX), and the activation of calcitonin gene-related peptide. In this study, we evaluated the gastroprotective effects of SK-MS10 in the nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage rat model. Methods The pretreatment effect of SK-MS10 was evaluated in the NSAID-induced gastric damage rat model using aspirin, indomethacin, and diclofenac in 7-week-old rats. Gastric damage was evaluated based on the gross ulcer index by gastroenterologists, and the damage area (%) was measured using the MetaMorph 7.0 video image analysis system. Myeloperoxidase (MPO) was measured by enzyme-linked immunosorbent assay, and Western blotting was used to analyze the levels of cyclooxygenase (COX)-1, COX-2, cPLA2, and 5-LOX. Results All NSAIDs induced gastric damage based on the gross ulcer index and damage area (p<0.05). Gastric damage was significantly attenuated by SK-MS10 pretreatment compared with NSAID treatment alone (p<0.05). The SK-MS10 pretreatment group exhibited lower MPO levels than the diclofenac group. The expression of cPLA2 and 5-LOX was decreased by SK-MS10 pretreatment in each of the three NSAID treatment groups. Conclusions SK-MS10 exhibited a gastroprotective effect against NSAID-induced acute gastric damage in rats. However, its protective mechanism may be different across the three types of NSAID-induced gastric damage models in rats. PMID:24516701

  5. The concentrations of inflammatory cytokines and acute-phase proteins in the peripheral blood and uterine washings in cows with pyometra.

    PubMed

    Brodzki, P; Kostro, K; Brodzki, A; Ziętek, J

    2015-06-01

    The development of pyometra in cows depends largely on the state of local immunity of the uterus. The objective of the study was to evaluate the concentration of the following proinflammatory cytokines: tumour necrosis factor (TNF-α) and interleukin-6 (IL-6); anti-inflammatory cytokine: interleukin-10 (IL-10); and acute-phase proteins (APPs): haptoglobin (Hp) and serum amyloid A (SAA), in serum and uterine washings in cows with pyometra and healthy animals. The study was performed on 20 cows divided into two groups based on the results of cytological and ultrasonographic tests: a pyometra and a healthy group (10 cows per group). Experimental material consisted of blood serum and uterine washings. The levels of the following cytokines, TNF-α, IL-6, IL-10 and APPs - Hp and SAA, in the study material were determined by ELISA. The results showed that the values of TNF-α, IL-6, IL-10 as well as SAA and Hp were significantly higher in serum of cows with pyometra compared to controls (p < 0.001). The uterine washings had significantly higher levels of IL-6, IL-10, and Hp in pyometra cows compared to the control (p < 0.001). Our results indicate that it is possible to monitor the course of pyometra in cows based on the evaluation of the concentration of cytokines and Hp in the serum and uterine washings. Simultaneous evaluation of selected indicators of antagonistic interaction can be helpful in determining the current status of local immunity of the uterus. On this basis, it could be possible to properly select an adjunctive therapy in the form of immunomodulating preparations. PMID:25704413

  6. Unique Inflammatory Mediators and Specific IgE Levels Distinguish Local from Systemic Reactions after Anthrax Vaccine Adsorbed Vaccination.

    PubMed

    Garman, Lori; Smith, Kenneth; Muns, Emily E; Velte, Cathy A; Spooner, Christina E; Munroe, Melissa E; Farris, A Darise; Nelson, Michael R; Engler, Renata J M; James, Judith A

    2016-08-01

    Although the U.S. National Academy of Sciences concluded that anthrax vaccine adsorbed (AVA) has an adverse event (AE) profile similar to those of other adult vaccines, 30 to 70% of queried AVA vaccinees report AEs. AEs appear to be correlated with certain demographic factors, but the underlying immunologic pathways are poorly understood. We evaluated a cohort of 2,421 AVA vaccinees and found 153 (6.3%) reported an AE. Females were more likely to experience AEs (odds ratio [OR] = 6.0 [95% confidence interval {CI} = 4.2 to 8.7]; P < 0.0001). Individuals 18 to 29 years of age were less likely to report an AE than individuals aged 30 years or older (OR = 0.31 [95% CI = 0.22 to 0.43]; P < 0.0001). No significant effects were observed for African, European, Hispanic, American Indian, or Asian ancestry after correcting for age and sex. Additionally, 103 AEs were large local reactions (LLRs), whereas 53 AEs were systemic reactions (SRs). In a subset of our cohort vaccinated 2 to 12 months prior to plasma sample collection (n = 75), individuals with LLRs (n = 33) had higher protective-antigen (PA)-specific IgE levels than matched, unaffected vaccinated individuals (n = 50; P < 0.01). Anti-PA IgE was not associated with total plasma IgE, hepatitis B-specific IgE, or anti-PA IgG in individuals who reported an AE or in matched, unaffected AVA-vaccinated individuals. IP-10 was also elevated in sera of individuals who developed LLRs (P < 0.05). Individuals reporting SRs had higher levels of systemic inflammation as measured from C-reactive protein (P < 0.01). Thus, LLRs and SRs are mediated by distinct pathways. LLRs are associated with a vaccine-specific IgE response and IP-10, whereas SRs demonstrate increased systemic inflammation without a skewed cytokine profile. PMID:27280620

  7. Compensatory cellular reactions to nonsteroidal anti-inflammatory drugs on osteogenic differentiation in canine bone marrow-derived mesenchymal stem cells.

    PubMed

    Oh, Namgil; Kim, Sangho; Hosoya, Kenji; Okumura, Masahiro

    2014-05-01

    The suppressive effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the bone healing process have remained controversial, since no clinical data have clearly shown the relationship between NSAIDs and bone healing. The aim of this study was to assess the compensatory response of canine bone marrow-derived mesenchymal stem cells (BMSCs) to several classes of NSAIDs, including carprofen, meloxicam, indomethacin and robenacoxib, on osteogenic differentiation. Each of the NSAIDs (10 µM) was administered during 20 days of the osteogenic process with human recombinant IL-1β (1 ng/ml) as an inflammatory stimulator. Gene expression of osteoblast differentiation markers (alkaline phosphatase and osteocalcin), receptors of PGE2 (EP2 and EP4) and enzymes for prostaglandin (PG) E2 synthesis (COX-1, COX-2, cPGES and mPGES-1) was measured by using quantitative reverse transcription-polymerase chain reaction. Protein production levels of alkaline phosphatase, osteocalcin and PGE2 were quantified using an alkaline phosphatase activity assay, osteocalcin immunoassay and PGE2 immunoassay, respectively. Histologic analysis was performed using alkaline phosphatase staining, von Kossa staining and alizarin red staining. Alkaline phosphatase and calcium deposition were suppressed by all NSAIDs. However, osteocalcin production showed no significant suppression by NSAIDs. Gene expression levels of PGE2-related receptors and enzymes were upregulated during continuous treatment with NSAIDs, while certain channels for PGE2 synthesis were utilized differently depending on the kind of NSAIDs. These data suggest that canine BMSCs have a compensatory mechanism to restore PGE2 synthesis, which would be an intrinsic regulator to maintain differentiation of osteoblasts under NSAID treatment. PMID:24419976

  8. TNF-Overexpression in Borna Disease Virus-Infected Mouse Brains Triggers Inflammatory Reaction and Epileptic Seizures

    PubMed Central

    Eisel, Ulrich L. M.; Herzog, Sibylle; Richt, Jürgen A.; Baumgärtner, Wolfgang; Herden, Christiane

    2012-01-01

    Proinflammatory state of the brain increases the risk for seizure development. Neonatal Borna disease virus (BDV)-infection of mice with neuronal overexpression of tumor necrosis factor-α (TNF) was used to investigate the complex relationship between enhanced cytokine levels, neurotropic virus infection and reaction pattern of brain cells focusing on its role for seizure induction. Viral antigen and glial markers were visualized by immunohistochemistry. Different levels of TNF in the CNS were provided by the use of heterozygous and homozygous TNF overexpressing mice. Transgenic TNF, total TNF (native and transgenic), TNF-receptor (TNFR1, TNFR2), IL-1 and N-methyl-D-aspartate (NMDA)-receptor subunit 2B (NR2B) mRNA values were measured by real time RT-PCR. BDV-infection of TNF-transgenic mice resulted in non-purulent meningoencephalitis accompanied by epileptic seizures with a higher frequency in homozygous animals. This correlated with lower weight gain, stronger degree and progression of encephalitis and early, strong microglia activation in the TNF-transgenic mice, most obviously in homozygous animals. Activation of astroglia could be more intense and associated with an unusual hypertrophy in the transgenic mice. BDV-antigen distribution and infectivity in the CNS was comparable in TNF-transgenic and wild-type animals. Transgenic TNF mRNA-expression was restricted to forebrain regions as the transgene construct comprised the promoter of NMDA-receptor subunit2B and induced up-regulation of native TNF mRNA. Total TNF mRNA levels did not increase significantly after BDV-infection in the brain of transgenic mice but TNFR1, TNFR2 and IL-1 mRNA values, mainly in the TNF overexpressing brain areas. NR2B mRNA levels were not influenced by transgene expression or BDV-infection. Neuronal TNF-overexpression combined with BDV-infection leads to cytokine up-regulation, CNS inflammation and glial cell activation and confirmed the presensitizing effect of elevated cytokine

  9. Asthma and Rhinitis Induced by Selective Immediate Reactions to Paracetamol and Non-steroidal Anti-inflammatory Drugs in Aspirin Tolerant Subjects.

    PubMed

    Pérez-Alzate, Diana; Blanca-López, Natalia; Doña, Inmaculada; Agúndez, José A; García-Martín, Elena; Cornejo-García, José A; Perkins, James R; Blanca, Miguel; Canto, Gabriela

    2016-01-01

    In subjects with non-steroidal anti-inflammatory drugs (NSAIDs)- exacerbated respiratory disease (NERD) symptoms are triggered by acetyl salicylic acid (ASA) and other strong COX-1 inhibitors, and in some cases by weak COX-1 or by selective COX-2 inhibitors. The mechanism involved is related to prostaglandin pathway inhibition and leukotriene release. Subjects who react to a single NSAID and tolerate others are considered selective responders, and often present urticaria and/or angioedema and anaphylaxis (SNIUAA). An immunological mechanism is implicated in these reactions. However, anecdotal evidence suggests that selective responders who present respiratory airway symptoms may also exist. Our objective was to determine if subjects might develop selective responses to NSAIDs/paracetamol that manifest as upper/lower airways respiratory symptoms. For this purpose, we studied patients reporting asthma and/or rhinitis induced by paracetamol or a single NSAID that tolerated ASA. An allergological evaluation plus controlled challenge with ASA was carried out. If ASA tolerance was found, we proceeded with an oral challenge with the culprit drug. The appearance of symptoms was monitored by a clinical questionnaire and by measuring FEV1 and/or nasal airways volume changes pre and post challenge. From a total of 21 initial cases, we confirmed the appearance of nasal and/or bronchial manifestations in ten, characterized by a significant decrease in FEV1% and/or a decrease in nasal volume cavity after drug administration. All cases tolerated ASA. This shows that ASA tolerant subjects with asthma and/or rhinitis induced by paracetamol or a single NSAID without skin/systemic manifestations exist. Whether these patients represent a new clinical phenotype to be included within the current classification of hypersensitivity reactions to NSAIDs requires further investigation. PMID:27489545

  10. Asthma and Rhinitis Induced by Selective Immediate Reactions to Paracetamol and Non-steroidal Anti-inflammatory Drugs in Aspirin Tolerant Subjects

    PubMed Central

    Pérez-Alzate, Diana; Blanca-López, Natalia; Doña, Inmaculada; Agúndez, José A.; García-Martín, Elena; Cornejo-García, José A.; Perkins, James R.; Blanca, Miguel; Canto, Gabriela

    2016-01-01

    In subjects with non-steroidal anti-inflammatory drugs (NSAIDs)- exacerbated respiratory disease (NERD) symptoms are triggered by acetyl salicylic acid (ASA) and other strong COX-1 inhibitors, and in some cases by weak COX-1 or by selective COX-2 inhibitors. The mechanism involved is related to prostaglandin pathway inhibition and leukotriene release. Subjects who react to a single NSAID and tolerate others are considered selective responders, and often present urticaria and/or angioedema and anaphylaxis (SNIUAA). An immunological mechanism is implicated in these reactions. However, anecdotal evidence suggests that selective responders who present respiratory airway symptoms may also exist. Our objective was to determine if subjects might develop selective responses to NSAIDs/paracetamol that manifest as upper/lower airways respiratory symptoms. For this purpose, we studied patients reporting asthma and/or rhinitis induced by paracetamol or a single NSAID that tolerated ASA. An allergological evaluation plus controlled challenge with ASA was carried out. If ASA tolerance was found, we proceeded with an oral challenge with the culprit drug. The appearance of symptoms was monitored by a clinical questionnaire and by measuring FEV1 and/or nasal airways volume changes pre and post challenge. From a total of 21 initial cases, we confirmed the appearance of nasal and/or bronchial manifestations in ten, characterized by a significant decrease in FEV1% and/or a decrease in nasal volume cavity after drug administration. All cases tolerated ASA. This shows that ASA tolerant subjects with asthma and/or rhinitis induced by paracetamol or a single NSAID without skin/systemic manifestations exist. Whether these patients represent a new clinical phenotype to be included within the current classification of hypersensitivity reactions to NSAIDs requires further investigation. PMID:27489545

  11. Investigation of whether the acute hemolysis associated with Rho(D) immune globulin intravenous (human) administration for treatment of immune thrombocytopenic purpura is consistent with the acute hemolytic transfusion reaction model

    PubMed Central

    Gaines, Ann Reed; Lee-Stroka, Hallie; Byrne, Karen; Scott, Dorothy E.; Uhl, Lynne; Lazarus, Ellen; Stroncek, David F.

    2012-01-01

    BACKGROUND Immune thrombocytopenic purpura and secondary thrombocytopenia patients treated with Rho(D) immune globulin intravenous (human; anti-D IGIV) have experienced acute hemolysis, which is inconsistent with the typical presentation of extravascular hemolysis—the presumed mechanism of action of anti-D IGIV. Although the mechanism of anti-D-IGIV–associated acute hemolysis has not been established, the onset, signs/symptoms, and complications appear consistent with the intravascular hemolysis of acute hemolytic transfusion reactions (AHTRs). In transfusion medicine, the red blood cell (RBC) antigen-antibody incompatibility(-ies) that precipitate AHTRs can be detected in vitro with compatibility testing. Under the premise that anti-D-IGIV–associated acute hemolysis results from RBC antigen-antibody–mediated complement activation, this study evaluated whether the incompatibility(-ies) could be detected in vitro with a hemolysin assay, which would support the AHTR model as the hemolytic mechanism. STUDY DESIGN AND METHODS Seven anti-D IGIV lots were tested to determine the RBC antibody identities in those lots, including four lots that had been implicated in acute hemolytic episodes. Hemolysin assays were performed that tested each of 73 RBC specimens against each lot, including the RBCs of one patient who had experienced acute hemolysis after anti-D IGIV administration. RESULTS Only two anti-D IGIV lots contained RBC antibodies beyond those expected. No hemolysis endpoint was observed in any of the hemolysin assays. CONCLUSION Although the findings did not support the AHTR model, the results are reported to contribute knowledge about the mechanism of anti-D-IGIV–associated acute hemolysis and to prompt continued investigation into cause(s), prediction, and prevention of this potentially serious adverse event. PMID:19220820

  12. Evidence of direct estrogenic regulation of human corticotropin-releasing hormone gene expression. Potential implications for the sexual dimophism of the stress response and immune/inflammatory reaction.

    PubMed Central

    Vamvakopoulos, N C; Chrousos, G P

    1993-01-01

    Corticotropin-releasing hormone (CRH) plays major roles in coordination of the stress response and regulation of the immune/inflammatory reaction, two important functions associated with sexual dimorphism. Two overlapping segments of the 5' flanking region of the human (h) CRH gene, the proximal 0.9 kb (containing two perfect half-palindromic estrogen-responsive elements [EREs]) and the 2.4 kb (including the former and containing two additional perfect half-palindromic EREs), were examined for their ability to confer estrogen-mediated transcriptional enhancement to a homologous or heterologous promoter. The level of estrogen-induced transactivation by the 0.9- and 2.4-kb segments was determined by chloramphenicol acetyltransferase analysis in CV-1 cells cotransfected with estrogen receptor (ER) cDNA expression plasmids, and found to be respectively approximately 10% and 20% of that of the strongly estrogen-responsive Xenopus vitellogenin A2 enhancer. Gel retardation and immunoprecipitation demonstrated specific association between the perfect half-palindromic EREs of hCRH gene and the DNA binding domain of hER in vitro. These findings may constitute the basis of sexual dimorphism in the expression of the CRH gene in the central nervous system and periphery, and might shed light in existing gender differences in stress response and immune regulation. Images PMID:8408641

  13. The impact of glutathione S-transferase genotype and phenotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases.

    PubMed

    Liu, Hui; Ding, Liang; Zhang, Fangbin; Zhang, Yu; Gao, Xiang; Hu, Pinjin; Bi, Huichang; Huang, Min

    2015-10-01

    Azathioprine (AZA) is a thiopurine prodrug which is widely used in patients with inflammatory bowel disease (IBD). However, the use is limited in one-third of patients because of adverse drug reactions (ADRs) or a lack of clinical response. It has been considered that the polymorphic enzyme thiopurine S-methyltransferase (TPMT) plays an important role in the in vivo process of AZA and the occurrence of its myelotoxicity. Glutathione S-transferase (GST) mutation is another pharmacogenetic polymorphism which is probably involved in AZA metabolism and tolerance. The aim of this study was to investigate the association among GST polymorphism, enzyme activity and AZA-related ADRs in Chinese Han patients with IBD. We found that the patients who became neutropenic had a significantly higher GSTs activity when compared with of the patients who did not develop ADRs (analysis of variance, P < 0.001). There was also a significant underrepresentation of GSTP1*-105V allele among patients developing ADRs (odds ratio [OR] = 0.125, 95% confidence interval [CI] = 0.022-0.709, P = 0.0012). The patients with higher GST activity constituted a pharmacogenetic high risk group for leucopenia during AZA treatment. GST-P1 Ile105/Ile105 genotype appeared to be a promising marker indicating predisposition to AZA-related ADRs. PMID:26432087

  14. Effects of dimethyl sulphoxide on the synthesis of plasma proteins in the human hepatoma HepG2. Induction of an acute-phase-like reaction.

    PubMed Central

    Iwasa, F; Galbraith, R A; Sassa, S

    1988-01-01

    Effects of dimethyl sulphoxide (Me2SO) on the synthesis of plasma proteins by the human hepatoma cell line HepG2 were examined. Me2SO treatment resulted in decreased synthesis of albumin and alpha-fetoprotein, and in increased synthesis of haptoglobin. Plasma-protein profiles induced by Me2SO treatment were very similar to those seen in acute-phase reactions. PMID:3140793

  15. Influence of Double-Strand Break Repair on Radiation Therapy-Induced Acute Skin Reactions in Breast Cancer Patients

    SciTech Connect

    Mumbrekar, Kamalesh Dattaram; Fernandes, Donald Jerard; Goutham, Hassan Venkatesh; Sharan, Krishna; Vadhiraja, Bejadi Manjunath; Satyamoorthy, Kapaettu; Bola Sadashiva, Satish Rao

    2014-03-01

    Purpose: Curative radiation therapy (RT)-induced toxicity poses strong limitations for efficient RT and worsens the quality of life. The parameter that explains when and to what extent normal tissue toxicity in RT evolves would be of clinical relevance because of its predictive value and may provide an opportunity for personalized treatment approach. Methods and Materials: DNA double-strand breaks and repair were analyzed by microscopic γ-H2AX foci analysis in peripheral lymphocytes from 38 healthy donors and 80 breast cancer patients before RT, a 2 Gy challenge dose of x-ray exposed in vitro. Results: The actual damage (AD) at 0.25, 3, and 6 hours and percentage residual damage (PRD) at 3 and 6 hours were used as parameters to measure cellular radiosensitivity and correlated with RT-induced acute skin reactions in patients stratified as non-overresponders (NOR) (Radiation Therapy Oncology Group [RTOG] grade <2) and overresponders (OR) (RTOG grade ≥2). The results indicated that the basal and induced (at 0.25 and 3 hours) γ-H2AX foci numbers were nonsignificant (P>.05) between healthy control donors and the NOR and OR groups, whereas it was significant between ORs and healthy donors at 6 hours (P<.001). There was a significantly higher PRD in OR versus NOR (P<.05), OR versus healthy donors (P<.001) and NOR versus healthy donors (P<.01), supported further by the trend analysis (r=.2392; P=.0326 at 6 hours). Conclusions: Our findings strongly suggest that the measurement of PRD by performing γ-H2AX foci analysis has the potential to be developed into a clinically useful predictive assay.

  16. Morin, a dietary bioflavonol suppresses monosodium urate crystal-induced inflammation in an animal model of acute gouty arthritis with reference to NLRP3 inflammasome, hypo-xanthine phospho-ribosyl transferase, and inflammatory mediators.

    PubMed

    Dhanasekar, Chitra; Rasool, Mahaboobkhan

    2016-09-01

    The anti-inflammatory effect of morin, a dietary bioflavanol was explored on monosodium urate (MSU) crystal-induced inflammation in rats, an experimental model for acute gouty arthritis. Morin treatment (30mg/kg b.wt) significantly attenuated the ankle swelling and the levels of lipid peroxidation, nitric oxide, serum pro-inflammatory cytokines (tumor necrosis factor (TNF) -α, interleukin (IL)-1β, and IL-6), monocyte chemoattractant protein (MCP)-1, vascular endothelial growth factor (VEGF), prostaglandin E2 (PGE2), and articular elastase along with an increased anti-oxidant status (catalase (CAT) and superoxide dismutase (SOD)) in the joint homogenate of MSU crystal-induced rats. Histological assessment revealed that morin limited the diffusion of joint space, synovial hyperplasia, and inflammatory cell infiltrations. The mRNA expression of NLRP3 (nucleotide oligomerization domain (NOD)-like receptor family, pyrin domain containing 3) inflammasome, caspase-1, pro-inflammatory cytokines, MCP-1, inflammatory enzymes (inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2)), and nuclear factor-kappa B (NF-κB) p65 was found downregulated and HPRT (hypo-xanthine phospho-ribosyl transferase) mRNA expression was upregulated in morin treated MSU crystal-induced rats. In addition, morin treatment reduced the protein expression of NF-κB p65, p-NF-κB p65, iNOS, COX-2, and TNF-α. The results clearly demonstrated tha