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Sample records for acute inflammatory process

  1. 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

  2. Acute hemolytic vascular inflammatory processes are prevented by nitric oxide replacement or a single dose of hydroxyurea.

    PubMed

    Almeida, Camila Bononi; Souza, Lucas Eduardo Botelho; Leonardo, Flavia Costa; Costa, Fabio Trindade Maranhão; Werneck, Claudio C; Covas, Dimas Tadeu; Costa, Fernando Ferreira; Conran, Nicola

    2015-08-06

    Hemolysis and consequent release of cell-free hemoglobin (CFHb) impair vascular nitric oxide (NO) bioavailability and cause oxidative and inflammatory processes. Hydroxyurea (HU), a common therapy for sickle cell disease (SCD), induces fetal Hb production and can act as an NO donor. We evaluated the acute inflammatory effects of intravenous water-induced hemolysis in C57BL/6 mice and determined the abilities of an NO donor, diethylamine NONOate (DEANO), and a single dose of HU to modulate this inflammation. Intravenous water induced acute hemolysis in C57BL/6 mice, attaining plasma Hb levels comparable to those observed in chimeric SCD mice. This hemolysis resulted in significant and rapid systemic inflammation and vascular leukocyte recruitment within 15 minutes, accompanied by NO metabolite generation. Administration of another potent NO scavenger (2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) to C57BL/6 mice induced similar alterations in leukocyte recruitment, whereas hemin-induced inflammation occurred over a longer time frame. Importantly, the acute inflammatory effects of water-induced hemolysis were abolished by the simultaneous administration of DEANO or HU, without altering CFHb, in an NO pathway-mediated manner. In vitro, HU partially reversed the Hb-mediated induction of endothelial proinflammatory cytokine secretion and adhesion molecule expression. In summary, pathophysiological levels of hemolysis trigger an immediate inflammatory response, possibly mediated by vascular NO consumption. HU presents beneficial anti-inflammatory effects by inhibiting rapid-onset hemolytic inflammation via an NO-dependent mechanism, independently of fetal Hb elevation. Data provide novel insights into mechanisms of hemolytic inflammation and further support perspectives for the use of HU as an acute treatment for SCD and other hemolytic disorders.

  3. Activation of circulated immune cells and inflammatory immune adherence are involved in the whole process of acute venous thrombosis

    PubMed Central

    Wang, Le-Min; Duan, Qiang-Lin; Yang, Fan; Yi, Xiang-Hua; Zeng, Yu; Tian, Hong-Yan; Lv, Wei; Jin, Yun

    2014-01-01

    Objective: To investigate localization and distribution of integrin subunit β1, β2 and β3 and morphological changes of ligand-recepter binding in thrombi of acute pulmonary embolism (PE) patients and explore activation of circulated immune cells, inflammatory immune adherence and coagulation response in acute venous thrombosis. Methods: Thrombi were collected from patients with acute PE. Immunohistochemistry was done to detect the expression and distribution of integrin β1, β2 and β3 in cells within thrombi, and ligands of integrin subunit β1, β2 and β3 were also determined by immunohistochemistry within the thrombi. Results: 1) Acute venous thrombi were red thrombi composed of skeletons and filamentous mesh containing large amounts of red blood cells and white blood cells; 2) Integrin subunit β1, β2 and β3 were expressed on lymphocytes, neutrophils and platelets; 3) No expression of integrin β1 ligands: Laminin, Fibronectin, Collagen I or Collagen-II on lymphocytes; integrin β2 ligands including ICAM, factor X and iC3b are distributed on neutrophils, and ligand fibrinogen bound to neutrophils; integrin β3 was expressed on platelets which form the skeleton of thrombi and bound to fibrinogen to construct mesh structure; 4) Factor Xa was expressed on the filamentous mesh; 5) Filamentous mesh was fully filled with red blood cell dominant blood cells. Conclusion: Acute venous thrombosis is an activation process of circulated lymphocytes, neutrophils and platelets mainly, and a whole process including integrin subunit β2 and β3 binding with their ligands. Activation of immune cells, inflammatory immune adherence and coagulation response are involved in the acute venous thrombosis. PMID:24753749

  4. [Inflammatory process, histopathological aspects].

    PubMed

    Diébold, J

    1995-01-01

    Inflammation occurs only in conjunctive tissue and is the result of a close cooperation of various cells: blood platelets, endothelial cells, leucocytes, mast cells, fibroblasts. Successive phases can be recognized, the first is characterized by vascular phenomenons defining the acute phase. The second by cellular reactions defining the chronic or granulomatous phase. Various morphological patterns can be recognized in acute or chronic inflammation. In addition, hypersensitivity is responsible of peculiar morphology of the inflammatory response. After tissue necrosis, tissular debris should be eliminated by detersion. Then, a granulation tissue develops representing the first step of the healing, which will not be described here.

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

    PubMed

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

    2009-05-01

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

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

    PubMed

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

    2014-08-01

    Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P < 0.001) and prolonged relative refractory period (P < 0.01), without changes in threshold electrotonus. In contrast, in patients with acute-onset chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P < 0.05; decreased subexcitability, P < 0.05) and increased

  7. [The systemic inflammatory response syndrome correction in acute destructive pancreatitis].

    PubMed

    Agapov, M A; Khoreva, M V; Gorskiĭ, V A

    2011-01-01

    Acute pancreatitis is a disease of variable severity. In which some patients experience mild, self-limited attacks while others manifest a severe, highly morbid, and frequently lethal attack. The exact mechanisms by which diverse etiological factors induce an attack are still unclear. Recent studies have established the role played by inflammatory mediators in the pathogenesis of acute pancreatitis. In our research we have estimated influence of not steroid anti-inflammatory preparation on synthesis pro-and anti-inflammatory Cytokines at healthy donors and at patients with Acute pancreatitis.

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

    PubMed

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

    2011-09-01

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

  9. [CT - diagnosis and differential diagnosis of inflammatory acute intestinal conditions].

    PubMed

    Wiesner, W

    2011-08-24

    Multidetector-row CT has shown over the past years that it is able to provide reliable diagnoses in various acute intestinal conditions. The presented article provides an overview of primary and secondary inflammatory acute intestinal pathologies and their differential diagnoses.

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

    PubMed

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

    2010-02-01

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

  11. Fibrin(ogen) mediates acute inflammatory responses to biomaterials

    PubMed Central

    1993-01-01

    Although "biocompatible" polymeric elastomers are generally nontoxic, nonimmunogenic, and chemically inert, implants made of these materials may trigger acute and chronic inflammatory responses. Early interactions between implants and inflammatory cells are probably mediated by a layer of host proteins on the material surface. To evaluate the importance of this protein layer, we studied acute inflammatory responses of mice to samples of polyester terephthalate film (PET) that were implanted intraperitoneally for short periods. Material preincubated with albumin is "passivated," accumulating very few adherent neutrophils or macrophages, whereas uncoated or plasma- coated PET attracts large numbers of phagocytes. Neither IgG adsorption nor surface complement activation is necessary for this acute inflammation; phagocyte accumulation on uncoated implants is normal in hypogammaglobulinemic mice and in severely hypocomplementemic mice. Rather, spontaneous adsorption of fibrinogen appears to be critical: (a) PET coated with serum or hypofibrinogenemic plasma attracts as few phagocytes as does albumin-coated material; (b) in contrast, PET preincubated with serum or hypofibrinogenemic plasma containing physiologic amounts of fibrinogen elicits "normal" phagocyte recruitment; (c) most importantly, hypofibrinogenemic mice do not mount an inflammatory response to implanted PET unless the material is coated with fibrinogen or the animals are injected with fibrinogen before implantation. Thus, spontaneous adsorption of fibrinogen appears to initiate the acute inflammatory response to an implanted polymer, suggesting an interesting nexus between two major iatrogenic effects of biomaterials: clotting and inflammation. PMID:8245787

  12. Peripheral NLCR4 inflammasome participates in the genesis of acute inflammatory pain.

    PubMed

    Lopes, Alexandre H; Talbot, Jhimmy; Silva, Rangel L; Lima, Jonilson B; França, Rafael O; Verri, Waldiceu A; Mascarenhas, Danielle P; Ryffel, Bernhard; Cunha, Fernando Q; Zamboni, Dario S; Cunha, Thiago M

    2015-03-01

    Inflammatory hyperalgesia is a complex process that depends on the sensitization of primary nociceptive neurons triggered by proinflammatory mediators, such as interleukin 1β (IL-1β). Recently, the peripheral activation of caspase-1 (previously known as IL-1β-converting enzyme) was implicated in the induction of acute inflammatory pain by promoting the processing of IL-1β from its precursor form, pro-IL-1β. Caspase-1 activation in several systems requires the assembly of an intracellular molecular platform called an inflammasome. Inflammasomes consist of 1 nucleotide-binding oligomerization domain-like receptor (NLR), the adapter molecule apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), and caspase-1. NLRP3 and NLRC4 inflammasomes are well described. However, the identity of the inflammasome that is involved in the peripheral activation of caspase-1 that accounts for acute inflammatory hyperalgesia has not been described. The present findings demonstrated that mice deficient in NLRC4 or ASC, but not in NLRP3, present reduced mechanical and thermal acute inflammatory hyperalgesia induced by carrageenan. The reduced hyperalgesia was accompanied by significant impairments in the levels of mature forms of IL-1β (p17) and caspase-1 (p20) compared to wild-type mice at the inflammatory site. Therefore, these results identified the inflammasome components NLRC4 and ASC as the molecular platform involved in the peripheral activation of caspase-1 and IL-1β maturation, which are responsible for the induction of acute inflammatory pain. In conclusion, our study provides new therapeutic targets for the control of acute inflammatory pain.

  13. Acute disseminated encephalomyelitis and other inflammatory demyelinating variants.

    PubMed

    Scolding, Neil

    2014-01-01

    Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory central nervous system disorder characterized by acute or subacute onset of multifocal neurologic deficits with headache and impaired conscious level. Acute haemorrhagic leuoko-encephalitis (AHEM) is a more sever, often fatal variant. These disorders often follows a viral illness or vaccination, and are usually monophasic, though (probably more commonly in childhood) a multiphasic variant of ADEM is recognized. Because of the relative non-specificity of the clinical presentation (a sub-acute encephalopathy with focal signs), the differential diagnosis is wide; and distinction from the first episode of relapsing-remitting multiple sclerosis can occasionally be difficult. Here the clinical and investigational features of these disorders and their treatment are discussed.

  14. Acute coronary syndromes as auto-inflammatory disorders.

    PubMed

    Suzuki, Makoto

    2012-01-01

    From the onset to the healing stage of acute coronary syndromes, an endless inflammation has been presented with complex, multiple cross-talk mechanisms at the molecular, cellular, and organ levels. Even though the early reperfusion treatment either by thrombolysis or percutaneous coronary intervention provides the excellent clinical benefits in patients with acute coronary syndromes, ischemia/ reperfusion injury may somewhat offset those great advantages. Inflammation, although potentially protective, has been deeply associated with those detrimental conditions. The hexagonal vascular inflammatory network which is composed of activated various leukocytes, vascular endothelial cells, vascular smooth muscle cells, platelets, excess reactive oxygen species, and cholesterol may contribute these vicious circles. To address these complex syndromes with more benefits regarding the prevention and treatment, this review comprehensively updates the pathogenesis of acute coronary syndromes from the view points of vascular inflammation.

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

    PubMed

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

    2015-07-01

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

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

    PubMed

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

    2014-10-01

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

  17. [Incidence of acute pancreatitis in children with inflammatory bowel disease].

    PubMed

    Stawarski, Andrzej; Iwańczak, Franciszek

    2004-07-01

    The aim of our study was to estimate the frequency of acute pancreatitis and the frequency of increased activity of pancreatic enzymes in serum of children with inflammatory bowel disease (IBD). Analysis comprises 101 children aged from 3 to 18-years treated because of IBD in the period of 1998-2002: 79 children with ulcerative colitis (UC) and 22 children Crohn's disease (CD). The authors analyzed together 191 admissions because of UC and 51 because of CD. Acute pancreatitis was observed in 4.5% of children with CD and in 5.1% of children with UC. Significantly more often acute pancreatitis was recognized in children with moderate and severe stage of UC. Hyperamylasemia was observed in 27.3% of children with CD and in 12.7% of children with UC. Hyperlipasemia was observed only in children with UC (3.8%), elevated urinary amylase was observed in 4.5% of children with CD and in 8.86% children with UC. No correlations between the frequency of acute pancreatitis and medication were observed.

  18. 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.

  19. Anti-inflammatory effects of melatonin in a rat model of caerulein-induced acute pancreatitis.

    PubMed

    Carrasco, Cristina; Marchena, Ana M; Holguín-Arévalo, María S; Martín-Partido, Gervasio; Rodríguez, Ana B; Paredes, Sergio D; Pariente, José A

    2013-10-01

    The purpose of our study was to evaluate the protective effect of melatonin in a rat model of caerulein-induced acute pancreatitis. For the induction of experimental acute pancreatitis, four subcutaneous injections of caerulein (20 mgkg–1 body weight) were given to Wistar rats at 2-h intervals. Melatonin was injected intraperitoneally (25 mg kg–1 body weight) 30 min before each caerulein injection. After 12 h, rats were sacrificed by decapitation. Blood and pancreas samples were collected and processed for serological and histopathological studies,respectively. Lipase, a-amylase, corticosterone, total antioxidant power and cytokines interleukin (IL)-1b, IL-4 and tumour necrosis factor(TNF)-a were determined using commercial kits. ANOVA and Tukey tests (P<0.05) were performed for the statistical analysis of the results.Results showed that the administration of melatonin reduced histological damage induced by caerulein treatment as well as the hyperamylasemia and hyperlipidemia. Corticosterone and antioxidant total power were also reverted to basal activities. Furthermore, melatonin pre-treatment reduced pro-inflammatory cytokines IL-1b and TNF-a and increased the serum levels of anti-inflammatory cytokine IL-4. In conclusion,the findings suggest that the protective effect of melatonin in caerulein-induced acute pancreatitis is mediated by the anti-inflammatory ability of this indolamine. Thus, melatonin may have a protective effect against acute pancreatitis.

  20. Induced inflammatory process in Peripatus acacioi Marcus et Marcus (Onychophora).

    PubMed

    Silva, J R; Coelho, M P; Nogueira, M I

    2000-01-01

    The inflammatory response induced by the implant of a suture thread in Peripatus acacioi muscle was characterized under light and transmission electron microscopy (TEM). After 24 and 48 h granulocytes were observed migrating through the connective tissue toward the suture thread. These cells contain cytoplasmic eosinophilic granules as well as free granules near to the thread. There were few spherule cells with eccentric smooth kidney-shaped acidophilic nuclei and basophilic granules. Cells with intermediary characteristics as well as cells with a central basophilic nucleus with scarce acidophilic cytoplasm devoid of granules were also found. Under TEM, the granulocytic coelomocytes show small and homogeneous electron dense granules, while the spherule cells possess spherules that can be heterogeneous, granular, or with myelin figures. An acute induced inflammatory process is described for the first time in Onychophora and contributes to the scarce available literature on the function of the coelomocytes within this group.

  1. 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.

  2. Early identification of ‘acute-onset’ chronic inflammatory demyelinating polyneuropathy

    PubMed Central

    Sung, Jia-Ying; Tani, Jowy; Park, Susanna B.; Kiernan, Matthew C.

    2014-01-01

    Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P < 0.001) and prolonged relative refractory period (P < 0.01), without changes in threshold electrotonus. In contrast, in patients with acute-onset chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P < 0.05; decreased subexcitability, P < 0.05) and increased

  3. Sleep Disturbance and Older Adults' Inflammatory Responses to Acute Stress

    PubMed Central

    Heffner, Kathi L.; Ng, H. Mei; Suhr, Julie A.; France, Christopher R.; Marshall, Gailen D.; Pigeon, Wilfred R.; Moynihan, Jan A.

    2013-01-01

    Objectives Poor sleep diminishes mental and physical health. The objective of this study was to examine associations between sleep disturbance and interleukin-6 (IL-6) responses to acute mental stress in older adults. Design Observational study of community-dwelling, healthy older adults. Setting Participants completed the study in a clinical research laboratory of a mid-sized university. Participants Generally healthy, community-dwelling men and women 50 years of age and older. Measurements IL-6 and negative affect at rest and following a series of challenging cognitive tests; sleep quality; depressive symptoms; perceived stress; loneliness. Results Participants categorized as poor sleepers based on Pittsburgh Sleep Quality Index scores had significantly larger IL-6 responses to the cognitive stressors compared to good sleepers. The association between poor sleep and heightened IL-6 response to acute stress was not explained by other psychosocial factors previously linked to immune dysregulation, including depressive symptoms, perceived stress, and loneliness. Conclusions Findings add to the growing evidence for poor sleep as an independent risk factor for poor mental and physical health. Older adults may be particularly vulnerable to effects of sleep disturbance due to significant age-related changes in both sleep and inflammatory regulation. PMID:22327621

  4. Aged neutrophils contribute to the first line of defense in the acute inflammatory response

    PubMed Central

    Uhl, Bernd; Vadlau, Yannick; Zuchtriegel, Gabriele; Nekolla, Katharina; Sharaf, Kariem; Gaertner, Florian; Massberg, Steffen; Krombach, Fritz

    2016-01-01

    Under steady-state conditions, aged neutrophils are removed from the circulation in bone marrow, liver, and spleen, thereby maintaining myeloid cell homeostasis. The fate of these aged immune cells under inflammatory conditions, however, remains largely obscure. Here, we demonstrate that in the acute inflammatory response during endotoxemia, aged neutrophils cease returning to the bone marrow and instead rapidly migrate to the site of inflammation. Having arrived in inflamed tissue, aged neutrophils were found to exhibit a higher phagocytic activity as compared with the subsequently recruited nonaged neutrophils. This distinct behavior of aged neutrophils under inflammatory conditions is dependent on specific age-related changes in their molecular repertoire that enable these “experienced” immune cells to instantly translate inflammatory signals into immune responses. In particular, aged neutrophils engage Toll-like receptor-4- and p38 MAPK-dependent pathways to induce conformational changes in β2 integrins that allow these phagocytes to effectively accomplish their mission in the front line of the inflammatory response. Hence, ageing in the circulation might represent a critical process for neutrophils that enables these immune cells to properly unfold their functional properties for host defense. PMID:27609642

  5. TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events.

    PubMed

    Cavassani, Karen A; Ishii, Makoto; Wen, Haitao; Schaller, Matthew A; Lincoln, Pamela M; Lukacs, Nicholas W; Hogaboam, Cory M; Kunkel, Steven L

    2008-10-27

    Ligands from dying cells are a source of Toll-like receptor (TLR) activating agents. Although TLR3 is known to respond to RNA from necrotic cells, the relative importance of this response in vivo during acute inflammatory processes has not been fully explored. We observed the involvement of TLR3 activation during experimental polymicrobial septic peritonitis and ischemic gut injury in the absence of an exogenous viral stimulus. In TLR3-deficient mice, increased chemokine/cytokine levels and neutrophil recruitment characterized the initial inflammatory responses in both injury models. However, the levels of inflammatory chemokines and tumor necrosis factor alpha quickly returned to baseline in tlr3(-/-) mice, and these mice were protected from the lethal effects of sustained inflammation. Macrophages from tlr3(-/-) mice responded normally to other TLR ligands but did not respond to RNA from necrotic neutrophils. Importantly, an immunoneutralizing antibody directed against TLR3 attenuated the generation of inflammatory chemokines evoked by byproducts from necrotic neutrophils cultured with wild-type macrophages. In vivo, anti-TLR3 antibody attenuated the tissue injury associated with gut ischemia and significantly decreased sepsis-induced mortality. Collectively, these data show that TLR3 is a regulator of the amplification of immune response and serves an endogenous sensor of necrosis, independent of viral activation.

  6. Novel hematologic inflammatory parameters to predict acute mesenteric ischemia.

    PubMed

    Toptas, Mehmet; Akkoc, İbrahim; Savas, Yildiray; Uzman, Sinan; Toptas, Yasar; Can, Mehmet Mustafa

    2016-03-01

    Acute mesenteric ischaemia (AMI) is an emergency condition that requires urgent diagnosis. Neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) have been studied as inflammatory biomarkers in atherosclerosis, but data regarding AMI are lacking. The study population included patients with AMI (n = 46) versus age and sex-matched healthy controls (n = 46). Computed multidetector tomographic angiography was performed to diagnose AMI. NLR and PLR were calculated using complete blood count. C-reactive protein (CRP) levels were also analyzed. Neutrophil levels and lymphocytes were significantly higher in patients with AMI than in the control individuals (P < 0.001 and P = 0.43, respectively). NLR levels were significantly higher in patients with AMI compared with that in the control individuals (P < 0.001). Platelet levels did not reach statistical significance between the groups (P = 0.709). However, patients with AMI had significantly higher PLR levels than the control group (P = 0.039). CRP levels on admission were higher in patients with AMI in comparison with control individuals. There was also a positive correlation between NLR and CRP (r = 0.548, P < 0.001), and between PLR and CRP (r = 0.528, P < 0.001). NLR level greater than 4.5, measured on admission, yielded an area under the curve value of 0.790 (95% confidence interval 0.681-0.799, sensitivity 77%, specificity 72%), and PLR level of greater than 157 yielded an area under the curve value of 0.604 (95% confidence interval 0.486-0.722, sensitivity 59%, specificity 65%). Patients with AMI had increased NLR, PLR, and CRP levels compared with controls. Increased NLR and PLR was an independent predictor of AMI.

  7. 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.

  8. [Clinical and microbiological study of acute pelvic inflammatory disease].

    PubMed

    Ovalle, A; Martínez, M A; Casals, A; Yuhaniak, R; Giglio, M S

    1993-01-01

    Upper genital tract infection was investigated in 46 women admitted to hospital with clinic diagnosis of acute pelvic inflammatory disease (PID) and 62 control women accepted to hospital for laparoscopy Fallopian tubes sterilization. Diagnosis was ratified by laparoscopy in mild and moderate salpingitis; culdocentesis and ultrasonography were performed in severe salpingitis and endometrial sample was made in endometritis. Microbiological specimens were taken from the cervix and abdomen. Antecedents and complete clinical studies were obtained. Patients were treated with antibiotic association sodic G penicillin, chloramphenicol and gentamicin. Risk factors to development PID were: single female (p < 0.05), multiple sexual partner (p < 0.01), previous PID (p < 0.05), infertility (p < 0.05), mean year of IUD use in severe salpingitis (p = 0.05) and mean years of age from women with sexually transmitted bacterias (STB) vs endogenous bacterias (EB) (p < 0.05). In the control group no abdomen bacterias were isolated. In patients with PID, C. trachomatis was detected by serology in 28.3%. N. gonorrhoeae was isolated from the cervix in 23.9% and from the abdomen 17.4%. Besides it was isolated from the abdomen: M. hominis 17.3% and E. coli 15.2%. STB were isolated in 54.3% and EB in 47.8% of the patients. Bacterial association was present on the 37%. Cervix isolation of G. vaginalis and Mycoplasma were not correlated with development of PID. Cervix microbiological samples were useful to know abdomen microbic etiology. They coincide with those in the 90.9%. EB were more frequently isolated from severe salpingitis (p = 0.05) and STB from mild and moderate salpingitis (p = 0.05). Antibiotic association cured all the mild and moderate salpingitis with independence of bacterial etiology. Failure occurred in 2 diffuse peritonitis and 13/14 tubo-ovarian abscesses. Surgery used in severe salpingitis and diffuse peritonitis, principally consisted in anexectomy, peritoneal toilet and

  9. Processing of Factor XII during Inflammatory Reactions

    PubMed Central

    Jukema, Bernard Nico; de Maat, Steven; Maas, Coen

    2016-01-01

    The contact system was originally identified as an obsolete part of the coagulation system, but it has been repeatedly implicated in inflammatory states, such as infection, as well as in allergic- and chronic inflammatory disease. Under these conditions, there is surprisingly little evidence that factor XII (FXII) acts as a coagulation factor, and its activity appears to be mainly directed toward activation of the kallikrein–kinin system. The contact system factors interact with pathogens as well as cells of the (innate) immune system on several levels. Among others, these cells may provide negatively charged surfaces that contribute to contact activation as well as release enzymes that feed into this system. Furthermore, cellular receptors have been identified that bind contact factors at sites of inflammation. Based on the accumulated evidence, we propose a model for enzymatic crosstalk between inflammatory cells and the plasma contact system. During these reactions, FXII is enzymatically cleaved by non-contact system enzymes. This generates unactivated FXII fragments that can subsequently be rapidly activated in the fluid phase. The resulting enzyme lacks procoagulant properties, but retains its pro-inflammatory characteristic as a prekallikrein activator. PMID:27867935

  10. Neurohormonal and Inflammatory Hyper-Responsiveness to Acute Mental Stress in Depression

    PubMed Central

    Weinstein, Ali A.; Deuster, Patricia A.; Francis, Jennifer L.; Bonsall, Robert W.; Tracy, Russell P.; Kop, Willem J.

    2010-01-01

    Depression is associated with dysregulated hypothalamic-pituitary-adrenal (HPA) axis function, overactivity of the sympathoadrenal system, and increased levels of inflammation markers. It is not known whether these biological processes are disproportionately elevated in response to acute negative emotional arousal by mental stress (MS). The present study investigates responses of neurohormones and inflammatory markers to MS in 14 clinically depressed (age: 42±10 years; 50% female) and 14 non-depressed control participants (age: 39±6 years; 50% female). Heightened acute MS reactivity was documented in depressed participants (adrenocorticotropic hormone, ρ=0.001; Norepinephrine, ρ=0.042; Epinephrine, ρ=0.039), and a delayed increase in cortisol was observed (ρ=0.002). Inflammation markers increased more strongly in depressed vs. non-depressed participants (IL-6, ρ=0.027; tumor necrosis factor-alpha, ρ=0.050; and recovery C-reactive protein, ρ=0.003). It is concluded that depressed individuals display hyper-reactivity of neuroimmunological markers in response to acute negative emotions. This hyper-reactivity may serve a pathologic role in the elevated morbidity and mortality risk associated with depression. PMID:20117167

  11. Anti-inflammatory effects of formoterol and ipratropium bromide against acute cadmium-induced pulmonary inflammation in rats.

    PubMed

    Zhang, Wenhui; Fievez, Laurence; Cheu, Esteban; Bureau, Fabrice; Rong, Weifang; Zhang, Fan; Zhang, Yong; Advenier, Charles; Gustin, Pascal

    2010-02-25

    In this study, the anti-inflammatory properties of formoterol and ipratropium bromide, alone or in combination, were investigated in a rat model of acute pulmonary inflammation induced by cadmium inhalation. Airway resistance and inflammatory responses, including matrix metalloproteinease-2 (MMP-2) and matrix metalloproteinease-9 (MMP-9) activities, were evaluated. Compared to values obtained in rats exposed to cadmium, pretreatment by bronchodilators administered alone significantly prevented the cadmium-induced increase of airway resistance. Formoterol elicited a significant decrease in total cell number, neutrophil and macrophage counts in bronchoalveolar lavage fluid, whereas ipratropium bromide reduced neutrophil numbers. The two compounds administered alone significantly attenuated the lung lesions associated with parenchyma inflammatory cell influx and congestion observed in the cadmium group. The increased MMP-9 activity was significantly attenuated. Although only formoterol induced a decrease protein concentration in bronchoalveolar lavage fluid, both compounds inhibited the pulmonary edema by reducing wet-to-dry weight ratio which returned to values similar to those recorded in the sham group. All the effects of formoterol on the cadmium-induced inflammatory responses were reversed by propranolol. Similar anti-inflammatory effects were obtained in rats pretreated with ilomastat which showed a significant reduction on inflammatory cell infiltration and MMP-9 activity in bronchoalveolar lavage fluid. Neither synergistic nor additive effects were obtained when the two bronchodilators were administered in combination. In conclusion, formoterol and ipratropium bromide partially protect the lungs against the inflammation by reducing neutrophilic infiltration. This protective effect is associated with reduced MMP-9 activity known to play an important pro-inflammatory role in acute inflammatory process.

  12. Fatigability Disrupts Cognitive Processes' Regulation of Inflammatory Reactivity in Old Age

    PubMed Central

    Lin, Feng; Roiland, Rachel; Polesskaya, Oksana; Chapman, Benjamin; Johnson, Melissa; Brasch, Judith; Chen, Ding-Geng; Mapstone, Mark

    2014-01-01

    Objectives High fatigability, a dysfunctional adaption to fatigue, may lead to difficulties performing otherwise regularly encountered cognitive activities and may be related to pro-inflammatory reactivity. The purpose of the study was to investigate the effect of fatigability on cognitive processes and inflammatory response following an acute cognitive stress task in older adults. Design An observational laboratory stress reactivity study. Setting A light- and temperature-controlled laboratory. Participants Fifty-five community-dwelling individuals aged 75 years or older. Measurements We measured interleukin (IL)-6, self-reported acute fatigue, and frontally-oriented cognitive processes as part of a demanding set of cognitive tasks intended to induce stress. Results Subjects were classified into groups of low and high fatigability based on cluster analysis of their self-report acute fatigue before and after the cognitive tasks. The two clusters were comparable on levels of baseline IL-6 and cognitive processes; however, the high fatigability cluster had significantly higher levels of IL-6 response than the low fatigability cluster. After controlling for multiple covariates, fatigability moderated the relationship between speed of processing and IL-6 reactivity. Further exploratory analyses indicated significant adverse associations between speed of processing and attention and IL-6 reactivity in the group with low but not high fatigability. Conclusions While observational, these data are consistent with the notion that pro-inflammatory states in older adults might be reduced by improvements in cognitive processes. Since fatigability was associated with increased acute inflammatory response and disrupted the normal stress regulation provided by the cognitive processes, future randomized studies might examine whether fatigability alleviation reduces IL-6. PMID:24388221

  13. Enhanced natural killer activity and production of pro-inflammatory cytokines in mice selected for high acute inflammatory response (AIRmax).

    PubMed

    Castoldi, Lindsey; Golim, Marjorie Assis; Filho, Orlando Garcia Ribeiro; Romagnoli, Graziela Gorete; Ibañez, Olga Célia Martinez; Kaneno, Ramon

    2007-03-01

    Strains of mice with maximal and minimal acute inflammatory responsiveness (AIRmax and AIRmin, respectively) were developed through selective breeding based on their high- or low-acute inflammatory responsiveness. Previous reports have shown that AIRmax mice are more resistant to the development of a variety of tumours than AIRmin mice, including spontaneous metastasis of murine melanoma. Natural killer activity is involved in immunosurveillance against tumour development, so we analysed the number and activity of natural killer cells (CD49b(+)), T-lymphocyte subsets and in vitro cytokine production by spleen cells of normal AIRmax and AIRmin mice. Analysis of lymphocyte subsets by flow cytometry showed that AIRmax mice had a higher relative number of CD49b(+) cells than AIRmin mice, as well as cytolytic activity against Yac.1 target cells. The number of CD3(+) CD8(+) cells was also higher in AIRmax mice. These findings were associated with the ability of spleen cells from AIRmax mice in vitro to produce higher levels of the pro-inflammatory cytokines tumour necrosis factor-alpha, interleukin-12p40 and interferon-gamma but not the anti-inflammatory interleukin-10. Taken together, our data suggest that the selective breeding to achieve the AIRmax and AIRmin strains was able to polarize the genes associated with cytotoxic activity, which can be responsible for the antitumour resistance observed in AIRmax mice.

  14. 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

  15. S100A8 promotes migration and infiltration of inflammatory cells in acute anterior uveitis

    PubMed Central

    Wang, Yuqin; Zhang, Zuhui; Zhang, Laihe; Li, Xinxin; Lu, Rui; Xu, Peipei; Zhang, Xuhong; Dai, Mali; Dai, Xiaodan; Qu, Jia; Lu, Fan; Chi, Zailong

    2016-01-01

    Uveitis, the pathologic condition of inflammation of the uvea, frequently leads to severe vision loss and blindness. S100A8 is a calcium-binding protein which mainly expresses in granulocytes and monocytes and plays a prominent role in the regulation of inflammatory processes and immune response. Here, we determined the role of S100A8-positive cells in acute anterior uveitis (AAU) and keratitis. In rat models of endotoxin (lipopolisaccharide, LPS) -induced uveitis (EIU) and keratitis, S100A8-positive granulocytes and monocytes increased significantly in the iris-ciliary body and cornea as well as in the blood. Interestingly, Glucocorticoids slightly increased S100A8 levels in leukocytes, but reduced its presence significantly in the iris-ciliary body after LPS injection. Moreover, inhibition of NF-kB activation remarkably suppressed both progression of AAU and total S100A8 levels in leukocytes and the iris-ciliary body after LPS administration. Additionally, S100A8 protein level was also found to be elevated in the serum of AAU patients parallel with the progression of AAU through the designated clinical stages. Thus, S100A8 plays a pivotal role in the processes of AAU through involvement in migration and infiltration of S100A8-positive cells. Our findings suggest that serum levels of S100A8 protein can be used to monitor inflammatory activity in AAU. PMID:27786310

  16. Synergistic effects of anethole and ibuprofen in acute inflammatory response.

    PubMed

    Wisniewski-Rebecca, Edirlene S; Rocha, Bruno A; Wiirzler, Luiz A M; Cuman, Roberto K N; Velazquez-Martinez, Carlos A; Bersani-Amado, Ciomar A

    2015-12-05

    This study assessed the effect of the combination of anethole and ibuprofen in comparison with monotherapy by either drug alone, using two in vivo inflammatory models, namely the pleurisy and paw edema in rats. We also measured the levels of the TNF protein in plasma, and the ability of anethole to inhibit, in vitro, the activity of the cyclooxygenase 1 and cyclooxygenase 2 enzymes. The test drugs (anethole; ibuprofen; anethole + ibuprofen), at different doses, were administered once (p.o.) 60 min before the induction of the inflammatory response. The association of anethole + ibuprofen inhibited the development of the inflammatory response in both models used. This effect can be partially explained by the inhibitory action on the production of TNF and of COX isoforms. The isobologram analysis evidenced a synergistic effect between ibuprofen and anethole, because the combination of drugs showed a higher inhibitory potential than either drug alone.

  17. [Target Molecule for a Demyelinating Type of Guillain-Barré Syndrome, Acute Inflammatory Demyelinating Polyneuropathy].

    PubMed

    Mori, Masahiro

    2015-11-01

    Guillain-Barré syndrome is classified into demyelinating type, acute inflammatory demyelinating polyneuropathy (AIDP) and axonal form, acute axonal motor neuropathy (AMAN). It has been clearly established that the target molecule for the former is a ganglioside. In contrast, despite years of effort, the target molecule for the latter has not been identified. Recently, molecules around the nodes of Ranvier have entered the spotlight, and "moesin" was reported to be a target molecule for cytomegalovirus associated-AIDP.

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

    PubMed

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

    2014-06-15

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

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

    PubMed Central

    Kokkonen, Tuomo S.; Karttunen, Tuomo J.

    2015-01-01

    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

  20. An animal model of chronic inflammatory pain: pharmacological and temporal differentiation from acute models.

    PubMed

    Wilson, Alex W; Medhurst, Stephen J; Dixon, Claire I; Bontoft, Nick C; Winyard, Lisa A; Brackenborough, Kim T; De Alba, Jorge; Clarke, Christopher J; Gunthorpe, Martin J; Hicks, Gareth A; Bountra, Chas; McQueen, Daniel S; Chessell, Iain P

    2006-08-01

    Clinically, inflammatory pain is far more persistent than that typically modelled pre-clinically, with the majority of animal models focussing on short-term effects of the inflammatory pain response. The large attrition rate of compounds in the clinic which show pre-clinical efficacy suggests the need for novel models of, or approaches to, chronic inflammatory pain if novel mechanisms are to make it to the market. A model in which a more chronic inflammatory hypersensitivity phenotype is profiled may allow for a more clinically predictive tool. The aims of these studies were to characterise and validate a chronic model of inflammatory pain. We have shown that injection of a large volume of adjuvant to the intra-articular space of the rat knee results in a prolonged inflammatory pain response, compared to the response in an acute adjuvant model. Additionally, this model also results in a hypersensitive state in the presence and absence of inflammation. A range of clinically effective analgesics demonstrate activity in this chronic model, including morphine (3mg/kg, t.i.d.), dexamethasone (1mg/kg, b.i.d.), ibuprofen (30mg/kg, t.i.d.), etoricoxib (5mg/kg, b.i.d.) and rofecoxib (0.3-10mg/kg, b.i.d.). A further aim was to exemplify the utility of this chronic model over the more acute intra-plantar adjuvant model using two novel therapeutic approaches; NR2B selective NMDA receptor antagonism and iNOS inhibition. Our data shows that different effects were observed with these therapies when comparing the acute model with the model of chronic inflammatory joint pain. These data suggest that the chronic model may be more relevant to identifying mechanisms for the treatment of chronic inflammatory pain states in the clinic.

  1. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome.

    PubMed

    Bhatia, Madhav; Moochhala, Shabbir

    2004-02-01

    Inflammatory response leading to organ dysfunction and failure continues to be the major problem after injury in many clinical conditions such as sepsis, severe burns, acute pancreatitis, haemorrhagic shock, and trauma. In general terms, systemic inflammatory response syndrome (SIRS) is an entirely normal response to injury. Systemic leukocyte activation, however, is a direct consequence of a SIRS and if excessive, can lead to distant organ damage and multiple organ dysfunction syndrome (MODS). When SIRS leads to MODS and organ failure, the mortality becomes high and can be more than 50%. Acute lung injury that clinically manifests as acute respiratory distress syndrome (ARDS) is a major component of MODS of various aetiologies. Inflammatory mediators play a key role in the pathogenesis of ARDS, which is the primary cause of death in these conditions. This review summarizes recent studies that demonstrate the critical role played by inflammatory mediators such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, platelet activating factor (PAF), IL-10, granulocyte macrophage-colony stimulating factor (GM-CSF), C5a, intercellular adhesion molecule (ICAM)-1, substance P, chemokines, VEGF, IGF-I, KGF, reactive oxygen species (ROS), and reactive nitrogen species (RNS) in the pathogenesis of ARDS. It is reasonable to speculate that elucidation of the key mediators in ARDS coupled with the discovery of specific inhibitors would make it possible to develop clinically effective anti-inflammatory therapy.

  2. Inflammatory triggers of acute rejection of organ allografts

    PubMed Central

    Mori, Daniel N.; Kreisel, Daniel; Fullerton, James N.; Gilroy, Derek W.; Goldstein, Daniel R.

    2014-01-01

    Summary Solid organ transplantation is a vital therapy for end stage diseases. Decades of research has established that the components of the adaptive immune system are critical for transplant rejection, but the role of the innate immune system in organ transplantation is just emerging. Accumulating evidence indicates that the innate immune system is activated at the time of organ implantation by the release of endogenous inflammatory triggers. This review discusses the nature of these triggers in organ transplantation and also potential mediators that may enhance inflammation resolution after organ implantation. PMID:24517430

  3. Aging predisposes to acute inflammatory induced pathology after tumor immunotherapy.

    PubMed

    Bouchlaka, Myriam N; Sckisel, Gail D; Chen, Mingyi; Mirsoian, Annie; Zamora, Anthony E; Maverakis, Emanual; Wilkins, Danice E C; Alderson, Kory L; Hsiao, Hui-Hua; Weiss, Jonathan M; Monjazeb, Arta M; Hesdorffer, Charles; Ferrucci, Luigi; Longo, Dan L; Blazar, Bruce R; Wiltrout, Robert H; Redelman, Doug; Taub, Dennis D; Murphy, William J

    2013-10-21

    Cancer commonly occurs in the elderly and immunotherapy (IT) is being increasingly applied to this population. However, the majority of preclinical mouse tumor models assessing potential efficacy and toxicities of therapeutics use young mice. We assessed the impact of age on responses to systemic immune stimulation. In contrast to young mice, systemic cancer IT regimens or LPS given to aged mice resulted in rapid and lethal toxicities affecting multiple organs correlating with heightened proinflammatory cytokines systemically and within the parenchymal tissues. This inflammatory response and increased morbidity with age was independent of T cells or NK cells. However, prior in vivo depletion of macrophages in aged mice resulted in lesser cytokine levels, increased survival, and decreased liver histopathology. Furthermore, macrophages from aged mice and normal human elderly volunteers displayed heightened TNF and IL-6 production upon in vitro stimulation. Treatment of both TNF knockout mice and in vivo TNF blockade in aged mice resulted in significant increases in survival and lessened pathology. Importantly, TNF blockade in tumor-bearing, aged mice receiving IT displayed significant anti-tumor effects. These data demonstrate the critical role of macrophages in the age-associated hyper-inflammatory cytokine responses to systemic immunostimulation and underscore the importance of performing preclinical assessments in aged mice.

  4. Aging predisposes to acute inflammatory induced pathology after tumor immunotherapy

    PubMed Central

    Bouchlaka, Myriam N.; Sckisel, Gail D.; Chen, Mingyi; Mirsoian, Annie; Zamora, Anthony E.; Maverakis, Emanual; Wilkins, Danice E.C.; Alderson, Kory L.; Hsiao, Hui-Hua; Weiss, Jonathan M.; Monjazeb, Arta M.; Hesdorffer, Charles; Ferrucci, Luigi; Longo, Dan L.; Blazar, Bruce R.; Wiltrout, Robert H.; Redelman, Doug; Taub, Dennis D.

    2013-01-01

    Cancer commonly occurs in the elderly and immunotherapy (IT) is being increasingly applied to this population. However, the majority of preclinical mouse tumor models assessing potential efficacy and toxicities of therapeutics use young mice. We assessed the impact of age on responses to systemic immune stimulation. In contrast to young mice, systemic cancer IT regimens or LPS given to aged mice resulted in rapid and lethal toxicities affecting multiple organs correlating with heightened proinflammatory cytokines systemically and within the parenchymal tissues. This inflammatory response and increased morbidity with age was independent of T cells or NK cells. However, prior in vivo depletion of macrophages in aged mice resulted in lesser cytokine levels, increased survival, and decreased liver histopathology. Furthermore, macrophages from aged mice and normal human elderly volunteers displayed heightened TNF and IL-6 production upon in vitro stimulation. Treatment of both TNF knockout mice and in vivo TNF blockade in aged mice resulted in significant increases in survival and lessened pathology. Importantly, TNF blockade in tumor-bearing, aged mice receiving IT displayed significant anti-tumor effects. These data demonstrate the critical role of macrophages in the age-associated hyper-inflammatory cytokine responses to systemic immunostimulation and underscore the importance of performing preclinical assessments in aged mice. PMID:24081947

  5. 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

  6. Pro-inflammatory effects of hydrogen sulphide on substance P in caerulein-induced acute pancreatitis.

    PubMed

    Bhatia, Madhav; Sidhapuriwala, Jenab N; Ng, Siaw Wei; Tamizhselvi, Ramasamy; Moochhala, Shabbir M

    2008-04-01

    Hydrogen sulphide (H(2)S), a novel gasotransmitter, has been recognized to play an important role in inflammation. Cystathionine-gamma-lyase (CSE) is a major H(2)S synthesizing enzyme in the cardiovascular system and DL-propargylglycine (PAG) is an irreversible inhibitor of CSE. Substance P (SP), a product of preprotachykinin-A (PPT-A) gene, is a well-known pro-inflammatory mediator which acts principally through the neurokinin-1 receptor (NK-1R). We have shown an association between H(2)S and SP in pulmonary inflammation as well as a pro-inflammatory role of H(2)S and SP in acute pancreatitis. The present study was aimed to investigate the interplay between pro-inflammatory effects of H(2)S and SP in a murine model of caerulein-induced acute pancreatitis. Acute pancreatitis was induced in mice by 10 hourly intraperitoneal injections of caerulein (50 (g/kg). PAG (100 mg/kg, i.p.) was administered either 1 hr before (prophylactic) or 1 hr after (therapeutic) the first caerulein injection. PAG, given prophylactically as well as therapeutically, significantly reduced plasma H(2)S levels and pancreatic H(2)S synthesizing activities as well as SP concentrations in plasma, pancreas and lung compared with caerulein-induced acute pancreatitis. Furthermore, prophylactic as well as therapeutic administration of PAG significantly reduced PPT-A mRNA expression and NK-1R mRNA expression in both pancreas and lung when compared with caerulein-induced acute pancreatitis. These results suggest that the pro-inflammatory effects of H(2)S may be mediated by SP-NK-1R pathway in acute pancreatitis.

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

    PubMed

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

    2012-01-01

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

  8. 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.

  9. 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.

  10. Anti-Inflammatory Properties of NAP in Acute Toxoplasma Gondii-Induced Ileitis in Mice.

    PubMed

    Heimesaat, Markus M; Fischer, André; Kühl, Anja A; Göbel, Ulf B; Gozes, Illana; Bereswill, Stefan

    2015-09-01

    The octapeptide NAP has been shown to exert neuroprotective properties. Here, we investigated potential anti-inflammatory effects of NAP in an acute ileitis model. To address this, C57BL/6j mice were perorally infected with Toxoplasma gondii (day 0). Within 1 week postinfection (p.i.), placebo (PLC)-treated mice developed acute ileitis due to Th1-type immune responses. Mice that were subjected to intraperitoneal NAP treatment from day 1 until day 6 p.i., however, developed less distinct macroscopic and microscopic disease as indicated by less body weight loss, less distinct histopathological ileal changes, and lower ileal apoptotic, but higher proliferating cell numbers, less abundance of neutrophils, macrophages, monocytes, and T lymphocytes, but higher numbers of regulatory T cells in the ileal mucosa and lamina propria, and lower concentrations of pro-inflammatory mediators in the ilea as compared to PLC controls at day 7 p.i. Remarkably, NAP-mediated anti-inflammatory effects could also be observed in extra-intestinal compartments including liver and spleen. Strikingly, lower MCP-1, TNF, and IL-12p70 serum concentrations in NAP as compared to PLC-treated mice at day 7 p.i. indicate a pronounced systemic anti-inflammatory effect of NAP in acute ileitis. These findings provide first evidence for NAP as a potential novel treatment option in intestinal inflammation.

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

    PubMed Central

    Szombath, Gergely; Rokonál, Patrik; Mátis, Gábor; Neogrády, Zsuzsanna

    2016-01-01

    Purpose. Dysfunction of matriptase-2 can be involved in iron regulatory disorder via downregulation of hepcidin expression. In the present study, we investigated the effects of 3-amidinophenylalanine-derived matriptase inhibitors on porcine hepatic inflammatory cell models. Methods. Hepatocyte-Kupffer cell cocultures (ratio of 2 : 1 and 6 : 1) were treated with four structurally related matriptase inhibitors at 50 μM. Cell cytotoxicity and relative expressions of IL-6 and IL-8 and the levels of hepcidin were determined by MTS and porcine-specific ELISA. The extracellular H2O2 contents were analyzed by Amplex Red method. Results. Matriptase inhibitors at 50 µM for 24 h did not increase cell death rate. The elevated ROS production observed after short-term application of inhibitor MI-441 could be correlated with lowered hepcidin expression. MI-460 could significantly enhance hepcidin levels in the supernatants of cocultures (by 62.21 ± 26.8% in hepatocyte-Kupffer cell, 2 : 1, and by 42.6 ± 14.3% in hepatocyte-Kupffer cell, 6 : 1, cocultures, resp.). No significant changes were found in IL-6 and IL-8 levels in cocultures exposed to matriptase inhibitors. Conclusions. Based on in vitro findings, administration of MI-460 via modulation of hepcidin expression without cytotoxic and oxidative stress inducing properties might be a reliable alternative to treat iron overload in human and veterinary clinical practice. PMID:27642598

  12. Intravenous immunoglobulin treatment for acute fulminant inflammatory cardiomyopathy: Series of six patients and review of literature

    PubMed Central

    Goland, Sorel; Czer, Lawrence SC; Siegel, Robert J; Tabak, Steven; Jordan, Stanley; Luthringer, Daniel; Mirocha, James; Coleman, Bernice; Kass, Robert M; Trento, Alfredo

    2008-01-01

    BACKGROUND: Although an autoimmune mechanism has been postulated for myocarditis and acute-onset inflammatory dilated cardiomyopathy (DCM), immunomodulatory treatment strategies are still under investigation. METHODS AND RESULTS: The clinical data of six patients with acute inflammatory DCM referred for evaluation for possible heart transplantation were reviewed. All patients were admitted with acute congestive heart failure and severely impaired left ventricular (LV) function and were treated with high-dose (2 g/kg) intravenous immunoglobulin (IVIG). The diagnosis of acute inflammatory DCM was based on recent onset of congestive heart failure (New York Heart Association functional class III or IV) with severely depressed LV ejection fraction ([LVEF] 30% or lower) occurring shortly after viral-like illness. All patients had inflammation on endomyocardial biopsy or elevated cardiac enzymes, as well as a normal coronary angiogram. All patients were in New York Heart Association class I or II at the time of hospital discharge. The mean LVEF improved from 21.7±7.5% at baseline to 50.3±8.6% at discharge (P=0.005). Four patients had complete recovery (LVEF 50% or higher) and two patients had partial LV recovery. Patients were followed for a median 13.2 months (range two to 24 months) and had a mean LVEF of 53±6% (P not significant versus LVEF at discharge). CONCLUSIONS: Therapy with intravenous high-dose IVIG may be a potentially useful treatment in selected patients if given early in the course of acute fulminant inflammatory DCM. A randomized, prospective trial is warranted to prove the real benefit of IVIG in this patient population. PMID:18612500

  13. 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

  14. Modulation of inflammatory response via α2-adrenoceptor blockade in acute murine colitis

    PubMed Central

    Bai, A; Lu, N; Guo, Y; Chen, J; Liu, Z

    2009-01-01

    Inflammatory bowel disease (IBD) is characterized by heavy production of proinflammatory cytokines such as tumour necrosis factor (TNF)-α and interleukin (IL)-1β. Interactions of the autonomic nervous system with local immune cells play an important role in the development of IBD, and the balance of autonomic nerve function is broken in IBD patients with sympathetic overactivity. However, the function of catecholamines in the progress of colitis is unclear. In this study, we examined the role of catecholamines via α2-adrenoreceptor in acute murine colitis. The expression of tyrosine hydroxylase (TH) and dopamine b-hydroxylase (DBH), two rate-limiting enzymes in catecholamine synthesis, was detected by immunohistochemistry in murine colitis. Murine colitis was induced by dextran sodium sulphate or trinitrobenzene sulphonic acid (TNBS), and the mice were administered RX821002 or UK14304, α2-adrenoceptor antagonists or agonists. Colitis was evaluated by clinical symptoms, myeloperoxidase assay, TNF-α and IL-1β production and histology. Lamina propria mononuclear cells (LPMCs) from mice with TNBS colitis were cultured in the absence or presence of RX821002 or UK14304, and stimulated further by lipopolysaccharide. TH and DBH are induced in LPMCs of inflamed colon, the evidence of catecholamine synthesis during the process of colitis. RX821002 down-regulates the production of proinflammatory cytokines from LPMCs, while UK14304 leads to exacerbation of colitis. Together, our data show a critical role of catecholamines via α2-adrenoreceptors in the progress of acute colitis, and suggest that use of the α2-adrenoceptor antagonist represents a novel therapeutic approach for the management of colitis. PMID:19250273

  15. 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

  16. Acute Hemorrhagic Myositis in Inflammatory Myopathy and Review of the Literature

    PubMed Central

    Van Gelder, Howard; Wu, Kim M.; Gharibian, Nayiri; Patel, Dharmi B.; Clements, Philip J.; Heinze, Emil R.; Morris, Robert I.; Wong, Andrew L.

    2014-01-01

    We describe two patients with dermatomyositis that presented with interstitial lung disease, positive V and Shawl sign who developed acute spontaneous abdominal/retroperitoneal bleed. Both patients expired despite aggressive treatment and resuscitation. Hemorrhagic myositis in these two patients with inflammatory myopathy is a very rare complication. The association of anti-Ro52 with this potentially very serious complication remains unclear. This potential relationship should be further evaluated in future studies. PMID:25379317

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

    PubMed

    Sanmugapriya, E; Shanmugasundaram, P; Venkataraman, S

    2005-01-01

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

  18. Inflammatory and Antioxidant Pattern Unbalance in “Clopidogrel-Resistant” Patients during Acute Coronary Syndrome

    PubMed Central

    Gori, Anna Maria; Cecchettini, Antonella; Parodi, Guido; Marcucci, Rossella; Parolini, Marina; Romagnuolo, Ilaria; Citti, Lorenzo; Abbate, Rosanna

    2015-01-01

    Background. In acute coronary syndrome (ACS), inflammation and redox response are associated with increased residual platelet reactivity (RPR) on clopidogrel therapy. We investigated whether clopidogrel interaction affects platelet function and modulates factors related to inflammation and oxidation in ACS patients differently responding to clopidogrel. Material and Methods. Platelet aggregation was measured in 29 ACS patients on dual (aspirin/clopidogrel) antiplatelet therapy. Nonresponders (NR) were defined as RPR ≥70% by ADP. Several inflammatory and redox parameters were assayed and platelet proteome was determined. Results. Eight (28%) out of 29 ACS patients resulted NR to clopidogrel. At 24 hours, the levels of Th2-type cytokines IL-4, IFNγ, and MCP-1 were higher in NR, while blood GSH (r-GSHbl) levels were lower in NR than responders (R). Proteomic analysis evidenced an upregulated level of platelet adhesion molecule, CD226, and a downregulation of the antioxidant peroxiredoxin-4. In R patients the proinflammatory cytokine IL-6 decreased, while the anti-inflammatory cytokine IL-1Ra increased. Conclusions. In patients with high RPR on clopidogrel therapy, an unbalance of inflammatory factors, platelet adhesion molecules, and circulatory and platelet antioxidant molecules was observed during the acute phase. Proinflammatory milieu persists in nonresponders for a long time after the acute event while antioxidant blood factors tend to conform to normal responsiveness. PMID:25873769

  19. Effect of Lead (Pb) on Inflammatory Processes in the Brain.

    PubMed

    Chibowska, Karina; Baranowska-Bosiacka, Irena; Falkowska, Anna; Gutowska, Izabela; Goschorska, Marta; Chlubek, Dariusz

    2016-12-19

    That the nervous system is the main target of lead (Pb) has long been considered an established fact until recent evidence has linked the Pb effect on the immune system to the toxic effects of Pb on the nervous system. In this paper, we present recent literature reports on the effect of Pb on the inflammatory processes in the brain, particularly the expression of selected cytokines in the brain (interleukin 6, TGF-β1, interleukin 16, interleukin 18, and interleukin 10); expression and activity of enzymes participating in the inflammatory processes, such as cyclooxygenase 2, caspase 1, nitrogen oxide synthase (NOS 2) and proteases (carboxypeptidases, metalloproteinases and chymotrypsin); and the expression of purine receptors P2X4 and P2X7. A significant role in the development of inflammatory processes in the brain is also played by microglia (residual macrophages in the brain and the spinal cord), which act as the first line of defense in the central nervous system, and astrocytes-Whose most important function is to maintain homeostasis for the proper functioning of neurons. In this paper, we also present evidence that exposure to Pb may result in micro and astrogliosis by triggering TLR4-MyD88-NF-κB signaling cascade and the production of pro-inflammatory cytokines.

  20. Effect of Lead (Pb) on Inflammatory Processes in the Brain

    PubMed Central

    Chibowska, Karina; Baranowska-Bosiacka, Irena; Falkowska, Anna; Gutowska, Izabela; Goschorska, Marta; Chlubek, Dariusz

    2016-01-01

    That the nervous system is the main target of lead (Pb) has long been considered an established fact until recent evidence has linked the Pb effect on the immune system to the toxic effects of Pb on the nervous system. In this paper, we present recent literature reports on the effect of Pb on the inflammatory processes in the brain, particularly the expression of selected cytokines in the brain (interleukin 6, TGF-β1, interleukin 16, interleukin 18, and interleukin 10); expression and activity of enzymes participating in the inflammatory processes, such as cyclooxygenase 2, caspase 1, nitrogen oxide synthase (NOS 2) and proteases (carboxypeptidases, metalloproteinases and chymotrypsin); and the expression of purine receptors P2X4 and P2X7. A significant role in the development of inflammatory processes in the brain is also played by microglia (residual macrophages in the brain and the spinal cord), which act as the first line of defense in the central nervous system, and astrocytes—Whose most important function is to maintain homeostasis for the proper functioning of neurons. In this paper, we also present evidence that exposure to Pb may result in micro and astrogliosis by triggering TLR4-MyD88-NF-κB signaling cascade and the production of pro-inflammatory cytokines. PMID:27999370

  1. Volume Exercise in Older Athletes Influences Inflammatory and Redox Responses to Acute Exercise.

    PubMed

    Estrela, Andre L; Zaparte, Aline; da Silva, Jefferson D; Moreira, José C; Turner, James E; Bauer, Moisés E

    2017-02-09

    To examine whether the volume of previous exercise training in older athletes influences inflammatory, redox and hormonal profiles, forty trained marathon runners were divided into higher-volume (HVG, ~480 min/week) and lower-volume groups (LVG, ~240 min/week). Plasma inflammatory proteins, redox biomarkers and salivary testosterone and cortisol, were assessed at rest and following two maximal acute exercise bouts. At rest, the LVG exhibited higher CRP, higher protein carbonyls and lower SOD activity compared to the HVG (p's<0.05). In response to exercise, TNF- declined similarly in both groups whereas CRP increased differentially (+60% LVG; +24% HVG; p's<0.05). Protein carbonyls decreased and thiols increased similarly in both groups, but SOD declined differentially between groups (-14% LVG; -20% HVG; p's<0.05). Salivary testosterone decreased similarly in both groups, whereas cortisol did not change. Higher-volume of training is associated with favorable inflammatory and redox profiles at rest, perhaps mediated by small inflammatory responses to acute exercise.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

    Hypothesis:Abnormal Vitamin D (Vit D) level could have consequences on the immuno-inflammatory processes in Ankylosing Spondylitis (AS). Aim:The purpose of this study was to analyze the role of Vitamin D in the interplay between immune and inflammation effectors in AS associated-Acute Anterior Uveitis (AAU). Methods and Results:25-hydroxyvitamin D (Vit D), LL-37 peptide, IL-8 and Serum Amyloid A (SAA) were identified and quantified in the serum/ plasma of thirty-four AS patients [eleven AS patients presenting AAU (AAU AS patients) and twenty-three AS patients without AAU (wAAU AS patients)] and eighteen healthy individuals (Control) using enzyme-linked immunosorbent assay. Acute-phase SAA level was significantly higher in AS patients compared to Controls. Contrary with wAAU AS patients, significantly elevated levels of IL-8, and diminished levels of Vit D characterized AAU AS patients. Regarding LL-37, its level decreased concomitantly with the level of Vit D. When AS patients were subgrouped based on AAU presence or on Vit D level, important associations between immuno-inflammatory assessed markers and AS features were noticed. Generally, Vit D levels were associated indirectly with leukocytes/ neutrophils number or with ESR, CRP, and Fibrinogen levels. The levels of SAA and IL-8 associated directly with AAU or with AAU relapses, especially in AS patients with Vit D insufficiency, while SAA associated directly with infection/ inflammatory markers and with disease activity indexes or with the degree of functional limitation. Discussion:Altered levels of Vit D affect the balance between LL-37, IL-8 and SAA, suggesting an association with AAU, an extra-articular manifestation of AS. Abbreviations:Vit D = Vitamin D, AS = Ankylosing Spondylitis, AAU = Acute Anterior Uveitis, AAU AS = AS patients with AAU, wAAU AS = AS patients without AAU, SSZ = Sulphasalazine, Leu = Leukocytes, Neu = Neutrophils. PMID:27713770

  4. Altered joint tribology in osteoarthritis: Reduced lubricin synthesis due to the inflammatory process. New horizons for therapeutic approaches.

    PubMed

    Szychlinska, M A; Leonardi, R; Al-Qahtani, M; Mobasheri, A; Musumeci, G

    2016-06-01

    Osteoarthritis (OA) is the most common form of joint disease. This review aimed to consolidate the current evidence that implicates the inflammatory process in the attenuation of synovial lubrication and joint tissue homeostasis in OA. Moreover, with these findings, we propose some evidence for novel therapeutic strategies for preventing and/or treating this complex disorder. The studies reviewed support that inflammatory mediators participate in the onset and progression of OA after joint injury. The flow of pro-inflammatory cytokines following an acute injury seems to be directly associated with altered lubricating ability in the joint tissue. The latter is associated with reduced level of lubricin, one of the major joint lubricants. Future research should focus on the development of new therapies that attenuate the inflammatory process and restore lubricin synthesis and function. This approach could support joint tribology and synovial lubrication leading to improved joint function and pain relief.

  5. Inflammatory Cytokine Gene Expression in Mesenteric Adipose Tissue during Acute Experimental Colitis

    PubMed Central

    Mustain, W. Conan; Starr, Marlene E.; Valentino, Joseph D.; Cohen, Donald A.; Okamura, Daiki; Wang, Chi; Evers, B. Mark; Saito, Hiroshi

    2013-01-01

    Background Production of inflammatory cytokines by mesenteric adipose tissue (MAT) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Animal models of colitis have demonstrated inflammatory changes within MAT, but it is unclear if these changes occur in isolation or as part of a systemic adipose tissue response. It is also unknown what cell types are responsible for cytokine production within MAT. The present study was designed to determine whether cytokine production by MAT during experimental colitis is depot-specific, and also to identify the source of cytokine production within MAT. Methods Experimental colitis was induced in 6-month-old C57BL/6 mice by administration of dextran sulfate sodium (2% in drinking water) for up to 5 days. The induction of cytokine mRNA within various adipose tissues, including mesenteric, epididymal, and subcutaneous, was analyzed by qRT-PCR. These adipose tissues were also examined for histological evidence of inflammation. The level of cytokine mRNA during acute colitis was compared between mature mesenteric adipocytes, mesenteric stromal vascular fraction (SVF), and mesenteric lymph nodes. Results During acute colitis, MAT exhibited an increased presence of infiltrating mononuclear cells and fibrotic structures, as well as decreased adipocyte size. The mRNA levels of TNF-α, IL-1β, and IL-6 were significantly increased in MAT but not other adipose tissue depots. Within the MAT, induction of these cytokines was observed mainly in the SVF. Conclusions Acute experimental colitis causes a strong site-specific inflammatory response within MAT, which is mediated by cells of the SVF, rather than mature adipocytes or mesenteric lymph nodes. PMID:24386254

  6. CCR2+Ly6Chi Inflammatory Monocyte Recruitment Exacerbates Acute Disability Following Intracerebral Hemorrhage

    PubMed Central

    Hammond, Matthew D.; Taylor, Roslyn A.; Mullen, Michael T.; Ai, Youxi; Aguila, Hector L.; Mack, Matthias; Kasner, Scott E.; McCullough, Louise D.

    2014-01-01

    Intracerebral hemorrhage (ICH) is a devastating type of stroke that lacks a specific treatment. An intense immune response develops after ICH, which contributes to neuronal injury, disability, and death. However, the specific mediators of inflammation-induced injury remain unclear. The objective of the present study was to determine whether blood-derived CCR2+Ly6Chi inflammatory monocytes contribute to disability. ICH was induced in mice and the resulting inflammatory response was quantified using flow cytometry, confocal microscopy, and neurobehavioral testing. Importantly, blood-derived monocytes were distinguished from resident microglia by differential CD45 staining and by using bone marrow chimeras with fluorescent leukocytes. After ICH, blood-derived CCR2+Ly6Chi inflammatory monocytes trafficked into the brain, outnumbered other leukocytes, and produced tumor necrosis factor. Ccr2−/− mice, which have few circulating inflammatory monocytes, exhibited better motor function following ICH than control mice. Chimeric mice with wild-type CNS cells and Ccr2−/− hematopoietic cells also exhibited early improvement in motor function, as did wild-type mice after inflammatory monocyte depletion. These findings suggest that blood-derived inflammatory monocytes contribute to acute neurological disability. To determine the translational relevance of our experimental findings, we examined CCL2, the principle ligand for the CCR2 receptor, in ICH patients. Serum samples from 85 patients were collected prospectively at two hospitals. In patients, higher CCL2 levels at 24 h were independently associated with poor functional outcome at day 7 after adjusting for potential confounding variables. Together, these findings suggest that inflammatory monocytes worsen early disability after murine ICH and may represent a therapeutic target for patients. PMID:24623768

  7. 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.

  8. 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

  9. Anti-Inflammatory Effects of Adrenomedullin on Acute Lung Injury Induced by Carrageenan in Mice

    PubMed Central

    Elena, Talero; Rosanna, Di Paola; Emanuela, Mazzon; Esposito, Emanuela; Virginia, Motilva; Salvatore, Cuzzocrea

    2012-01-01

    Adrenomedullin (AM) is a 52 amino acid peptide that has shown predominant anti-inflammatory activities. In the present study, we evaluated the possible therapeutic effect of this peptide in an experimental model of acute inflammation, the carrageenan- (CAR-) induced pleurisy. Pleurisy was induced by injection of CAR into the pleural cavity of mice. AM (200 ng/kg) was administered by intraperitoneal route 1 h after CAR, and the animals were sacrificed 4 h after that. AM treatment attenuated the recruitment of leucocytes in the lung tissue and the generation and/or the expression of the proinflammatory cytokines as well as the expression of the intercellular cell adhesion molecules. Moreover, AM inhibited the induction of inducible nitric oxide synthase (iNOS), thereby abating the generation of nitric oxide (NO) and prevented the oxidative and nitroxidative lung tissue injury, as shown by the reduction of nitrotyrosine, malondialdehyde (MDA), and poly (ADP-ribose) polymerase (PARP) levels. Finally, we demonstrated that these anti-inflammatory effects of AM were associated with the inhibition of nuclear factor-κB (NF-κB) activation. All these parameters were markedly increased by intrapleural CAR in the absence of any treatment. We report that treatment with AM significantly reduces the development of acute lung injury by downregulating a broad spectrum of inflammatory factors. PMID:22685374

  10. 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

  11. Effect of Previous High Glutamine Infusion on Inflammatory Mediators and Mortality in an Acute Pancreatitis Model

    PubMed Central

    Garib, Ricardo; Garla, Priscila; Moretti, Ana I. S.; Machado, Marcel C. C.; Waitzberg, Dan L.

    2016-01-01

    Parenteral glutamine supplementation in acute inflammatory conditions is controversial. We evaluated the inflammatory and survival responses after parenteral glutamine infusion in sodium taurocholate-induced acute pancreatitis (AP) model. Lewis rats received 1 g/kg parenteral glutamine (n = 42), saline (n = 44), or no treatment (n = 45) for 48 h before AP induction. Blood, lung, and liver samples were collected 2, 12, and 24 h after AP to measure serum cytokines levels and tissue heat shock protein (HSP) expression. From each group, 20 animals were not sacrificed after AP for a 7-day mortality study. Serum cytokine levels did not differ among groups at any time point, but the intragroup analysis over time showed higher interferon-γ only in the nontreatment and saline groups at 2 h (versus 12 and 24 h; both p ≤ 0.05). The glutamine group exhibited greater lung and liver HSP90 expression than did the nontreatment group at 2 and 12 h, respectively; greater liver HSP90 and HSP70 expression than did the saline group at 12 h; and smaller lung HSP70 and liver HSP90 expression than did the nontreatment group at 24 h (all p ≤ 0.019). The 7-day mortality rate did not differ among groups. In experimental AP, pretreatment with parenteral glutamine was safe and improved early inflammatory mediator profiles without affecting mortality. PMID:28070142

  12. Peripheral Inflammatory Markers and Antioxidant Response during the Post-Acute and Chronic Phase after Severe Traumatic Brain Injury

    PubMed Central

    Licastro, Federico; Hrelia, Silvana; Porcellini, Elisa; Malaguti, Marco; Di Stefano, Cristina; Angeloni, Cristina; Carbone, Ilaria; Simoncini, Laura; Piperno, Roberto

    2016-01-01

    Traumatic brain injury (TBI) is a mechanical insult to the brain caused by external forces and associated with inflammation and oxidative stress. The patients may show different profiles of neurological recovery and a combination of oxidative damage and inflammatory processes can affect their courses. It is known that an overexpression of cytokines can be seen in peripheral blood in the early hours/days after the injury, but little is known about the weeks and months encompassing the post-acute and chronic phases. In addition, no information is available about the antioxidant responses mediated by the major enzymes that regulate reactive oxygen species levels: superoxide dismutase, catalase, peroxidases, and GSH-related enzymes. This study investigates the 6-month trends of inflammatory markers and antioxidant responses in 22 severe TBI patients with prolonged disorders of consciousness, consecutively recruited in a dedicated neurorehabilitation facility. Patients with a high degree of neurological impairment often show an uncertain outcome. In addition, the profiles of plasma activities were related to the neurological recovery after 12 months. Venous peripheral blood samples were taken blindly as soon as clinical signs and laboratory markers confirmed the absence of infections, 3 and 6 months later. The clinical and neuropsychological assessment continued up to 12 months. Nineteen patients completed the follow-up. In the chronic phase, persistent high plasma levels of cytokines can interfere with cognitive functioning and higher post-acute levels of cytokines [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL1b, IL6] are associated with poorer cognitive recoveries 12 months later. Moreover, higher IFN-γ, higher TNF-α, and lower glutathione peroxidase activity are associated with greater disability. The results add evidence of persistent inflammatory response, provide information about long-term imbalance of antioxidant activity, and suggest that

  13. Peripheral Inflammatory Markers and Antioxidant Response during the Post-Acute and Chronic Phase after Severe Traumatic Brain Injury.

    PubMed

    Licastro, Federico; Hrelia, Silvana; Porcellini, Elisa; Malaguti, Marco; Di Stefano, Cristina; Angeloni, Cristina; Carbone, Ilaria; Simoncini, Laura; Piperno, Roberto

    2016-01-01

    Traumatic brain injury (TBI) is a mechanical insult to the brain caused by external forces and associated with inflammation and oxidative stress. The patients may show different profiles of neurological recovery and a combination of oxidative damage and inflammatory processes can affect their courses. It is known that an overexpression of cytokines can be seen in peripheral blood in the early hours/days after the injury, but little is known about the weeks and months encompassing the post-acute and chronic phases. In addition, no information is available about the antioxidant responses mediated by the major enzymes that regulate reactive oxygen species levels: superoxide dismutase, catalase, peroxidases, and GSH-related enzymes. This study investigates the 6-month trends of inflammatory markers and antioxidant responses in 22 severe TBI patients with prolonged disorders of consciousness, consecutively recruited in a dedicated neurorehabilitation facility. Patients with a high degree of neurological impairment often show an uncertain outcome. In addition, the profiles of plasma activities were related to the neurological recovery after 12 months. Venous peripheral blood samples were taken blindly as soon as clinical signs and laboratory markers confirmed the absence of infections, 3 and 6 months later. The clinical and neuropsychological assessment continued up to 12 months. Nineteen patients completed the follow-up. In the chronic phase, persistent high plasma levels of cytokines can interfere with cognitive functioning and higher post-acute levels of cytokines [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL1b, IL6] are associated with poorer cognitive recoveries 12 months later. Moreover, higher IFN-γ, higher TNF-α, and lower glutathione peroxidase activity are associated with greater disability. The results add evidence of persistent inflammatory response, provide information about long-term imbalance of antioxidant activity, and suggest that

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

    PubMed

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

    2014-07-03

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

  15. 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

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

    PubMed

    Li, Haiying; Miao, Weiguo; Ma, Jingfen; Xv, Zhen; Bo, Hai; 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.

  17. 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

  18. The Acute Inflammatory Response to Absorbed Collagen Sponge Is Not Enhanced by BMP-2

    PubMed Central

    Huang, Hairong; Wismeijer, Daniel; Hunziker, Ernst B.; Wu, Gang

    2017-01-01

    Absorbed collagen sponge (ACS)/bone morphogenetic protein-2 (BMP-2) are widely used in clinical practise for bone regeneration. However, the application of this product was found to be associated with a significant pro-inflammatory response, particularly in the early phase after implantation. This study aimed to clarify if the pro-inflammatory activities, associated with BMP-2 added to ACS, were related to the physical state of the carrier itself, i.e., a wet or a highly dehydrated state of the ACS, to the local degree of vascularisation and/or to local biomechanical factors. ACS (0.8 cm diameter)/BMP-2 were implanted subcutaneously in the back of 12 eight-week-old Sprague Dawley rats. Two days after surgery, the implanted materials were retrieved and analysed histologically and histomorphometrically. The acute inflammatory response following implantation of ACS was dependent of neither the presence or absence of BMP-2 nor the degree of vascularization in the surrounding tissue nor the hydration state (wet versus dry) of the ACS material at the time of implantation. Differential micro biomechanical factors operating at the implantation site appeared to have an influence on the thickness of inflammation. We conclude that the degree of the early inflammatory response of the ACS/BMP-2 may be associated with the physical and chemical properties of the carrier material itself. PMID:28245606

  19. Acute aerocystitis in Piaractus mesopotamicus: participation of eicosanoids and pro-inflammatory cytokines.

    PubMed

    Claudiano, Gustavo da Silva; Petrillo, Thalita R; Manrique, Wilson G; Castro, Marcello P; Loureiro, Bruna A; Marcusso, Paulo F; Belo, Marco A A; Moraes, Julieta R E; de Moraes, Flávio Ruas

    2013-05-01

    A total of 360 pacus (Piaractus mesopotamicus) were used to study vascular permeability (VP) and inflammatory cell component (CC) in induced aerocystitis in P. mesopotamicus through inoculation of inactivated Aeromonas hydrophila, and the effect of steroidal and nonsteroidal anti-inflammatory drugs. It was observed that after inoculation of A. hydrophila, the maximum VP occurred 180 min post-stimulus (MPS). Pretreatment with anti-inflammatory drugs inhibited VP, and the inhibitory effect of dexamethasone was seen earlier than the effects caused by meloxicam and indomethacin. Inoculation of the bacterium caused a gradual increase in the accumulation of cells, which reached a maximum 24 h post-stimulus (HPS). Pretreatment with dexamethasone, indomethacin and meloxicam reduced the accumulation of lymphocytes, thrombocytes, granulocytes and macrophages. There was no significant difference between the different doses of the drugs tested. The results suggest that eicosanoids and pro-inflammatory cytokines participate in chemical mediation in acute inflammation in pacus.

  20. 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.

  1. Trajectories of relationship stress and inflammatory processes in adolescence.

    PubMed

    Ehrlich, Katherine B; Miller, Gregory E; Rohleder, Nicolas; Adam, Emma K

    2016-02-01

    Researchers have identified cross-sectional links between interpersonal stress and inflammation. Little is known, however, about how these dynamics unfold over time, what underlying immune pathways might exist, or whether moderators such as race could alter the strength of the connection between interpersonal stress and inflammatory processes. We examined whether adolescent girls whose relationship trajectories were characterized by chronic stress would exhibit a proinflammatory phenotype marked by systemic inflammation, heightened cytokine responses to bacterial challenges, and resistance to the anti-inflammatory properties of cortisol. Significant Stress × Race interactions revealed that family stress trajectories predicted glucocorticoid sensitivity and peer stress trajectories predicted cytokine production for White but not Asian girls. Relationship stress trajectories were not associated with systemic inflammation, however. These findings suggest that particular subgroups of adolescent girls who face chronic and elevated stress in their close relationships may be at risk for disruptions to the immune system.

  2. 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.

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

    PubMed

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

    1999-02-19

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

  4. Systems analysis uncovers inflammatory Th/Tc17-driven modules during acute GVHD in monkey and human T cells

    PubMed Central

    Watkins, Benjamin; Tkachev, Victor; Panoskaltsis-Mortari, Angela; Betz, Kayla; Brown, Melanie; Hunt, Daniel J.; Schell, John B.; Zeleski, Katie; Yu, Alison; Giver, Cynthia R.; Waller, Edmund K.; Miller, Jeffrey S.; Blazar, Bruce R.

    2016-01-01

    One of the central challenges of transplantation is the development of alloreactivity despite the use of multiagent immunoprophylaxis. Effective control of this immune suppression–resistant T-cell activation represents one of the key unmet needs in the fields of both solid-organ and hematopoietic stem cell transplant (HCT). To address this unmet need, we have used a highly translational nonhuman primate (NHP) model to interrogate the transcriptional signature of T cells during breakthrough acute graft-versus-host disease (GVHD) that occurs in the setting of clinically relevant immune suppression and compared this to the hyperacute GVHD, which develops in unprophylaxed or suboptimally prophylaxed transplant recipients. Our results demonstrate the complex character of the alloreactivity that develops during ongoing immunoprophylaxis and identify 3 key transcriptional hallmarks of breakthrough acute GVHD that are not observed in hyperacute GVHD: (1) T-cell persistence rather than proliferation, (2) evidence for highly inflammatory transcriptional programming, and (3) skewing toward a T helper (Th)/T cytotoxic (Tc)17 transcriptional program. Importantly, the gene coexpression profiles from human HCT recipients who developed GVHD while on immunosuppressive prophylactic agents recapitulated the patterns observed in NHP, and demonstrated an evolution toward a more inflammatory signature as time posttransplant progressed. These results strongly implicate the evolution of both inflammatory and interleukin 17–based immune pathogenesis in GVHD, and provide the first map of this evolving process in primates in the setting of clinically relevant immunomodulation. This map represents a novel transcriptomic resource for further systems-based efforts to study the breakthrough alloresponse that occurs posttransplant despite immunoprophylaxis and to develop evidence-based strategies for effective treatment of this disease. PMID:27758873

  5. Urinalysis for interleukin-8 in the non-invasive diagnosis of acute and chronic inflammatory diseases

    PubMed Central

    Taha, A; Grant, V; Kelly, R

    2003-01-01

    Background and aims: Given its role in mediating inflammation, the use of urinary interleukin-8 (IL-8) was assessed in the non-invasive diagnosis of acute and chronic inflammatory diseases. Methods: IL-8 was measured by an enzyme linked immunosorbent assay in random urine samples (1 ml each) carrying code numbers and taken from 208 patients: 177 adults and 31 children presenting with a range of active or inactive inflammatory conditions. Results: In the appropriate controls and in patients with inactive inflammation, the median urinary IL-8 levels ranged from 7–12 pg/ml, compared with 104 pg/ml in active ulcerative colitis (p = 0.002), 54 in active Crohn's disease (p = 0.025), 93 in active rheumatoid arthritis (p = 0.001), 107 in acute cholecystitis (p<0.0001), 127 in acute appendicitis (p = 0.0001), and 548 pg/ml in urinary tract infection (p<0.0001). Children with non-viral inflammation/infection also had higher IL-8 values (median, 199 pg/ml; p = 0.0001) than those with viral infection (median, 7 pg/ml) or non-specific conditions (median, 10 pg/ml). In the study group as a whole urinary IL-8 values correlated positively with peripheral blood white cell count (r = 0.32; p < 0.001), erythrocyte sedimentation rate (r = 0.41; p<0.001), and C-reactive protein (r = 0.33; p<0.001). Conclusion: Taking the appropriate clinical situation into account, urinary IL-8 measurement helps in the non-invasive assessment of active inflammation in at least a number of common acute and chronic conditions. PMID:12697917

  6. Rapid dendritic cell recruitment is a hallmark of the acute inflammatory response at mucosal surfaces

    PubMed Central

    1994-01-01

    Immunohistochemical analysis of challenge sites such as skin and the peritoneal cavity has identified neutrophils as virtually the sole cellular participants in acute bacterial inflammation, peak influx occurring 24-48 h in advance of mononuclear cell populations associated with adaptive immunity. This study challenges the general applicability of this paradigm. We demonstrate here that the earliest detectable cellular response after inhalation of Moraxella catarrhalis organisms is the recruitment of putative class II major histocompatibility complex-bearing dendritic cell (DC) precursors into the airway epithelium, the initial wave arriving in advance of the neutrophil influx. Unlike the neutrophils which rapidly transit into the airway lumen, the DC precursors remain within the epithelium during the acute inflammatory response where they differentiate, and develop the dendriform morphology typical of resident DC found in the normal epithelium. During the ensuing 48-h period, these cells then migrate to the regional lymph nodes. No comparable DC response was observed after epidermal or intraperitoneal challenge, and it may be that mucosal surfaces are unique in their requirement for rapid DC responses during acute inflammation. We hypothesize that the role of the DC influx during acute inflammation may be surveillance for opportunistic viruses, and that this covert protective mechanism is operative at a restricted number of mucosal tissue sites. PMID:8145044

  7. Relationship between production of acute-phase proteins and strength of inflammatory stimulation in rats.

    PubMed

    Kuribayashi, Takashi; Tomizawa, Misaki; Seita, Tetsurou; Tagata, Kazutoshi; Yamamoto, Shizuo

    2011-07-01

    The relationship between intensity of inflammatory stimulation and production of α(2)-macroglobulin (α2M) and α(1)-acid glycoprotein (AAG) in rats was investigated. Sprague-Dawley rats were injected with turpentine oil at doses of 0.05, 0.2 or 0.4 mL/rat. Serum levels of α2M, interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) were measured by enzyme-linked immunosorbent assay, and AAG was measured by single radial immunodiffusion. Peak serum levels of α2M and AAG in rats injected at 0.05 mL/rat were significantly lower than those at 0.2 or 0.4 mL/rat. However, no significant differences were observed for peak serum levels of these acute-phase proteins between 0.2 and 0.4 mL/rat. Furthermore, peak serum levels of IL-6 and CINC-1 in rats injected at 0.05 mL/rat were significantly lower than those at 0.2 or 0.4 mL/rat. Thus, the production of these acute-phase proteins has upper limits, even under increased strength of inflammatory stimulation in rats injected with turpentine oil.

  8. 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.

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

    PubMed Central

    Al Shahi, Hamad; Shimada, Kazunori; Miyauchi, Katsumi; Yoshihara, Takuma; Sai, Eiryu; Shiozawa, Tomoyuki; Naito, Ryo; Aikawa, Tatsuro; Ouchi, Shohei; Kadoguchi, Tomoyasu; Miyazaki, Tetsuro; Daida, Hiroyuki

    2015-01-01

    Objective. We evaluated inflammatory cytokines and chemokine in peripheral blood mononuclear cells (PBMCs) in patients with either acute coronary syndrome (ACS) or stable coronary artery disease (CAD). Methods. We enrolled 20 ACS patients and 50 stable CAD patients without previous history of ACS who underwent cardiac catheterization. Patients with an estimated glomerular filtration rate of ≤30 mL/min/1.73 m2 and C-reactive protein of ≥1.0 mg/dL were excluded. Blood samples were collected from the patients just before catheterization, and PBMCs were isolated from the whole blood. The levels of inflammatory cytokines and chemokine were measured by using real-time quantitative polymerase chain reaction and immunoassays. Results. The expression of tumor necrosis factor alpha (TNF-α), interleukin- (IL-) 6, IL-10, IL-23A, IL-27, and IL-37 was significantly higher in the ACS group than in the CAD group (P < 0.05). In contrast, the expression of IL-33 was significantly lower in the ACS group than in the CAD group (P < 0.05). The ACS patients had higher plasma levels of TNF-α, IL-6, and IL-10 in the ACS group than in the CAD group. Conclusion. Circulating levels of pro-/anti-inflammatory cytokines, including IL-23A, IL-27, IL-33, and IL-37, may be associated with the pathogenesis of atherosclerosis in ACS patients. PMID:26504600

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

    PubMed

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

    2013-01-01

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

  11. 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

    2015-12-22

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

  13. Functional Role of Monocytes and Macrophages for the Inflammatory Response in Acute Liver Injury

    PubMed Central

    Zimmermann, Henning W.; Trautwein, Christian; Tacke, Frank

    2012-01-01

    Different etiologies such as drug toxicity, acute viral hepatitis B, or acetaminophen poisoning can cause acute liver injury or even acute liver failure (ALF). Excessive cell death of hepatocytes in the liver is known to result in a strong hepatic inflammation. Experimental murine models of liver injury highlighted the importance of hepatic macrophages, so-called Kupffer cells, for initiating and driving this inflammatory response by releasing proinflammatory cytokines and chemokines including tumor necrosis factor (TNF), interleukin-6 (IL-6), IL-1beta, or monocyte-chemoattractant protein-1 (MCP-1, CCL2) as well as activating other non-parenchymal liver cells, e.g., endothelial or hepatic stellate cells. Many of these proinflammatory mediators can trigger hepatocytic cell death pathways, e.g., via caspase activation, but also activate protective signaling pathways, e.g., via nuclear factor kappa B (NF-κB). Recent studies in mice demonstrated that these macrophage actions largely depend on the recruitment of monocytes into the liver, namely of the inflammatory Ly6c+ (Gr1+) monocyte subset as precursors of tissue macrophages. The chemokine receptor CCR2 and its ligand MCP-1/CCL2 promote monocyte subset infiltration upon liver injury. In contrast, the chemokine receptor CX3CR1 and its ligand fractalkine (CX3CL1) are important negative regulators of monocyte infiltration by controlling their survival and differentiation into functionally diverse macrophage subsets upon injury. The recently identified cellular and molecular pathways for monocyte subset recruitment, macrophage differentiation, and interactions with other hepatic cell types in the injured liver may therefore represent interesting novel targets for future therapeutic approaches in ALF. PMID:23091461

  14. Diagnostic value of blood inflammatory markers for detection of acute appendicitis in children

    PubMed Central

    Sack, Ulrich; Biereder, Birgit; Elouahidi, Tino; Bauer, Katrin; Keller, Thomas; Tröbs, Ralf-Bodo

    2006-01-01

    Background Acute appendicitis (AA) is a common surgical problem that is associated with an acute-phase reaction. Previous studies have shown that cytokines and acute-phase proteins are activated and may serve as indicators for the severity of appendicitis. The aim of this study was to compare diagnostic value of different serum inflammatory markers in detection of phlegmonous or perforated appendicitis in children. Methods Data were collected prospectively on 211 consecutive children. Laparotomy was performed for suspected AA for 189 patients. Patients were subdivided into groups: nonsurgical abdominal pain, early appendicitis, phlegmonous or gangrenous appendicitis, perforated appendicitis. White blood cell count (WBC), serum C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), acid α1-glycoprotein (α1GP), endotoxin, and erythrocyte sedimentation reaction (ESR) were estimated ad the time of admission. The diagnostic performance was analyzed using receiver operating characteristic (ROC) curves. Results WBC count, CRP and IL-6 correlated significantly with the severity of appendiceal inflammation. Identification of children with severe appendicitis was supported by IL-6 or CRP but not WBC. Between IL-6 and CRP, there were no significant differences in diagnostic use. Conclusion Laboratory results should be considered to be integrated within the clinical assessment. If used critically, CRP and IL-6 equally provide surgeons with complementary information in discerning the necessity for urgent operation. PMID:17132173

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

    PubMed

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

    2016-01-01

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

  16. Relationship of Acute Lung Inflammatory Injury to Fas/FasL System

    PubMed Central

    Neff, Thomas A.; Guo, Ren-Feng; Neff, Simona B.; Sarma, J. Vidya; Speyer, Cecilia L.; Gao, Hongwei; Bernacki, Kurt D.; Huber-Lang, Markus; McGuire, Stephanie; Hoesel, L. Marco; Riedemann, Niels C.; Beck-Schimmer, Beatrice; Zetoune, Firas S.; Ward, Peter A.

    2005-01-01

    There is mounting evidence that apoptosis plays a significant role in tissue damage during acute lung injury. To evaluate the role of the apoptosis mediators Fas and FasL in acute lung injury, Fas (lpr)- or FasL (gld)-deficient and wild-type mice were challenged with intrapulmonary deposition of IgG immune complexes. Lung injury parameters (125I-albumin leak, accumulation of myeloperoxidase, and wet lung weights) were measured and found to be consistently reduced in both lpr and gld mice. In wild-type mice, lung injury was associated with a marked increase in Fas protein in lung. Inflamed lungs of wild-type mice showed striking evidence of activated caspase-3, which was much diminished in inflamed lungs from lpr mice. Intratracheal administration of a monoclonal Fas-activating antibody (Jo2) in wild-type mice induced MIP-2 and KC production in bronchoalveolar lavage fluids, and a murine alveolar macrophage cell line (MH-S) showed significantly increased MIP-2 production after incubation with this antibody. Bronchoalveolar lavage fluid content of MIP-2 and KC was substantially reduced in lpr mice after lung injury when compared to levels in wild-type mice. These data suggest that the Fas/FasL system regulates the acute lung inflammatory response by positively affecting CXC-chemokine production, ultimately leading to enhanced neutrophil influx and tissue damage. PMID:15743781

  17. Chemokines and their receptors in the allergic airway inflammatory process.

    PubMed

    Velazquez, Juan Raymundo; Teran, Luis Manuel

    2011-08-01

    The development of the allergic airway disease conveys several cell types, such as T-cells, eosinophils, mast cells, and dendritic cells, which act in a special and temporal synchronization. Cellular mobilization and its complex interactions are coordinated by a broad range of bioactive mediators known as chemokines. These molecules are an increasing family of small proteins with common structural motifs and play an important role in the recruitment and cell activation of both leukocytes and resident cells at the allergic inflammatory site via their receptors. Trafficking and recruitment of cell populations with specific chemokines receptors assure the presence of reactive allergen-specific T-cells in the lung, and therefore the establishment of an allergic inflammatory process. Different approaches directed against chemokines receptors have been developed during the last decades with promising therapeutic results in the treatment of asthma. In this review we explore the role of the chemokines and chemokine receptors in allergy and asthma and discuss their potential as targets for therapy.

  18. 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

  19. Effect of acute intradialytic strength physical exercise on oxidative stress and inflammatory responses in hemodialysis patients

    PubMed Central

    Esgalhado, Marta; Stockler-Pinto, Milena Barcza; de França Cardozo, Ludmila Ferreira Medeiros; Costa, Cinthia; Barboza, Jorge Eduardo; Mafra, Denise

    2015-01-01

    Background Oxidative stress and inflammation are common findings in chronic kidney disease (CKD) patients, and they are directly related to the increased risk of developing cardiovascular disease, which is the major cause of death in these patients, particularly for those undergoing hemodialysis (HD). Strength physical exercise is a new therapeutic approach to reduce these complications in CKD patients. Following this, the purpose of this study was to assess the effect of acute intradialytic strength physical exercise on oxidative stress and inflammatory responses in HD patients. Methods Sixteen HD patients were studied (11 women; 44.4±14.6 years; body mass index 23.3±4.9 kg/m2; 61.6±43.1 months of dialysis) and served as their own controls. Acute (single session) intradialytic physical exercise were performed at 60% of the one-repetition maximum test for three sets of 10 repetitions for four exercise categories in both lower limbs during 30 minutes. Blood samples were collected on two different days at exactly the same time (30 minutes and 60 minutes after initiating the dialysis—with and without exercise). Antioxidant enzymes activity [superoxide dismutase (SOD), catalase, and glutathione peroxidase], lipid peroxidation marker levels (malondialdehyde), and inflammatory marker levels (high-sensitivity C-reactive protein) were determined. Results SOD plasma levels were significantly reduced after acute physical exercise from 244.8±40.7 U/mL to 222.4±28.9 U/mL (P=0.03) and, by contrast, increased on the day without exercise (218.2±26.5 U/mL to 239.4±38.6 U/mL, P=0.02). There was no alteration in plasma catalase, glutathione peroxidase, malondialdehyde, or high-sensitivity C-reactive protein levels in on either day (with or without exercise). Additionally, there was no association between these markers and clinical, anthropometric, or biochemical parameters. Conclusion These data suggest that acute intradialytic strength physical exercise was unable to

  20. The effect of polyglycerol sulfate branching on inflammatory processes.

    PubMed

    Paulus, Florian; Schulze, Ronny; Steinhilber, Dirk; Zieringer, Maximilian; Steinke, Ingo; Welker, Pia; Licha, Kai; Wedepohl, Stefanie; Dernedde, Jens; Haag, Rainer

    2014-05-01

    In this study, the extent to which the scaffold architecture of polyglycerol sulfates affects inflammatory processes and hemocompatibility is investigated. Competitive L-selectin binding assays, cellular uptake studies, and blood compatibility readouts are done to evaluate distinct biological properties. Fully glycerol based hyperbranched polyglycerol architectures are obtained by either homopolymerization of glycidol (60% branching) or a new copolymerization strategy of glycidol with ethoxyethyl glycidyl ether. Two polyglycerols with 24 and 42% degree of branching (DB) are synthesized by using different monomer feed ratios. A perfectly branched polyglycerol dendrimer is synthesized according to an iterative two-step protocol based on allylation of the alcohol and subsequent catalytic dihydroxylation. All the polyglycerol sulfates are synthesized with a comparable molecular weight and degree of sulfation. The DB make the different polymer conjugates perform different ways. The optimal DB is 60% in all biological assays.

  1. Immuno-inflammatory activation in acute cardio-embolic strokes in comparison with other subtypes of ischaemic stroke.

    PubMed

    Licata, Giuseppe; Tuttolomondo, Antonino; Di Raimondo, Domenico; Corrao, Salvatore; Di Sciacca, Riccardo; Pinto, Antonio

    2009-05-01

    Few studies have examined the relationship between inflammatory biomarker blood levels, cardioembolic stroke subtype and neurological deficit. So the aim of our study is to evaluate plasma levels of immuno-inflammatory variables in patients with cardio-embolic acute ischaemic stroke compared to other diagnostic subtypes and to evaluate the relationship between immuno-inflammatory variables, acute neurological deficit and brain infarct volume. One hundred twenty patients with acute ischaemic stroke and 123 controls without a diagnosis of acute ischaemic stroke were evaluated. The type of acute ischaemic stroke was classified according to the TOAST classification. We evaluated plasma levels of IL-1beta, TNF-alpha, IL-6 and IL-10, E-selectin, P-selectin, sICAM-1,sVCAM-1, vWF, TPA and PAI-1. Patients with ischaemic stroke classified as cardio-embolic (CEI) showed, compared to other subtypes, significantly higher median plasma levels of TNF-alpha , IL-6 and IL-1beta. Furthermore stroke patients classified as lacunar showed, compared to other subtypes, significantly lower median plasma levels of TNF-alpha, IL-6 and IL-1beta. Multiple linear regression showed a significant association between the Scandinavian Stroke Scale (SSS) score at admission and diagnostic subtype, infarct volume of cardio-embolic strokes and some inflammatory variables. Our findings confirm that cardio-embolic strokes have a worse clinical presentation and produce larger and more disabling strokes than other ischaemic stroke subtypes reporting a possible explanation of higher immuno-inflammatory activation of the acute phase.

  2. The role of marine omega-3 (n-3) fatty acids in inflammatory processes, atherosclerosis and plaque stability.

    PubMed

    Calder, Philip C

    2012-07-01

    Atherosclerosis has an important inflammatory component and acute cardiovascular events can be initiated by inflammatory processes occurring in advanced plaques. Fatty acids influence inflammation through a variety of mechanisms; many of these are mediated by, or associated with, the fatty acid composition of cell membranes. Human inflammatory cells are typically rich in the n-6 fatty acid arachidonic acid, but the contents of arachidonic acid and of the marine n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can be altered through oral administration of EPA and DHA. Eicosanoids produced from arachidonic acid have roles in inflammation. EPA also gives rise to eicosanoids and these are usually biologically weak. EPA and DHA give rise to resolvins which are anti-inflammatory and inflammation resolving. EPA and DHA also affect production of peptide mediators of inflammation (adhesion molecules, cytokines, etc.). Thus, the fatty acid composition of human inflammatory cells influences their function; the contents of arachidonic acid, EPA and DHA appear to be especially important. The anti-inflammatory effects of marine n-3 polyunsaturated fatty acids (PUFAs) may contribute to their protective actions towards atherosclerosis and plaque rupture.

  3. Acute ethanol intake attenuates inflammatory cytokines after brain injury in rats: a possible role for corticosterone.

    PubMed

    Gottesfeld, Zehava; Moore, Anthony N; Dash, Pramod K

    2002-03-01

    It has been reported that acute ethanol intoxication exerts dose-dependent effects, both beneficial and detrimental, on the outcome of traumatic brain injury (TBI), although the mechanism(s) has not been determined. Given that pro-inflammatory cytokines are either neuroprotective or neurotoxic, depending on their tissue levels, ethanol-induced alterations in brain cytokine production may be involved in determining the recovery after TBI. The present study was undertaken to examine the effect of acute ethanol pretreatments (producing blood alcohol concentrations of 100+/-16 mg/dL, and 220+/-10 mg/dL, considered low and intoxicating doses, respectively) on interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) levels in discrete brain regions. In addition, serum corticosterone levels were also examined because the hormone is a modulator of cytokine production, its secretion is stimulated by ethanol, and it has been associated with the severity of post-injury neurologic dysfunction. The data presented in this report demonstrate that moderate cortical impact brain injury elicits a marked increase in IL-1beta and TNF-alpha in the injured cortex as well as in the hippocampus ipsilateral to the injury. Ethanol pretreatment lowered cytokine levels in the cortex, hippocampus and hypothalamus in a dose-dependent manner after TBI compared to the untreated injured rats. Serum corticosterone levels were markedly increased in the injured rats, and were further augmented in the ethanol-pretreated injured animals in a dose-dependent manner. Our findings suggest that ethanol-induced decrease in pro-inflammatory cytokine production may be linked to increased circulating corticosterone, both of which may contribute to the outcome of brain injury.

  4. Analgesic and anti-inflammatory actions of robenacoxib in acute joint inflammation in dog.

    PubMed

    Schmid, V B; Spreng, D E; Seewald, W; Jung, M; Lees, P; King, J N

    2010-04-01

    The objectives of this study were to establish dose-response and blood concentration-response relationships for robenacoxib, a novel nonsteroidal anti-inflammatory drug with selectivity for inhibition of the cyclooxygenase (COX)-2 isoenzyme, in a canine model of synovitis. Acute synovitis of the stifle joint was induced by intra-articular injection of sodium urate crystals. Robenacoxib (0.25, 0.5, 1.0, 2.0 and 4.0 mg/kg), placebo and meloxicam (0.2 mg/kg) were administered subcutaneously (s.c.) 3 h after the urate crystals. Pharmacodynamic endpoints included data from forceplate analyses, clinical orthopaedic examinations and time course of inhibition of COX-1 and COX-2 in ex vivo whole blood assays. Blood was collected for pharmacokinetics. Robenacoxib produced dose-related improvement in weight-bearing, pain and swelling as assessed objectively by forceplate analysis (estimated ED(50) was 1.23 mg/kg for z peak force) and subjectively by clinical orthopaedic assessments. The analgesic and anti-inflammatory effects of robenacoxib were significantly superior to placebo (0.25-4 mg/kg robenacoxib) and were non-inferior to meloxicam (0.5-4 mg/kg robenacoxib). All dosages of robenacoxib produced significant dose-related inhibition of COX-2 (estimated ED(50) was 0.52 mg/kg) but no inhibition of COX-1. At a dosage of 1-2 mg/kg administered s.c., robenacoxib should be at least as effective as 0.2 mg/kg of meloxicam in suppressing acute joint pain and inflammation in dogs.

  5. 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.

  6. Anti-inflammatory activity of Ajmodadi Churna extract against acute inflammation in rats

    PubMed Central

    Ram, H. N. Aswatha; Sriwastava, Neeraj K.; Makhija, Inder K.; Shreedhara, C. S.

    2012-01-01

    Background: Ayurvedic polyherbal formulations are widely prescribed for a wide range of inflammatory conditions, yet, despite widespread use, there has been no systematic documentation of their safety and efficacy. Objective: The present study was undertaken to evaluate the anti-inflammatory activity of aqueous extracts of Ajmodadi churna (AJM) in rats. Materials and Methods: Carrageenan-induced hind paw edema and air pouch inflammation models were used for the study. Results: The extracts showed significant antiinflammatory activity, reducing paw edema volume by 0.417 ± 0.097 and 0.379 ± 0.049, respectively. In the carrageenan-induced air pouch model, AJM reduced total leukocyte count by 73.09 ± 7.13 and 62.17 ± 10.53, granulocyte count by 69.48 ± 5.44 and 63.33 ± 4.13, and myeloperoxidase activity by 14.84 ± 0.91 and 18.44 ± 3.18, respectively, compared to controls. Discussion and Conclusion: AJM significantly reduced paw edema, during the second phase of edema development. In the carrageenan-induced air pouch model, AJM inhibited cellular infiltration into the air pouch fluid. We conclude that AJM is an effective candidate for prevention or treatment of acute inflammation PMID:22529678

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

    PubMed

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

    2012-05-01

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

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

    PubMed Central

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

    2012-01-01

    We report the case of a woman with a history of chronic alcohol abuse who was hospitalized with diarrhea, severe hypokalemia refractory to potassium infusion, nausea, vomiting, abdominal pain, alternations of high blood pressure with phases of hypotension, irritability and increased urinary 5-hydroxyindoleacetic acid and cortisol. Although carcinoid syndrome was hypothesized, abdominal computed tomography and colonoscopy showed non-specific inflammatory bowel disease with severe colic wall thickening, and multiple colic biopsies confirmed non-specific inflammation with no evidence of carcinoid cells. During the following days diarrhea slowly decreased and the patient's condition progressively improved. One year after stopping alcohol consumption, the patient was asymptomatic and serum potassium was normal. Chronic alcohol exposure is known to have several deleterious effects on the intestinal mucosa and can favor and sustain local inflammation. Chronic alcohol intake may also be associated with high blood pressure, behavior disorders, abnormalities in blood pressure regulation with episodes of hypotension during hospitalization due to impaired baroreflex sensitivity in the context of an alcohol withdrawal syndrome, increased urinary 5-hydroxyindoleacetic acid as a result of malabsorption syndrome, and increased urinary cortisol as a result of hypothalamic-pituitary-adrenal axis dysregulation. These considerations, together with the regression of symptoms and normalization of potassium levels after stopping alcohol consumption, suggest the intriguing possibility of a alcohol-related acute inflammatory bowel disease mimicking carcinoid syndrome. PMID:22949895

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

    SciTech Connect

    Nelson, R.L.; Subramanian, K.; Gasparaitis, A.; Abcarian, H.; Pavel, D.G. )

    1990-06-01

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

  10. Hydroxysafflor yellow A attenuates the expression of inflammatory cytokines in acute soft tissue injury

    PubMed Central

    Dong, Fang; Xue, Changjiang; Wang, Yu; Peng, Yuanyuan; Zhang, Yadan; Jin, Ming; Zang, Baoxia

    2017-01-01

    We examined the effect of hydroxysafflor yellow A (HSYA) on the inflammatory response to strike-induced acute soft tissue injury in rats. Soft tissue injury was induced in rat leg muscles using a strike hammer, followed by intraperitoneal administration of HSYA at 16, 32, or 64 mg/kg. After 24 h, the rats were anaesthetized, blood and muscle samples were taken. Plasma levels of interleukin (IL)-6, IL-1β, and tumour necrosis factor (TNF)-αwere measured by enzyme-linked immunosorbent assay. Total RNA and protein were isolated from muscle tissue to determine the mRNA levels of IL-6, IL-1β, TNF-α, vascular cell adhesion molecule (VCAM)-1, and intercellular adhesion molecule (ICAM)-1, and the protein level of phosphorylated p38 mitogen-activated protein kinase (MAPK). Nuclear factor (NF)-κB expression was determined by muscle histopathology and immunohistochemistry. HSYA attenuated pathologic changes instrike-induced soft tissue inflammation. Treatment with HSYA also alleviated strike-induced increases in TNF-α, IL-1β, IL-6, VCAM-1, and ICAM-1mRNA levels and inhibited the increased activation of NF-κB and phosphorylation of p38 MAPK in muscle tissue. These findings suggest that HSYA effectively inhibits strike-induced inflammatory signal transduction in rats. PMID:28074914

  11. The in vivo quantitation and kinetics of monocyte migration into acute inflammatory tissue.

    PubMed Central

    Issekutz, T. B.; Issekutz, A. C.; Movat, H. Z.

    1981-01-01

    Mononuclear leukocytes isolated from the blood of rabbits, were labeled with 51Cr and returned to the animal intravenously. 51Cr-labeled monocytes disappeared from the blood with a half-life of 39.0 +/- 2.51 hours. Numerous acute inflammatory lesions were produced by the intradermal injection of Escherichia coli into the skin of the back of a rabbit. The animal was sacrificed after 1 hour, and the radioactivity in each lesion was determined. Monocyte accumulation was substantial by the time a lesion was 1 hour old. The maximum rate of accumulation occurred at 3--4 hours, and monocytes continued to enter the lesions at 25% of the maximal rate for at least 24 hours. Monocytes initially migrate into bacterial inflammatory sites simultaneously with neutrophils and histologically become the predominant cell type after 12 hours because they continue to migrate into these lesions long after neutrophils have stopped. The kinetics of monocyte migration is related to other aspects of inflammation. Images Figure 4 Figure 5 PMID:7013494

  12. PKC δ mediates pro-inflammatory responses in a mouse model of caerulein-induced acute pancreatitis.

    PubMed

    Ramnath, Raina Devi; Sun, Jia; Bhatia, Madhav

    2010-10-01

    Acute pancreatitis is an inflammatory disorder of the pancreas. Protein kinase C (PKC) δ plays an important role in mediating chemokine production in mouse pancreatic acinar cells. This study aims to investigate the role of PKC δ in the pathogenesis of acute pancreatitis and to explore the mechanisms through which PKC δ mediates pro-inflammatory signaling. Acute pancreatitis was induced in mice by ten hourly intraperitoneal injections of caerulein. PKC δ translocation inhibitor peptide (δV1-1) at a dose of 1.0 mg/kg or Tat (carrier peptide) at a dose of 1.0 mg/kg was administered to mice either 1 h before or 1 h after the first caerulein injection. One hour after the last caerulein injection, the mice were killed and pancreas, lungs, and blood were collected. Prophylactic and therapeutic treatment with δV1-1 attenuated caerulein-induced plasma amylase levels and pancreatic edema. Treatment with δV1-1 decreased myeloperoxidase activity and monocyte chemotactic protein-1 levels in both pancreas and plasma. PKC δ mediated acute pancreatitis by activating pancreatic nuclear factor κB, activator protein-1, and mitogen-activated protein kinases. Moreover, blockade of PKC δ attenuated lung myeloperoxidase activity and edema. Histological examination of pancreatic and lung sections confirmed protection against acute pancreatitis. Treatment with Tat had no protective effect on acute pancreatitis. Blockade of PKC δ represents a promising prophylactic and/or therapeutic tool for the treatment of acute pancreatitis.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  14. 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...

  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 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...

  16. 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...

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

    PubMed

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

    2013-02-01

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

  18. Acute anti-inflammatory effects of inhaled budesonide in asthma: a randomized controlled trial.

    PubMed

    Gibson, P G; Saltos, N; Fakes, K

    2001-01-01

    Corticosteroids can have acute effects on airway function and methacholine airway responsiveness in asthma as early as 6 h after dosing, suggesting there may be an acute anti-inflammatory effect of inhaled corticosteroid in asthma. This study aimed to determine the effects of a single dose of inhaled budesonide on sputum eosinophils and mast cells in adults with asthma, and to examine whether the mechanism of clearance of eosinophils was by apoptosis. A randomized, double-blind, placebo-controlled, crossover study was conducted. At the screening visit, adults with stable asthma (n = 41) ceased inhaled corticosteroid therapy for 4 d and those with significant sputum eosinophilia (> or = 7%) were randomized (n = 26) to a single dose of budesonide 2,400 microg or placebo via Turbuhaler, on two separate study days. Symptoms and lung function were followed for 6 h, then sputum was induced and airway responsiveness to hypertonic saline determined. Sputum eosinophils (mean, SE) were significantly lower 6 h after budesonide (25%, 4.5), compared with placebo (37%, 6.2, p < 0.05). There was a 2.2-fold (95% CI 1.45 to 3.33) improvement in airway responsiveness with budesonide. No significant difference was seen on mast cells, apoptotic eosinophils, symptoms, or lung function. In conclusion, a single dose of inhaled corticosteroids has beneficial effects on airway inflammation and airway hyperresponsiveness as early as 6 h after dosing. This may be clinically useful as therapy during mild exacerbations of asthma.

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

    PubMed

    Ralya, Andrew; McCarson, Kenneth E

    2014-07-11

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

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

    SciTech Connect

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

    2016-01-13

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

  1. Role of the 5-Lipoxygenase–activating Protein (FLAP) in Murine Acute Inflammatory Responses

    PubMed Central

    Byrum, Robert S.; Goulet, Jennifer L.; Griffiths, Richard J.; Koller, Beverly H.

    1997-01-01

    Leukotrienes are potent inflammatory mediators synthesized from arachidonic acid (AA) predominately by cells of myeloid origin. The synthesis of these lipids is believed to be dependent not only on the expression of the enzyme 5-lipoxygenase (5-LO), which catalyzes the first steps in the synthesis of leukotrienes, but also on expression of a nuclear membrane protein termed the 5-LO–activating protein (FLAP). To study the relationship of these two proteins in mediating the production of leukotrienes in vivo and to determine whether the membrane protein FLAP has additional functions in various inflammatory processes, we have generated a mouse line deficient in this protein. FLAP-deficient mice develop normally and are healthy. However, an array of assays comparing inflammatory reactions in FLAP-deficient mice and in normal controls revealed that FLAP plays a role in a subset of these reactions. Although examination of DTH and IgE-mediated passive anaphylaxis showed no difference between wild-type and FLAP-deficient animals, mice without FLAP possessed a blunted inflammatory response to topical AA and had increased resistance to platelet-activating factor–induced shock compared to controls. Also, edema associated with Zymosan A–induced peritonitis was markedly reduced in animals lacking FLAP. To determine whether these differences relate solely to a deficit in leukotriene production, or whether they reflect an additional role for FLAP in inflammation, we compared the FLAP-deficient mice to 5-LO–deficient animals. Evaluation of mice lacking FLAP and 5-LO indicated that production of leukotrienes during inflammatory responses is dependent upon the availability of FLAP and did not support additional functions for FLAP beyond its role in leukotriene production. PMID:9091580

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

    PubMed

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

    2012-10-01

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

  3. Inflammatory neuropathies.

    PubMed

    Whitesell, Jackie

    2010-09-01

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

  4. 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.

  5. Cyclic strain inhibits acute pro-inflammatory gene expression in aortic valve interstitial cells.

    PubMed

    Smith, Kathryn E; Metzler, Scott A; Warnock, James N

    2010-02-01

    Mechanical in vitro preconditioning of tissue engineered heart valves is viewed as an essential process for tissue development prior to in vivo implantation. However, a number of pro-inflammatory genes are mechanosensitive and their elaboration could elicit an adverse response in the host. We hypothesized that the application of normal physiological levels of strain to isolated valve interstitial cells would inhibit the expression of pro-inflammatory genes. Cells were subjected to 0, 5, 10, 15 and 20% strain. Expression of VCAM-1, MCP-1, GM-CSF and OPN was then measured using qRT-PCR. With the exception of OPN, all genes were significantly up regulated when no strain was applied. MCP-1 expression was significantly lower in the presence of strain, although strain magnitude did not affect the expression level. VCAM-1 and GM-CSF had the lowest expression levels at 15% strain, which represent normal physiological conditions. These findings were confirmed using confocal microscopy. Additionally, pSMAD 2/3 and IkappaBalpha expression were imaged to elucidate potential mechanisms of gene expression. Data showed that 15% strain increased pSMAD 2/3 expression and prevented phosphorylation of IkappaBalpha. In conclusion, cyclic strain reduces expression of pro-inflammatory genes, which may be beneficial for the in vitro pre-conditioning of tissue engineered heart valves.

  6. The impact of inflammatory rheumatic diseases on the presentation, severity, and outcome of acute coronary syndrome.

    PubMed

    Ben-Zvi, Ilan; Goldenberg, Ilan; Matetzky, Shlomi; Grossman, Chagai; Elis, Avishay; Gavrielov-Yusim, Natalie; Livneh, Avi

    2016-01-01

    Patients with inflammatory rheumatic diseases (IRD) have a high burden of cardiovascular disease (CVD), leading to increased mortality and morbidity. However, it is not clear whether increased CVD mortality in IRD is due to a higher incidence or worse outcome of cardiovascular events (higher case fatality). In this observational case-control study, we assessed the outcome of acute coronary syndrome (ACS) in patients with IRDs compared to matched controls without IRD, using data from the Acute Coronary Syndrome Israeli Survey (ACSIS), a large, national, real-life registry detailing the extent, severity, and outcome of ACS. Of 2,193 subjects enrolled to the ACSIS, 20 (nine men) were identified with IRD, including 11 patients with rheumatoid arthritis, five patients with systemic lupus erythematosus (SLE), three patients with ankylosing spondylitis (AS), and one patient with psoriatic arthritis (PsA). The study patients were compared to 120 matched control patients (adjusted for age and risk factors for CVD) without IRD. Compared to controls, IRD patients had similar clinical presentation and similar type of ACS and received identical initial treatment at the ER. The two groups had comparable rates of complications including major adverse cardiovascular events (death, recurrent myocardial infarction, stroke, major bleeding, and definite stent thrombosis) (10 vs. 11.7% in the study and control group, respectively, p > 0.05), re-hospitalization (20 vs. 21.1%, respectively, p > 0.05), and severe congestive heart failure (7.7 vs. 6.9%, respectively, p > 0.05) within 30 days. The outcome and prognosis of ACS in patients with IRD is not worse than that of control, supporting the higher prevalence of CVD in this population as the cause for their excess mortality.

  7. 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.

  8. Development of anti-inflammatory drugs - the research and development process.

    PubMed

    Knowles, Richard Graham

    2014-01-01

    The research and development process for novel drugs to treat inflammatory diseases is described, and several current issues and debates relevant to this are raised: the decline in productivity, attrition, challenges and trends in developing anti-inflammatory drugs, the poor clinical predictivity of experimental models of inflammatory diseases, heterogeneity within inflammatory diseases, 'improving on the Beatles' in treating inflammation, and the relationships between big pharma and biotechs. The pharmaceutical research and development community is responding to these challenges in multiple ways which it is hoped will lead to the discovery and development of a new generation of anti-inflammatory medicines.

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

    PubMed

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

    2015-05-01

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

  10. Alteration in inflammatory/apoptotic pathway and histone modifications by nordihydroguaiaretic acid prevents acute pancreatitis in swiss albino mice.

    PubMed

    Mahajan, Ujwal Mukund; Gupta, Chanchal; Wagh, Preshit Ravindra; Karpe, Pinakin Arun; Tikoo, Kulbhushan

    2011-11-01

    Reactive oxygen radicals, pro-inflammatory mediators and cytokines have been implicated in caerulein induced acute pancreatitis. Nordihydroguaiaretic acid (NDGA), a plant lignin, has marked anti-inflammatory properties. The present study aimed to investigate the possible protective effect of NDGA against caerulein induced pancreatitis. Acute pancreatitis was induced by intraperitoneal administration of eight doses of caerulein in male swiss albino mice. NDGA was administered after 9 h of acute pancreatitis induction. Pancreatic damage and the protective effect of NDGA were assessed by oxidative stress parameters and histopathology of pancreas. The mRNA expression of heat shock proteins (DNAJ C15 and HSPD1) was examined by real-time RT-PCR analysis. Expression of HSP 27, NF-κB, TNF-α, p-p38, Bcl-2, p-PP2A, procaspase-3, caspase-3 and histone modifications were examined by western blotting. NDGA attenuated the oxidative stress, led to increased plasma α-amylase and decreased IGF-1 in AP mice. It modulated the mRNA and protein levels of heat shock proteins and reduced the expression of NF-κB, TNF-α and p-p38. It increased the number of TUNEL positive apoptotic cells in the pancreas of AP mice. In addition, NDGA prevented the changes in modifications of histone H3 in acute pancreatitis. To best of our knowledge, this is the first report which suggests that NDGA prevents the progression of acute pancreatitis by involving alteration of histone H3 modifications and modulating the expression of genes involved in inflammatory/apoptotic cascade, which may be responsible for decreased necrosis and increased apoptosis in this model of acute pancreatitis.

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

    PubMed

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

    2014-11-01

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

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

    PubMed

    Boyko, Matthew; Nassar, Ahmad; Kaplanski, Jacob; Zlotnik, Alexander; Sharon-Granit, Yael; Azab, Abed N

    2015-01-01

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

  13. Headaches in Multiple Sclerosis Patients Might Imply an Inflammatorial Process

    PubMed Central

    Zettl, Uwe K.

    2013-01-01

    Recent studies on Multiple Sclerosis (MS) pathology mention the involvement of “tertiary B cell follicles” in MS pathogenesis. This inflammatory process, which occurs with interindividually great variance, might be a link between MS pathology and headaches. The aim of this study was to detect the prevalence of headaches and of subtypes of headaches (migraine, cluster, tension-type headache [TTH]) in an unselected MS collective and to compile possibly influencing factors. Unselected MS patients (n = 180) with and without headache were examined by a semi-structured interview using a questionnaire about headache, depression and the health status. Additionally clinical MS data (expanded disability state score [EDSS], MS course, medication, disease duration) were gathered. N = 98 MS patients (55.4%) reported headaches in the previous 4 weeks. We subsequently grouped headache patients according to the IHS criteria and detected 16 (16.3%) MS patients suffering from migraine (migraine with aura: 2 [2%]; migraine without aura: 14 [14.3%]), 23 (23.5%) suffering from TTH and none with a cluster headache. Thus, headaches of 59 (60.2%) MS patients remained unclassified. When comparing MS patients with and without headaches significant differences in age, gender, MS course, physical functioning, pain and social functioning occurred. MS patients with headaches were significantly younger of age (p = 0.001), female (p = 0.001) and reported more often of a clinically isolated syndrome (CIS) and relapsing/remitting MS (RRMS) instead of secondary chronic progressive MS (SCP). EDSS was significantly lower in MS patients suffering from headaches compared to the MS patients without headaches (p = 0.001). In conclusion headache in MS patients is a relevant symptom, especially in early stages of the MS disease. Especially unclassified headache seems to represent an important symptom in MS course and requires increased attention. PMID:23940524

  14. 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

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

    PubMed Central

    2016-01-01

    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

  16. Mouse Hepatitis Virus Infection Induces a Toll-Like Receptor 2-Dependent Activation of Inflammatory Functions in Liver Sinusoidal Endothelial Cells during Acute Hepatitis

    PubMed Central

    Bleau, Christian; Filliol, Aveline; Samson, Michel

    2016-01-01

    ABSTRACT Under physiological conditions, the liver sinusoidal endothelial cells (LSECs) mediate hepatic immune tolerance toward self or foreign antigens through constitutive expression of anti-inflammatory mediators. However, upon viral infection or Toll-like receptor 2 (TLR2) activation, LSECs can achieve proinflammatory functions, but their role in hepatic inflammation during acute viral hepatitis is unknown. Using the highly virulent mouse hepatitis virus type 3 (MHV3) and the attenuated variants 51.6-MHV3 and YAC-MHV3, exhibiting lower tropism for LSECs, we investigated in vivo and in vitro the consequence of LSEC infection on their proinflammatory profiles and the aggravation of acute hepatitis process. In vivo infection with virulent MHV3, in comparison to attenuated strains, resulted in fulminant hepatitis associated with higher hepatic viral load, tissue necrosis, and levels of inflammatory mediators and earlier recruitment of inflammatory cells. Such hepatic inflammatory disorders correlated with disturbed production of interleukin-10 (IL-10) and vascular factors by LSECs. We next showed in vitro that infection of LSECs by the virulent MHV3 strain altered their production of anti-inflammatory cytokines and promoted higher release of proinflammatory and procoagulant factors and earlier cell damage than infection by attenuated strains. This higher replication and proinflammatory activation in LSECs by the virulent MHV3 strain was associated with a specific activation of TLR2 signaling by the virus. We provide evidence that TLR2 activation of LSCEs by MHV3 is an aggravating factor of hepatic inflammation and correlates with the severity of hepatitis. Taken together, these results indicate that preservation of the immunotolerant properties of LSECs during acute viral hepatitis is imperative in order to limit hepatic inflammation and damage. IMPORTANCE Viral hepatitis B and C infections are serious health problems affecting over 350 million and 170 million

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

    PubMed

    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

  18. Pequi (Caryocar brasiliense Camb.) almond oil attenuates carbon tetrachloride-induced acute hepatic injury in rats: Antioxidant and anti-inflammatory effects.

    PubMed

    Torres, Lucillia R de O; Santana, Fernanda C de; Torres-Leal, Francisco L; Melo, Illana L P de; Yoshime, Luciana T; Matos-Neto, Emidio M; Seelaender, Marília C L; Araújo, Cintia M M; Cogliati, Bruno; Mancini-Filho, Jorge

    2016-11-01

    Carbon tetrachloride (CCl4) is a potent hepatotoxin, capable of generating free radicals that lead to oxidative stress and the inflammation process. Pequi almond oil (PAO) has been reported to possess unsaturated fatty acid and antioxidant compounds related to beneficial effects on oxidation and inflammatory conditions. The present study was undertaken to evaluate the hepatoprotective effects of handmade and coldpressed PAO on CCl4-induced acute liver injury. The possible mechanisms underlying the effect on liver injury enzymes, histopathological parameters, lipid profile, lipid peroxidation, and antioxidant and detoxification defense systems, as well as inflammatory parameters, were determined. Rats treated with PAO (3 or 6 mL/kg) for 21 days before CCl4 induction (3 mL/kg, 70%) showed significantly decreased levels of alanine aminotransferase and aspartate aminotransferase, milder hepatic lesions and higher levels of serum high-density lipoprotein compared to CCl4 group. Moreover, PAO enhanced antioxidant capacity by increasing hepatic glutathione peroxidase and glutathione reductase enzyme activities, as well as reducing circulating concentrations of leptin and inflammatory mediators such as interleukin-6, leukotrienes -4 and -5 and the tumor necrosis factor receptor. In summary, PAO, especially cold-pressed oil, attenuated the CCl4-induced alterations in serum and hepatic tissue in rats due to its antioxidant and anti-inflammatory properties.

  19. TRPA1 contributes to the acute inflammatory response and mediates carrageenan-induced paw edema in the mouse.

    PubMed

    Moilanen, Lauri J; Laavola, Mirka; Kukkonen, Meiju; Korhonen, Riku; Leppänen, Tiina; Högestätt, Edward D; Zygmunt, Peter M; Nieminen, Riina M; Moilanen, Eeva

    2012-01-01

    Transient receptor potential ankyrin 1 (TRPA1) is an ion channel involved in thermosensation and nociception. TRPA1 is activated by exogenous irritants and also by oxidants formed in inflammatory reactions. However, our understanding of its role in inflammation is limited. Here, we tested the hypothesis that TRPA1 is involved in acute inflammatory edema. The TRPA1 agonist allyl isothiocyanate (AITC) induced inflammatory edema when injected intraplantarly to mice, mimicking the classical response to carrageenan. Interestingly, the TRPA1 antagonist HC-030031 and the cyclo-oxygenase (COX) inhibitor ibuprofen inhibited not only AITC but also carrageenan-induced edema. TRPA1-deficient mice displayed attenuated responses to carrageenan and AITC. Furthermore, AITC enhanced COX-2 expression in HEK293 cells transfected with human TRPA1, a response that was reversed by HC-030031. This study demonstrates a hitherto unknown role of TRPA1 in carrageenan-induced inflammatory edema. The results also strongly suggest that TRPA1 contributes, in a COX-dependent manner, to the development of acute inflammation.

  20. Polymorphisms in key pulmonary inflammatory pathways and the development of acute respiratory distress syndrome

    PubMed Central

    Brown, Samuel M.; Grissom, Colin K.; Rondina, Matthew T.; Hoidal, John R.; Scholand, Mary Beth; Wolff, Roger K.; Morris, Alan H.; Paine, Robert

    2015-01-01

    Purpose/Aim Acute Respiratory Distress Syndrome (ARDS) is an important clinical and public health problem. Why some at-risk individuals develop ARDS and others do not is unclear but may be related to differences in inflammatory and cell signaling systems. The Receptor for Advanced Glycation Endproducts (RAGE) and Granulocyte-Monocyte Stimulating Factor (GM-CSF) pathways have recently been implicated in pulmonary pathophysiology; whether genetic variation within these pathways contributes to ARDS risk or outcome is unknown. Materials and Methods We studied 842 patients from three centers in Utah and 14 non-Utah ARDS Network centers. We studied patients at risk for ARDS and patients with ARDS to determine whether Single Nucleotide Polymorphisms (SNPs) in the RAGE and GM-CSF pathways were associated with development of ARDS. We studied 29 SNPs in 5 genes within the two pathways and controlled for age, sepsis as ARDS risk factor, and severity of illness, while targeting a false discovery rate of ≤5%. In a secondary analysis we evaluated associations with mortality. Results Of 842 patients, 690 had ARDS, and 152 were at-risk. Sepsis was the risk factor for ARDS in 250 (30%) patients. When controlling for age, APACHE III score, sepsis as risk factor, and multiple comparisons, no SNPs were significantly associated with ARDS. In a secondary analysis, only rs743564 in CSF2 approached significance with regard to mortality (OR 2.17, unadjusted p = 0.005, adjusted p = 0.15). Conclusions Candidate SNPs within 5 genes in the RAGE and GM-CSF pathways were not significantly associated with development of ARDS in this multi-centric cohort. PMID:25513711

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

    PubMed

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

    2015-08-01

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

  2. 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

  3. Epac1 and Epac2 are differentially involved in inflammatory and remodeling processes induced by cigarette smoke

    PubMed Central

    Oldenburger, Anouk; Timens, Wim; Bos, Sophie; Smit, Marieke; Smrcka, Alan V.; Laurent, Anne-Coline; Cao, Junjun; Hylkema, Machteld; Meurs, Herman; Maarsingh, Harm; Lezoualc'h, Frank; Schmidt, Martina

    2014-01-01

    Cigarette smoke (CS) induces inflammatory responses characterized by increase of immune cells and cytokine release. Remodeling processes, such as mucus hypersecretion and extracellular matrix protein production, are also directly or indirectly induced by CS. Recently, we showed that activation of the exchange protein directly activated by cAMP (Epac) attenuates CS extract-induced interleukin (IL)-8 release from cultured airway smooth muscle cells. Using an acute, short-term model of CS exposure, we now studied the role of Epac1, Epac2, and the Epac effector phospholipase-Cε (PLCε) in airway inflammation and remodeling in vivo. Compared to wild-type mice exposed to CS, the number of total inflammatory cells, macrophages, and neutrophils and total IL-6 release was lower in Epac2−/− mice, which was also the case for neutrophils and IL-6 in PLCε−/− mice. Taken together, Epac2, acting partly via PLCε, but not Epac1, enhances CS-induced airway inflammation in vivo. In total lung homogenates of Epac1−/− mice, MUC5AC and matrix remodeling parameters (transforming growth factor-β1, collagen I, and fibronectin) were increased at baseline. Our findings suggest that Epac1 primarily is capable of inhibiting remodeling processes, whereas Epac2 primarily increases inflammatory processes in vivo.—Oldenburger, A., Timens, W., Bos, S., Smit, M., Smrcka, A. V., Laurent, A.-C., Cao, J., Hylkema, M., Meurs, H., Maarsingh, H., Lezoualc'h, F., and Schmidt, M. Epac1 and Epac2 are differentially involved in inflammatory and remodeling processes induced by cigarette smoke. PMID:25103224

  4. Anti-inflammatory activity of aqueous fruit pulp extract of Hunteria umbellata K. Schum in acute and chronic inflammation.

    PubMed

    Igbe, Ighodaro; Ching, Fidelis P; Eromon, Aigbe

    2010-01-01

    The anti-inflammatory effect of the aqueous fruit pulp extract of Hunteria umbellata K. Schum (Apocynaceae) was evaluated using the carrageenan- and dextran-induced rat paw edema, xylene-induced ear edema and formalin-induced arthritis inflammation tests. Oral administration of the extract produced significant (p < 0.05) antiedematogenic effect with a dose of 500 mg/kg throughout the period of the experiment in the dextran induced paw edema and at the 3 h in the carrageenan model. The extract (250 and 500 mg/kg) exhibited a dose-related and significant (p < 0.01) inhibition of xylene induced ear edema and the effect was similar to that produced by dexamethasone (1 mg/kg). In the chronic inflammation (formalin induced arthritis) the extract did not show any significant anti-inflammatory activity. Oral acute toxicity assays did not show any mortality at 15 g/kg of the plant extract. The results indicate that the aqueous extract of H. umbellata possesses acute inflammatory activity which may be mediated by either inhibition or by blocking the release of prostaglandins and histamine, thus supporting the usage of the plant in traditional medicine treatment of inflammation.

  5. The degree of mutual anisotropy of biological liquids polycrystalline nets as a parameter in diagnostics and differentiations of hominal inflammatory processes

    NASA Astrophysics Data System (ADS)

    Angelsky, O. V.; Ushenko, Yu. A.; Balanetska, V. O.

    2012-01-01

    To characterize the degree of consistency of parameters of the optically uniaxial birefringent protein nets of blood plasma a new parameter - complex degree of mutual anisotropy is suggested. The technique of polarization measuring the coordinate distributions of the complex degree of mutual anisotropy of blood plasma is developed. It is shown that statistic approach to the analysis of the complex degree of mutual anisotropy distributions of blood plasma is effective during the diagnostics and differentiation of an acute inflammatory processes as well as acute and gangrenous appendicitis.

  6. 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

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

    PubMed

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

    2016-01-01

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

  8. Nicotine and serotonin in immune regulation and inflammatory processes: a perspective.

    PubMed

    Cloëz-Tayarani, Isabelle; Changeux, Jean-Pierre

    2007-03-01

    Nicotine and serotonin modulate the innate and adaptive immune responses and the inflammatory states. Several nicotinic cholinergic and serotonergic receptor subtypes have been characterized in B and T lymphocytes, monocytes, macrophages, and dendritic cells. The use of knockout mice has allowed a better characterization of nicotinic receptors and their role in anti-inflammatory processes in these cells. Cytokines play a crucial role in controlling inflammatory reactions. Nicotine and serotonin have been reported to regulate cytokine release. Cholinergic mechanisms also play an important role in inflammation through endogenous acetylcholine. Nicotine mimics this effect by activating the cholinergic anti-inflammatory pathways. New concepts of reciprocal interactions between nicotine and serotonin are emerging. The role of nicotine as an anti-inflammatory agent has been established, whereas that of serotonin remains more controversial.

  9. Acute effects of anti-inflammatory drugs on neodymium:yttrium aluminum garnet laser-induced uveitis in dogs.

    PubMed

    Millichamp, N J; Dziezyc, J; Rohde, B H; Chiou, G C; Smith, W B

    1991-08-01

    Dogs were treated with flunixin meglumine, a cyclooxygenase inhibitor; L-651,896, a 5-lipoxygenase inhibitor; and matrine, a herbal anti-inflammatory drug. Acute inflammation was induced in the eyes by disruption of the anterior lens capsule, using a neodymium:yttrium aluminum garnet laser. Intraocular pressure, pupil diameter, and eicosanoid production in the aqueous humor were measured. Statistically significant effects were seen in the eyes of flunixin meglumine-treated dogs where mydriasis was maintained and aqueous prostaglandin E2 concentration was reduced.

  10. Acute cold stress improved the transcription of pro-inflammatory cytokines of Chinese soft-shelled turtle against Aeromonas hydrophila.

    PubMed

    Zhang, Zuobing; Chen, Bojian; Yuan, Lin; Niu, Cuijuan

    2015-03-01

    Chinese soft-shelled turtle, Pelodiscus sinensis, is widely cultured in East and Southeast Asian countries. It frequently encounters the stress of abrupt temperature changes, which leads to mass death in most cases. However, the mechanism underlying the stress-elicited death remains unknown. We have suspected that the stress impaired the immune function of Chinese soft-shelled turtle, which could result in the mass death, as we noticed that there was a clinical syndrome of infection in dead turtles. To test our hypothesis, we first performed bioinformatic annotation of several pro-inflammatory molecules (IL-1β, TNFα, IL-6, IL-12β) of Chinese soft-shelled turtle. Then, we treated the turtles in six groups, injected with Aeromonas hydrophila before acute cold stress (25 °C) and controls, after acute cold stress (15 °C) and controls as well as after the temperature was restored to 25 °C and controls, respectively. Subsequently, real-time PCR for several pro-inflammatory cytokines (IL-1β, TNFα, IL-6, IL-12β, IL-8 and IFNγ) was performed to assess the turtle immune function in spleen and intestine, 24 hours after the injection. We found that the mRNA expression levels of the immune molecules were all enhanced after acute cold stress. This change disappeared when the temperature was restored back to 25 °C. Our results suggest that abrupt temperature drop did not suppress the immune function of Chinese soft-shelled turtle in response to germ challenge after abrupt temperature drop. In contrast, it may even increase the expression of various cytokines at least, within a short time after acute cold stress.

  11. Early Activation of Th2/Th22 Inflammatory and Pruritogenic Pathways in Acute Canine Atopic Dermatitis Skin Lesions.

    PubMed

    Olivry, Thierry; Mayhew, David; Paps, Judy S; Linder, Keith E; Peredo, Carlos; Rajpal, Deepak; Hofland, Hans; Cote-Sierra, Javier

    2016-10-01

    Determining inflammation and itch pathway activation in patients with atopic dermatitis (AD) is fraught with the inability to precisely assess the age of skin lesions, thus affecting the analysis of time-dependent mediators. To characterize inflammatory events occurring during early experimental acute AD lesions, biopsy samples were collected 6, 24, and 48 hours after epicutaneous application of Dermatophagoides farinae house dust mites to sensitized atopic dogs. The skin transcriptome was assessed using a dog-specific microarray and quantitative PCR. Acute canine AD skin lesions had a significant up-regulation of genes encoding T helper (Th) 2 (e.g., IL4, IL5, IL13, IL31, and IL33), Th9 (IL9), and Th22 (IL22) cytokines as well as Th2-promoting chemokines such as CCL5 and CCL17. Proinflammatory (e.g., IL6, LTB, and IL18) cytokines were also up-regulated. Other known pruritogenic pathways were also activated: there was significant up-regulation of genes encoding proteases cathepsin S (CTSS), mast cell chymase (CMA1), tryptase (TPS1) and mastin, neuromedin-B (NMB), nerve growth factor (NGF), and leukotriene-synthesis enzymes (ALOX5, ALOX5AP, and LTA4H). Experimental acute canine house dust mite-induced AD lesions exhibit an activation of innate and adaptive immune responses and pruritogenic pathways similar to those seen in humans with acute AD, thereby validating this model to test innovative therapeutics modalities for this disease.

  12. Inflammatory markers following acute fuel oil exposure or bacterial lipopolysaccharide in mallard ducks (Anas platyrhynchos).

    PubMed

    Lee, Kelly A; Tell, Lisa A; Mohr, F Charles

    2012-12-01

    Adult mallard ducks (Anas platyrhynchos) were orally dosed with bunker C fuel oil for 5 days, and five different inflammatory markers (haptoglobin, mannan-binding lectin, ceruloplasmin, unsaturated iron-binding capacity, and plasma iron) were measured in blood plasma prior to and 8, 24, 48, and 72 hr following exposure. In order to contrast the response to fuel oil with that of a systemic inflammatory response, an additional five ducks were injected intramuscularly with bacterial lipopolysaccharide (LPS). Oil-treated birds had an inflammatory marker profile that was significantly different from control and LPS-treated birds, showing decreases in mannan-binding lectin-dependent hemolysis and unsaturated iron-binding capacity, but no changes in any of the other inflammatory markers. Birds treated with oil also exhibited increased liver weights, decreased body and splenic weights, and decreased packed cell volume.

  13. [The role of IRA B cells in selected inflammatory processes].

    PubMed

    Zasada, Magdalena; Rutkowska-Zapała, Magdalena; Lenart, Marzena; Kwinta, Przemko

    2016-03-16

    The first report about the discovery of new, previously unknown immune cells named IRA B cells (innate response activator B cells) appeared in 2012. So far, their presence has been verified in both mice and humans. However, IRA B cells belong to the family of B lymphocytes and have a number of characteristics unique to this group of cells. IRA B cells are formed from activated B1a lymphocytes after their contact with a pathogen. B1a lymphocytes mainly reside within body cavities. Activated by the pathogen, they move on into secondary lymphoid organs (spleen, lymph nodes) where they differentiate into IRA B cells. IRA B cells are a rich source of granulocyte-macrophage colony stimulating factor (GM-CSF). GM-CSF can stimulate IRA B cells in an autocrine manner for the secretion of intracellular stocks of immunoglobulin M (IgM), which can facilitate pathogens' phagocytosis by neutrophils. GM-CSF also stimulates neutrophils into active phagocytosis. Rapid eradication of the pathogen can prevent the development of an excessive inflammatory response, which can be dangerous for the organism. Until now the involvement of IRA B lymphocytes in the pathogenesis of sepsis and pneumonia has been proven, as well as their role in the progression of atherosclerotic lesions in mice. There is research in progress on the possibility of increasing the number of IRA B cells, for example by intravenous supply of modified immunoglobulins. It is necessary to characterize human IRA B cells and to determine their role in the functioning of the immune system.

  14. Effects of low-intensity ultrahigh frequency electromagnetic radiation on inflammatory processes.

    PubMed

    Lushnikov, K V; Shumilina, Yu V; Yakushina, V S; Gapeev, A B; Sadovnikov, V B; Chemeris, N K

    2004-04-01

    Low-intensity ultrahigh frequency electromagnetic radiation (42 GHz, 100 microW/cm(2)) reduces the severity of inflammation and inhibits production of active oxygen forms by inflammatory exudate neutrophils only in mice with inflammatory process. These data suggest that some therapeutic effects of electromagnetic radiation can be explained by its antiinflammatory effect which is realized via modulation of functional activity of neutrophils in the focus of inflammation.

  15. Discovery of a New Inhibitor of Myeloid Differentiation 2 from Cinnamamide Derivatives with Anti-Inflammatory Activity in Sepsis and Acute Lung Injury.

    PubMed

    Chen, Gaozhi; Zhang, Yali; Liu, Xing; Fang, Qilu; Wang, Zhe; Fu, Lili; Liu, Zhiguo; Wang, Yi; Zhao, Yunjie; Li, Xiaokun; Liang, Guang

    2016-03-24

    Acute inflammatory diseases, including acute lung injury and sepsis, remain the most common life-threatening illness in intensive care units worldwide. Cinnamamide has been incorporated in several synthetic compounds with therapeutic potentials including anti-inflammatory properties. However, the possible mechanism and direct molecular target of cinnamamides for their anti-inflammatory effects were rarely investigated. In this study, we synthesized a series of cinnamamides and evaluated their anti-inflammatory activities. The most active compound, 2i, was found to block LPS-induced MD2/TLR4 pro-inflammatory signaling activation in vitro and to attenuate LPS-caused sepsis and acute lung injury in vivo. Mechanistically, we demonstrated that 2i exerts its anti-inflammatory effects by directly targeting and binding MD2 in Arg90 and Tyr102 residues and inhibiting MD2/TLR4 complex formation. Taken together, this work presents a novel MD2 inhibitor, 2i, which has the potential to be developed as a candidate for the treatment of sepsis, and provides a new lead structure for the development of anti-inflammatory agents targeting MD2.

  16. 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

  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.

  18. 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.

  19. An ensemble of models of the acute inflammatory response to bacterial lipopolysaccharide in rats: results from parameter space reduction.

    PubMed

    Daun, Silvia; Rubin, Jonathan; Vodovotz, Yoram; Roy, Anirban; Parker, Robert; Clermont, Gilles

    2008-08-21

    In previous work, we developed an 8-state nonlinear dynamic model of the acute inflammatory response, including activated phagocytic cells, pro- and anti-inflammatory cytokines, and tissue damage, and calibrated it to data on cytokines from endotoxemic rats. In the interest of parsimony, the present work employed parametric sensitivity and local identifiability analysis to establish a core set of parameters predominantly responsible for variability in model solutions. Parameter optimization, facilitated by varying only those parameters belonging to this core set, was used to identify an ensemble of parameter vectors, each representing an acceptable local optimum in terms of fit to experimental data. Individual models within this ensemble, characterized by their different parameter values, showed similar cytokine but diverse tissue damage behavior. A cluster analysis of the ensemble of models showed the existence of a continuum of acceptable models, characterized by compensatory mechanisms and parameter changes. We calculated the direct correlations between the core set of model parameters and identified three mechanisms responsible for the conversion of the diverse damage time courses to similar cytokine behavior in these models. Given that tissue damage level could be an indicator of the likelihood of mortality, our findings suggest that similar cytokine dynamics could be associated with very different mortality outcomes, depending on the balance of certain inflammatory elements.

  20. 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

  1. 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.

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

    PubMed

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

    2015-08-01

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

  3. CXCR2 deficient mice display macrophage-dependent exaggerated acute inflammatory responses

    PubMed Central

    Dyer, Douglas P.; Pallas, Kenneth; Ruiz, Laura Medina; Schuette, Fabian; Wilson, Gillian J.; Graham, Gerard J.

    2017-01-01

    CXCR2 is an essential regulator of neutrophil recruitment to inflamed and damaged sites and plays prominent roles in inflammatory pathologies and cancer. It has therefore been highlighted as an important therapeutic target. However the success of the therapeutic targeting of CXCR2 is threatened by our relative lack of knowledge of its precise in vivo mode of action. Here we demonstrate that CXCR2-deficient mice display a counterintuitive transient exaggerated inflammatory response to cutaneous and peritoneal inflammatory stimuli. In both situations, this is associated with reduced expression of cytokines associated with the resolution of the inflammatory response and an increase in macrophage accumulation at inflamed sites. Analysis using neutrophil depletion strategies indicates that this is a consequence of impaired recruitment of a non-neutrophilic CXCR2 positive leukocyte population. We suggest that these cells may be myeloid derived suppressor cells. Our data therefore reveal novel and previously unanticipated roles for CXCR2 in the orchestration of the inflammatory response. PMID:28205614

  4. Roles of inflammatory caspases during processing of zebrafish interleukin-1β in Francisella noatunensis infection

    USGS Publications Warehouse

    Vojtech, Lucia N.; Scharping, Nichole; Woodson, James C.; Hansen, John D.

    2012-01-01

    The interleukin-1 family of cytokines are essential for the control of pathogenic microbes but are also responsible for devastating autoimmune pathologies. Consequently, tight regulation of inflammatory processes is essential for maintaining homeostasis. In mammals, interleukin-1 beta (IL-1β) is primarily regulated at two levels, transcription and processing. The main pathway for processing IL-1β is the inflammasome, a multiprotein complex that forms in the cytosol and which results in the activation of inflammatory caspase (caspase 1) and the subsequent cleavage and secretion of active IL-1β. Although zebrafish encode orthologs of IL-1β and inflammatory caspases, the processing of IL-1β by activated caspase(s) has never been examined. Here, we demonstrate that in response to infection with the fish-specific bacterial pathogen Francisella noatunensis, primary leukocytes from adult zebrafish display caspase-1-like activity that results in IL-1β processing. Addition of caspase 1 or pancaspase inhibitors considerably abrogates IL-1β processing. As in mammals, this processing event is concurrent with the secretion of cleaved IL-1β into the culture medium. Furthermore, two putative zebrafish inflammatory caspase orthologs, caspase A and caspase B, are both able to cleave IL-1β, but with different specificities. These results represent the first demonstration of processing and secretion of zebrafish IL-1β in response to a pathogen, contributing to our understanding of the evolutionary processes governing the regulation of inflammation.                   

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

    PubMed

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

    2004-04-15

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

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

    PubMed

    Woodward, Bill

    2016-04-11

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

  7. Differential diagnosis of pelvic cystic lesions caused by hemorrhage from inflammatory abscess using CT attenuation in women with acute abdomen.

    PubMed

    Sato, Kazuko; Kajihara, Takeshi; Miki, Akinori; Hirabayashi, Eriko; Shintani, Daisuke; Niitsu, Mamoru; Ishihara, Osamu; Itakura, Atsuo

    2015-11-01

    To determine the efficacy of computed tomography (CT) attenuation of cystic lesions measured on an image browsing system to distinguish abscess from hematoma in women with acute abdomen. The medical records of female patients of reproductive age with acute abdomen who were treated over a 7-year period in a single center and who had undergone laparotomy or laparoscopic surgery and preoperative pelvic CT scanning were retrospectively analyzed to identify those with hematoma or abscess cyst formation. Nineteen patients with tubo-ovarian abscess (abscess group) and six patients with hematoma (hematoma group) formation in the pelvis were included in the analysis. The preoperative CT images of the tubo-ovarian cyst were retrospectively investigated on the basis of cyst attenuation. CT attenuation of the cyst measured by both two gynecologists could be used to clearly distinguish inflammatory disease with abscess formation from bleeding disease with hematoma. CT attenuation on a picture archiving and communication system can distinguish hematoma from abscess in women with acute abdomen. This may significantly contribute to making differential diagnosis without interpretation by a medical radiologist.

  8. 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

  9. Acute postoperative inflammatory polyarthritis associated with a lone IgM cardiolipin antibody

    PubMed Central

    Chua, Ignatius; Jawad, Ali

    2015-01-01

    While the most recognised complication after joint surgery is septic arthritis, other forms of joint pathology may occur. We present a case of postoperative polyarthritis with high inflammatory markers, which responded to a course of prednisolone. The occurrence of high IgM cardiolipin antibodies that normalised with treatment suggests that this condition is a form of transient autoimmunity. PMID:25733090

  10. Carbon dioxide is largely responsible for the acute inflammatory effects of tobacco smoke.

    PubMed

    Schwartz, Laurent; Guais, Adeline; Chaumet-Riffaud, Philippe; Grévillot, Georges; Sasco, Annie J; Molina, Thierry Jo; Mohammad, Abolhassani

    2010-06-01

    Tobacco smoking is responsible for a vast array of diseases, particularly chronic bronchitis and lung cancer. It is still unclear which constituent(s) of the smoke is responsible for its toxicity. The authors decided to focus on carbon dioxide, since its level of concentration in mainstream cigarette smoke is about 200 times higher than in the atmosphere. The authors previously demonstrated that inhalation of carbon dioxide concentrations above 5% has a deleterious effect on lungs. In this study, the authors assessed the inflammatory potential of carbon dioxide contained in cigarette smoke. Mice were exposed to cigarette smoke containing a high or reduced CO(2) level by filtration through a potassium hydroxyde solution. The inflammatory response was evaluated by histological analysis, protein phosphatase 2 A (PP2A) and nuclear factor (NF)-kappaB activation, and proinflammatory cytokine secretion measurements. The data show that the toxicity of cigarette smoke may be largely due to its high level of CO(2). Pulmonary injuries consequent to tobacco smoke inhalation observed by histology were greatly diminished when CO(2) was removed. Cigarette smoke exposure causes an inflammatory response characterized by PP2A and NF-kappaB activation followed by proinflammatory cytokine secretion. This inflammatory response was reduced when the cigarette smoke was filtered through a potassium hydroxide column, and reestablished when CO(2) was injected downstream from the filtration column.Given that there is an extensive literature linking a chronic inflammatory response to the major smoking-related diseases, these data suggest that carbon dioxide may play a key role in the causation of these diseases by tobacco smoking.

  11. 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

  12. [Combination of two signals of danger--a principal cause of activation of chronic inflammatory processes].

    PubMed

    Lebedev, K A

    2012-01-01

    Chronic inflammatory processes have long current during which there is a change of remission by an aggravation of disease. Until recently was considered, that occurrence and activation of chronic inflammatory process is caused by one signal of danger. Most often it are served with microorganisms. The sum of our end literary data shows that activation is connected with accumulation in the center of an inflammation of macrophages and their hyperactivation as a result of action of two signals of danger--microorganisms and xenobiotics.

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

    PubMed Central

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

    2017-01-01

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

  14. Fibromyalgia: Anti-Inflammatory and Stress Responses after Acute Moderate Exercise

    PubMed Central

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

    2013-01-01

    Fibromyalgia (FM) is characterized in part by an elevated inflammatory status, and “modified exercise” is currently proposed as being a good therapeutic help for these patients. However, the mechanisms involved in the exercise-induced benefits are still poorly understood. The objective was to evaluate the effect of a single bout of moderate cycling (45 min at 55% VO2 max) on the inflammatory (serum IL-8; chemotaxis and O2− production by neutrophils; and IL-1β, TNF-α, IL-6, IL-10, and IL-18 release by monocytes) and stress (cortisol; NA; and eHsp72) responses in women diagnosed with FM compared with an aged-matched control group of healthy women (HW). IL-8, NA, and eHsp72 were determined by ELISA. Cytokines released by monocytes were determined by Bio-Plex® system (LUMINEX). Cortisol was determined by electrochemoluminiscence, chemotaxis was evaluated in Boyden chambers and O2− production by NBT reduction. In the FM patients, the exercise induced a decrease in the systemic concentration of IL-8, cortisol, NA, and eHsp72; as well as in the neutrophil’s chemotaxis and O2− production and in the inflammatory cytokine release by monocytes. This was contrary to the completely expected exercise-induced increase in all those biomarkers in HW. In conclusion, single sessions of moderate cycling can improve the inflammatory status in FM patients, reaching values close to the situation of aged-matched HW at their basal status. The neuroendocrine mechanism seems to be an exercise-induced decrease in the stress response of these patients. PMID:24023948

  15. Development of a new humanized mouse model to study acute inflammatory arthritis

    PubMed Central

    2012-01-01

    Background Substantial advances have been generated in understanding the pathogenesis of rheumatoid arthritis (RA). Current murine models of RA-like disease have provided great insights into the molecular mechanism of inflammatory arthritis due to the use of genetically deficient or transgenic mice. However, these studies are limited by differences that exist between human and murine immune systems. Thus, the development of an animal model that utilizes human immune cells, will afford the opportunity to study their function in the initiation and propagation of inflammatory arthritis. Methods One to two-day old irradiated NOD-scid IL2rγnull (NSG) mice were reconstituted with human CD34+ cord blood stem cells. Leukocytes were analyzed by flow cytometry and circulating antibodies were determined by ELISA. Arthritis was induced by injecting complete Freund’s adjuvant into knee or ankle joints. Mice were also treated with the TNF inhibitor, Etanercept, or PBS and joints were analyzed histologically. Results Humanized mice were established with high reconstitution rates and were able to spontaneously produce human immunoglobulins as well as specific IgG in response to immunization. Intraperitoneal injection of thioglycolate or injection of complete Freund’s adjuvant into joints resulted in migration of human immune cells to the injected sites. Arthritic humanized mice treated with Etanercept had markedly less inflammation, which was associated with decreased total numbers of human CD45+ cells, including human lymphocytes and neutrophils. Conclusions The humanized mouse model is a new model to study inflammatory arthritis disease using human leukocytes without rejection of engrafted tissue. Future studies may adapt this system to incorporate RA patient cord blood and develop a chimeric animal model of inflammatory arthritis using genetically predisposed immune cells. PMID:22974474

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

    PubMed

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

    2015-06-01

    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.

  17. THE ACUTE INFLAMMATORY REACTION IN THE RABBIT EAR CHAMBER WITH PARTICULAR REFERENCE TO THE PHENOMENON OF LEUKOCYTIC MIGRATION

    PubMed Central

    Cliff, W. J.

    1966-01-01

    Responses to injections of various materials into rabbit ear chambers were studied by in vivo microscopy. The acute inflammatory responses provoked by injections of antibody-antigen complexes were both quantitatively and qualitatively different from the responses obtained after injections of either homologous sera or the antigens alone. The sticking of leukocytes to endothelium during these responses occurred only in the venules draining the injection sites and was frequently present only on the sides of the venules towards the injection sites. An explanation of this finding was proposed in terms of absorption by the minute vessels related to the injection sites of postulated mediator(s) with specific activity on venular endothelium. Analysis of the rates and direction of movement of leukocytes during the reactions produced by the antibody-antigen complexes was performed with the aid of time-lapse cinemicroscopy. The leukocytes that were sticking to the venular endothelium frequently exhibited amoeboid locomotion within the vessels. Twice as many of these cells moved against the direction of blood flow as with it. This finding was discussed and an explanation proposed. A method for detecting a drift in the overall population of emigrated leukocytes within the inflamed tissue was described and revealed that four times as many amoeboid cells moved away from the injection sites as towards them. This result was discussed in the light of the in vitro chemotactic properties of antibody-antigen complexes demonstrated for rabbit leukocytes. An alternative explanation was proposed in terms of variation in the population density of these cells and their random movements and collisions. The rates of amoeboid movement of leukocytes during the acute inflammatory reactions produced by antibody-antigen complexes were similar to the rates found during turpentine inflammation and were compared to other published values. PMID:5922284

  18. Systematic analysis of axonal damage and inflammatory response in different white matter tracts of acutely injured rat spinal cord.

    PubMed

    Gomes-Leal, W; Corkill, D J; Picanço-Diniz, C W

    2005-12-20

    The mechanisms of white matter (WM) damage during secondary degeneration are a fundamental issue in the pathophysiology of central nervous system (CNS) diseases. Our main goal was to describe the pattern of an acute inflammatory response and secondary damage to axons in different WM tracts of acutely injured rat spinal cord. Adult rats were deeply anesthetized and injected with 20 nmol of NMDA into the spinal cord ventral horn on T7. Animals were perfused after survival times of 1 day, 3 days and 7 days. Ten micrometer sections were submitted to immunocytochemical analysis for activated macrophages/microglia, neutrophils and damaged axons. There were inflammatory response and progressive tissue destruction of ventral WM (VWM) with formation of microcysts in both VWM and lateral WM (LWM). In the VWM, the number of beta-amyloid precursor protein (beta-APP) end-bulbs increased from 1 day with a peak at 3 days, decreasing by 7 days following the injection. APP end-bulbs were present in the dorsal WM (DWM) at 3 days survival time but were not in the LWM. Electron microscopic analysis revealed different degrees of myelin disruption and axonal pathology in the vacuolated WM up to 14 mm along the rostrocaudal axis. Quantitative analysis revealed a significant loss of medium and large axons (P < 0.05), but not of small axons (P > 0.05). Our results suggest that bystander axonal damage and myelin vacuolation are important secondary component of the pathology of WM tracts following rat SCI. Further studies are needed to understand the mechanisms of these pathological events.

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

    PubMed Central

    Xiping, Zhang; Hua, Tian; Hanqing, Chen; Li, Chen; Binyan, Yu; Jing, Ma

    2009-01-01

    BACKGROUND: To investigate the effects of Baicalin and Octreotide on inflammatory mediators and pancreatic acinar cells apoptosis of rats with severe acute pancreatitis (SAP). METHODS: SD rats were randomly divided into sham operated group (I group), model control group (II group), Baicalin treated group (III group) and Octreotide treated group (IV group). Each group was also divided into subgroup of 3, 6 and 12 h (n = 15). The mortality rate, ascites/body weight ratio as well as the level of endotoxin, NO and ET-1 in blood were measured. The pathological severity score of pancreas, apoptotic indexes, and expression levels of Bax and Bcl-2 proteins in each group were investigated. RESULTS: The survival rate of III and IV group has a significant difference compared with II group (P12 h < 0.05). The ascites volume, contents of inflammatory mediators in blood and pathological severity score of pancreas of III and IV group declined at different degrees compared to II group (P < 0.05, P < 0.01 or P < 0.001). Apoptotic index in III group was significantly higher than that in II group at 3 and 6 h (P3, 6 h < 0.05). Apoptotic index in IV group was significantly higher than that in II group at pancreatic tail at 6 h (P6 h < 0.05). Expression level of Bax in III group was significantly higher than that in II group (pancreatic head P3 h,6 h < 0.01, pancreatic tail P3 h < 0.001). CONCLUSIONS: Compared with Octreotide in the treatment of SAP, the protective mechanisms of Baicalin include reducing the excessive inflammatory mediators’ release, inducing the pancreatic acinar cells apoptosis. PMID:21772857

  20. Does chronic physical activity level modify the airway inflammatory response to an acute bout of exercise in the postprandial period?

    PubMed

    Kurti, Stephanie P; Rosenkranz, Sara K; Chapes, Stephen K; Teeman, Colby S; Cull, Brooke J; Emerson, Sam R; Levitt, Morton H; Smith, Joshua R; Harms, Craig A

    2017-02-01

    Recent studies have confirmed that a single high-fat meal (HFM) leads to increased airway inflammation. However, exercise is a natural anti-inflammatory and may modify postprandial airway inflammation. The postprandial airway inflammatory response is likely to be modified by chronic physical activity (PA) level. This study investigated whether chronic PA modifies the airway inflammatory response to an acute bout of exercise in the postprandial period in both insufficiently active and active subjects. Thirty-nine nonasthmatic subjects (20 active, 13 males/7 females) who exceeded PA guidelines (≥150 min moderate-vigorous PA/week) and 19 insufficiently active (6 males/13 females) underwent an incremental treadmill test to exhaustion to determine peak oxygen uptake. Subjects were then randomized to a condition (COND), either remaining sedentary (CON) or exercising (EX) post-HFM. Exercise was performed at the heart rate corresponding to 60% peak oxygen uptake on a treadmill for 1 h post-HFM (63% fat, 10 kcal/kg body weight). Blood lipids and exhaled nitric oxide (eNO: marker of airway inflammation) were measured at baseline and 2 h and 4 h post-HFM. Sputum differential cell counts were performed at baseline and 4 h post-HFM. The mean eNO response for all groups increased at 2 h post-HFM (∼6%) and returned to baseline by 4 h (p = 0.03). There was a time × COND interaction (p = 0.04), where EX had a greater eNO response at 4 h compared with CON. Sputum neutrophils increased at 4 h post-HFM (p < 0.05). These findings suggest that airway inflammation occurs after an HFM when exercise is performed in the postprandial period, regardless of habitual activity level.

  1. 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

  2. Anti-inflammatory and Anti-oxidative Effects of Dexpanthenol on Lipopolysaccharide Induced Acute Lung Injury in Mice.

    PubMed

    Li-Mei, Wan; Jie, Tan; Shan-He, Wan; Dong-Mei, Meng; Peng-Jiu, Yu

    2016-10-01

    The aim of this study is to investigate the effects of dexpanthenol in a model of acute lung injury (ALI) induced by lipopolysaccharides (LPS). Lung injury was induced by exposure to atomized LPS. Mice were randomly divided into four groups: control group; Dxp (500 mg/kg) group; LPS group; LPS + Dxp (500 mg/kg) group. The effects of dexpanthenol on LPS-induced neutrophil recruitment, cytokine levels, total protein concentration, myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) contents were examined. Additionally, lung tissue was examined by histology to investigate the changes in pathology in the presence and absence of dexpanthenol. In LPS-challenged mice, dexpanthenol significantly improved lung edema. Dexpanthenol also markedly inhibited the LPS-induced neutrophiles influx, protein leakage, and release of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF). Furthermore, dexpanthenol attenuated MPO activity and MDA contents and increased SOD and GSH activity in the LPS-challenged lung tissue. These data suggest that dexpanthenol protects mice from LPS-induced acute lung injury by its anti-inflammatory and anti-oxidative activities.

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

    PubMed Central

    Belmonte, Liliana; Coëffier, Moïse; Pessot, Florence Le; Miralles-Barrachina, Olga; Hiron, Martine; Leplingard, Antony; Lemeland, Jean-François; Hecketsweiler, Bernadette; Daveau, Maryvonne; Ducrotté, Philippe; Déchelotte, Pierre

    2007-01-01

    AIM: To evaluate the effect of glutamine on intestinal mucosa integrity, glutathione stores and acute phase response in protein-depleted rats during an inflammatory shock. METHODS: Plasma acute phase proteins (APP), jejunal APP mRNA levels, liver and jejunal glutathione concentrations were measured before and one, three and seven days after turpentine injection in 4 groups of control, protein-restricted, protein-restricted rats supplemented with glutamine or protein powder. Bacterial translocation in mesenteric lymph nodes and intestinal morphology were also assessed. RESULTS: Protein deprivation and turpentine injection significantly reduced jejunal villus height, and crypt depths. Mucosal glutathione concentration significantly decreased in protein-restricted rats. Before turpentine oil, glutamine supplementation restored villus heights and glutathione concentration (3.24 ± 1.05 vs 1.72 ± 0.46 μmol/g tissue, P < 0.05) in the jejunum, whereas in the liver glutathione remained low. Glutamine markedly increased jejunal α1-acid glycoprotein mRNA level after turpentine oil but did not affect its plasma concentration. Bacterial translocation in protein-restricted rats was not prevented by glutamine or protein powder supplementation. CONCLUSION: Glutamine restored gut glutathione stores and villus heights in malnourished rats but had no preventive effect on bacterial translocation in our model. PMID:17569119

  4. Prognostic relations between inflammatory markers and mortality in diabetic patients with non-ST elevation acute coronary syndrome

    PubMed Central

    Sanchez, P L; Morinigo, J L; Pabon, P; Martin, F; Piedra, I; Palacios, I F; Martin-Luengo, C

    2004-01-01

    Objective: To determine the differences in the inflammatory status between diabetic and non-diabetic patients and to evaluate the usefulness of C reactive protein, fibrinogen, and leucocyte count as predictors of death in diabetic patients with unstable coronary disease. Design: Nested case-control comparisons of the inflammatory status between diabetic and non-diabetic patients. Prospective cohort analysis of C reactive protein concentration, fibrinogen concentration, and leucocyte count as predictors of cardiovascular death in diabetic patients. Setting: Coronary care unit in Spain. Participants: 83 diabetic patients with non-ST elevation acute coronary syndrome and 83 sex and aged matched patients selected from 361 non-diabetic patients with non-ST elevation acute coronary syndrome. Main outcome measures: Plasma concentrations of C reactive protein and fibrinogen, and leucocyte count. Investigators contacted patients to assess clinical events. Results: Concentrations of C reactive protein and fibrinogen, and leucocyte count on admission were higher in diabetic than in non-diabetic patients (7 mg/l v 5 mg/l, p  =  0.020; 3.34 g/l v 2.90 g/l, p  =  0.013; and 8.8 × 109/l v 7.8 × 109/l, p  =  0.040). Among diabetic patients, these values were also higher in those who died during the 22 month follow up (13 mg/l v 6 mg/l, p  =  0.001; 3.95 g/l v 3.05 g/l, p < 0.001; and 11.4 × 109/l v 8.4 × 109/l, p  =  0.005). After adjustment for confounding factors, diabetic patients in the highest tertile of C reactive protein had a hazard ratio for cardiovascular death of 4.51 (95% confidence interval (CI) 1.62 to 12.55). Similar hazard ratios were for fibrinogen 3.74 (95% CI 1.32 to 10.62) and for leucocyte count 3.64 (95% CI 1.37 to 9.68). Conclusions: Inflammation appears more evident in diabetic than in non-diabetic patients with acute coronary syndrome. C reactive protein concentration, fibrinogen concentration, and leucocyte count constitute

  5. Acute inflammatory response secondary to intrapleural administration of two types of talc.

    PubMed

    Rossi, V F; Vargas, F S; Marchi, E; Acencio, M M P; Genofre, E H; Capelozzi, V L; Antonangelo, L

    2010-02-01

    Intrapleural instillation of talc has been used in the treatment of recurrent pleural effusions but can, in rare instances, result in respiratory failure. Side-effects seem to be related to composition, size and inflammatory power of talc particles. The aim of this study was to evaluate the inflammatory response to intrapleural injection of talc containing small particles (ST) or talc containing particles of mixed size (MT). 100 rabbits received intrapleural talc, 50 with ST (median 6.41 mum) and 50 with MT (median 21.15 mum); the control group was composed of 35 rabbits. Cells, lactate dehydrogenase, C-reactive protein (CRP), interleukin (IL)-8 and vascular endothelial growth factor were evaluated in serum and bronchoalveolar lavage at 6, 24, 48, 72 and 96 h. Lung histology and the presence of talc were also analysed. Statistics were performed using ANOVA and an unpaired t-test. Most of the parameters showed greater levels in the animals injected with talc than in the controls, suggesting a systemic and pulmonary response. Higher serum levels of CRP and IL-8 were observed in the animals injected with ST. Talc particles were observed in both lungs with no differences between groups. Lung cell infiltrate was more evident in the ST group. In conclusion, talc with larger particles should be the preferred choice in clinical practice in order to induce safer pleurodesis.

  6. 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

  7. 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.

  8. Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease.

    PubMed

    Seemungal, T; Harper-Owen, R; Bhowmik, A; Moric, I; Sanderson, G; Message, S; Maccallum, P; Meade, T W; Jeffries, D J; Johnston, S L; Wedzicha, J A

    2001-11-01

    The effects of respiratory viral infection on the time course of chronic obstructive pulmonary disease (COPD) exacerbation were examined by monitoring changes in systemic inflammatory markers in stable COPD and at exacerbation. Eighty-three patients with COPD (mean [SD] age, 66.6 [7.1] yr, FEV(1), 1.06 [0.61] L) recorded daily peak expiratory flow rate and any increases in respiratory symptoms. Nasal samples and blood were taken for respiratory virus detection by culture, polymerase chain reaction, and serology, and plasma fibrinogen and serum interleukin-6 (IL-6) were determined at stable baseline and exacerbation. Sixty-four percent of exacerbations were associated with a cold occurring up to 18 d before exacerbation. Seventy-seven viruses (39 [58.2%] rhinoviruses) were detected in 66 (39.2%) of 168 COPD exacerbations in 53 (64%) patients. Viral exacerbations were associated with frequent exacerbators, colds with increased dyspnea, a higher total symptom count at presentation, a longer median symptom recovery period of 13 d, and a tendency toward higher plasma fibrinogen and serum IL-6 levels. Non-respiratory syncytial virus (RSV) respiratory viruses were detected in 11 (16%), and RSV in 16 (23.5%), of 68 stable COPD patients, with RSV detection associated with higher inflammatory marker levels. Respiratory virus infections are associated with more severe and frequent exacerbations, and may cause chronic infection in COPD. Prevention and early treatment of viral infections may lead to a decreased exacerbation frequency and morbidity associated with COPD.

  9. Coconut water of different maturity stages ameliorates inflammatory processes in model of inflammation

    PubMed Central

    Rao, Sadia Saleem; Najam, Rahila

    2016-01-01

    Aim: Coconut water is a natural beverage that is a part of daily diet of many people. This study was designed to explore the anti-inflammatory activity of coconut water of different maturation stages (young and mature) with rat paw edema model of inflammation using plethysmometer. Methodology: For this study, albino rats were selected and divided into four equal groups (10 rats in each group). Group 1 was set as control and administered distilled water 1 ml orally; Groups 2 and 3 were treated with young and mature coconut water, respectively, at 4 ml/100 g dose orally. Group 4 was treated with the standard drug (ibuprofen) at 400 mg/70 kg. 0.1 ml of 1% w/v acetic acid was administered in the subplantar tissue of rat paw 30 min after oral treatments of groups. Plethysmometer was used to measure rat paw edema. Results: Results revealed that both coconut water possess significant anti-inflammatory activity (P < 0.001). In comparison to control, percent inhibition by young coconut water was 20.22%, 35.13%, 42.52%, and 36% at 1, 2, 3, and 4 h of acetic acid administration, respectively. However, maximum percent inhibition (42.52%) was observed in the second phase of the inflammatory process. On the other hand, percent inhibition by mature coconut water was 18.80%, 25.94%, 24.13%, and 18.66% at 1, 2, 3, and 4 h of acetic acid administration, respectively. However, maximum percent inhibition (25.94%) was observed in the first phase of the inflammatory process. Conclusions: This study strongly suggests the use of young coconut water for potent anti-inflammatory effect and mature coconut water for moderate anti-inflammatory effect. PMID:27366350

  10. 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

  11. Predictive value of inflammatory markers for irrigation and debridement of acute TKA infection.

    PubMed

    Stryker, Louis S; Abdel, Matthew P; Hanssen, Arlen D

    2013-06-01

    The roles of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are well established in the diagnosis of total joint infection. However, it is not entirely clear what value preoperative CRP and ESR have in predicting outcomes following irrigation and debridement with insert exchange for acute hematogenous total knee arthroplasty infection. The total joint registry at the authors' institution was reviewed to identify all patients who underwent irrigation and debridement with insert exchange for a diagnosis of acute hematogenous infection of a primary total knee arthroplasty. Patient medical records were then reviewed for preoperative white blood cell count and CRP and ESR levels; interval from symptom onset to surgery; infecting organism; and any additional surgery for infection. Average patient age was 72 years (range, 51-91 years). Forty-four patients were men and 26 were women. Mean follow-up was 54 months (range, 12-176 months). Seventy-two procedures (69 patients) met the inclusion criteria. Of these, 20 (28%) additional procedures for infection were performed and were classified as treatment failures. Average CRP was 173.7 mg/L in the successful group and 159.0 mg/L in the failed group (P=.31). Mean ESR at the time of irrigation and debridement with insert exchange was 61.3 mm/hr in both groups (P=.49). Although CRP and ESR are well established in the diagnosis of infection, no role currently exists for them in predicting the outcomes of irrigation and debridement with insert exchange for the treatment of acute hematogenous total knee arthroplasty infection.

  12. Status epilepticus does not induce acute brain inflammatory response in the Amazon rodent Proechimys, an animal model resistant to epileptogenesis.

    PubMed

    Scorza, Carla A; Marques, Marcia J G; Gomes da Silva, Sérgio; Naffah-Mazzacoratti, Maria da Graça; Scorza, Fulvio A; Cavalheiro, Esper A

    2017-02-22

    Mesial temporal lobe epilepsy is a serious brain disorder in adults that is often preceded by an initial brain insult, such as status epilepticus (SE), that after a latent period leads to recurrent seizures. Post-SE models are widely used for studies on epileptogenic processes. Previous findings of our laboratory suggested that the Neotropical rodents Proechimys exhibit endogenous antiepileptogenic mechanisms in post-SE models. Strong body of research supports that SE triggers a rapid and dramatic upregulation of inflammatory mediators and vascular endothelial growth factor (VEGF). In this work we found that, in the epilepsy-resistant Proechimys, hippocampal and cortical levels of inflammatory cytokines (IL-1β, IL-6, IL-10, TNF-α) and VEGF remained unchanged 24h after SE, strongly contrasting to the high levels of post-SE changes observed in Wistar rats. Furthermore, substantial differences in the brain baseline levels of these proteins were encountered between animal species studied. Since inflammatory cytokines and VEGF have been recognized as major orchestrators of the epileptogenic process, our results suggest their role in the antiepileptogenic mechanisms previously described in Proechimys.

  13. Anti-inflammatory treatment in dysfunction of pulmonary surfactant in meconium-induced acute lung injury.

    PubMed

    Mokra, D; Drgova, A; Kopincova, J; Pullmann, R; Calkovska, A

    2013-01-01

    Inflammation, oxidation, lung edema, and other factors participate in surfactant dysfunction in meconium aspiration syndrome (MAS). Therefore, we hypothesized that anti-inflammatory treatment may reverse surfactant dysfunction in the MAS model. Oxygen-ventilated rabbits were given meconium intratracheally (25 mg/ml, 4 ml/kg; Mec) or saline (Sal). Thirty minutes later, meconium-instilled animals were treated by glucocorticoids budesonide (0.25 mg/kg, i.t.) and dexamethasone (0.5 mg/kg, i.v.), or phosphodiesterase inhibitors aminophylline (2 mg/kg, i.v.) and olprinone (0.2 mg/kg, i.v.), or the antioxidant N-acetylcysteine (10 mg/kg, i.v.). Healthy, non-ventilated animals served as controls (Con). At the end of experiments, left lung was lavaged and a differential leukocyte count in sediment was estimated. The supernatant of lavage fluid was adjusted to a concentration of 0.5 mg phospholipids/ml. Surfactant quality was evaluated by capillary surfactometer and expressed by initial pressure and the time of capillary patency. The right lung was used to determine lung edema by wet/dry (W/D) weight ratio. Total antioxidant status (TAS) in blood plasma was evaluated. W/D ratio increased and capillary patency time shortened significantly, whereas the initial pressure increased and TAS decreased insignificantly in Sal vs. Con groups. Meconium instillation potentiated edema formation and neutrophil influx into the lungs, reduced capillary patency and TAS, and decreased the surfactant quality compared with both Sal and Con groups (p > 0.05). Each of the anti-inflammatory agents reduced lung edema and neutrophil influx into the lung and partly reversed surfactant dysfunction in the MAS model, with a superior effect observed after glucocorticoids and the antioxidant N-acetylcysteine.

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

    PubMed Central

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

    2010-01-01

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

  15. Inflammatory and immune processes in the human lung in health and disease: evaluation by bronchoalveolar lavage.

    PubMed Central

    Hunninghake, G. W.; Gadek, J. E.; Kawanami, O.; Ferrans, V. J.; Crystal, R. G.

    1979-01-01

    Bronchoalveolar lavage is an invaluable means of accurately evaluating the inflammatory and immune processes of the human lung. Although lavage recovers only those cells and proteins present on the epithelial surface of the lower respiratory tract, comparison with open lung biopsies shows that these constituents are representative of the inflammatory and immune systems of the alveolar structures. With the use of these techniques, sufficient materials are obtained from normal individuals to allow characterization of not only the types of cells and proteins present but their functions as well. Such observations have been useful in defining the inflammatory and immune capabilities of the normal lung and provide a basis for the study of lung disease. Lavage methods have been used to characterize inflammatory and immune processes of the lower respiratory tract in destructive, infectious, neoplastic, and interstitial disorders. From the data already acquired, it is apparent that bronchoalveolar lavage will yield major insights into the pathogenesis, staging, and therapy decisions involved in these disorders. (Am J Pathol 97:149--206, 1979). Images Figure 9 Figure 1 Figure 2 Figure 10 Figure 7 Figure 8 Figure 4 Figure 5 Figure 6 Figure 3 PMID:495693

  16. The role of immune and inflammatory processes in the development of macrovascular disease in diabetes.

    PubMed

    Lopes-Virella, Maria F; Virella, Gabriel

    2003-09-01

    Diabetes is associated with a high incidence of cardiovascular disease, which is the major cause of morbidity and mortality in this disease. There is considerable interest in defining factors responsible for the accelerated development of atherosclerosis in diabetes. There is no evidence to suggest that the inflammatory process in diabetic patients is different from those in non-diabetic individuals. The main difference may lie on factors able to trigger the inflammatory process. Diabetes is a major predisposing factor for the generation of modified proteins though advanced glycation and oxidation, two intimately interrelated processes. Advanced glycation end-products modified low density lipoprotein (AGE-LDL) and other AGE-modified proteins as well as oxidized LDL (oxLDL) are able to interact with a variety of cells and induce cell dysfunction and the release of pro-inflammatory mediators. But AGE-LDL and oxLDL are also immunogenic. Activated T lymphocytes reacting with peptides derived from oxidized LDL have been detected in atheromatous lesions. Their pro-inflammatory potential is directly linked to the release of interferon-gamma and other cytokines able to activate macrophages, smooth muscle cells, and endothelial cells. On the other hand, antibodies to oxidized and AGE-modified LDL have been isolated from diabetic patients and shown to belong predominantly to the IgG isotype, subclasses 1 and 3, which have well-defined proinflammatory properties. These autoantibodies to modified lipoproteins have sufficient affinity to form stable antigen-antibody complexes, which have been also shown to have pro-atheromatous and pro-inflammatory properties.

  17. Myrrh attenuates oxidative and inflammatory processes in acetic acid-induced ulcerative colitis

    PubMed Central

    Fatani, Amal Jamil; Alrojayee, Fatima Salih; Parmar, Mihir Yogeshkumar; Abuohashish, Hatem Mustafa; Ahmed, Mohammed Mahboobuddin; Al-Rejaie, Salim Salih

    2016-01-01

    The pathogenesis of ulcerative colitis (UC) has been associated with a weakened antioxidant capacity and increased inflammatory processes. Myrrh is traditionally used for the treatment of inflammatory diseases due to its antioxidant and anti-inflammatory properties. The present study aimed to evaluate the effects of myrrh on an experimental rat model of UC. UC was induced in rats using acetic acid (AA) after pre-treatment with myrrh (125, 250 or 500 mg/kg/day) or mesalazine (MES; 300 mg/kg/day) for 7 days. The levels of various inflammatory cytokines, prostaglandin E2 (PGE2) and nitric oxide (NO) in the rat colon tissues were assessed. In addition, the colonic levels of thiobarbituric acid reactive substances (TBARS) and non-protein sulfhydryl groups (NP-SH), as well as the activities of superoxide dismutase (SOD) and catalase (CAT), were estimated. Furthermore, total protein (TP) contents and the levels of DNA and RNA were measured, and histopathological changes in colonic tissues were analyzed. The results indicated that the levels of pro-inflammatory cytokines, PGE2, NO and TBARS were markedly increased. By contrast, the levels of interleukin-10, NP-SH, TP and nucleic acids, and the enzymatic activities of SOD and CAT were significantly decreased in the AA model group. In addition, pretreatment with myrrh and MES was able to attenuate the impaired oxidative stress response and upregulation of inflammatory biomarkers. Furthermore, the enzymatic activities of SOD and CAT were near to normal in the myrrh and MES pretreated groups. The ability of myrrh to protect against UC was further confirmed by histopathological analysis, and the high dose of myrrh exerted an effect comparable to MES. In conclusion, the results of the present study suggested that myrrh has potent therapeutic value in the amelioration of experimental colitis in laboratory animals by downregulating the expression of proinflammatory mediators and improving endogenous antioxidative activities. PMID

  18. Anti-Inflammatory Cytokines Predominate in Acute Human Plasmodium knowlesi Infections

    PubMed Central

    Cox-Singh, Janet; Singh, Balbir; Daneshvar, Cyrus; Planche, Timothy; Parker-Williams, John; Krishna, Sanjeev

    2011-01-01

    Plasmodium knowlesi has entered the human population of Southeast Asia. Naturally acquired knowlesi malaria is newly described with relatively little available data, including data on the host response to infection. Therefore pre-treatment cytokine and chemokine profiles were determined for 94 P. knowlesi, and for comparison, 20, P. vivax and 22 P. falciparum, patients recruited in Malaysian Borneo. Nine, five and one patient with P. knowlesi, P. falciparum and P. vivax respectively had complicated malaria as defined by World Health Organisation. Patients with uncomplicated P. knowlesi had lower levels of the pro-inflammatory cytokines IL-8 and TNFα than those with complicated disease (both p<0.05, Dunn's post test, DPT). The anti-inflammatory cytokines IL-1ra and IL-10 were detected in all patients in the study. IL-1ra, the most abundant cytokine measured, correlated with parasitaemia in P. knowlesi (rs = 0.47, p =  <0.0001), P. vivax (rs = 0.61, p = 0.0042) and P. falciparum (rs = 0.57,p = 0.0054) malaria. IL-10 correlated with parasitaemia in both P. knowlesi (rs = 0.54, p =  <0.0001) and P. vivax (rs = 0.78, p =  <0.0001) infections. There were between group differences in soluble markers of macrophage activation (MIP-1β and MCP-1). P. knowlesi patients had significantly lower levels of MIP-1β than P. falciparum (DPT, p =  <0.01). Uncomplicated P. knowlesi patients had significantly lower levels of MCP-1 than uncomplicated P. falciparum patients (DPT, p =  <0.001). There was no significant difference between complicated and uncomplicated P. knowlesi infections. MCP-1, MIP-1β, IL-8 and TNFα increased in complicated P. knowlesi but decreased in complicated P. falciparum infections. Descriptions of human knowlesi malaria provide a comparative means to discover mediators of pathophysiology in severe P. knowlesi as well as P. falciparum malaria. Crucially, P. knowlesi may be the disease and experimental primate

  19. Cryotherapy Reduces Inflammatory Response Without Altering Muscle Regeneration Process and Extracellular Matrix Remodeling of Rat Muscle

    PubMed Central

    Vieira Ramos, Gracielle; Pinheiro, Clara Maria; Messa, Sabrina Peviani; Delfino, Gabriel Borges; Marqueti, Rita de Cássia; Salvini, Tania de Fátima; Durigan, Joao Luiz Quagliotti

    2016-01-01

    The application of cryotherapy is widely used in sports medicine today. Cooling could minimize secondary hypoxic injury through the reduction of cellular metabolism and injury area. Conflicting results have also suggested cryotherapy could delay and impair the regeneration process. There are no definitive findings about the effects of cryotherapy on the process of muscle regeneration. The aim of the present study was to evaluate the effects of a clinical-like cryotherapy on inflammation, regeneration and extracellular matrix (ECM) remodeling on the Tibialis anterior (TA) muscle of rats 3, 7 and 14 days post-injury. It was observed that the intermittent application of cryotherapy (three 30-minute sessions, every 2 h) in the first 48 h post-injury decreased inflammatory processes (mRNA levels of TNF-α, NF-κB, TGF-β and MMP-9 and macrophage percentage). Cryotherapy did not alter regeneration markers such as injury area, desmin and Myod expression. Despite regulating Collagen I and III and their growth factors, cryotherapy did not alter collagen deposition. In summary, clinical-like cryotherapy reduces the inflammatory process through the decrease of macrophage infiltration and the accumulation of the inflammatory key markers without influencing muscle injury area and ECM remodeling. PMID:26725948

  20. Cryotherapy Reduces Inflammatory Response Without Altering Muscle Regeneration Process and Extracellular Matrix Remodeling of Rat Muscle.

    PubMed

    Vieira Ramos, Gracielle; Pinheiro, Clara Maria; Messa, Sabrina Peviani; Delfino, Gabriel Borges; Marqueti, Rita de Cássia; Salvini, Tania de Fátima; Durigan, Joao Luiz Quagliotti

    2016-01-04

    The application of cryotherapy is widely used in sports medicine today. Cooling could minimize secondary hypoxic injury through the reduction of cellular metabolism and injury area. Conflicting results have also suggested cryotherapy could delay and impair the regeneration process. There are no definitive findings about the effects of cryotherapy on the process of muscle regeneration. The aim of the present study was to evaluate the effects of a clinical-like cryotherapy on inflammation, regeneration and extracellular matrix (ECM) remodeling on the Tibialis anterior (TA) muscle of rats 3, 7 and 14 days post-injury. It was observed that the intermittent application of cryotherapy (three 30-minute sessions, every 2 h) in the first 48 h post-injury decreased inflammatory processes (mRNA levels of TNF-α, NF-κB, TGF-β and MMP-9 and macrophage percentage). Cryotherapy did not alter regeneration markers such as injury area, desmin and Myod expression. Despite regulating Collagen I and III and their growth factors, cryotherapy did not alter collagen deposition. In summary, clinical-like cryotherapy reduces the inflammatory process through the decrease of macrophage infiltration and the accumulation of the inflammatory key markers without influencing muscle injury area and ECM remodeling.

  1. Serum trace elements are associated with hemostasis, lipid spectrum and inflammatory markers in men suffering from acute ischemic stroke.

    PubMed

    Skalny, Anatoly V; Klimenko, Lydmila L; Turna, Aliya A; Budanova, Maria N; Baskakov, Ivan S; Savostina, Marina S; Mazilina, Aksana N; Deyev, Anatoly I; Skalnaya, Margarita G; Tinkov, Alexey A

    2017-02-20

    The primary objective of the study is investigation of the association between trace elements status and hemostasis, lipid spectrum and inflammatory markers in acute ischemic stroke (AIS). A total of 30 men suffering from AIS and 30 healthy controls were involved in the current survey. Blood count, serum lipid spectrum, complement components C4 and C3a, vascular endothelial growth factor (VEGF), S100B protein, NR2 antibodies (NR2Ab), and total antioxidant status (TAS), as well as plasma fibrinogen, and D-dimer levels and activated partial thromboplastin time (APTT) were assessed. Serum trace elements were analyzed using inductively coupled plasma mass spectrometry. AIS patients were characterized by significantly increased fibrinogen, D-dimer, TG, C3a, C4, NR2Ab, and VEGF levels. The leukocyte count, erythrocyte sedimentation rate and serum atherogenic index were also increased in stroke patients. Oppositely, TAS and APTT values, bleeding and blood coagulation time were decreased. AIS patients were characterized by significantly decreased serum Fe and Co concentrations, whereas the level of Cu, I, Li, Mn, Se, Zn, As, Pb, Ni, and especially V and B in serum was significantly increased. Serum V and B tightly correlated with the procoagulant state and inflammatory markers. Multiple regression analysis revealed a significant inverse association between serum Se levels and stroke markers after adjustment for covariates. Therefore, it is hypothesized that elements like vanadium and boron may be closely involved in stroke pathogenesis by modulation of hemostasis and inflammation, whereas the observed increase in Se levels may be considered as a compensatory reaction.

  2. 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

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

    PubMed

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

    2014-08-27

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

  4. Algae Polysaccharides' Chemical Characterization and their Role in the Inflammatory Process.

    PubMed

    Florez, Noelia; Gonzalez-Munoz, Maria Jesus; Ribeiro, Daniela; Fernandes, Eduarda; Dominguez, Herminia; Freitas, Marisa

    2017-01-01

    Polysaccharides are abundant components in marine macroalgae with potential applications in different areas such as pharmaceutical, biomedical, cosmetics and nutrition. The current interest in these compounds is due to their known bioactivities, conferred by their antiallergic, neuroprotective, gastroprotective, cardioprotective, cytotoxic, anticoagulant/antithrombotic, antiviral, antilipidemic, antinociceptive, and immunomodulatory properties, making them promising bioactive products and biomaterials. The inflammatory process is a complex event mediated by the immune system that culminates in the neutralization and elimination of the offending insult protecting the host and restoring tissue homeostasis. This review focuses on the extraction procedures and chemical characterization of polysaccharides from different classes of algae (Phaeophyceae, Rhodophyceae and Chlorophyceae) and on the studies on their inflammatory process modulatory effect.

  5. 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

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

    PubMed Central

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

    2013-01-01

    Background. The diagnosis of acute myocarditis (AMC) and inflammatory cardiomyopathy (DCMi) can be difficult. Speckle tracking echocardiography with accurate assessments of regional contractility could have an outstanding importance for the diagnosis. Methods and Results. N = 25 patients with clinically diagnosed AMC who underwent endomyocardial biopsies (EMBs) were studied prospectively. Speckle tracking imaging was examined at the beginning and during a mean follow-up period of 6.2 months. In the acute phase patients had markedly decreased left ventricular (LV) systolic function (mean LV ejection fraction (LVEF) 40.4 ± 10.3%). At follow-up in n = 8 patients, inflammation persists, correlating with a significantly reduced fractional shortening (FS, 21.5 ± 6.0%) in contrast to those without inflammation in EMB (FS 32.1 ± 7.1%, P < 0.05). All AMC patients showed a reduction in global systolic longitudinal strain (LS, −8.36 ± −3.47%) and strain rate (LSR, 0.53 ± 0.29 1/s). At follow-up, LS and LRS were significantly lower in patients with inflammation, in contrast to patients without inflammation (−9.4 ± 1.4 versus −16.8 ± 2.0%, P < 0.0001; 0.78 ± 0.4 versus 1.3 ± 0.3 1/s). LSR and LS correlate significantly with lymphocytic infiltrates (for CD3 r = 0.7, P < 0.0001, and LFA-1 r = 0.8, P < 0.0001). Conclusion. Speckle tracking echocardiography is a useful adjunctive assisting tool for evaluation over the course of intramyocardial inflammation in patients with AMC and DCMi. PMID:23576857

  7. Light-emitting diodes at 940nm attenuate colitis-induced inflammatory process in mice.

    PubMed

    Belém, Mônica O; de Andrade, Giovana M M; Carlos, Thalita M; Guazelli, Carla F S; Fattori, Victor; Toginho Filho, Dari O; Dias, Ivan F L; Verri, Waldiceu A; Araújo, Eduardo J A

    2016-09-01

    Inflammatory bowel disease (IBD) presents intense inflammatory infiltrate, crypt abscesses, ulceration and even loss of function. Despite the clinical relevance of IBD, its current therapy remains poorly effective. Infrared wavelength phototherapy shows therapeutic potential on inflammation. Our goal was to evaluate whether light-emitting diodes (LED) at 940nm are capable of mitigating the colitis-induced inflammatory process in mice. Forty male Swiss mice were assigned into five groups: control; control treated with LED therapy; colitis without treatment; colitis treated with LED therapy; colitis treated with Prednisolone. Experimental colitis was induced by acetic acid 7.5% (pH2.5) rectal administration. LED therapy was performed with light characterized by wavelength of 940nm, 45nm bandwidth, intensity of 4.05J/cm(2), total power of 270mW and total dose of 64.8J for 4min in a single application. Colitis-induced intestinal transit delay was inhibited by LED therapy. Colitis caused an increase of colon dimensions (length, diameter, total area) and colon weight (edema), which were inhibited by LED therapy. LED therapy also decreased colitis-induced tissue gross lesion, myeloperoxidase activity, microscopic tissue damage score and the presence of inflammatory infiltrate in all intestinal layers. Furthermore, LED therapy inhibited colitis-induced IL-1β, TNF-α, and IL-6 production. We conclude LED therapy at 940nm inhibited experimental colitis-induced colon inflammation in mice, therefore, rendering it a promising therapeutic approach that deserves further investigation.

  8. Preoperative Acute Inflammatory Markers as Predictors for Postoperative Complications in Primary Total Knee Arthroplasty

    PubMed Central

    Godoy, Gustavo; Sumarriva, Gonzalo; Ochsner, J. Lockwood; Chimento, George; Schmucker, Dana; Dasa, Vinod; Meyer, Mark

    2016-01-01

    Background: C-reactive protein (CRP) has been suggested as an independent risk factor for cardiovascular pathology in the nonsurgical setting. While postoperative CRP and erythrocyte sedimentation rate (ESR) have an established role in aiding the diagnosis of periprosthetic joint infections, some authors suggest a link between preoperative CRP and postoperative complications in patients undergoing total joint arthroplasty. Methods: We conducted a retrospective cohort study of 351 patients who underwent unilateral primary total knee arthroplasty by a single surgeon during a 28-month period (January 2013 through April 2015). Patient medical records were reviewed for the following complications occurring within 90 days postoperatively: myocardial infarction, arrhythmia, pulmonary embolism, wound infection, acute renal failure, and reoperation. Results: We found no statistically significant link between postoperative complications and preoperative CRP levels (P=0.5005) or ESR levels (P=0.1610). Conclusion: The results of this study do not support the routine inclusion of CRP and ESR analysis as part of the preoperative evaluation for elective total knee arthroplasty. PMID:27999506

  9. Acute Brain Injury Triggers MyD88-Dependent, TLR2/4-Independent Inflammatory Responses

    PubMed Central

    Koedel, Uwe; Merbt, Ulrike Michaela; Schmidt, Caroline; Angele, Barbara; Popp, Bernadette; Wagner, Hermann; Pfister, Hans-Walter; Kirschning, Carsten J.

    2007-01-01

    Endogenous molecules released from disrupted cells and extracellular matrix degradation products activate Toll-like receptors (TLRs) and, thus, might contribute to immune activation after tissue injury. Here, we show that aseptic, cold-induced cortical injury triggered an acute immune response that involves increased production of multiple cytokines/chemokines accompanied by neutrophil recruitment to the lesion site. We observed selective reductions in injury-induced cytokine/chemokine expression as well as in neutrophil accumulation in mice lacking the common TLR signaling adaptor MyD88 compared with wild-type mice. Notably, attenuation of the immune response was paralleled by a reduction in lesion size. Neutrophil depletion of wild-type mice and transplantation of MyD88-deficient bone marrow into lethally irradiated wild-type recipients had no substantial impact on injury-induced expression of cytokines/chemokines and on lesion development. In contrast to MyD88 deficiency, double deficiency of TLR2 and TLR4—despite the two receptors being activated by specific endogenous molecules associated to danger and signal through MyD88—altered neither immune response nor extent of tissue lesion size on injury. Our data indicate modulation of the neuroinflammatory response and lesion development after aseptic cortical injury through MyD88-dependent but TLR2/4-independent signaling by central nervous system resident nonmyeloid cells. PMID:17591966

  10. Could Pyelonephritic Scarring Be Prevented by Anti-Inflammatory Treatment? An Experimental Model of Acute Pyelonephritis

    PubMed Central

    Bahat Özdoğan, Elif; Özdemir, Tuğba; Arslansoyu Çamlar, Seçil; İmamoğlu, Mustafa; Çobanoğlu, Ümit; Sönmez, Bircan; Tosun, İlknur; Doğan, İsmail

    2014-01-01

    Objectives. This study aimed to demonstrate if the addition of anti-inflammatory treatment to antibiotic therapy shows any superiority to the treatment with antibiotic only. Methods. Forty-nine Wistar rats were divided into 7 groups. Pyelonephritis was performed by E. coli injection to upper pole of kidneys except control group. Group 2 was not treated. Ceftriaxone, ketoprofen, “ceftriaxone + ketoprofen,” methylprednisolone, and “ceftriaxone + methylprednisolone” were given in the groups. The technetium-99m-dimercaptosuccinic acid scintigraphies were performed in 3rd day to detect pyelonephritis and 10th week to detect renal scarring. All kidneys were also histopathologically evaluated. Results. When 3rd day and 10th week scintigraphies were compared, initial 2.00 ± 0.30 point pyelonephritis score resulted in 0.71 ± 0.36 renal scar score in “ceftriaxone + ketoprofen” group (P = 0.039). Initial 2.00 ± 0.43 point pyelonephritis score resulted in 0.86 ± 0.26 renal scar score in “ceftriaxone + methylprednisolone” group (P = 0.041). Renal scar score was declined in “ceftriaxone + ketoprofen” group and “ceftriaxone + methylprednisolone” group compared with no-treatment group on 10th week of the study (P = 0.026, P = 0.044). On histopathological evaluation, it was seen that renal scar prevalence and expansion declined significantly in “ceftriaxone + ketoprofen and ceftriaxone + methylprednisolone” (P = 0.011, P = 0.023). Conclusion. It was evidenced that ceftriaxone treatment in combination with ketoprofen or methylprednisolone declined scar formation in scintigraphic and histopathologic examinations of the kidneys. PMID:25105116

  11. 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

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

    PubMed

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

    2016-03-01

    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.

  13. 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

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

    PubMed

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

  15. Relationship between Inflammatory Markers and New Cardiovascular Events in Patients with Acute Myocardial Infarction Who Underwent Primary Angioplasty

    PubMed Central

    Franca, Eluisa La; Caruso, Marco; Sansone, Angela; Iacona, Rosanna; Ajello, Laura; Mancuso, Dario; Castellano, Fabiana; Novo, Salvatore; Assennato, Pasquale

    2013-01-01

    Introduction: The determination of inflammation markers in circulation has enabled an important improvement in the study of cardiovascular diseases. It was tested the hypothesis that non-specific markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and fibrinogen may provide prognostic information in patients with acute myocardial infarction with persistent ST-segment elevation (STEMI) undergoing primary angioplasty (PCI). Methods: Patients: A cohort of 197 consecutive patients with STEMI undergoing primary PCI was enrolled, evaluating during hospitalization, the peak values of the following markers of inflammation: ESR, CRP and fibrinogen. A telephone follow-up has been made in order to investigate any possible new cardiovascular events after hospital discharge and the procedure performed. Results: Higher values of CRP were statistically associated with adverse future events as composite endpoint and with the single endpoint of death. Furthermore, higher age, presence of hypertension, history of previous cardiovascular events, were statistically significantly associated with cardiac events at follow up. In this group were also overrepresented subjects with anterior myocardial infarction in the anterior localization and with an EF ≤ 35% at discharge. Conclusions: CRP appears to be a predictor of future cardiovascular events, confirming that a pro-inflammatory state promotes the progression of atherosclerotic disease and its complications. PMID:23777720

  16. 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

  17. Sex-differences in resident immune cell phenotype underlies more efficient acute inflammatory responses in female mice

    PubMed Central

    Scotland, Ramona S.; Stables, Melanie J.; Madalli, Shimona; Watson, Peter; Gilroy, Derek W.

    2017-01-01

    Females are protected against mortality arising from severe sepsis. The precise mechanisms that confer this survival advantage in females over males are unclear. Resident leukocytes in resting tissues have a significant influence on circulating cytokine levels and recruitment of blood leukocytes during acute inflammatory responses. Whether the phenotype of resident leukocytes is distinct in females is unknown. Herein we show that the numbers of leukocytes occupying the naive peritoneal and pleural cavities is higher in female than in male mice and rats, comprising more T- and B-lymphocytes as well as macrophages. The altered immune cell composition of the female peritoneum is controlled by elevated tissue chemokine expression. Female resident macrophages also exhibit greater Toll-like receptor expression, as well as enhanced phagocytosis and NADPHoxidase-mediated bacterial killing. However, macrophage-derived cytokine production is diminished by proportionally more resident immunomodulatory CD4+ T-lymphocytes. Ovarian hormones regulate macrophage phenotype, function, and numbers but have no significant impact on T-lymphocyte populations in females. Thus we have identified a fundamental sex-difference in phenotype of resident leukocytes. We propose that the distinct resident leukocyte population in females allows aggressive recognition and elimination of diverse infectious stimuli without recruitment of circulating neutrophils or excessive cytokine production. PMID:21911834

  18. Study of biochemical behavior of some exported and nonexported hepatic proteins during an acute inflammatory reaction in the rat.

    PubMed

    Mahu, J L; Feldmann, G

    1984-01-01

    Haptoglobin, albumin, glucose-6-phosphatase, p-nitrophenol uridine diphosphate (UDP)-glucuronosyltransferase and cytochrome P-450 were measured in liver microsomes from normal rats and from rats undergoing an acute inflammatory reaction (AIR) induced either by subcutaneous administration of turpentine or by intrapleural injection of calcium pyrophosphate. 24 h after the beginning of the AIR induced by subcutaneous administration of turpentine, haptoglobin and albumin, two exported proteins, had risen to a peak (+313%), and dropped considerably (-52%) whereas nonexported protein levels did not change except for cytochrome P-450, which diminished (-38%). In the same way, intrapleural injection of calcium pyrophosphate was followed after 24 h by significant but smaller variations in haptoglobin (+60%) and cytochrome P-450 (-20%) concentrations. Albumin levels, glucose-6-phosphatase and p-nitrophenol UDP-glucuronosyltransferase activities were unchanged in this experimental model. The drop in cytochrome P-450 under all these conditions and also the diminution of albumin in the first model suggest that all the proteins produced by liver cells might not be synthesized in equal amounts. The decrease in cytochrome P-450 could interfere in hepatic drug metabolism during an AIR.

  19. Pro-inflammatory-Related Loss of CXCL12 Niche Promotes Acute Lymphoblastic Leukemic Progression at the Expense of Normal Lymphopoiesis.

    PubMed

    Balandrán, Juan Carlos; Purizaca, Jessica; Enciso, Jennifer; Dozal, David; Sandoval, Antonio; Jiménez-Hernández, Elva; Alemán-Lazarini, Leticia; Perez-Koldenkova, Vadim; Quintela-Núñez Del Prado, Henry; Rios de Los Ríos, Jussara; Mayani, Héctor; Ortiz-Navarrete, Vianney; Guzman, Monica L; Pelayo, Rosana

    2016-01-01

    Pediatric oncology, notably childhood acute lymphoblastic leukemia (ALL), is currently one of the health-leading concerns worldwide and a biomedical priority. Decreasing overall leukemia mortality in children requires a comprehensive understanding of its pathobiology. It is becoming clear that malignant cell-to-niche intercommunication and microenvironmental signals that control early cell fate decisions are critical for tumor progression. We show here that the mesenchymal stromal cell component of ALL bone marrow (BM) differ from its normal counterpart in a number of functional properties and may have a key role during leukemic development. A decreased proliferation potential, contrasting with the strong ability of producing pro-inflammatory cytokines and an aberrantly loss of CXCL12 and SCF, suggest that leukemic lymphoid niches in ALL BM are unique and may exclude normal hematopoiesis. Cell competence ex vivo assays within tridimensional coculture structures indicated a growth advantage of leukemic precursor cells and their niche remodeling ability by CXCL12 reduction, resulting in leukemic cell progression at the expense of normal niche-associated lymphopoiesis.

  20. Pro-inflammatory-Related Loss of CXCL12 Niche Promotes Acute Lymphoblastic Leukemic Progression at the Expense of Normal Lymphopoiesis

    PubMed Central

    Balandrán, Juan Carlos; Purizaca, Jessica; Enciso, Jennifer; Dozal, David; Sandoval, Antonio; Jiménez-Hernández, Elva; Alemán-Lazarini, Leticia; Perez-Koldenkova, Vadim; Quintela-Núñez del Prado, Henry; Rios de los Ríos, Jussara; Mayani, Héctor; Ortiz-Navarrete, Vianney; Guzman, Monica L.; Pelayo, Rosana

    2017-01-01

    Pediatric oncology, notably childhood acute lymphoblastic leukemia (ALL), is currently one of the health-leading concerns worldwide and a biomedical priority. Decreasing overall leukemia mortality in children requires a comprehensive understanding of its pathobiology. It is becoming clear that malignant cell-to-niche intercommunication and microenvironmental signals that control early cell fate decisions are critical for tumor progression. We show here that the mesenchymal stromal cell component of ALL bone marrow (BM) differ from its normal counterpart in a number of functional properties and may have a key role during leukemic development. A decreased proliferation potential, contrasting with the strong ability of producing pro-inflammatory cytokines and an aberrantly loss of CXCL12 and SCF, suggest that leukemic lymphoid niches in ALL BM are unique and may exclude normal hematopoiesis. Cell competence ex vivo assays within tridimensional coculture structures indicated a growth advantage of leukemic precursor cells and their niche remodeling ability by CXCL12 reduction, resulting in leukemic cell progression at the expense of normal niche-associated lymphopoiesis. PMID:28111575

  1. Studies on the pathogenesis of acute inflammation. I. The inflammatory reaction to thermal injury as observed in the rabbit ear chamber.

    PubMed

    ALLISON, F; SMITH, M R; WOOD, W B

    1955-12-01

    A special adaptation of the rabbit ear chamber has been devised to study in vivo, under high magnification, the acute inflammatory reaction to thermal injury. Systematic observations of the cellular response have led to the following conclusions. 1. Contrary to the commonly accepted view, vasodilatation does not always precede the adherence of leucocytes to vascular endothelium. 2. The fact that leucocytes often adhere to one another as well as to the endothelium indicates that the increased adhesiveness characteristic of the early stages of inflammation is not limited to the surfaces of the endothelial cells. 3. The sharing of erythrocytes and platelets in this increased stickiness suggests that a "plasma factor" is involved. There is indirect but as yet inconclusive evidence that the plasma factor may concern the clotting mechanism of the blood. 4. The adherence of leucocytes to the endothelium is usually first noted on the side of the vessel closest to the site of injury. This previously undescribed phenomenon of "unilateral sticking" is in keeping with the concept that the vascular reaction is caused by products of cellular damage which diffuse to the vessel from the site of injury. 5. Leucocytes always become adherent to the endothelium before penetrating the vessel wall. They often migrate about for some time on the endothelial surface before undergoing diapedesis. 6. Although no definite stomata are at any time visible in the endothelium, penetrating leucocytes may leave behind temporary defects through which other leucocytes and even erythrocytes may pass. 7. The diapedesis of leucocytes appears to depend primarily upon cellular motility. It may occur in static vessels where there is presumably little if any hydrostatic pressure. 8. The diapedesis of erythrocytes, on the other hand, is a passive process depending upon intravascular pressure. Its occurrence is greatly exaggerated in areas in which intravascular pressure becomes elevated. Such elevations

  2. The Oxidative and Inflammatory State in Patients with Acute Renal Graft Dysfunction Treated with Tacrolimus

    PubMed Central

    Carrillo-Ibarra, Sandra; Cerrillos-Gutiérrez, José Ignacio; Escalante-Núñez, Ariadna; Rojas-Campos, Enrique; Gómez-Navarro, Benjamín; Sifuentes-Franco, Sonia

    2016-01-01

    Objective. To determine the oxidative stress/inflammation behavior in patients with/without acute graft dysfunction (AGD) with Tacrolimus. Methods. Cross-sectional study, in renal transplant (RT) recipients (1-yr follow-up). Patients with AGD and without AGD were included. Serum IL-6, TNF-α, 8-isoprostanes (8-IP), and Nitric Oxide (NO) were determined by ELISA; C-reactive protein (CRP) was determined by nephelometry; lipid peroxidation products (LPO) and superoxide dismutase (SOD) were determined by colorimetry. Results. The AGD presentation was at 5.09 ± 3.07 versus 8.27 ± 3.78 months (p < 0.001); CRP >3.19 mg/L was found in 21 versus 19 in the N-AGD group (p = 0.83); TNF-α 145.53 ± 18.87 pg/mL versus 125.54 ± 15.92 pg/mL in N-AGD (p = 0.64); IL-6 2110.69 ± 350.97 pg/mL versus 1933.42 ± 235.38 pg/mL in N-AGD (p = 0.13). The LPO were higher in AGD (p = 0.014): 4.10 ± 0.69 µM versus 2.41 ± 0.29 µM; also levels of 8-IP were higher in AGD 27.47 ± 9.28 pg/mL versus 8.64 ± 1.54 pg/mL (p = 0.01). Serum levels of NO in AGD were lower 138.44 ± 19.20 µmol/L versus 190.57 ± 22.04 µmol/L in N-AGD (p = 0.042); antioxidant enzyme SOD activity was significantly diminished in AGD with 9.75 ± 0.52 U/mL versus 11.69 ± 0.55 U/mL in N-AGD (p = 0.012). Discussion. Patients with RT present with a similar state of the proinflammatory cytokines whether or not they have AGD. The patients with AGD showed deregulation of the oxidative state with increased LPO and 8-IP and decreased NO and SOD. PMID:27872679

  3. Morphological and molecular analysis of the collagen fibers in inflammatory process

    NASA Astrophysics Data System (ADS)

    de Carvalho, Luis Felipe das Chagas e. Silva; Alves, Mônica Ghislaine Oliveira; Soares, Carlos Alexandre; Almeida, Janete Dias; da Silva Martinho, Herculano

    2011-07-01

    Collagen makes up one third of the total protein in humans, being formed by the connection of three polypeptide chains arranged in a triple helix. This protein has fundamental importance in the formation of extracellular matrix of connective tissue. This study aimed to analyze the structural changes of collagen, which are resulting from inflammatory processes in oral mucosa, and to make the comparative analysis between the histopathology and the Raman spectra. The samples of tissues with inflammatory fibrous hyperplasia (IFH) and normal mucosa (NM) were evaluated by Raman Spectroscopy, hematoxylin-eosin and Massons trichrome stain. The histological analysis in both stains showed differences in collagen fibers, which was presented as thin fibers and arranged in parallel direction in NM and as collagen fibers are thick, mature and not organized, showing that these types of stain show morphological changes of collagen in IFH. The Raman Spectroscopy discriminate the groups of NM and IFH based on vibrational modes of proline, hydroxiproline and CH3, CH2. The histological stains only shows information from morphological data, and can be complemented by Raman spectra. This technique could demonstrate that inflammatory process caused some changes in collagen structure which is related to aminoacids such as proline and hidroxyproline.

  4. Anti-inflammatory and anti-apoptotic effects of (RS)-glucoraphanin bioactivated with myrosinase in murine sub-acute and acute MPTP-induced Parkinson's disease.

    PubMed

    Galuppo, Maria; Iori, Renato; De Nicola, Gina Rosalinda; Bramanti, Placido; Mazzon, Emanuela

    2013-09-01

    This study was focused on the possible neuroprotective role of (RS)-glucoraphanin, bioactivated with myrosinase enzyme (bioactive RS-GRA), in an experimental mouse model of Parkinson's disease (PD). RS-GRA is one of the most important glucosinolates, a thiosaccharidic compound found in Brassicaceae, notably in Tuscan black kale seeds. RS-GRA was extracted by one-step anion exchange chromatography, further purified by gel-filtration and analyzed by HPLC. Following, pure RS-GRA was characterized by (1)H and (13)C NMR spectrometry and the purity was assayed by HPLC analysis of the desulfo-derivative according to the ISO 9167-1 method. The obtained purity has been of 99%. To evaluate the possible pharmacological efficacy of bioactive RS-GRA (administrated at the dose of 10mg/kg, ip +5μl/mouse myrosinase enzyme), C57BL/6 mice were used in two different sets of experiment (in order to evaluate the neuroprotective effects in different phases of the disease), according to an acute (2 injections·40mg/kg MPTP) and a sub-acute (5 injections·20mg/kg MPTP) model of PD. Behavioural test, body weight changes measures and immunohistochemical localization of the main PD markers were performed and post-hoc analysis has shown as bioactive RS-GRA is able to reduce dopamine transporter degradation, tyrosine hydroxylase expression, IL-1β release, as well as the triggering of neuronal apoptotic death pathway (data about Bax/Bcl-2 balance and dendrite spines loss) and the generation of radicalic species by oxidative stress (results focused on nitrotyrosine, Nrf2 and GFAP immunolocalization). These effects have been correlated with the release of neurotrophic factors, such as GAP-43, NGF and BDNF, that, probably, play a supporting role in the neuroprotective action of bioactive RS-GRA. Moreover, after PD-induction mice treated with bioactive RS-GRA are appeared more in health than animals that did not received the treatment both for phenotypic behaviour and for general condition

  5. [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.

  6. Targeting pro-inflammatory cytokines following joint injury: acute intra-articular inhibition of interleukin-1 following knee injury prevents post-traumatic arthritis

    PubMed Central

    2014-01-01

    Introduction Post-traumatic arthritis (PTA) is a progressive, degenerative response to joint injury, such as articular fracture. The pro-inflammatory cytokines, interleukin 1(IL-1) and tumor necrosis factor alpha (TNF-α), are acutely elevated following joint injury and remain elevated for prolonged periods post-injury. To investigate the role of local and systemic inflammation in the development of post-traumatic arthritis, we targeted both the initial acute local inflammatory response and a prolonged 4 week systemic inflammatory response by inhibiting IL-1 or TNF-α following articular fracture in the mouse knee. Methods Anti-cytokine agents, IL-1 receptor antagonist (IL-1Ra) or soluble TNF receptor II (sTNFRII), were administered either locally via an acute intra-articular injection or systemically for a prolonged 4 week period following articular fracture of the knee in C57BL/6 mice. The severity of arthritis was then assessed at 8 weeks post-injury in joint tissues via histology and micro computed tomography, and systemic and local biomarkers were assessed in serum and synovial fluid. Results Intra-articular inhibition of IL-1 significantly reduced cartilage degeneration, synovial inflammation, and did not alter bone morphology following articular fracture. However, systemic inhibition of IL-1, and local or systemic inhibition of TNF provided no benefit or conversely led to increased arthritic changes in the joint tissues. Conclusion These results show that intra-articular IL-1, rather than TNF-α, plays a critical role in the acute inflammatory phase of joint injury and can be inhibited locally to reduce post-traumatic arthritis following a closed articular fracture. Targeted local inhibition of IL-1 following joint injury may represent a novel treatment option for PTA. PMID:24964765

  7. 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

    2014-02-05

    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.

  8. 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

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

    PubMed Central

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

    2017-01-01

    Background Recently, the d-galactose (d-gal)-induced mimetic aging rat model has been widely used in studies of age-associated diseases, which have shown that chronic d-gal exposure induces premature aging similar to natural aging in rats. With the increasing rate of sepsis in the geriatric population, an easy-access animal model for preclinical studies of elderly sepsis is urgently needed. This study investigates whether a sepsis model that is established in d-gal-induced aging rats can serve as a suitable model for preclinical studies of elderly patients with sepsis. Objective To investigate the acute kidney injury (AKI) and inflammatory response of sepsis following cecal ligation and puncture (CLP) in d-gal-induced aging rats. Methods Twelve-week-old male Sprague Dawley rats were divided into low-dose d-gal (L d-gal, 125 mg/kg/d), high-dose d-gal (H d-gal, 500 mg/kg/d), and control groups. After daily subcutaneous injection of d-gal for 6 weeks, the CLP method was used to establish a sepsis model. Results The mortality was 73.3%, 40%, and 33.3% in the H d-gal, L d-gal, and control groups, respectively. Blood urea nitrogen, creatinine, plasma neutrophil gelatinase-associated lipocalin, interleukin-6, interleukin-10, and tumor necrosis factor-α were markedly increased in the H d-gal group after establishment of the sepsis model (H d-gal vs control, P<0.05 at 12 h and 24 h post-CLP). The rate of severe AKI (RIFLE-F) at 24 h post-CLP was 43% for both the control and L d-gal groups and 80% for the H d-gal group. Conclusion High-dose- d-gal-induced aging rats are more likely to die from sepsis than are young rats, and probably this is associated with increased severity of septic AKI and an increased inflammatory response. Therefore, use of the high-dose- d-gal-induced aging rat model of sepsis for preclinical studies can provide more useful information for the treatment of sepsis in elderly patients.

  10. Peculiarities of the Inflammatory Process in the Reproductive Organs of C57Bl/6 Female Mice with Experimental Tuberculosis.

    PubMed

    Sukhikh, G T; Kayukova, S I; Bocharova, I V; Donnikov, A E; Lepekha, L N; Demikhova, O V; Uvarova, E V; Berezovskii, Yu S; Smirnova, T G

    2016-04-01

    Intravenous infection of C57Bl/6 female mice with M. tuberculosis H37Rv led to involvement of the lungs and dissemination of the tuberculous infection to the abdominal and pelvic organs. M. tuberculosis were detected in the lungs and spleen in 14, 35, and 90 days and in the uterine horns in 90 days after infection. Morphological analysis of organs showed successive development of exudative necrotic tuberculosis of the lungs, acute and chronic nonspecific inflammation in the reproductive organs (vagina, uterus, and uterine horns). The inflammatory process in the reproductive organs was associated with the development of anaerobic dysbiosis, that was most pronounced in 35 days after infection. Antituberculous therapy was followed by reduction of M. tuberculosis count in the lungs and spleen in 60 and 90 days after infection, eliminatation of M. tuberculosis in the uterine horns, arrest of nonspecific inflammation in female reproductive organs, recovery of the balance between aerobic and anaerobic microflora, and development of candidiasis of the urogenital mucosa.

  11. Protective effect of polyphenols in an inflammatory process associated with experimental pulmonary fibrosis in mice.

    PubMed

    Impellizzeri, Daniela; Talero, Elena; Siracusa, Rosalba; Alcaide, Antonio; Cordaro, Marika; Maria Zubelia, Jose; Bruschetta, Giuseppe; Crupi, Rosalia; Esposito, Emanuela; Cuzzocrea, Salvatore; Motilva, Virginia

    2015-09-28

    Polyphenols have been described to have a wide range of biological activities, and many reports, published during recent years, have highlighted the beneficial effects of phenolic compounds, illustrating their promising role as therapeutic tools in several acute and chronic disorders. The purpose of study was to evaluate, in an already-assessed model of lung injury caused by bleomycin (BLM) administration, the role of resveratrol and quercetin, as well as to explore the potential beneficial properties of a mango leaf extract, rich in mangiferin, and a grape leaf extract, rich in dihydroquercetin (DHQ), on the same model. Mice were subjected to intra-tracheal administration of BLM, and polyphenols were administered by oral route immediately after BLM instillation and daily for 7 d. Treatment with resveratrol, mangiferin, quercetin and DHQ inhibited oedema formation and body weight loss, as well as ameliorated polymorphonuclear infiltration into the lung tissue and reduced the number of inflammatory cells in bronchoalveolar lavage fluid. Moreover, polyphenols suppressed inducible nitric oxide synthase expression, and prevented oxidative and nitroxidative lung injury, as shown by the reduced nitrotyrosine and poly (ADP-ribose) polymerase levels. The degree of apoptosis, as evaluated by Bid and Bcl-2 balance, was also suppressed after polyphenol treatment. Finally, these natural products down-regulated cyclo-oxygenase-2, extracellular signal-regulated kinase phosphorylated expression and reduced NF-κBp65 translocation. Our findings confirmed the anti-inflammatory effects of resveratrol and quercetin in BLM-induced lung damage, and highlight, for the first time, the protective properties of exogenous administration of mangiferin and DHQ on experimental pulmonary fibrosis.

  12. Retinal Mueller glial cells trigger the hallmark inflammatory process in autoimmune uveitis.

    PubMed

    Hauck, Stefanie M; Schoeffmann, Stephanie; Amann, Barbara; Stangassinger, Manfred; Gerhards, Hartmut; Ueffing, Marius; Deeg, Cornelia A

    2007-06-01

    Spontaneous equine recurrent uveitis (ERU) is an incurable autoimmune disease affecting the eye. Although retinal-autoantigen specific T-helper 1 cells have been demonstrated to trigger disease progression and relapses, the molecular processes leading to retinal degeneration and consequent blindness remain unknown. To elucidate such processes, we studied changes in the total retinal proteome of ERU-diseased horses compared to healthy controls. Severe changes in the retinal proteome were found for several markers for blood-retinal barrier breakdown and whose emergence depended upon disease severity. Additionally, uveitic changes in the retina were accompanied by upregulation of aldose 1-epimerase, selenium-binding protein 1, alpha crystallin A chain, phosphatase 2A inhibitor (SET), and glial fibrillary acidic protein (GFAP), the latter indicating an involvement of retinal Mueller glial cells (RMG) in disease process. To confirm this, we screened for additional RMG-specific markers and could demonstrate that, in uveitic retinas, RMG concomitantly upregulate vimentin and GFAP and downregulate glutamine synthetase. These expression patterns suggest for an activated state of RMG, which further downregulate the expression of pigment epithelium-derived factor (PEDF) and begin expressing interferon-gamma, a pro-inflammatory cytokine typical for T-helper 1 cells. We thus propose that RMG may play a fatal role in uveitic disease progression by directly triggering inflammatory processes through the expression and secretion of interferon-gamma.

  13. The effects of berberine on the magnitude of the acute inflammatory response induced by Escherichia coli lipopolysaccharide in broiler chickens.

    PubMed

    Shen, Y B; Piao, X S; Kim, S W; Wang, L; Liu, P

    2010-01-01

    One hundred twenty-six 19-d-old male broiler chickens were used to determine the effects of berberine on the magnitude of the acute inflammatory response induced by Escherichia coli lipopolysaccharide (LPS). The birds were weighed and randomly allotted to 1 of 3 treatments at d 19 (3 treatments x 7 replicates x 6 birds). The treatments comprised a control group in which saline was injected at d 21, an LPS-treated group in which LPS (3 mg/kg of BW) was injected at d 21, and finally a berberine and LPS-treated group in which berberine (15 mg/kg of BW) was orally administered from d 19 to d 24 with LPS injection (3 mg/kg of BW) at d 21. Injection of LPS alone decreased (P < 0.01) weight gain, feed intake, and feed conversion compared with the control and the berberine-administered group. Relative liver weight was increased (P < 0.05) in the LPS-treated group 72 h postinjection compared with the control and the berberine-treated group. Total counts of white blood cells and lymphocytes were also increased (P < 0.05) in the LPS-treated group 72 h postinjection. The heterophil concentration of the LPS-treated group was greater (P < 0.05) than that of both the control and the berberine-administered group 24 h postinjection. Broilers in the LPS-treated group had greater (P < 0.05) total serum protein compared with birds in the control and the berberine-administered group both 24 and 72 h postinjection. In addition, the plasma interleukin-6 level of the LPS-treated group was significantly elevated (P < 0.01) at 24 h compared with that of the control and the berberine-administered group. Our results indicate that LPS injection initiated a series of physiological changes typical of an acute phase response in broiler chickens. These effects were largely mitigated by oral administration of berberine.

  14. 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.

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

    PubMed

    Marchini, T; Magnani, N D; Paz, M L; Vanasco, V; Tasat, D; González Maglio, D H; Alvarez, S; Evelson, P A

    2014-01-15

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

  16. 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.

  17. [A model of inflammatory process in the abdominal cavity in experiment].

    PubMed

    Sukhin, I A

    2014-02-01

    The model of chronic inflammatory process in abdominal cavity was elaborated in experiment on big laboratory animals. Intraoperatively in 12 laboratory pigs a chronic infiltrate was formatted between adducting and abducting intestinal loops with its mesenterium; in a region of gastroduodenal ligament and liver; between spleen and great omentum. Dynamics of the infiltrate formation was studied on the 60th, 90th, 120th and 180th day in accordance to data of bacteriological and histological investigations. Application of the method proposed permits to create chronic infiltrate with prognosticated course, to reduce the experiment duration and quantity of experimental animals used.

  18. Acquired inflammatory demyelinating neuropathies.

    PubMed

    Ensrud, E R; Krivickas, L S

    2001-05-01

    The acquired demyelinating neuropathies can be divided into those with an acute onset and course and those with a more chronic course. The acute neuropathies present as Guillain-Barré syndrome and include acute inflammatory demyelinating polyradiculoneuropathy (AIDP), Miller Fisher syndrome, acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and acute pandysautonomia. The chronic neuropathies are collectively known as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and include MADSAM (multifocal acquired demyelinating sensory and motor neuropathy, also know as Lewis-Sumner syndrome) and DADS (distal acquired demyelinating symmetric neuropathy) as variants. The clinical features, pathology, pathogenesis, diagnosis, treatment, rehabilitation, and prognosis of these neuropathies are discussed.

  19. Endogenous Acute Phase Serum Amyloid A Lacks Pro-Inflammatory Activity, Contrasting the Two Recombinant Variants That Activate Human Neutrophils through Different Receptors

    PubMed Central

    Christenson, Karin; Björkman, Lena; Ahlin, Sofie; Olsson, Maja; Sjöholm, Kajsa; Karlsson, Anna; Bylund, Johan

    2013-01-01

    Most notable among the acute phase proteins is serum amyloid A (SAA), levels of which can increase 1000-fold during infections, aseptic inflammation, and/or trauma. Chronically elevated SAA levels are associated with a wide variety of pathological conditions, including obesity and rheumatic diseases. Using a recombinant hybrid of the two human SAA isoforms (SAA1 and 2) that does not exist in vivo, numerous in vitro studies have given rise to the notion that acute phase SAA is a pro-inflammatory molecule with cytokine-like properties. It is however unclear whether endogenous acute phase SAA per se mediates pro-inflammatory effects. We tested this in samples from patients with inflammatory arthritis and in a transgenic mouse model that expresses human SAA1. Endogenous human SAA did not drive production of pro-inflammatory IL-8/KC in either of these settings. Human neutrophils derived from arthritis patients displayed no signs of activation, despite being exposed to severely elevated SAA levels in circulation, and SAA-rich sera also failed to activate cells in vitro. In contrast, two recombinant SAA variants (the hybrid SAA and SAA1) both activated human neutrophils, inducing L-selectin shedding, production of reactive oxygen species, and production of IL-8. The hybrid SAA was approximately 100-fold more potent than recombinant SAA1. Recombinant hybrid SAA and SAA1 activated neutrophils through different receptors, with recombinant SAA1 being a ligand for formyl peptide receptor 2 (FPR2). We conclude that even though recombinant SAAs can be valuable tools for studying neutrophil activation, they do not reflect the nature of the endogenous protein. PMID:23626589

  20. Quantification of Pulmonary Inflammatory Processes Using Chest Radiography: Tuberculosis as the Motivating Application.

    PubMed

    Giacomini, Guilherme; Miranda, José R A; Pavan, Ana Luiza M; Duarte, Sérgio B; Ribeiro, Sérgio M; Pereira, Paulo C M; Alves, Allan F F; de Oliveira, Marcela; Pina, Diana R

    2015-07-01

    The purpose of this work was to develop a quantitative method for evaluating the pulmonary inflammatory process (PIP) through the computational analysis of chest radiography exams in posteroanterior (PA) and lateral views. The quantification procedure was applied to patients with tuberculosis (TB) as the motivating application.A study of high-resolution computed tomography (HRCT) examinations of patients with TB was developed to establish a relation between the inflammatory process and the signal difference-to-noise ratio (SDNR) measured in the PA projection. A phantom essay was used to validate this relation, which was implemented using an algorithm that is able to estimate the volume of the inflammatory region based solely on SDNR values in the chest radiographs of patients.The PIP volumes that were quantified for 30 patients with TB were used for comparisons with direct HRCT analysis for the same patient. The Bland-Altman statistical analyses showed no significant differences between the 2 quantification methods. The linear regression line had a correlation coefficient of R = 0.97 and P < 0.001, showing a strong association between the volume that was determined by our evaluation method and the results obtained by direct HRCT scan analysis.Since the diagnosis and follow-up of patients with TB is commonly performed using X-rays exams, the method developed herein can be considered an adequate tool for quantifying the PIP with a lower patient radiation dose and lower institutional cost. Although we used patients with TB for the application of the method, this method may be used for other pulmonary diseases characterized by a PIP.

  1. A role of hydrogen peroxide producing commensal bacteria present in colon of adolescents with inflammatory bowel disease in perpetuation of the inflammatory process.

    PubMed

    Strus, M; Gosiewski, T; Fyderek, K; Wedrychowicz, A; Kowalska-Duplaga, K; Kochan, P; Adamski, P; Heczko, P B

    2009-12-01

    Bacteria in the gut play a central role in the initiation and progress of inflammatory bowel disease (IBD). This study was prepared to elucidate the role in the inflammatory process of the bacterial species which are able to produce hydrogen peroxide, present in samples taken from colon lesions in adolescents with inflammatory bowel disease. Fifty eight adolescents were enrolled into the study from January 2004 to October 2006 in Cracow, Poland. Biopsies and stool samples were collected. Bacteriological examinations and measurements of hydrogen peroxide production by enterococci, streptococci and lactobacilli were performed. For the first time it has been shown here that HP producing bacteria may contribute to increased amounts of hydrogen peroxide in the inflamed mucosa of Crohn's disease and ulcerative colitis patients. Moreover, we have been able to demonstrate an increase of total populations of aerobic bacteria but not anaerobes in the studied samples of mucosa of adolescents with inflammatory bowel disease which is an indirect evidence of higher oxygen tension present in inflamed tissues in IBD. We have also been able to demonstrate the direct relationship between presence of blood in stools of IBD adolescents and increased populations of Enterobacteriaceae but not streptococci in samples of colon mucosa. It is, therefore, possible that different products of Enterobacteriaceae and especially their lipopolysaccharides may also contribute to perpetuation of the chronic colon inflammation.

  2. Nobiletin ameliorates cisplatin-induced acute kidney injury due to its anti-oxidant, anti-inflammatory and anti-apoptotic effects.

    PubMed

    Malik, Salma; Bhatia, Jagriti; Suchal, Kapil; Gamad, Nanda; Dinda, Amit Kumar; Gupta, Yogender Kumar; Arya, Dharamvir Singh

    2015-01-01

    Cisplatin is an effective anti-cancer drug which causes remarkable toxicity to kidney by generating reactive oxygen species and by stimulating inflammatory and apoptotic pathway. Citrus flavonoid, like nobiletin has been reported to possess anti-oxidant, anti-inflammatory and anti-apoptotic properties. Hence, the present study was aimed to evaluate these properties of nobiletin, a polymethoxy flavone in cisplatin-induced acute renal injury. Adult male albino Wistar rats were divided into 6 groups. Nobiletin was administered at the dose of 1.25, 2.5 and 5mg/kg for a period of 10 days. On 7th day, a single injection of cisplatin (8 mg/kg) was injected to rats. Cisplatin administration resulted in renal dysfunction as evident by increase in serum creatinine and BUN levels. Oxidative stress in cisplatin group was reflected by increase in MDA level, and depletion of anti-oxidants such as glutathione, superoxide dismutase and catalase in renal tissue. Furthermore, cisplatin increased the expressions of Bax, caspase-3 and DNA damage along with decreased expression of Bcl-2 in the renal tissue. Histological analysis also revealed acute tubular necrosis. However, pretreatment with nobiletin preserved renal function and restored anti-oxidant status. Nobiletin supplementation inhibited activation of apoptotic pathways and DNA damage. It also attenuated tubular injury histologically. Collectively, the result of this study suggests the nephroprotective potential of nobiletin which may be related to its anti-oxidant, anti-apoptotic and anti-inflammatory effects.

  3. Antinociceptive, anti-inflammatory effects and acute toxicity of aqueous and ethanolic extracts of Myrtus communis L. Aerial parts in mice.

    PubMed

    Hosseinzadeh, Hossein; Khoshdel, Mohammad; Ghorbani, Maryam

    2011-12-01

    Myrtus communis L. aerial parts have been used in traditional medicine for the treatment of inflammatory disease. In this study 350 mice were divided into three main groups: negative (saline), positive (morphine or diclofenac) controls, and test groups. The acute toxicity was assessed for 2 days. Antinociceptive activity was performed using hot plate and writhing tests. The anti-inflammatory effect was investigated using xylene-induced ear edema and a cotton pellet test. According to phytochemical screening, the extracts contained tannins, alkaloids, and flavonoids. The LD50 values of the aqueous and ethanolic extracts were 0.473 and 0.79 g/kg, respectively. In hot plate test, the aqueous and ethanolic extracts showed significant antinociceptive activity that was inhibited by naloxone. The extracts exhibited antinociceptive activity against acetic acid-induced writhing and also showed significant activity against acute inflammation which was dose dependent for aqueous extract. The ethanolic (0.05 g/kg) and aqueous extracts (0.005, 0.015, and 0.03 g/kg) demonstrated anti-inflammatory effects against chronic inflammation. The aqueous and ethanolic extracts of the aerial parts of M communis L. showed antinociceptive effects and these may be mediated by opioid receptors.

  4. 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.

  5. Carbon monoxide-bound hemoglobin vesicles ameliorate multiorgan injuries induced by severe acute pancreatitis in mice by their anti-inflammatory and antioxidant properties

    PubMed Central

    Nagao, Saori; Taguchi, Kazuaki; Sakai, Hiromi; Yamasaki, Keishi; Watanabe, Hiroshi; Otagiri, Masaki; Maruyama, Toru

    2016-01-01

    Carbon monoxide (CO) has attracted attention as a possible therapeutic agent for affecting anti-inflammatory and antioxidant activities. Previously, CO-bound hemoglobin vesicle (CO-HbV) was developed as a nanotechnology-based CO donor, and its safety profile and therapeutic potential as a clinically applicable carrier of CO were examined in vitro and in vivo. In the present study, the therapeutic efficacy of CO-HbV against severe acute pancreatitis was examined with secondary distal organ-injured model mice that were fed with a choline-deficient ethionine-supplemented diet. A CO-HbV treatment significantly reduced the mortality of the acute pancreatitis model mice compared to saline and HbV. Biochemical and histological evaluations clearly showed that CO-HbV suppressed acute pancreatitis by inhibiting the production of systemic proinflammatory cytokines, neutrophil infiltration, and oxidative injuries in pancreatic tissue. Interestingly, CO-HbV also diminished the subsequent damage to distal organs including liver, kidneys, and lungs. This could be due to the suppression of neutrophil infiltration into tissues and the subsequently enhanced oxidative injuries. In contrast, O2-bound HbV, the inactive form of CO-HbV, was ineffective against both pancreatitis and distal organ injuries, confirming that CO was directly responsible for the protective effects of CO-HbV in acute pancreatitis. These findings suggest that CO-HbV has anti-inflammatory and antioxidant characteristics of CO and consequently exerts a superior protective effect against acute pancreatitis-induced multiorgan damage. PMID:27822039

  6. Lycopene Modulates THP1 and Caco2 Cells Inflammatory State through Transcriptional and Nontranscriptional Processes

    PubMed Central

    Makon-Sébastien, Njock; Francis, Fouchier; Eric, Seree; Henri, Villard Pierre; François, Landrier Jean; Laurent, Pechere; Yves, Barra; Serge, Champion

    2014-01-01

    We revisited the action of a carotenoid, the lycopene, on the expression of proinflammatory genes, reactive oxygen species (ROS) production, and metalloprotease (MMP9) activity. THP1 and Caco2 cell lines were used as in vitro models for the two main cell types found in intestine tissue, that is, monocytes and epithelial cells. Proinflammatory condition was induced using either phorbol ester acetate (PMA), lipopolysaccharide (LPS) or tumor necrosis factor (TNF). In THP1 cells, short term pretreatment (2 h) with a low concentration (2 μM) of lycopene reinforce proinflammatory gene expression. The extent of the effect of lycopene is dependent on the proinflammtory stimulus (PMA, LPS or TNF) used. Lycopene enhanced MMP9 secretion via a c-AMP-dependent process, and reduced ROS production at higher concentrations than 2 μM. Cell culture media, conditioned by PMA-treated monocytes and then transferred on CaCo-2 epithelial cells, induced a proinflammatory state in these cells. The extent of this inflammatory effect was reduced when cells has been pretreated (12 h) with lycopene. At low concentration (2 μM or less), lycopene appeared to promote an inflammatory state not correlated with ROS modulation. At higher concentration (5 μM–20 μM), an anti-inflammatory effect takes place as a decrease of ROS production was detected. So, both concentration and time have to be considered in order to define the exact issue of the effect of carotenoids present in meals. PMID:24891766

  7. Protein Processing and Inflammatory Signaling in Cystic Fibrosis: Challenges and Therapeutic Strategies

    PubMed Central

    Belcher, C.N.; Vij, N.

    2010-01-01

    Cystic Fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) that regulates epithelial surface fluid secretion in respiratory and gastrointestinal tracts. The deletion of phenylalanine at position 508 (ΔF508) in CFTR is the most common mutation that results in a temperature sensitive folding defect, retention of the protein in the endoplasmic reticulum (ER), and subsequent degradation by the proteasome. ER associated degradation (ERAD) is a major quality control pathway of the cell. The majority (99%) of the protein folding, ΔF508-, mutant of CFTR is known to be degraded by this pathway to cause CF. Recent studies have revealed that inhibition of ΔF508-CFTR ubiquitination and proteasomal degradation can increase its cell surface expression and may provide an approach to treat CF. The finely tuned balance of ER membrane interactions determine the cytosolic fate of newly synthesized CFTR. These ER membrane interactions induce ubiquitination and proteasomal targeting of ΔF508- over wild type- CFTR. We discuss here challenges and therapeutic strategies targeting protein processing of ΔF508-CFTR with the goal of rescuing functional ΔF508-CFTR to the cell surface. It is evident from recent studies that CFTR plays a critical role in inflammatory response in addition to its well-described ion transport function. Previous studies in CF have focused only on improving chloride efflux as a marker for promising treatment. We propose that methods quantifying the therapeutic efficacy and recovery from CF should not include only changes in chloride efflux, but also recovery of the chronic inflammatory signaling, as evidenced by positive changes in inflammatory markers (in vitro and ex vivo), lung function (pulmonary function tests, PFT), and chronic lung disease (state of the art molecular imaging, in vivo). This will provide novel therapeutics with greater opportunities of potentially

  8. Effect of 4-Allyl-1-hydroxy-2-methoxybenzene (Eugenol) on Inflammatory and Apoptosis Processes in Dental Pulp Fibroblasts

    PubMed Central

    Martínez-Herrera, Andrea; Ruiz-Rodríguez, Socorro; Vértiz-Hernández, Antonio

    2016-01-01

    Eugenol (mixed with zinc oxide powder) is widely used as direct capping material during pulp therapy in primary teeth. The aim of the present study was to evaluate the effect of eugenol on diverse genes involved in inflammatory and cell apoptosis processes. The regulatory effect of eugenol on the expression of inflammation and apoptotic genes was evaluated in dental pulp fibroblasts from extracted third molars, cultured under concentration of eugenol of 13 μM. Eugenol allowed the expression of inflammatory and apoptotic genes when compared with positive and negative controls. Eugenol is a proinflammatory agent when it is in direct contact with healthy tissues and behaves as an anti-inflammatory agent in tissues undergoing inflammatory/apoptotic processes, as in cases of pulp inflammation in primary teeth. These findings are relevant for dentistry, when considering the application of safer pulp treatments to grossly carious children's teeth. PMID:28044068

  9. 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

    neuroinflammation. Pathologic activity of the complement/coagulation cascade has been shown in patients suffering from a chronic form of ciguatera poisoning and is of particular interest in this model. Anti-inflammatory processes were at work not only in the brain but were also seen in whole blood and liver of these animals, creating a systemic anti-inflammatory environment to protect against the initial cellular damage caused by the toxin. PMID:20796285

  10. Reduction of acute toxicity and genotoxicity of dye effluent using Fenton-coagulation process.

    PubMed

    Zhang, Jing; Chen, Shuo; Zhang, Ying; Quan, Xie; Zhao, Huimin; Zhang, Yaobin

    2014-06-15

    Dye wastewater exhibits significant ecotoxicity even though its physico-chemical parameters meet the discharge standards. In this work, the acute toxicity and genotoxicity of dye effluent were tested, and the Fenton-coagulation process was carried out to detoxify this dye effluent. The acute toxicity was evaluated according to the mortality rate of zebrafish, and genotoxicity was evaluated by micronucleus (MN) and comet assays. Removal of color and chemical oxygen demand (COD) was also investigated. The results indicated that the dye effluent showed strong acute toxicity and genotoxicity to zebrafish. After 4h of treatment by Fenton-coagulation process, the dye effluent exhibited no significant acute toxicity and genotoxicity to zebrafish. In addition, its COD was less than 50mg/L, which met the discharge standard. It demonstrates that Fenton-coagulation process can comprehensively reduce the acute toxicity and genotoxicity as well as the COD of the dye effluent.

  11. Acute-Phase Serum Amyloid A: An Inflammatory Adipokine and Potential Link between Obesity and Its Metabolic Complications

    PubMed Central

    Yang, Rong-Ze; Lee, Mi-Jeong; Hu, Hong; Pollin, Toni I; Ryan, Alice S; Nicklas, Barbara J; Snitker, Soren; Horenstein, Richard B; Hull, Kristen; Goldberg, Nelson H; Goldberg, Andrew P; Shuldiner, Alan R; Fried, Susan K; Gong, Da-Wei

    2006-01-01

    Background Obesity is associated with low-grade chronic inflammation, and serum markers of inflammation are independent risk factors for cardiovascular disease (CVD). However, the molecular and cellular mechanisms that link obesity to chronic inflammation and CVD are poorly understood. Methods and Findings Acute-phase serum amyloid A (A-SAA) mRNA levels, and A-SAA adipose secretion and serum levels were measured in obese and nonobese individuals, obese participants who underwent weight-loss, and persons treated with the insulin sensitizer rosiglitazone. Inflammation-eliciting activity of A-SAA was investigated in human adipose stromal vascular cells, coronary vascular endothelial cells and a murine monocyte cell line. We demonstrate that A-SAA was highly and selectively expressed in human adipocytes. Moreover, A-SAA mRNA levels and A-SAA secretion from adipose tissue were significantly correlated with body mass index ( r = 0.47; p = 0.028 and r = 0.80; p = 0.0002, respectively). Serum A-SAA levels decreased significantly after weight loss in obese participants ( p = 0.006), as well as in those treated with rosiglitazone ( p = 0.033). The magnitude of the improvement in insulin sensitivity after weight loss was significantly correlated with decreases in serum A-SAA ( r = −0.74; p = 0.034). SAA treatment of vascular endothelial cells and monocytes markedly increased the production of inflammatory cytokines, e.g., interleukin (IL)-6, IL-8, tumor necrosis factor alpha, and monocyte chemoattractant protein-1. In addition, SAA increased basal lipolysis in adipose tissue culture by 47%. Conclusions A-SAA is a proinflammatory and lipolytic adipokine in humans. The increased expression of A-SAA by adipocytes in obesity suggests that it may play a critical role in local and systemic inflammation and free fatty acid production and could be a direct link between obesity and its comorbidities, such as insulin resistance and atherosclerosis. Accordingly, improvements in

  12. Extracellular phospholipases A2 in relation to systemic inflammatory response syndrome (SIRS) and systemic complications in severe acute pancreatitis.

    PubMed

    Hietaranta, A; Kemppainen, E; Puolakkainen, P; Sainio, V; Haapiainen, R; Peuravuori, H; Kivilaakso, E; Nevalainen, T

    1999-05-01

    The pathophysiology of severe acute pancreatitis (AP) resembles other conditions with systemic inflammatory response syndrome (SIRS) such as sepsis predisposing to remote organ failure. Because extracellular phospholipases A2 (PLA2) have been implicated in AP, their serum concentrations were analyzed with respect to SIRS and systemic complications in patients with severe AP. The serum samples were collected daily for 12 days in 57 patients with severe AP. SIRS, early organ complications, local complications, and outcome of AP were recorded. Time-resolved fluoroimmunoassays were used for group I and group II PLA2 measurements. Thirty-nine (68.4%) patients fulfilled the criteria of SIRS within 12 days from admission. Pancreatic necrosis was detected in 43 (75.4%) patients. Infected necrosis was found preoperatively or at operation in five (8.8%) patients. Twenty-six (45.6%) and eight (14.0%) patients had respiratory or renal failure, respectively. Seven (12.3%) patients died of their disease. All patients with systemic complications fulfilled the criteria of SIRS. The increasing number of positive SIRS criteria was associated with increased frequency of systemic complications. Pancreatic necrosis was not significantly associated with SIRS. The serum concentration of group II PLA2 was significantly higher in patients with SIRS (p < 0.05) compared with patients without from day 7 onward. The concentration of group II PLA2 increased (p < 0.01) in patients with SIRS but decreased in patients without. The serum concentration of group II PLA2 did not differ significantly with respect to systemic complications. The concentration of group I PLA2 decreased (p < 0.05) similarly in patients with and without SIRS or systemic complications during follow-up, respectively. Early systemic complications of severe AP are associated with SIRS with increasing frequency as the number of positive SIRS criteria increases. Group II PLA2 but not group I PLA2 may have pathophysiologic

  13. Optical biopsy of pre-malignant or degenerative lesions: the role of the inflammatory process

    NASA Astrophysics Data System (ADS)

    da Silva Martinho, Herculano

    2011-03-01

    Recent technological advances in fiber optics, light sources, detectors, and molecular biology have stimulated unprecedented development of optical methods to detect pathological changes in tissues. These methods, collectively termed "optical biopsy," are nondestructive in situ and real-time assays. Optical biopsy techniques as fluorescence spectroscopy, polarized light scattering spectroscopy, optical coherence tomography, confocal reflectance microscopy, and Raman spectroscopy had been extensively used to characterize several pathological tissues. In special, Raman spectroscopy technique had been able to probe several biochemical alterations due to pathology development as change in the DNA, glycogen, phospholipid, non-collagenous proteins. All studies claimed that the optical biopsy methods were able to discriminate normal and malignant tissues. However, few studies had been devoted to the discrimination of very common subtle or early pathological states as inflammatory process, which are always present on, e.g., cancer lesion border. In this work we present a systematic comparison of optical biopsy data on several kinds of lesions were inflammatory infiltrates play the role (breast, cervical, and oral lesion). It will be discussed the essential conditions for the optimization of discrimination among normal and alterated states based on statistical analysis.

  14. Sol-gel processing of anti-inflammatory entrapment in silica, release kinetics, and bioactivity.

    PubMed

    Catauro, M; Melisi, D; Curcio, A; Rimoli, M G

    2008-12-15

    Controlled and local drug-delivery systems for anti-inflammatory agents are drawing increasing attention for possible pharmaceutical and biomedical applications, because of their extended therapeutic effect and reduced side effects. A single-step sol-gel process was used to precipitate silica microspheres containing Ketoprofen, Indomethacin, Ketorolac tris salt, or Triamcinolone acetonide, for controlled drug delivery applications. The amorphous nature of the gels was ascertained by X-ray diffraction analysis. Release kinetics in a simulated body fluid (SBF) has been subsequently investigated. The amount of drug released has been detected by UV-vis spectroscopy. The pure anti-inflammatory agent exhibited linear release with time, while sol-gel silica-entrapped drugs were released with a logarithmic time dependence, starting with an initial burst effect followed by a gradual decrease. Finally, SEM micrography and EDS analysis showed the formation of a hydroxyapatite layer on the surface of the samples soaked in SBF. All the materials showed good release and therefore could be used as drug-delivery systems.

  15. Usage of low-intensity laser radiation for the treatment of the inflammatory processes of the oral cavity mucosa after applying removable plate dentures

    NASA Astrophysics Data System (ADS)

    Kalivradzhiyan, Edvard; Lesnykh, Nikolay; Kunin, Vadim; Mutafyan, Mikhail

    1995-04-01

    Effective methods of reveling overload zones of the oral mucosa under the bases of plane dentures, the effect of low intensity laser radiation ont he increase of its resistance are discussed. At present removable plate dentures of different modifications to a certain degree restore aesthetic proportions of the face, phonetics and malfunction of the teeth and jaws. Besides, removable bridge are known not to secure even distribution of mastication pressure along the whole dentures bed which results in the development of inflammatory and dystrophic processes, and, finally in the accelerated atrophy of the oral mucosa and bony tissue of the alveolar process of upper and alveolar parts of the mandible. Many papers are devoted to the anti-inflammatory effect of laser therapy. Improvement of metabolic processes and revascularization of the dentures bed mucosa, normalization of the oral microflora structure, anesthetizing effect is noted too. At the same time there are no papers about studying the therapeutic effect of low intensity laser radiation intraumatic dentures stomatitis, inflammation of the oral mucosa in the literature available for us. To increase the functional effectiveness of removable plate dentures, profilaxy of inflammation and dystrophic phenomena and to decrease adaptation period we have developed methods of early detection of overload zone of oral mucosa at the initial stages of acute inflammation with the help of macrohistochemical reaction. Visible with the naked eye for the timely and precise correction of the dentures.

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

    PubMed

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

    2015-10-01

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

  17. Anti-Inflammatory Effects of a Polyphenols-Rich Extract from Tea (Camellia sinensis) Flowers in Acute and Chronic Mice Models

    PubMed Central

    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

  18. Anti-inflammatory activity of four solvent fractions of ethanol extract of Mentha spicata L. investigated on acute and chronic inflammation induced rats.

    PubMed

    Arumugam, P; Priya, N Gayatri; Subathra, M; Ramesh, A

    2008-07-01

    Anti-inflammatory effects of four solvent fractions of ethanol extract of Mentha spicata were evaluated in acute and chronic inflammation induced in Wistar albino rats. Lipid peroxidation (LPO) and some antioxidants produced during chronic inflammation were quantitated. Hexane (320mg/kg of body weight in 25% DMSO), chloroform (320mg/kg body weight in 25% DMSO), ethyl acetate (160mg/kg body weight in 25% DMSO), aqueous (320mg/kg of body weight in ddH(2)O) fractions, two negative control groups (25% DMSO and ddH(2)O) and two anti-inflammatory drugs (Diclofenac: 25mg/kg of body weight; Indomethacin: 10mg/kg of body weight both in ddH(2)O) were administered by oral intubations to the eight groups of rats consisting six animals, each. In acute study, 1% carrageenan was injected subcutaneously in the sub-plantar region of the right hind paw after 1h of administration of test doses. The increased paw edema was measured at 0.5, 1, 2, 4, 8, 16 and 24h intervals. In the chronic study, the oral administration was carried out for seven consecutive days. On eighth day, four sterile cotton pellets (50mg each) were implanted subcutaneously in the dorsal region of the rats. On the sixteenth day, the rats were sacrificed and the cotton pellets with granulomatous tissue were dissected out and weighed (fresh and dry). Both in chronic and acute inflammation, ethyl acetate (EAF) and aqueous fraction (AF) were effective. EAF is comparable with the positive standards in chronic inflammation. The results indicate that EAF's anti-inflammatory activity is largely due to its ability to modulate in vivo antioxidants.

  19. Connection between inflammatory processes and transmittor function-Modulatory effects of interleukin-1.

    PubMed

    Spulber, Stefan; Schultzberg, Marianne

    2010-02-09

    Cells in the nervous system can respond to different kinds of stress, e.g. injury, with production and release of inflammatory molecules, including cytokines. One of the most important proinflammatory cytokines is interleukin-1, affecting most organs of the body. The high constitutive expression of interleukin-1 in the adrenal gland provides a source for local and systemic actions, in addition to activated monocytes. In the brain, the constitutive expression is low, but activated microglia produce and release interleukin-1 during pathological conditions such as neurodegenerative disorders (e.g. stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease). Interleukin-1 has an important role in mediating 'sickness symptoms' such as fever, in response to infections. Its role in neurodegeneration is not fully elucidated, but there is evidence for involvement in both amyloidosis and tau pathology, major neuropathological hallmarks of Alzheimer's disease. The interleukin-1 family at present consists of 11 members, one of which is the endogenous receptor antagonist. Overexpression of this antagonist in the CNS in a transgenic mouse strain, Tg hsIL-1ra, has allowed studies on morphological and functional effects of blocking interleukin-1 receptor-mediated activity in the brain. Marked alterations of brain morphology such as reduced hippocampal and cortical volume correlate with behavioural deficits. Decreased anxiety and impaired long-term memory are among the consequences. Intact interleukin-1 signalling is important for the brain's ability to adapt to acute and chronic neuroinflammation. Increased amplitude and prolongation of proinflammatory cytokine production underly the behavioural alterations characteristic for ageing. Moreover, deregulated expression of interleukin-1 is associated with ageing-related chronic neurodegenerative disorders.

  20. L-651,392, a potent leukotriene inhibitor, controls inflammatory process in Escherichia coli pyelonephritis.

    PubMed Central

    Tardif, M; Beauchamp, D; Bergeron, Y; Lessard, C; Gourde, P; Bergeron, M G

    1994-01-01

    In this study, the relationship between leukotrienes, peritubular cell infiltration with polymorphonuclear cells (PMNs) and renal tubular damage was investigated in a rat model of acute ascending pyelonephritis. Infection was induced by the injection of 10(5) CFU of Escherichia coli into the bladder and occlusion of the left ureter for 24 h. Treatment of infected animals was started 24 h after the induction of pyelonephritis with either hydrocortisone (25 mg/kg of body weight per day), the leukotriene inhibitor L-651,392 (10 mg/kg/day), or the vehicle of L-651,392 and was maintained for 5 days. At the end of treatment, the animals were killed, serum was collected, and both kidneys were removed for colony counts and histopathology. Renal function was evaluated by the measurement of blood urea nitrogen levels and creatinine clearance. The numbers of PMNs and mononuclear cells (MNs) in the cortex and medulla were recorded for all groups on plastic sections done from the left kidney. Infection alone (vehicle of L-651,392) resulted in intensive interstitial infiltration and a severe tubular destruction in the cortex. Treatment with hydrocortisone did not prevent PMN migration and tissue damage. By contrast, treatment with L-651,392 resulted in a significant reduction in PMNs (P < 0.001 in comparisons with all other groups) and greater preservation of the tubular structure despite identical bacterial counts than in the group receiving hydrocortisone. We conclude that L-651,392 prevents inflammatory cells from reaching the site of infection and protects the kidney from tubular damage associated with inflammation during pyelonephritis. Inhibitors of leukotrienes should be further investigated for their potential benefit as adjuvants to antibiotherapy in the treatment of pyelonephritis. Images PMID:7979288

  1. Acute Submandibular Sialadenitis—A Case Report

    PubMed Central

    Chandak, Rakhi; Degwekar, Shirish; Chandak, Manoj; Rawlani, Shivlal

    2012-01-01

    Many conditions affect the salivary glands. Acute sialadenitis is infectious or inflammatory disorders of the salivary glands. The exact frequency of submandibular sialadenitis is unclear. The acute conditions more typically involve the parotid and submandibular glands. During an acute inflammatory process, there is swelling of the affected gland, overlying pain, gland tenderness, fever, and on occasion difficulty in opening the mouth. Initial treatment should include rehydration oral antistaphylococcal antibiotic should be started while awaiting culture results. Hygiene and repeated massaging of the gland when tenderness had subsided. The present report describes a case of acute submandibular sialadenitis in a 70-year-old female. PMID:22888457

  2. Degradation of the anti-inflammatory drug ibuprofen by electro-peroxone process.

    PubMed

    Li, Xiang; Wang, Yujue; Yuan, Shi; Li, Zhaoxin; Wang, Bin; Huang, Jun; Deng, Shubo; Yu, Gang

    2014-10-15

    Electro-peroxone (E-peroxone) treatment of the anti-inflammatory drug ibuprofen aqueous solution was investigated in this study. The E-peroxone process combined conventional ozonation with electrolysis processes, and used a carbon-polytetrafluorethylene cathode to electrochemically generate H2O2 from O2 in the sparged ozone generator effluent (O2 and O3 mixture). The in-situ generated H2O2 then reacted with the sparged O3 to produce aqueous •OH, which can in turn oxidize pollutants effectively in the bulk solution. The E-peroxone process overcomes several intrinsic limitations of conventional ozonation and electrolysis processes for pollutant degradation such as the selective oxidation with O3 and mass transfer limitations of pollutants to the electrodes, and thus significantly enhanced both ibuprofen degradation and total organic carbon (TOC) mineralization. Results show that ibuprofen could be completely degraded much more rapidly in the E-peroxone process (e.g., 5-15 min under all tested reaction conditions) than in ozonation (≥30 min) and electrolysis (several hours) processes. In addition, thanks to the powerful and non-selective oxidation capacity of •OH, toxic intermediates formed during ibuprofen degradation could be completely mineralized in the E-peroxone process. The E-peroxone effluent (2 h) thus exhibited much lower toxicity (5% inhibition of bioluminescence of Vibrio fisheri) than the ozonation and electrolysis effluents (22% and 88% inhibition, respectively). The results of this study indicate that the E-peroxone process may provide a promising technology for pharmaceutical wastewater treatment.

  3. A New Population of Parvocellular Oxytocin Neurons Controlling Magnocellular Neuron Activity and Inflammatory Pain Processing.

    PubMed

    Eliava, Marina; Melchior, Meggane; Knobloch-Bollmann, H Sophie; Wahis, Jérôme; da Silva Gouveia, Miriam; Tang, Yan; Ciobanu, Alexandru Cristian; Triana del Rio, Rodrigo; Roth, Lena C; Althammer, Ferdinand; Chavant, Virginie; Goumon, Yannick; Gruber, Tim; Petit-Demoulière, Nathalie; Busnelli, Marta; Chini, Bice; Tan, Linette L; Mitre, Mariela; Froemke, Robert C; Chao, Moses V; Giese, Günter; Sprengel, Rolf; Kuner, Rohini; Poisbeau, Pierrick; Seeburg, Peter H; Stoop, Ron; Charlet, Alexandre; Grinevich, Valery

    2016-03-16

    Oxytocin (OT) is a neuropeptide elaborated by the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Magnocellular OT neurons of these nuclei innervate numerous forebrain regions and release OT into the blood from the posterior pituitary. The PVN also harbors parvocellular OT cells that project to the brainstem and spinal cord, but their function has not been directly assessed. Here, we identified a subset of approximately 30 parvocellular OT neurons, with collateral projections onto magnocellular OT neurons and neurons of deep layers of the spinal cord. Evoked OT release from these OT neurons suppresses nociception and promotes analgesia in an animal model of inflammatory pain. Our findings identify a new population of OT neurons that modulates nociception in a two tier process: (1) directly by release of OT from axons onto sensory spinal cord neurons and inhibiting their activity and (2) indirectly by stimulating OT release from SON neurons into the periphery.

  4. Drug-disease interactions: reduced β-adrenergic and potassium channel antagonist activities of sotalol in the presence of acute and chronic inflammatory conditions in the rat

    PubMed Central

    Kulmatycki, Kenneth M; Abouchehade, Kassem; Sattari, Saeed; Jamali, Fakhreddin

    2001-01-01

    Inflammation may influence response to pharmacotherapy. We investigated the effect of inflammation on response to sotalol, a β-adrenergic receptor and potassium channel antagonist. Racemic sotalol (40 mg kg−1) was administered to healthy, acutely (interferonα 2a-induced) and chronically (Mycobacterium butyricum-induced adjuvant arthritis) inflamed male Sprague-Dawley rats (n=4 – 6/group). Another group of interferon-treated rats received 3 mg kg−1 of anti-TNF antibody infliximab. Electrocardiogram (ECG) recorded and plasma sotalol concentration monitored for 6 h. The study was repeated in acutely inflamed rats following administration of stereochemically pure individual sotalol enantiomers [40 mg kg−1 S (potassium channel blocker) or 20 mg kg−1 R (β-adrenergic/potassium channel blocker)]. Chronic arthritis was readily evident. Acute arthritis was associated with elevated segmented neutrophils and increased plasma nitrite and tumour necrosis factor (TNF) concentrations. Sotalol affected ECG in all rats. In both inflamed groups, however, response to sotalol in prolongation of QT interval (potassium channel sensitivity) was reduced. The effect of PR interval (β-adrenergic activity) was also reduced following administration of the racemate and R-enantiomer. No significant differences in pharmacokinetics were observed between control and inflamed rats. Infliximab reduced nitrite and TNF concentrations and reversed the effect of acute inflammation on both PR and QT intervals. The reduced electrocardiographic responses to sotalol is likely due to the influence of inflammation on the action of the drug on both β-adrenergic and potassium channel receptors secondary to over-expression of pro-inflammatory cytokines and/or nitric oxide. Our observation may have therapeutic consequences in all conditions where inflammatory mediators are increased. PMID:11350865

  5. Post-conditioning experience with acute or chronic inflammatory pain reduces contextual fear conditioning in the rat.

    PubMed

    Johnston, Ian N; Maier, Steven F; Rudy, Jerry W; Watkins, Linda R

    2012-01-15

    There is evidence that pain can impact cognitive function in people. The present study evaluated whether Pavlovian fear conditioning in rats would be reduced if conditioning were followed by persistent inflammatory pain induced by a subcutaneous injection of dilute formalin or complete Freund's adjuvant (CFA) on the dorsal lumbar surface of the back. Formalin-induced pain specifically impaired contextual fear conditioning but not auditory cue conditioning (Experiment 1A). Moreover, formalin pain only impaired contextual fear conditioning if it was initiated within 1h of conditioning and did not have a significant effect if initiated 2, 8 or 32 h after (Experiments 1A and 1B). Experiment 2 showed that formalin pain initiated after a session of context pre-exposure reduced the ability of that pre-exposure to facilitate contextual fear when the rat was limited to a brief exposure to the context during conditioning. Similar impairments in context- but not CS-fear conditioning were also observed if the rats received an immediate post-conditioning injection with CFA (Experiment 3). Finally, we confirmed that formalin and CFA injected s.c. on the back induced pain-indicative behaviours, hyperalgesia and allodynia with a similar timecourse to intraplantar injections (Experiment 4). These results suggest that persistent pain impairs learning in a hippocampus-dependent task, and may disrupt processes that encode experiences into long-term memory.

  6. Acute and chronic stress models differentially impact the inflammatory and antibody titer responses to respiratory vaccination in naive beef steers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this research was to determine the effect of an acute vs. chronic stress model on serum antibody titer and acute phase responses. Seronegative beef steers (n=32; 209 +/- 8 kg) were stratified by body weight and assigned randomly to 1 of 3 treatments: 1) Chronic stress (CHR), 0.5 mg/...

  7. 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

  8. Persistent Oxytetracycline Exposure Induces an Inflammatory Process That Improves Regenerative Capacity in Zebrafish Larvae

    PubMed Central

    Barros-Becker, Francisco; Romero, Jaime; Pulgar, Alvaro; Feijóo, Carmen G.

    2012-01-01

    Background The excessive use of antibiotics in aquaculture can adversely affect not only the environment, but also fish themselves. In this regard, there is evidence that some antibiotics can activate the immune system and reduce their effectiveness. None of those studies consider in detail the adverse inflammatory effect that the antibiotic remaining in the water may cause to the fish. In this work, we use the zebrafish to analyze quantitatively the effects of persistent exposure to oxytetracycline, the most common antibiotic used in fish farming. Methodology We developed a quantitative assay in which we exposed zebrafish larvae to oxytetracycline for a period of 24 to 96 hrs. In order to determinate if the exposure causes any inflammation reaction, we evaluated neutrophils infiltration and quantified their total number analyzing the Tg(mpx:GFP)i114 transgenic line by fluorescence stereoscope, microscope and flow cytometry respectively. On the other hand, we characterized the process at a molecular level by analyzing several immune markers (il-1β, il-10, lysC, mpx, cyp1a) at different time points by qPCR. Finally, we evaluated the influence of the inflammation triggered by oxytetracycline on the regeneration capacity in the lateral line. Conclusions Our results suggest that after 48 hours of exposure, the oxytetracycline triggered a widespread inflammation process that persisted until 96 hours of exposure. Interestingly, larvae that developed an inflammation process showed an improved regeneration capacity in the mechanosensory system lateral line. PMID:22590621

  9. Processed tart cherry products--comparative phytochemical content, in vitro antioxidant capacity and in vitro anti-inflammatory activity.

    PubMed

    Ou, Boxin; Bosak, Kristen N; Brickner, Paula R; Iezzoni, Dominic G; Seymour, E Mitchell

    2012-05-01

    Processing of fruits and vegetables affects their phytochemical and nutrient content. Tart cherries are commercially promoted to possess antioxidant and anti-inflammatory activity. However, processing affects their phytochemical content and may affect their related health benefits. The current study compares the in vitro antioxidant capacity and anti-inflammatory cyclooxygenase activity of processed tart cherry (Prunus cerasus) products-cherry juice concentrate, individually quick-frozen cherries, canned cherries, and dried cherries. Cherry products were analyzed for total anthocyanin and proanthocyanidin content and profile. On a per serving basis, total anthocyanins were highest in frozen cherries and total proanthocyanidins were highest in juice concentrate. Total phenolics were highest in juice concentrate. Juice concentrate had the highest oxygen radical absorbance capacity (ORAC) and peroxynitrite radical averting capacity (NORAC). Dried cherries had the highest hydroxyl radical averting capacity (HORAC) and superoxide radical averting capacity (SORAC). Processed tart cherry products compared very favorably to the U.S. Dept. of Agriculture-reported ORAC of other fresh and processed fruits. Inhibition of in vitro inflammatory COX-1 activity was greatest in juice concentrate. In summary, all processed tart cherry products possessed antioxidant and anti-inflammatory activity, but processing differentially affected phytochemical content and in vitro bioactivity. On a per serving basis, juice concentrate was superior to other tart cherry products.

  10. The effect of phototherapy on systemic inflammatory process in patients with plaque psoriasis.

    PubMed

    Batycka-Baran, Aleksandra; Besgen, Petra; Wolf, Ronald; Szepietowski, Jacek C; Prinz, Joerg C

    2016-08-01

    Psoriasis is a common, chronic immune-mediated inflammatory disease. The inflammatory process in psoriasis has systemic effects and may influence the development of psoriatic comorbidities. The systemic action of phototherapy in patients with psoriasis has been so far poorly elucidated. We aimed to investigate the expression of genes encoding selected psoriasis-related cytokines in peripheral blood mononuclear cells (PBMCs) isolated from patients with psoriasis before and after treatment with phototherapy. 17 patients with mild to moderate plaque psoriasis were treated with narrow band-UVB (NB-UVB), 8 patients with moderate to severe plaque psoriasis with bath-psoralen-ultraviolet A therapy (PUVA). PBMCs were isolated by Ficoll gradient density centrifugation. Expression of genes encoding TNF-α, IL-17A, IL-6, IL-1 β, INF-γ, and IL-10 in PBMCs of patients with psoriasis before and after phototherapy was analyzed with quantitative RT-PCR. Treatment with NB-UVB therapy led to a significant decrease in IL-17A, TNF-α, and IL-6 mRNA levels in PBMCs (p=0.003; p=0.042; p=0.019, respectively). Following treatment with bath-PUVA therapy, we observed a significant decrease in TNF-α and IL-6 mRNA levels in PBMCs (p=0.031, p=0.035, respectively). Treatment with phototherapy in patients with psoriasis may affect systemic inflammation by downregulation of the expression of genes encoding proinflammatory cytokines in PBMCs, implicated in the development of psoriasis and psoriatic comorbidities.

  11. Mast cells modulate the inflammatory process in endotoxin-induced uveitis

    PubMed Central

    Sebastião da Silva, Pierre; Girol, Ana Paula

    2011-01-01

    Purpose To investigate the role of mast cells and annexin-A1 (Anxa1) in endotoxin-induced uveitis (EIU). Methods EIU was induced by injection of lipopolysaccharide (LPS) into the paws of rats, which were then sacrificed after 24 and 48 h. To assess EIU in the absence of mast cells, groups of animals were pretreated with compound 48/80 (c48/80) and sacrificed after 24 h after no treatment or EIU induction. The eyes were used for histological studies and the aqueous humor (AqH) pool was used for the analysis of transmigrated cells and Anxa1 levels. In inflammatory cells, Anxa1 expression was monitored by immunohistochemistry. Results After 24 h, rats with EIU exhibited degranulated mast cells, associated with elevated numbers of infiltrating leukocytes and the high expression of Anxa1 in the AqH and the neutrophils. After 48 h of EIU, the mast cells were intact, indicating granule re-synthesis, and there was a reduction of neutrophil transmigration and an increase in the number of mononuclear phagocytic cells in ocular tissues. Anxa1 expression was decreased in neutrophils but increased in mononuclear phagocytic cells. In the animals pretreated with c48/80 and subjected to EIU, mast cells responded to this secretagogue by degranulating and few transmigrated neutrophils were observed. Conclustions We report that mast cells are a potential source of pharmacological mediators that are strongly linked to the pathophysiology of EIU, and the endogenous protein Anxa1 is a mediator in the homeostasis of the inflammatory process with anti-migratory effects on leukocytes, which supports further studies of this protein as an innovative therapy for uveitis. PMID:21633711

  12. Assessment of anti-inflammatory, lipid peroxidation and acute toxicity of extracts obtained from wild higher basidiomycetes mushrooms collected from Akure (southwest Nigeria).

    PubMed

    Oyetayo, Victor O; Nieto-Camacho, Antonio; Rodriguez, Baldomero Esquivel; Jimenez, Manuel

    2012-01-01

    Ethanolic extracts of three wild medicinal mushrooms, namely Lenzites betulina (LET), Trametes versicolor (TET), and Coriolopsis polyzona (CET), collected from Akure, southwest Nigeria, were assessed for their lipid peroxidation, anti-inflammatory, and acute toxicity effects. The inhibition of the formation of thiobarbituric acid reactive species (TBARS) by extracts was concentration dependent and ranged from 86.99% to 92.18% at 1000 µg/ mL. The IC50 of the extracts was also in the range of 222.81 µg/mL to 737.13 µg/mL. The anti-inflammatory effect measured by inhibition of mice ear edema was higher and significantly different (P ≤ 0.05) than the control. The acute toxicity test also revealed tolerance to the three ethanolic extracts by Artemia salina at concentrations of 10 µg/mL to 1000 µg/mL, except for ethanolic extracts of LET and TET, which exhibited toxicity against this invertebrate at 1000 µg/mL. This research has shown that ethanolic extracts of these three macrofungi could be good sources of safe and effective antioxidant and antinflammatory agents for biopharmaceutical exploitation.

  13. 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

  14. Role of parathyroid hormone-related protein in the pro-inflammatory and pro-fibrogenic response associated with acute pancreatitis.

    PubMed

    Bhatia, Vandanajay; Kim, Sung O K; Aronson, Judith F; Chao, Celia; Hellmich, Mark R; Falzon, Miriam

    2012-04-10

    Pancreatitis is a common and potentially lethal necro-inflammatory disease with both acute and chronic manifestations. Current evidence suggests that the accumulated damage incurred during repeated bouts of acute pancreatitis (AP) can lead to chronic disease, which is associated with an increased risk of pancreatic cancer. While parathyroid hormone-related protein (PTHrP) exerts multiple effects in normal physiology and disease states, its function in pancreatitis has not been previously addressed. Here we show that PTHrP levels are transiently elevated in a mouse model of cerulein-induced AP. Treatment with alcohol, a risk factor for both AP and chronic pancreatitis (CP), also increases PTHrP levels. These effects of cerulein and ethanol are evident in isolated primary acinar and stellate cells, as well as in the immortalized acinar and stellate cell lines AR42J and irPSCc3, respectively. Ethanol sensitizes acinar and stellate cells to the PTHrP-modulating effects of cerulein. Treatment of acinar cells with PTHrP (1-36) increases expression of the inflammatory mediators interleukin-6 (IL-6) and intracellular adhesion protein (ICAM-1), suggesting a potential autocrine loop. PTHrP also increases apoptosis in AR42J cells. Stellate cells mediate the fibrogenic response associated with pancreatitis; PTHrP (1-36) increases procollagen I and fibronectin mRNA levels in both primary and immortalized stellate cells. The effects of cerulein and ethanol on levels of IL-6 and procollagen I are suppressed by the PTH1R antagonist, PTHrP (7-34). Together these studies identify PTHrP as a potential mediator of the inflammatory and fibrogenic responses associated with alcoholic pancreatitis.

  15. Acute kidney injury and inflammatory immune reconstitution syndrome in mixed genotype (A/E) hepatitis B virus co-infection in HIV-associated lymphoma.

    PubMed

    Tajima, Katsushi; Kohno, Kei; Shiono, Yosuke; Suzuki, Ikuko; Kato, Yuichi; Hiroshima, Yuki; Yamamoto, Masakazu; Ohtake, Hiroya; Iwaba, Akiko; Yamakawa, Mitsunori; Kato, Takeo

    2013-01-01

    We report a first case of HIV-associated lymphoma (HAL) presenting with acute kidney injury (AKI) and inflammatory immune reconstitution syndrome (IRIS). A 39-year-old male, treated with nonsteroidal anti-inflammatory drugs (NSAIDs) for one month prior to admission, developed AKI, left testicular tumor, and recurrent swelling of the right parotid gland. A resected testicular tumor exhibited features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Renal biopsy showed hydro-degeneration of renal tubules, interstitial inflammatory cells, and a small number of lymphoma cells in the sub-capsule, compatible with acute interstitial nephritis. His renal dysfunction rapidly recovered following chemotherapy and combination antiretroviral therapy (cART). He developed pneumonia concomitantly with a decrease in HIV-RNA level and an increase in CD4+ cells after the first cycle of chemotherapy, which spontaneously resolved after the second cycle of chemotherapy without additional anti-infection drugs; thus, his pneumonia fulfilled the diagnostic criteria for IRIS. We suggest that IRIS may frequently develop during chemotherapy for HAL, but may be overlooked. He was coinfected with hepatitis B virus (HBV), which genotypes known as is associated with liver-related mortality and response to antiviral therapy; recently, an intimate interplay between HIV and HBV in the onset of lymphoma has been reported. Therefore, we addressed the HBV genotype in the patient. The analysis revealed that he exhibited a mixed genotype (A/E) not native to Japan and primarily found in Europe and North America or West Africa. These findings suggest that universal vaccination for juveniles against HBV is warranted in Japan.

  16. Correlation between altered central pain processing and concentration of peritoneal fluid inflammatory cytokines in endometriosis patients with chronic pelvic pain.

    PubMed

    Neziri, Alban Y; Bersinger, Nick A; Andersen, Ole K; Arendt-Nielsen, Lars; Mueller, Michael D; Curatolo, Michele

    2014-01-01

    Translational research has not yet elucidated whether alterations in central pain processes are related to peripheral inflammatory processes in chronic pain patients. We tested the hypothesis that the concentration of cytokines in the peritoneal fluid of endometriosis patients with chronic pain correlate with parameters of hyperexcitability of the nociceptive system. The concentrations of 15 peritoneal fluid cytokines were measured in 11 patients with chronic pelvic pain and a diagnosis of endometriosis. Six parameters assessing central pain processes were recorded. Positive correlations between concentration of some cytokines in the peritoneal fluid and amplification of central pain processing were found. The results suggest that inflammatory mechanisms may be important in the pathophysiology of altered central pain processes and that cytokines produced in the environment of endometriosis could act as mediators between the peripheral lesion and changes in central nociceptive processes.

  17. Effect of acute stress on auditory processing: a systematic review of human studies.

    PubMed

    Jafari, Zahra; Kolb, Bryan E; Mohajerani, Majid H

    2017-01-01

    Stress is an integral part of modern life. Although there is a large body of literature regarding the harmful effects of chronic stress on different aspects of human life, acute stress is the most common form of stress, resulting from the demands and pressures of the recent past and the anticipated demands and pressures of the near future. In spite of its pervasive nature, less attention has been paid to the impact of acute stress on sensory processing than to the consequences of chronic stress, particularly concerning auditory processing. In this systematic review, the impact of experimental acute stress on the auditory processing of healthy adults was investigated. The results revealed the adverse effects of acute physical and psychological stresses on auditory processing. According to the open field of research on stress and the auditory system and the high possibility of experiencing different types of acute stresses in various life environments, including testing places, it seems that more investigations are needed to identify and manage different types of acute stresses in both clinical and research situations.

  18. Ablation of the Regulatory IE1 Protein of Murine Cytomegalovirus Alters In Vivo Pro-inflammatory TNF-alpha Production during Acute Infection

    PubMed Central

    Wilhelmi, Vanessa; Lisnic, Vanda Juranic; Hsieh, Wei Yuan; Blanc, Mathieu; Livingston, Andrew; Busche, Andreas; Tekotte, Hille; Messerle, Martin; Auer, Manfred; Fraser, Iain; Jonjic, Stipan; Angulo, Ana; Reddehase, Matthias J.; Ghazal, Peter

    2012-01-01

    Little is known about the role of viral genes in modulating host cytokine responses. Here we report a new functional role of the viral encoded IE1 protein of the murine cytomegalovirus in sculpting the inflammatory response in an acute infection. In time course experiments of infected primary macrophages (MΦs) measuring cytokine production levels, genetic ablation of the immediate-early 1 (ie1) gene results in a significant increase in TNFα production. Intracellular staining for cytokine production and viral early gene expression shows that TNFα production is highly associated with the productively infected MΦ population of cells. The ie1- dependent phenotype of enhanced MΦ TNFα production occurs at both protein and RNA levels. Noticeably, we show in a series of in vivo infection experiments that in multiple organs the presence of ie1 potently inhibits the pro-inflammatory cytokine response. From these experiments, levels of TNFα, and to a lesser extent IFNβ, but not the anti-inflammatory cytokine IL10, are moderated in the presence of ie1. The ie1- mediated inhibition of TNFα production has a similar quantitative phenotype profile in infection of susceptible (BALB/c) and resistant (C57BL/6) mouse strains as well as in a severe immuno-ablative model of infection. In vitro experiments with infected macrophages reveal that deletion of ie1 results in increased sensitivity of viral replication to TNFα inhibition. However, in vivo infection studies show that genetic ablation of TNFα or TNFRp55 receptor is not sufficient to rescue the restricted replication phenotype of the ie1 mutant virus. These results provide, for the first time, evidence for a role of IE1 as a regulator of the pro-inflammatory response and demonstrate a specific pathogen gene capable of moderating the host production of TNFα in vivo. PMID:22952450

  19. Effects of Ketamine on Levels of Inflammatory Cytokines IL-6, IL-1β, and TNF-α in the Hippocampus of Mice Following Acute or Chronic Administration.

    PubMed

    Li, Yanning; Shen, Ruipeng; Wen, Gehua; Ding, Runtao; Du, Ao; Zhou, Jichuan; Dong, Zhibin; Ren, Xinghua; Yao, Hui; Zhao, Rui; Zhang, Guohua; Lu, Yan; Wu, Xu

    2017-01-01

    Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile, ketamine has been shown to modulate the levels of inflammatory cytokines. We hypothesized that the effects of ketamine on the central nervous system are associated with inflammatory cytokines. Therefore, we set out to establish acute and chronic ketamine administration models in C57BL/6 mice, to evaluate spatial recognition memory and emotional response, to analyze the changes in the levels of the inflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the mouse hippocampus, employing behavioral tests, Western blot, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunohistochemistry. Our results showed that ketamine at the dose of 60 mg/kg induced spatial recognition memory deficit and reduced anxiety-like behaviors in mice after chronic administration. Moreover, we found that ketamine increased the hippocampal levels of IL-6 and IL-1β after single, multiple and long-term administration in a dose-dependent manner. However, the expression level of TNF-α differed in the mouse hippocampus under different conditions. Single administration of ketamine increased the level of TNF-α, whereas multiple and long-term administration decreased it significantly. We considered that TNF-α expression could be controlled by a bi-directional regulatory pathway, which was associated with the dose and duration of ketamine administration. Our results suggest that the alterations in the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α may be involved in the neurotoxicity of ketamine.

  20. Effects of Ketamine on Levels of Inflammatory Cytokines IL-6, IL-1β, and TNF-α in the Hippocampus of Mice Following Acute or Chronic Administration

    PubMed Central

    Li, Yanning; Shen, Ruipeng; Wen, Gehua; Ding, Runtao; Du, Ao; Zhou, Jichuan; Dong, Zhibin; Ren, Xinghua; Yao, Hui; Zhao, Rui; Zhang, Guohua; Lu, Yan; Wu, Xu

    2017-01-01

    Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile, ketamine has been shown to modulate the levels of inflammatory cytokines. We hypothesized that the effects of ketamine on the central nervous system are associated with inflammatory cytokines. Therefore, we set out to establish acute and chronic ketamine administration models in C57BL/6 mice, to evaluate spatial recognition memory and emotional response, to analyze the changes in the levels of the inflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the mouse hippocampus, employing behavioral tests, Western blot, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunohistochemistry. Our results showed that ketamine at the dose of 60 mg/kg induced spatial recognition memory deficit and reduced anxiety-like behaviors in mice after chronic administration. Moreover, we found that ketamine increased the hippocampal levels of IL-6 and IL-1β after single, multiple and long-term administration in a dose-dependent manner. However, the expression level of TNF-α differed in the mouse hippocampus under different conditions. Single administration of ketamine increased the level of TNF-α, whereas multiple and long-term administration decreased it significantly. We considered that TNF-α expression could be controlled by a bi-directional regulatory pathway, which was associated with the dose and duration of ketamine administration. Our results suggest that the alterations in the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α may be involved in the neurotoxicity of ketamine. PMID:28373844

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

    PubMed

    Heine, Markus; Bartelt, Alexander; Bruns, Oliver T; Bargheer, Denise; Giemsa, Artur; Freund, Barbara; Scheja, Ludger; Waurisch, Christian; Eychmüller, Alexander; Reimer, Rudolph; Weller, Horst; Nielsen, Peter; Heeren, Joerg

    2014-01-01

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

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

    PubMed Central

    Bargheer, Denise; Giemsa, Artur; Freund, Barbara; Scheja, Ludger; Waurisch, Christian; Eychmüller, Alexander; Reimer, Rudolph; Weller, Horst; Nielsen, Peter

    2014-01-01

    Summary Semiconductor quantum dots (QD) and superparamagnetic iron oxide nanocrystals (SPIO) have exceptional physical properties that are well suited for biomedical applications in vitro and in vivo. For future applications, the direct injection of nanocrystals for imaging and therapy represents an important entry route into the human body. Therefore, it is crucial to investigate biological responses of the body to nanocrystals to avoid harmful side effects. In recent years, we established a system to embed nanocrystals with a hydrophobic oleic acid shell either by lipid micelles or by the amphiphilic polymer poly(maleic anhydride-alt-1-octadecene) (PMAOD). The goal of the current study is to investigate the uptake processes as well as pro-inflammatory responses in the liver after the injection of these encapsulated nanocrystals. By immunofluorescence and electron microscopy studies using wild type mice, we show that 30 min after injection polymer-coated nanocrystals are primarily taken up by liver sinusoidal endothelial cells. In contrast, by using wild type, Ldlr -/- as well as Apoe -/- mice we show that nanocrystals embedded within lipid micelles are internalized by Kupffer cells and, in a process that is dependent on the LDL receptor and apolipoprotein E, by hepatocytes. Gene expression analysis of pro-inflammatory markers such as tumor necrosis factor alpha (TNFα) or chemokine (C-X-C motif) ligand 10 (Cxcl10) indicated that 48 h after injection internalized nanocrystals did not provoke pro-inflammatory pathways. In conclusion, internalized nanocrystals at least in mouse liver cells, namely endothelial cells, Kupffer cells and hepatocytes are at least not acutely associated with potential adverse side effects, underlining their potential for biomedical applications. PMID:25247125

  3. The role of miRNAs in the regulation of inflammatory processes during hepatofibrogenesis

    PubMed Central

    Roy, Sanchari; Benz, Fabian; Luedde, Tom

    2015-01-01

    Liver cirrhosis represents the end stage of most chronic inflammatory liver diseases and is a major global health burden. Despite the enormous relevance of cirrhotic disease, pharmacological strategies for prevention or treatment of hepatic fibrosis are still limited, underlining the need to establish a better understanding of the molecular mechanisms underlying the pathogenesis of hepatic cirrhosis. Recently, miRNAs have emerged as a new class of RNAs that do not withhold the information to encode for proteins but regulate whole gene expression networks during different physiological and pathological processes. Various authors demonstrated that miRNA species are functionally involved in the regulation of chronic liver damage and development of liver cirrhosis in inflamed livers. Moreover, circulating miRNA patterns were suggested to serve as blood-based biomarkers indicating liver injury and progression to hepatic cirrhosis and cancer. Here we summarize current findings on a potential role of miRNAs in the cascade leading from liver inflammation to liver fibrosis and finally hepatocellular carcinoma. We compare data from animal models with findings on miRNAs dysregulated in human patients and finally highlight a potential use of miRNAs as biomarkers for liver injury, fibrosis and cancer. PMID:25713802

  4. Positive affect and health-related neuroendocrine, cardiovascular, and inflammatory processes.

    PubMed

    Steptoe, Andrew; Wardle, Jane; Marmot, Michael

    2005-05-03

    Negative affective states such as depression are associated with premature mortality and increased risk of coronary heart disease, type 2 diabetes, and disability. It has been suggested that positive affective states are protective, but the pathways through which such effects might be mediated are poorly understood. Here we show that positive affect in middle-aged men and women is associated with reduced neuroendocrine, inflammatory, and cardiovascular activity. Positive affect was assessed by aggregating momentary experience samples of happiness over a working day and was inversely related to cortisol output over the day, independently of age, gender, socioeconomic position, body mass, and smoking. Similar patterns were observed on a leisure day. Happiness was also inversely related to heart rate assessed by using ambulatory monitoring methods over the day. Participants underwent mental stress testing in the laboratory, where plasma fibrinogen stress responses were smaller in happier individuals. These effects were independent of psychological distress, supporting the notion that positive well-being is directly related to health-relevant biological processes.

  5. Effect of nitric oxide inhibitor and donor substances on the inflammatory process caused by endodontic irrigants

    PubMed Central

    de BRITO, Luciana Malheiro; CARREIRA, Cláudia de Moura; RALDI, Denise Pontes; LAGE-MARQUES, José Luiz; HABITANTE, Sandra Márcia; SAAD, Wilson Abraão

    2011-01-01

    Nitric oxide (NO) has been considered a key molecule in inflammation Objective The aim of this study was to evaluate the effect of treatment with L-NAME and sodium nitroprussiate, substances that inhibit and release NO, respectively, on tissue tolerance to endodontic irrigants. Material and Methods The vital dye exudation method was used in a rat subcutaneous tissue model. Injections of 2% Evans blue were administered intravenously into the dorsal penial vein of 14 male rats (200-300 g). The NO inhibitor and donor substances were injected into the subcutaneous tissue in the dorsal region, forming two groups of animals: G1 was inoculated with L-NAME and G2 with sodium nitroprussiate. Both groups received injections of the test endodontic irrigants: acetic acid, 15% citric acid, 17% EDTA-T and saline (control). After 30 min, analysis of the extravasated dye was performed by light absorption spectrophotometry (620 nm). Results There was statistically significant difference (p<0.05) between groups 1 and 2 for all irrigants. L-NAME produced a less intense inflammatory reaction and nitroprussiate intensified this process. Conclusion Independently of the administration of NO inhibitors and donors, EDTA-T produced the highest irritating potential in vital tissue among the tested irrigating solutions. PMID:21552711

  6. 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

  7. 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.

  8. In vitro studies on the relationship between the anti-inflammatory activity of Physalis peruviana extracts and the phagocytic process.

    PubMed

    Martínez, Willington; Ospina, Luis Fernando; Granados, Diana; Delgado, Gabriela

    2010-03-01

    The study of plants used in traditional medicine has drawn the attention of researchers as an alternative in the development of new therapeutics agents, such as the American Solanaceae Physalis peruviana, which has significant anti-inflammatory activity. The Physalis peruviana anti-inflammatory effect of ethanol or ether calyces extracts on the phagocytic process was assessed by using an in vitro phagocytosis model (Leishmania panamensis infection to murine macrophages). The Physalis peruviana extracts do not inhibit microorganism internalization and have no parasiticide effect. Most ET and EP extracts negatively affected the parasite's invasion of macrophages (Infected cells increased.). This observation might result from a down-regulation of the macrophage's microbicide ability associated with a selective reduction of proinflammatory cytokines levels. Physalis peruviana's anti-inflammatory activity described in this model is related to an immunomodulatory effect exerted on macrophages infected, which directly or indirectly "blocks" their ability to secrete soluble proinflammatory mediators.

  9. Micronization of anti-inflammatory drugs for pulmonary delivery by a controlled crystallization process.

    PubMed

    Rasenack, Norbert; Steckel, Hartwig; Müller, Bernd W

    2003-01-01

    Jet-milling as the common way for micronization of drugs shows several disadvantages. Drug powder properties are decisive for pulmonary use because, besides a small particle size, a good deagglomeration behavior is required. In this study, several anti-inflammatory drugs [beclomethasone-17,21-dipropionate (BDP), betamethasone-17-valerate (BV), triamcinolone acetonide, ECU-R2, budesonide, and prednisolone] were micronized by controlled crystallization without any milling processes. First the drug is dissolved in an organic solvent (BDP/BV: 4%; ECU-R2: 1% in acetone) and precipitated by a solvent change method in the presence of a cellulose ether (hydroxypropylmethylcellulose) as stabilizing hydrocolloid. By rapid pouring the solution of hydroxypropylmethylcellulose in water (BDP/BV: 0.005%; ECU-R2: 0.025%) into the drug solution under stirring in a relationship (v/v) of 1:16 (BDP/BV), 1:4 (ECU-R2), the previously molecularly dispersed drug was associated to small particles and stabilized against crystal growth simultaneously. This dispersion was spray-dried, resulting in a drug powder with a uniform particle-size distribution and a drug load of up to 98% (BDP, BV). The mean particle size of the drug was lower than 5 microm in most cases and consequently in the respirable range. Whereas the fine particle fraction (<5 microm, measured without excipients and without an inhalation device) of jet-milled drugs is 9.5 (BDP) or 13.1 (ECU-R2), fine particle fractions of 25.6% (BDP) resp. 78.2% (ECU-R2) are obtained with the spray-dried powders. As the formation of the small crystals requires a rapid solvent change process, the affinity of the hydrocolloid, and a high difference between the solubility in the solvent and nonsolvent, the drug's partition coefficient limits the method as drugs which are more hydrophilic form larger particles.

  10. Signs of enhanced sleep and sleep-associated memory processing following the anti-inflammatory antibiotic minocycline in men.

    PubMed

    Besedovsky, Luciana; Schmidt, Eva-Maria; Linz, Barbara; Diekelmann, Susanne; Lange, Tanja; Born, Jan

    2017-02-01

    Pro-inflammatory cytokines can promote sleep and neuronal processes underlying memory formation. However, this has mainly been revealed in animal studies. In this double-blind, placebo-controlled within-subject designed study, we examined how changes in the balance between pro- and anti-inflammatory signalling affect sleep and sleep-associated memory consolidation in humans. After learning declarative memory tasks (word pairs, texts) and a procedural memory task (finger tapping) in the evening, 21 healthy young men orally received either 200 mg of the anti-inflammatory antibiotic minocycline or placebo shortly before nocturnal sleep. Sleep was allowed between 23:00 and 07:00 h and recorded polysomnographically. Retrieval of memories was tested two days later. Because of outliers or missing data, final sample size was reduced to n = 14-19. Our data suggest that rather than weakening sleep as expected based on animal studies, the anti-inflammatory agent promoted sleep and memory consolidation. Specifically, minocycline increased slow-wave activity (0.68-4.0 Hz) during non-rapid eye movement sleep stage 2 and selectively enhanced episodic aspects in memory (i.e. memory for the temporal order of events in the texts). In combination with previous results, our findings indicate that, in humans, reducing pro-inflammatory signalling can act towards deepening non-rapid eye movement sleep and enhancing its memory forming efficacy.

  11. Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology?

    PubMed

    Calder, Philip C

    2013-03-01

    Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 fatty acids found in oily fish and fish oil supplements. These fatty acids are able to inhibit partly a number of aspects of inflammation including leucocyte chemotaxis, adhesion molecule expression and leucocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n-6 fatty acid arachidonic acid, production of inflammatory cytokines and T cell reactivity. In parallel, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonioc acid and EPA and DHA give rise to anti-inflammatory and inflammation resolving resolvins and protectins. Mechanisms underlying the anti-inflammatory actions of n-3 fatty acids include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor kappa B so reducing expression of inflammatory genes, activation of the anti-inflammatory transcription factor NR1C3 (i.e. peroxisome proliferator activated receptor γ) and binding to the G protein coupled receptor GPR120. These mechanisms are interlinked. In adult humans, an EPA plus DHA intake greater than 2 g day⁻¹ seems to be required to elicit anti-inflammatory actions, but few dose finding studies have been performed. Animal models demonstrate benefit from n-3 fatty acids in rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and asthma. Clinical trials of fish oil in patients with RA demonstrate benefit supported by meta-analyses of the data. Clinical trails of fish oil in patients with IBD and asthma are inconsistent with no overall clear evidence of efficacy.

  12. Facial Emotion Processing in Acutely Ill and Euthymic Patients with Pediatric Bipolar Disorder

    ERIC Educational Resources Information Center

    Schenkel, Lindsay S.; Pavuluri, Mani N.; Herbener, Ellen S.; Harral, Erin M.; Sweeney, John A.

    2007-01-01

    Objective: Past investigations indicate facial emotion-processing abnormalities in pediatric bipolar disorder (PBD) subjects. However, the extent to which these deficits represent state- and trait-related factors is unclear. We investigated facial affect processing in acutely ill and clinically stabilized children with PBD and matched healthy…

  13. The acute phase inflammatory response to maximal exercise testing in children and young adults with sickle cell anaemia.

    PubMed

    Liem, Robert I; Onyejekwe, Kasiemobi; Olszewski, Marie; Nchekwube, Chisalu; Zaldivar, Frank P; Radom-Aizik, Shlomit; Rodeghier, Mark J; Thompson, Alexis A

    2015-12-01

    Although individuals with sickle cell anaemia (SCA) have elevated baseline inflammation and endothelial activation, the acute phase response to maximal exercise has not been evaluated among children with SCA. We measured the acute phase response to maximal exercise testing for soluble vascular cell adhesion molecule (sVCAM) as well as interleukin 6 (IL6), total white blood cell (WBC) count, C-reactive protein (CRP) and D-dimer in a cohort of children with SCA and matched controls at baseline, immediately after, and 30, 60 and 120 min following exercise. Despite higher baseline levels of all biomarkers except CRP, the acute phase response from baseline to immediately after exercise was significantly greater in subjects versus controls for CRP (2·1 vs. 0·2 mg/l, P = 0·02) and D-dimer (160 vs. 10 μg/l, P < 0·01) only. Similar between-group trends were observed over time for all biomarkers, including sVCAM, IL6, total WBC, CRP and D-dimer. Lower fitness, defined by peak oxygen consumption (VO2 ), was independently associated with greater acute phase responses to exercise for sVCAM. Our results suggest maximal exercise may not be associated with any greater escalation of endothelial activation or inflammation in SCA and provide preliminary biomarker evidence for the safety of brief, high-intensity physical exertion in children with SCA.

  14. 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...

  15. Redox signaling in acute pancreatitis

    PubMed Central

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

    2015-01-01

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

  16. Redox signaling in acute pancreatitis.

    PubMed

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

    2015-08-01

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

  17. 2-Chloroadenosine (2-CADO) treatment modulates the pro-inflammatory immune response to prevent acute lung inflammation in BALB/c mice suffering from Klebsiella pneumoniae B5055-induced pneumonia.

    PubMed

    Kumar, Vijay; Harjai, Kusum; Chhibber, Sanjay

    2010-06-01

    Acute lung inflammation (ALI) is a life-threatening pathology and can develop during the course of several clinical conditions such as pneumonia, acid aspiration or sepsis. Adenosine plays a significant role in controlling acute inflammation via binding to A(2A) receptors on inflammatory cells, i.e. neutrophils or macrophages. The present study was designed to evaluate the anti-inflammatory and immunomodulatory effects of 2-chloroadenosine (2-CADO), alone or in combination with amoxicillin/clavulanic acid (AMC), in Klebsiella pneumoniae B5055-induced acute lung infection in mice. Acute lung infection in mice was induced by directly instilling the selected dose (10(4) colony-forming units/mL) of bacteria intranasally. Histopathological examination of the lungs was performed to reveal neutrophil infiltration into the lung alveoli. In addition to the major pro-inflammatory cytokines tumour necrosis factor-alpha (TNFalpha) and interleukin (IL)-1alpha, levels of the anti-inflammatory cytokine IL-10 were also determined. Intranasal instillation of bacteria caused profound neutrophil infiltration into the lung alveoli as well as a significant increase in the levels of pro-inflammatory mediators (i.e. TNFalpha and IL-1alpha). However, intravenous administration of 2-CADO 10 microg/kg/day, alone or in combination with an antibiotic (i.e. AMC), significantly decreased neutrophil infiltration into the lung alveoli. A significant decrease in TNFalpha and IL-1alpha along with elevation of IL-10 levels in the lung homogenate of mice with acute lung infection was observed upon treatment with 2-CADO alone, with no significant decrease in bacterial counts. Moreover, in combination with AMC, 2-CADO exhibited its immunomodulatory action in acute lung infection and prevented ALI, whilst an antibacterial action was exhibited by AMC.

  18. Characterization of the oxidant generation by inflammatory cells lavaged from rat lungs following acute exposure to ozone

    SciTech Connect

    Esterline, R.L.; Bassett, D.J.; Trush, M.A.

    1989-06-15

    Following exposure to 2 ppm ozone for 4 hr, two distinct effects on rat lung inflammatory cell oxidant generation were observed. TPA- and opsonized zymosan-stimulated superoxide production by the inflammatory cell population was found to be maximally inhibited 24 hr following ozone exposure. In contrast, luminol-amplified chemiluminescence increased 24 hr following ozone exposure, coinciding with an increase in the percentage of neutrophils and myeloperoxidase in the inflammatory cell population. Supporting the involvement of myeloperoxidase in the enhanced oxidant-generating status of these cells, the luminol-amplified chemiluminescence was found to be azide-, but not superoxide dismutase-inhibitable. Additionally, this cell population was found to generate taurine chloramines, a myeloperoxidase-dependent function which was absent prior to the ozone exposure and also demonstrated enhanced activation of benzo(a)pyrene-7,8-dihydrodiol to its light-emitting dioxetane intermediate. Addition of myeloperoxidase to control alveolar macrophages resulted in enhanced luminol-amplified chemiluminescence, taurine chloramine generation, and enhanced chemiluminescence from benzo(a)pyrene-7,8-dihydrodiol demonstrating that, in the presence of myeloperoxidase, alveolar macrophages are capable of supporting myeloperoxidase-dependent reactions. The possibility of such an interaction occurring in vivo is suggested by the detection of myeloperoxidase activity in the cell-free lavagates of ozone-exposed rats. These studies suggest that neutrophils recruited to ozone-exposed lungs alter the oxidant-generating capabilities in the lung which could further contribute to lung injury or to the metabolism of inhaled xenobiotics.

  19. 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

  20. Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance.

    PubMed

    Calder, Philip C

    2015-04-01

    Inflammation is a condition which contributes to a range of human diseases. It involves a multitude of cell types, chemical mediators, and interactions. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 (n-3) fatty acids found in oily fish and fish oil supplements. These fatty acids are able to partly inhibit a number of aspects of inflammation including leukocyte chemotaxis, adhesion molecule expression and leukocyte-endothelial adhesive interactions, production of eicosanoids like prostaglandins and leukotrienes from the n-6 fatty acid arachidonic acid, production of inflammatory cytokines, and T-helper 1 lymphocyte reactivity. In addition, EPA gives rise to eicosanoids that often have lower biological potency than those produced from arachidonic acid and EPA and DHA give rise to anti-inflammatory and inflammation resolving mediators called resolvins, protectins and maresins. Mechanisms underlying the anti-inflammatory actions of marine n-3 fatty acids include altered cell membrane phospholipid fatty acid composition, disruption of lipid rafts, inhibition of activation of the pro-inflammatory transcription factor nuclear factor kappa B so reducing expression of inflammatory genes, activation of the anti-inflammatory transcription factor peroxisome proliferator activated receptor γ and binding to the G protein coupled receptor GPR120. These mechanisms are interlinked, although the full extent of this is not yet elucidated. Animal experiments demonstrate benefit from marine n-3 fatty acids in models of rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and asthma. Clinical trials of fish oil in RA demonstrate benefit, but clinical trials of fish oil in IBD and asthma are inconsistent with no overall clear evidence of efficacy. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance".

  1. Ginkgo biloba extracts attenuate lipopolysaccharide-induced inflammatory responses in acute lung injury by inhibiting the COX-2 and NF-κB pathways.

    PubMed

    Yao, Xin; Chen, Nan; Ma, Chun-Hua; Tao, Jing; Bao, Jian-An; Zong-Qi, Cheng; Chen, Zu-Tao; Miao, Li-Yan

    2015-01-01

    In the present study, we analyzed the role of Ginkgo biloba extract in lipopolysaccharide(LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS. G. biloba extract (12 and 24 mg·kg(-1)) and dexamethasone (2 mg·kg(-1)), as a positive control, were given by i.p. injection. The cells in the bronchoalveolar lavage fluid (BALF) were counted. The degree of animal lung edema was evaluated by measuring the wet/dry weight ratio. The superoxidase dismutase (SOD) and myeloperoxidase (MPO) activities were assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators, tumor necrosis factor-a, interleukin-1b, and interleukin-6, were assayed by enzyme-linked immunosorbent assay. Pathological changes of lung tissues were observed by H&E staining. The levels of NF-κB p65 and COX-2 expression were detected by Western blotting. Compared to the LPS group, the treatment with the G. biloba extract at 12 and 24 mg·kg(-1) markedly attenuated the inflammatory cell numbers in the BALF, decreased NF-κB p65 and COX-2 expression, and improved SOD activity, and inhibited MPO activity. The histological changes of the lungs were also significantly improved. The results indicated that G. biloba extract has a protective effect on LPS-induced acute lung injury in mice. The protective mechanism of G. biloba extract may be partly attributed to the inhibition of NF-κB p65 and COX-2 activation.

  2. 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

  3. Englerin A induces an acute inflammatory response and reveals lipid metabolism and ER stress as targetable vulnerabilities in renal cell carcinoma

    PubMed Central

    Batova, Ayse; Altomare, Diego; Creek, Kim E.; Naviaux, Robert K.; Wang, Lin; Li, Kefeng; Green, Erica; Williams, Richard; Naviaux, Jane C.; Diccianni, Mitchell; Yu, Alice L.

    2017-01-01

    Renal cell carcinoma (RCC) is among the top ten most common forms of cancer and is the most common malignancy of the kidney. Clear cell renal carcinoma (cc-RCC), the most common type of RCC, is one of the most refractory cancers with an incidence that is on the rise. Screening of plant extracts in search of new anti-cancer agents resulted in the discovery of englerin A, a guaiane sesquiterpene with potent cytotoxicity against renal cancer cells and a small subset of other cancer cells. Though a few cellular targets have been identified for englerin A, it is still not clear what mechanisms account for the cytotoxicity of englerin A in RCC, which occurs at concentrations well below those used to engage the targets previously identified. Unlike any prior study, the current study used a systems biology approach to explore the mechanism(s) of action of englerin A. Metabolomics analyses indicated that englerin A profoundly altered lipid metabolism by 24 h in cc-RCC cell lines and generated significant levels of ceramides that were highly toxic to these cells. Microarray analyses determined that englerin A induced ER stress signaling and an acute inflammatory response, which was confirmed by quantitative PCR and Western Blot analyses. Additionally, fluorescence confocal microscopy revealed that englerin A at 25 nM disrupted the morphology of the ER confirming the deleterious effect of englerin A on the ER. Collectively, our findings suggest that cc-RCC is highly sensitive to disruptions in lipid metabolism and ER stress and that these vulnerabilities can be targeted for the treatment of cc-RCC and possibly other lipid storing cancers. Furthermore, our results suggest that ceramides may be a mediator of some of the actions of englerin A. Lastly, the acute inflammatory response induced by englerin A may mediate anti-tumor immunity. PMID:28296891

  4. Englerin A induces an acute inflammatory response and reveals lipid metabolism and ER stress as targetable vulnerabilities in renal cell carcinoma.

    PubMed

    Batova, Ayse; Altomare, Diego; Creek, Kim E; Naviaux, Robert K; Wang, Lin; Li, Kefeng; Green, Erica; Williams, Richard; Naviaux, Jane C; Diccianni, Mitchell; Yu, Alice L

    2017-01-01

    Renal cell carcinoma (RCC) is among the top ten most common forms of cancer and is the most common malignancy of the kidney. Clear cell renal carcinoma (cc-RCC), the most common type of RCC, is one of the most refractory cancers with an incidence that is on the rise. Screening of plant extracts in search of new anti-cancer agents resulted in the discovery of englerin A, a guaiane sesquiterpene with potent cytotoxicity against renal cancer cells and a small subset of other cancer cells. Though a few cellular targets have been identified for englerin A, it is still not clear what mechanisms account for the cytotoxicity of englerin A in RCC, which occurs at concentrations well below those used to engage the targets previously identified. Unlike any prior study, the current study used a systems biology approach to explore the mechanism(s) of action of englerin A. Metabolomics analyses indicated that englerin A profoundly altered lipid metabolism by 24 h in cc-RCC cell lines and generated significant levels of ceramides that were highly toxic to these cells. Microarray analyses determined that englerin A induced ER stress signaling and an acute inflammatory response, which was confirmed by quantitative PCR and Western Blot analyses. Additionally, fluorescence confocal microscopy revealed that englerin A at 25 nM disrupted the morphology of the ER confirming the deleterious effect of englerin A on the ER. Collectively, our findings suggest that cc-RCC is highly sensitive to disruptions in lipid metabolism and ER stress and that these vulnerabilities can be targeted for the treatment of cc-RCC and possibly other lipid storing cancers. Furthermore, our results suggest that ceramides may be a mediator of some of the actions of englerin A. Lastly, the acute inflammatory response induced by englerin A may mediate anti-tumor immunity.

  5. Brain-Derived Neurotrophic Factor Expression in Asthma. Association with Severity and Type 2 Inflammatory Processes.

    PubMed

    Watanabe, Tetsuya; Fajt, Merritt L; Trudeau, John B; Voraphani, Nipasiri; Hu, Haizhen; Zhou, Xiuxia; Holguin, Fernando; Wenzel, Sally E

    2015-12-01

    Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, exists in several isoforms, which differentially impacts neuronal and immune cell survival and differentiation. The role of BDNF and its isoforms in asthma remains unclear. The objectives of this study were to compare the BDNF protein isoforms and specific splice variant expression in sputum and bronchoscopic samples from healthy control subjects and participants with asthma, and to relate these changes to findings in IL-13-stimulated human airway epithelial cells. Sputum and bronchoscopic samples from healthy control subjects and participants with asthma were evaluated for BDNF protein (ELISA and Western blot) and BDNF mRNA (gel and quantitative real-time PCR) in relation to asthma severity and type 2 inflammatory processes. BDNF mRNA was measured in cultured primary human airway epithelial cells after IL-13 stimulation. Total BDNF protein differed among the groups, and its mature isoform was significantly higher in sputum from subjects with severe asthma compared with healthy control subjects (overall P = 0.008, P = 0.027, respectively). Total BDNF was higher in those with elevated fractional exhaled nitric oxide and sputum eosinophilia. In vitro, IL-13 increased BDNF exon VIb splice variant and the ratio to BDNF common exon IX mRNA (P < 0.001, P = 0.003, respectively). Epithelial brushing exon VIb mRNA and total BDNF protein differed among the groups and were higher in subjects with severe asthma than in healthy control subjects (overall P = 0.01, P = 0.02, respectively). The mature BDNF isoform and the exon VIb splice variant are increased in human asthmatic airways. The in vitro increase in response to IL-13 suggests that type 2 cytokines regulate BDNF levels and activity in asthma.

  6. Ethanol extract of Synurus deltoides (Aiton) Nakai suppresses in vitro LPS-induced cytokine production in RAW 264.7 macrophages and in vivo acute inflammatory symptoms

    PubMed Central

    Jiang, Yunyao

    2014-01-01

    Synurus deltoides (Aiton) Nakai, belonging to the Compositae family, is an edible plant widely distributed in Northeast Asia. In this study, we examined the mechanisms underlying the immunomodulative effects of the ethanol extract of S. deltoides (SDE). The SDE extract strongly down-regulated the mRNA expression of the inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumour necrosis factor (TNF)-α, thereby inhibiting the production of nitric oxide (NO), prostaglandin E2 (PGE2), and TNF-α in the lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Furthermore, SDE also suppressed the nuclear translocation of the activation protein (AP)-1 and the nuclear factor-κB (NF-κB), and simultaneously decreased the phosphorylation of extracellular signal-regulated protein kinases (ERK), p38, and Akt. In agreement with the in vitro observations, the orally administered SDE ameliorated the acute inflammatory symptoms in the arachidonic acid-induced ear edema and the EtOH/HCl-induced gastritis in mice. Therefore, S. deltoides have a potential anti-inflammatory capacity in vitro and in vivo, suggesting the potential therapeutic use in the inflammation-associated disorders. PMID:24611100

  7. 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.

  8. Does chronic physical activity level modify the airway inflammatory response to an acute bout of exercise in the post-prandial period?

    PubMed Central

    Kurti, Stephanie P.; Rosenkranz, Sara K.; Chapes, Stephen K.; Teeman, Colby S.; Cull, Brooke J.; Emerson, Sam R.; Levitt, Morton H.; Smith, Joshua R.; Harms, Craig A.

    2017-01-01

    Recent studies have confirmed that a single high-fat meal (HFM) leads to increased airway inflammation. However exercise is a natural anti-inflammatory and may modify post-prandial airway inflammation. The post-prandial airway inflammatory response is likely to be modified by chronic physical activity (PA) level. Purpose To investigate whether chronic PA modifies the airway inflammatory response to an acute bout of exercise in the post-prandial period in both insufficiently active and active subjects. Methods Thirty-nine non-asthmatic subjects (twenty active (ACT), 13M/7F) who exceeded PA guidelines (≥150 min moderate-vigorous PA/week) and (nineteen insufficiently active (IN), 6M/13F) underwent an incremental treadmill test to exhaustion to determine VO2peak. Subjects were then randomized to a condition (COND), either remaining sedentary (CON) or exercising (EX) post-HFM. Exercise was performed at the heart rate corresponding to 60% VO2peak on a treadmill one-hour post-HFM (63% fat, 10kcal/kgbw). Blood lipids and exhaled nitric oxide (eNO: marker of airway inflammation) were measured at baseline, 2 h and 4 h post-HFM. Sputum differential cell counts were performed at baseline and 4 h post-HFM. Results The mean eNO response for all groups increased at 2 h post-HFM (∼6%) and returned to baseline by 4 h (p=0.03). There was a time*COND interaction (p=0.04), where EX had a greater eNO response at 4 hours compared to CON. Sputum neutrophils increased at 4 hours post-HFM (p<0.05). Conclusion These findings suggest that airway inflammation occurs after a HFM when exercise is performed in the postprandial period, regardless of habitual activity level. PMID:28121185

  9. 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

    2014-08-28

    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.

  10. Acute anti-inflammatory activity of four saponins isolated from ivy: alpha-hederin, hederasaponin-C, hederacolchiside-E and hederacolchiside-F in carrageenan-induced rat paw edema.

    PubMed

    Gepdiremen, A; Mshvildadze, V; Süleyman, H; Elias, R

    2005-06-01

    The anti-inflammatory potential of alpha-hederin (monodesmoside) and hederasaponin-C from Hedera helix, and hederacolchisides-E and -F (bidesmosides) from H. colchica was investigated in carrageenan-induced acute paw edema in rats. Saponins and indomethacin were given orally in concentrations of 0.02 and 20mg/kg body wt. For the first phase of acute inflammation, indomethacin was found as the most potent drug. Alpha-hederin and hederasaponin-C were found ineffective, while hederacolchisides-E and -F showed slight anti-inflammatory effects on the first phase. For the second phase of acute inflammation, indomethacin and hederacolchiside-F were determined as very potent compounds. alpha-hederin was found ineffective for the second phase, either. Despite hederasaponin-C and -E were found effective in the second phase of inflammation, they were not found as effective as indomethacin and hederacolchiside-F. As a conclusion, hederasaponin-C, -E and -F, may exert their anti-inflammatory effects by blocking bradykinin or other inflammation mediators. The latter affect may occur via affecting prostaglandin pathways. Regarding the structure activity relationship, it is likely that sugars at C3 position and Rha7-Glcl-6Glc moiety at C28 position are essential for the acute anti-inflammatory effect.

  11. Metabotropic glutamate antagonists alone and in combination with morphine: comparison across two models of acute pain and a model of persistent, inflammatory pain.

    PubMed

    Picker, Mitchell J; Daugherty, Dana; Henry, Fredrick E; Miller, Laurence L; Dykstra, Linda A

    2011-12-01

    The present study examined the effects of the mGluR1 antagonist JNJ16259685 (JNJ) and the mGluR5 antagonist 2-methyl-6-phenylethynylpyridine (MPEP) alone and in combination with morphine in two acute pain models (hotplate, warm water tail-withdrawal), and a persistent, inflammatory pain model (capsaicin). In the hotplate and warm water tail-withdrawal procedures, JNJ and MPEP were ineffective when administered alone. In both procedures, JNJ potentiated morphine antinociception. In the hotplate procedure, MPEP potentiated morphine antinociception at the highest dose examined, whereas in the warm water tail-withdrawal procedure MPEP attenuated morphine antinociception at a moderate dose and potentiated morphine antinociception at a high dose. For both JNJ and MPEP, the magnitude of this morphine potentiation was considerably greater in the hotplate procedure. In the capsaicin procedure, the highest dose of MPEP produced intermediate levels of antihyperalgesia and also attenuated the effects of a dose of morphine that produced intermediate levels of antihyperalgesia. In contrast, JNJ had no effect when administered alone in the capsaicin procedure and did not alter morphine-induced antihyperalgesia. The present findings suggest that the effects produced by mGluR1 and mGluR5 antagonists alone and in combination with morphine can be differentiated in models of both acute and persistent pain.

  12. Anti-inflammatory effect of alpha, beta-Amyrin, a pentacyclic triterpene from Protium heptaphyllum in rat model of acute periodontitis.

    PubMed

    Holanda Pinto, S A; Pinto, L M S; Cunha, G M A; Chaves, M H; Santos, F A; Rao, V S

    2008-02-01

    This study was aimed to evaluate the anti-inflammatory potential of triterpene alpha, beta-amyrin in rats on acute phase periodontitis. Periodontitis was induced by ligature placement around the maxillary right second molar tooth. Rats (n = 8/group) were pretreated with alpha, beta-amyrin (5 and 10 mg/kg, p. o.), two hours before the induction of periodontal inflammation. Sham-operated and positive controls (lumiracoxib and dexamethasone) were included. Six hours later, plasma levels of TNF-alpha were analysed. Rats were sacrificed at 24 h, and the gingival tissue analysed for myeloperoxidase (MPO) and thiobarbituric acid-reactive substances (TBARS), as measures of neutrophil influx and lipid-peroxidation, respectively alpha, beta-Amyrin as well as dexamethasone significantly inhibited the periodontitis-associated increases of TNF-alpha, and the gingival MPO and TBARS. alpha, beta-Amyrin effect was more prominent at 5 mg/kg. Lumiracoxib manifested varied influence on the studied parameters. These results provide evidence to show that alpha, beta-Amyrin retards acute inflammation in rat model of periodontitis and warrant further study on its efficacy to prevent chronic periodontitis-associated bone loss.

  13. Single intrathecal administration of the transcription factor decoy AYX1 prevents acute and chronic pain after incisional, inflammatory, or neuropathic injury.

    PubMed

    Mamet, Julien; Klukinov, Michael; Yaksh, Tony L; Malkmus, Shelle A; Williams, Samantha; Harris, Scott; Manning, Donald C; Taylor, Bradley K; Donahue, Renee R; Porreca, Frank; Xie, Jennifer Y; Oyarzo, Janice; Brennan, Timothy J; Subieta, Alberto; Schmidt, William K; Yeomans, David C

    2014-02-01

    The persistence of pain after surgery increases the recovery interval from surgery to a normal quality of life. AYX1 is a DNA-decoy drug candidate designed to prevent post-surgical pain following a single intrathecal injection. Tissue injury causes a transient activation of the transcription factor EGR1 in the dorsal root ganglia-dorsal horn network, which then triggers changes in gene expression that induce neuronal hypersensitivity. AYX1 is a potent, specific inhibitor of EGR1 activity that mimics the genomic EGR1-binding sequence. Administered in the peri-operative period, AYX1 dose dependently prevents mechanical hypersensitivity in models of acute incisional (plantar), inflammatory (CFA), and chronic neuropathic pain (SNI) in rats. Furthermore, in a knee surgery model evaluating functional measures of postoperative pain, AYX1 improved weight-bearing incapacitance and spontaneous rearing compared to control. These data illustrate the potential clinical therapeutic benefits of AYX1 for preventing the transition of acute to chronic post-surgical pain.

  14. Febrile syndrome of unknown origin: Indications for (18)F-FDG PET/CT in inflammatory and infectious processes.

    PubMed

    García, J R

    2016-09-23

    Fever of unknown origin is defined as a body temperature greater than 38.3°C lasting more than three weeks for which the cause could not be found within one week of hospital admission. More than 200 causes have been reported, and these can be classified into four categories: infections, inflammatory diseases, oncologic processes, and miscellaneous conditions. Noninvasive diagnostic techniques are used in 69.2% of cases and invasive techniques in 30.8%. Structural imaging techniques show the morphological changes from infectious, inflammatory, and tumor-related processes, but they do not allow the detection of the early changes brought about by these processes. The metabolic information provided by (18)F-FDG PET/CT has a promising role in these patients. (18)F-FDG uptake is based on the cells' use of glucose as a source of energy, so it can be observed in infectious, inflammatory, and tumor-related processes. The established non-oncologic indications for (18)F-FDG PET/CT are sarcoidosis, osteomyelitis, spondylodiscitis, fever of unknown origin, and vasculitis, which together account for more than 85% of studies.

  15. 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

  16. 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

  17. Enzymatically-Processed Wheat Bran Enhances Macrophage Activity and Has in Vivo Anti-Inflammatory Effects in Mice

    PubMed Central

    Kang, Hee; Lee, Mi-Gi; Lee, Jae-Kang; Choi, Yong-Hyun; Choi, Yong-Seok

    2016-01-01

    Wheat bran is a rich source of dietary fiber, of which arabinoxylan is the most abundant non-starch polysaccharide. Arabinoxylan has been known to exert in vivo immunological activities. Based on prior findings, we pretreated wheat bran with enzymatic hydrolysis to increase the release of soluble arabinoxylan and investigated whether oral administration of wheat bran altered macrophage activity in a mouse model. After four weeks of treatment, we isolated peritoneal macrophages for phagocytic receptor analysis and lipopolysaccharide (LPS)-induced inflammatory changes. In the second experiment, mice given wheat bran were intraperitoneally stimulated with LPS and serum levels of pro- and anti-inflammatory cytokines were determined. The expression of SRA and CD36, and phagocytic activity increased (p < 0.05, respectively). Ex vivo stimulation of macrophages by LPS resulted in reduced surface expression of CD40 (p < 0.05) and decreased production of nitric oxide (p < 0.005), tumor necrosis factor (TNF)-α (p < 0.005), interleukin (IL)-6 (p < 0.01), and IL-12 (p < 0.05). Mice treated with wheat bran showed decreased levels of serum TNF-α and IL-6 (p < 0.05, respectively) and an increased level of serum anti-inflammatory IL-10 (p < 0.05) in response to intraperitoneal LPS. Enzymatically-processed wheat bran boosts macrophage phagocytic capacity possibly through up-regulation of scavenger receptors and confers anti-inflammatory effects, indicating its potential as an immuno-enhancing functional food. PMID:27043618

  18. 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

  19. Macrophage activation and polarization modify P2X7 receptor secretome influencing the inflammatory process

    PubMed Central

    de Torre-Minguela, Carlos; Barberà-Cremades, Maria; Gómez, Ana I.; Martín-Sánchez, Fátima; Pelegrín, Pablo

    2016-01-01

    The activation of P2X7 receptor (P2X7R) on M1 polarized macrophages induces the assembly of the NLRP3 inflammasome leading to the release of pro-inflammatory cytokines and the establishment of the inflammatory response. However, P2X7R signaling to the NLRP3 inflammasome is uncoupled on M2 macrophages without changes on receptor activation. In this study, we analyzed P2X7R secretome in wild-type and P2X7R-deficient macrophages polarized either to M1 or M2 and proved that proteins released after P2X7R stimulation goes beyond caspase-1 secretome. The characterization of P2X7R-secretome reveals a new function of this receptor through a fine-tuning of protein release. We found that P2X7R stimulation in macrophages is able to release potent anti-inflammatory proteins, such as Annexin A1, independently of their polarization state suggesting for first time a potential role for P2X7R during resolution of the inflammation and not linked to the release of pro-inflammatory cytokines. These results are of prime importance for the development of therapeutics targeting P2X7R. PMID:26935289

  20. Safety Assessment of Commonly Used Nanoparticles in Biomedical Applications: Impact on Inflammatory Processes

    NASA Astrophysics Data System (ADS)

    Alnasser, Yossef

    Nanotechnology offers great promise in the biomedical field. Current knowledge of nanoparticles' (NPs) safety and possible mechanisms of various particle types' toxicity is insufficient. The role of particle properties and the route of particles administration in toxic reactions remain unexplored. In this thesis, we aimed to inspect the interrelationship between particle size, chemical composition and toxicological effects of four candidate NPs for drug delivery systems: gold (Au), chitosan, silica, and poly (lactide-co-glycolide) (PLGA). Mice model was combined with in vitro study to explore NPs' safety. We investigated mice survival, weight, behavior, and pro-inflammatory changes. NF-kappaB induction was assessed in vitro using the Luciferase Assay System. As observed in mice, Au NPs had a higher toxicity profile at a shorter duration than the other NPs. This was significantly in concordance with pro-inflammatory changes which may be the key routes of Au NPs toxicity. Although silica NPs induced NF-kappaB, they were less toxic to the mice than Au NPs and did not lead to the pro-inflammatory changes. Chitosan NPs were toxic to the mice but failed to cause significant NF-kappaB induction and pro-inflammatory changes. These findings indicate that chitosan NPs might not have the same pathophysiologic mechanism as the Au NPs. Comparative analysis in this model demonstrated that PLGA NPs is the safest drug delivery candidate to be administered subcutaneously.

  1. Cognitive Processing Therapy for Acute Stress Disorder Resulting from an Anti-Gay Assault

    ERIC Educational Resources Information Center

    Kaysen, Debra; Lostutter, Ty W.; Goines, Marie A.

    2005-01-01

    This case study describes Cognitive Processing Therapy (CPT) with a 30-year-old gay man with symptoms of acute stress disorder (ASD) following a recent homophobic assault. Treatment addressed assault-related posttraumatic stress disorder symptoms and depressive symptoms. Also addressed were low self-esteem, helplessness, and high degrees of…

  2. Behavioral training promotes multiple adaptive processes following acute hearing loss

    PubMed Central

    Keating, Peter; Rosenior-Patten, Onayomi; Dahmen, Johannes C; Bell, Olivia; King, Andrew J

    2016-01-01

    The brain possesses a remarkable capacity to compensate for changes in inputs resulting from a range of sensory impairments. Developmental studies of sound localization have shown that adaptation to asymmetric hearing loss can be achieved either by reinterpreting altered spatial cues or by relying more on those cues that remain intact. Adaptation to monaural deprivation in adulthood is also possible, but appears to lack such flexibility. Here we show, however, that appropriate behavioral training enables monaurally-deprived adult humans to exploit both of these adaptive processes. Moreover, cortical recordings in ferrets reared with asymmetric hearing loss suggest that these forms of plasticity have distinct neural substrates. An ability to adapt to asymmetric hearing loss using multiple adaptive processes is therefore shared by different species and may persist throughout the lifespan. This highlights the fundamental flexibility of neural systems, and may also point toward novel therapeutic strategies for treating sensory disorders. DOI: http://dx.doi.org/10.7554/eLife.12264.001 PMID:27008181

  3. Usefulness of Serum Procalcitonin Levels in Predicting Tubo-Ovarian Abscess in Patients with Acute Pelvic Inflammatory Disease.

    PubMed

    Erenel, Hakan; Yilmaz, Nevin; Oncul, Mahmut; Acikgoz, Abdullah Serdar; Karatas, Suat; Ayhan, Isil; Aslan, Berna; Tuten, Abdullah

    2016-09-03

    We aimed to investigate the clinical importance of serum procalcitonin (PCT) levels in the diagnosis of tubo-ovarian abscess (TOA). Patients diagnosed with pelvic inflammatory disease (PID; n = 36) and patients diagnosed with TOA (n = 42) were included in the study. Sociodemographic characteristics, laboratory and clinical parameters were compared between the 2 groups. Mean PCT level was higher in the TOA group (p = 0.004). Mean length of stay in hospital was longer in patients with TOA (p < 0.001). White blood cell count, neutrophil count, percentage of neutrophils and C-reactive protein levels were higher than normal limits in all patients; however, no differences in these parameters were observed between the groups. A cutoff level of 0.330 ng/ml for PCT revealed 62% sensitivity and 75% specificity in predicting TOA. Serum PCT is a promising inexpensive marker for the diagnosis of TOA in PID patients.

  4. Acute Δ(9)-tetrahydrocannabinol blocks gastric hemorrhages induced by the nonsteroidal anti-inflammatory drug diclofenac sodium in mice.

    PubMed

    Kinsey, Steven G; Cole, Erica C

    2013-09-05

    Nonsteroidal anti-inflammatory drugs (NSAIDs), which are among the most widely used analgesics in the world, cause gastrointestinal inflammation that is potentially life-threatening. Although inhibitors of endocannabinoid catabolic enzymes protect against gastropathy in fasted NSAID-treated mice, the gastroprotective effects of Δ(9)-tetrahydrocannabinol (THC), the primary psychoactive component of marijuana, have yet to be investigated. Male C57BL/6J mice were fasted, administered vehicle or Δ(9)-THC (.01-50mg/kg; oral or intraperitoneal), and then treated with the NSAID diclofenac sodium (100mg/kg, p.o.) to induce gastric lesions. In separate groups of mice, the cannabimimetic behavioral effects of Δ(9)-THC given via each route of administration were compared using a battery of tests, consisting of assessment of locomotor activity, nociception in the tail withdrawal test, catalepsy in the bar test, and hypothermia. Δ(9)-THC dose-dependently attenuated diclofenac-induced gastric hemorrhagic streaks through both p.o. and i.p. routes of administration (ED50 (95% confidence interval)=0.64 (0.26-1.55)mg/kg and 0.06 (0.01-0.34) mg/kg, respectively). Δ(9)-THC given i.p. was 2-3 orders of magnitude more potent in reducing diclofenac-induced gastric ulcers than in producing locomotor immobility, antinociception, hypothermia, and catalepsy, while the potency of ratio of p.o. Δ(9)-THC between each behavior measure was 7-18. These data indicate that the phytocannabinoid Δ(9)-THC protects against diclofenac-induced gastric inflammatory tissue damage at doses insufficient to cause common cannabinoid side effects.

  5. 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.

  6. Acute Δ9-tetrahydrocannabinol blocks gastric hemorrhages induced by the nonsteroidal anti-inflammatory drug diclofenac sodium in mice

    PubMed Central

    Kinsey, Steven G.; Cole, Erica C.

    2013-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs), which are among the most widely used analgesics in the world, cause gastrointestinal inflammation that is potentially life-threatening. Although inhibitors of endocannabinoid catabolic enzymes protect against gastropathy in fasted NSAID-treated mice, the gastroprotective effects of Δ9-tetrahydrocannabinol (THC), the primary psychoactive component of marijuana, have yet to be investigated. Male C57BL/6J mice were fasted, administered vehicle or Δ9-THC (.01–50 mg/kg; oral or intraperitoneal), and then treated with the NSAID diclofenac sodium (100 mg/kg, p.o.) to induce gastric lesions. In separate groups of mice, the cannabimimetic behavioral effects of Δ9-THC given via each route of administration were compared using a battery of tests, consisting of assessment of locomotor activity, nociception in the tail withdrawal test, catalepsy in the bar test, and hypothermia. Δ9-THC dose-dependently attenuated diclofenac-induced gastric hemorrhagic streaks through both p.o. and i.p. routes of administration (ED50 (95% confidence interval) = 0.64 (0.26 – 1.55) mg/kg and 0.06 (0.01 – 0.34) mg/kg, respectively). Δ9-THC given i.p. was 2–3 orders of magnitude more potent in reducing diclofenac-induced gastric ulcers than in producing locomotor immobility, antinociception, hypothermia, and catalepsy, while the potency of ratio of p.o. Δ9-THC between each behavior measure was 7–18. These data indicate that the phytocannabinoid Δ9-THC protects against diclofenac-induced gastric inflammatory tissue damage at doses insufficient to cause common cannabinoid side effects. PMID:23769745

  7. An overview of the effects of annexin 1 on cells involved in the inflammatory process.

    PubMed

    Kamal, Ahmad M; Flower, Roderick J; Perretti, Mauro

    2005-03-01

    The concept of anti-inflammation is currently evolving with the definition of several endogenous inhibitory circuits that are important in the control of the host inflammatory response. Here we focus on one of these pathways, the annexin 1 (ANXA1) system. Originally identified as a 37 kDa glucocorticoid-inducible protein, ANXA1 has emerged over the last decade as an important endogenous modulator of inflammation. We review the pharmacological effects of ANXA1 on cell types involved in inflammation, from blood-borne leukocytes to resident cells. This review reveals that there is scope for more research, since most of the studies have so far focused on the effects of the protein and its peptido-mimetics on neutrophil recruitment and activation. However, many other cells central to inflammation, e.g. endothelial cells or mast cells, also express ANXA1: it is foreseen that a better definition of the role(s) of the endogenous protein in these cells will open the way to further pharmacological studies. We propose that a more systematic analysis of ANXA1 physio-pharmacology in cells involved in the host inflammatory reaction could aid in the design of novel anti-inflammatory therapeutics based on this endogenous mediator.

  8. Assessment of LED (λ 850 +/- 10 nm) phototherapy in the inflammatory process of rat's TMJ induced by carrageenan

    NASA Astrophysics Data System (ADS)

    de Castro, Isabele C. V.; Rosa, Cristiane B.; Carvalho, Carolina M.; Soares, Luiz Guilherme P.; Cangussu, Maria Cristina T.; dos Santos, Jean N.; Pinheiro, Antônio L. B.

    2015-03-01

    Temporomandibular disorders (TMD) are commonly found in the population and usually involve inflammatory processes. Previous studies have shown positive effects of LED (Light emitting diodes) phototherapies on TMD but its action and mechanism in the inflammatory infiltrate of the temporomandibular joint are still poorly understood. The aim of this study was to assess through histological analysis the effectiveness LED (10 J/cm2, λ850 nm, 100 mW, CW) on the inflammation of the temporomandibular joint of rats induced by carrageenan. Thirty animals were divided in two groups with five animals per subgroup according to the experimental times of two, three and seven days: Inflammation and Inflammation + LED phototherapy. The first irradiation was performed 24 h after induction with an interval of 48 h between sessions. After animal death, specimens were processed and stained with HE and Picrosirius. Then the samples were examined histologically. Data were statistically analyzed. The inflammation group showed mild to moderate chronic inflammatory infiltrate among the bone trabecules of the condyle. Over the time-course of the study in the LED group the condyle showed aspects of normality and absent inflammation in some specimens. In all the time-points, no statistically significant differences were found for collagen deposition in the in the condyle and disc when LED was compared to Inflammation group. LED treated groups also demonstrated a smaller number of the layers of the synovial membrane when compared to the non-irradiated groups. It was concluded that, in general, LED phototherapy resulted in a reduction of inflammatory infiltrate in the temporomandibular joint of rat.

  9. Protective effect of brown Brazilian propolis against acute vaginal lesions caused by herpes simplex virus type 2 in mice: involvement of antioxidant and anti-inflammatory mechanisms.

    PubMed

    Sartori, Gláubia; Pesarico, Ana Paula; Pinton, Simone; Dobrachinski, Fernando; Roman, Silvane Souza; Pauletto, Fernanda; Rodrigues, Luiz Carlos; Prigol, Marina

    2012-01-01

    Propolis has been highlighted for its antioxidant, anti-inflammatory and antiviral properties. The purpose of this study was to investigate if brown Brazilian hydroalcoholic propolis extract (HPE) protects against vaginal lesions caused by herpes simplex virus type 2 (HSV-2) in female BALB/c mice. The treatment was divided in 5 days of pre-treatment with HPE [50 mg · kg(-1), once a day, intragastric (i.g.)], HSV-2 infection [10 µl of a solution 1 × 10(2) plaque-forming unit (PFU · ml(-1) HSV-2), intravaginal inoculation at day 6] and post-treatment with HPE (50 mg · kg(-1)) for 5 days more. At day 11, the animals were killed, and the in vivo analysis (score of lesions) and ex vivo analysis [haematological and histological evaluation; superoxide dismutase (SOD), catalase (CAT) and myeloperoxidase (MPO) activities; reactive species (RS), tyrosine nitration levels, non-protein thiols (NPSH) and ascorbic acid (AA) levels] were carried out. HPE treatment reduced extravaginal lesions and the histological damage caused by HSV-2 infection in vaginal tissues of animals. HPE was able to decrease RS, tyrosine nitration, AA levels and MPO activity. Also, it protected against the inhibition of CAT activity in vaginal tissues of mice. HPE promoted protective effect on HSV-2 infected animals by acting on inflammatory and oxidative processes, and this effect probably is caused by its antioxidant and anti-inflammatory properties.

  10. Variants of CEP68 gene are associated with acute urticaria/angioedema induced by multiple non-steroidal anti-inflammatory drugs.

    PubMed

    Cornejo-García, José Antonio; Flores, Carlos; Plaza-Serón, María C; Acosta-Herrera, Marialbert; Blanca-López, Natalia; Doña, Inmaculada; Torres, María J; Mayorga, Cristobalina; Guéant-Rodríguez, Rosa M; Ayuso, Pedro; Fernández, Javier; Laguna, José J; Agúndez, José A G; García-Martín, Elena; Guéant, Jean-Louis; Canto, Gabriela; Blanca, Miguel

    2014-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are the most consumed drugs worldwide because of their efficacy and utility in the treatment of pain and inflammatory diseases. However, they are also responsible for an important number of adverse effects including hypersensitivity reactions. The most important group of these reactions is triggered by non-immunological, pharmacological mechanisms catalogued under the denomination of cross-intolerance (CRI), with acute urticaria/angioedema induced by multiple NSAIDs (MNSAID-UA) the most frequently associated clinical entity. A recent genome-wide association study identified the gene encoding the centrosomal protein of 68 KDa (CEP68) as the major locus associated with aspirin intolerance susceptibility in asthmatics. In this study, we aimed to assess the role of this locus in susceptibility to CRI to NSAIDs by examining 53 common gene variants in a total of 635 patients that were classified as MNSAID-UA (n = 399), airway exacerbations (n = 110) or blended pattern (n = 126), and 425 controls. We found in the MNSAID-UA group a number of variants (17) associated (lowest p-value = 1.13 × 10(-6)), including the non-synonymous Gly74Ser variant (rs7572857) previously associated with aspirin intolerance susceptibility in asthmatics. Although not being significant in the context of multiple testing, eight of these variants were also associated with exacerbated respiratory disease or blended reactions. Our results suggest that CEP68 gene variants may play an important role in MNSAID-UA susceptibility and, despite the different regulatory mechanisms involved depending on the specific affected organ, in the development of hypersensitivity reactions to NSAIDs.

  11. 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

    Montrucchio, Deise Prehs; Córdova, Marina Machado; Santos, Adair Roberto Soares

    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.

  12. IRF3 is an important molecule in the UII/UT system and mediates immune inflammatory injury in acute liver failure

    PubMed Central

    Liu, Liang-ming; Tu, Wen-juan; Zhu, Tong; Wang, Xiao-ting; Tan, Zhi-li; Zhong, Huan; Gao, De-yong; Liang, Dong-yu

    2016-01-01

    The urotensin II/urotensin receptor (UII/UT) system can mediate inflammatory liver injury in acute liver failure (ALF); however; the related mechanism is not clear. In this study, we confirmed that lipopolysaccharide/D-galactosamine (LPS/D-GalN) induced up-regulation of liver interferon regulatory factor 3 (IRF3) in ALF mice, whereas the UT antagonist urantide inhibited the up-regulated liver IRF3. LPS stimulation induced IRF3 transcription and nuclear translocation and promoted the secretion of interleukin-6 (IL-6), interferon (IFN)-β, and IFN-γ in Kupffer cells (KCs); these effects in LPS-stimulated KCs were inhibited by urantide. Knockdown of IRF3 using an adenovirus expressing an IRF3 shRNA inhibited IFN-β transcription and secretion as well as tumor necrosis factor (TNF)-α and IL-1β secretion from LPS-stimulated KCs; additionally, IL-10 transcription and secretion were promoted in response to LPS. However, LPS-stimulated TNF-α and IL-1β mRNA was not affected in the KCs. The IRF3 shRNA also did not have a significant effect on the NF-κB p65 subunit and p38MAPK protein phosphorylation levels in the nuclei of LPS-stimulated KCs. Therefore, IRF3 expression and activation depended on the signal transduction of the UII/UT system, and played important roles in UII/UT-mediated immune inflammatory injury in the liver but did not affect NF-κB and p38 MAPK activity. PMID:27448985

  13. 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

  14. Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw.

    PubMed

    Costa, Barbara; Colleoni, Mariapia; Conti, Silvia; Parolaro, Daniela; Franke, Chiara; Trovato, Anna Elisa; Giagnoni, Gabriella

    2004-03-01

    Cannabidiol, the major non-psychoactive component of marijuana, has various pharmacological actions of clinical interest. It is reportedly effective as an anti-inflammatory and anti-arthritic in murine collagen-induced arthritis. The present study examined the anti-inflammatory and anti-hyperalgesic effects of cannabidiol, administered orally (5-40 mg/kg) once a day for 3 days after the onset of acute inflammation induced by intraplantar injection of 0.1 ml carrageenan (1% w/v in saline) in the rat. At the end of the treatment prostaglandin E2 (PGE2) was assayed in the plasma, and cyclooxygenase (COX) activity, production of nitric oxide (NO; nitrite/nitrate content), and of other oxygen-derived free radicals (malondialdehyde) in inflamed paw tissues. All these markers were significantly increased following carrageenan. Thermal hyperalgesia, induced by carrageenan and assessed by the plantar test, lasted 7 h. Cannabidiol had a time- and dose-dependent anti-hyperalgesic effect after a single injection. Edema following carrageenan peaked at 3 h and lasted 72 h; a single dose of cannabidiol reduced edema in a dose-dependent fashion and subsequent daily doses caused further time- and dose-related reductions. There were decreases in PGE2 plasma levels, tissue COX activity, production of oxygen-derived free radicals, and NO after three doses of cannabidiol. The effect on NO seemed to depend on a lower expression of the endothelial isoform of NO synthase. In conclusion, oral cannabidiol has a beneficial action on two symptoms of established inflammation: edema and hyperalgesia.

  15. Variants of CEP68 Gene Are Associated with Acute Urticaria/Angioedema Induced by Multiple Non-Steroidal Anti-Inflammatory Drugs

    PubMed Central

    Cornejo-García, José Antonio; Flores, Carlos; Plaza-Serón, María C.; Acosta-Herrera, Marialbert; Blanca-López, Natalia; Doña, Inmaculada; Torres, María J.; Mayorga, Cristobalina; Guéant-Rodríguez, Rosa M.; Ayuso, Pedro; Fernández, Javier; Laguna, José J.; Agúndez, José A. G.; García-Martín, Elena; Guéant, Jean-Louis; Canto, Gabriela; Blanca, Miguel

    2014-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are the most consumed drugs worldwide because of their efficacy and utility in the treatment of pain and inflammatory diseases. However, they are also responsible for an important number of adverse effects including hypersensitivity reactions. The most important group of these reactions is triggered by non-immunological, pharmacological mechanisms catalogued under the denomination of cross-intolerance (CRI), with acute urticaria/angioedema induced by multiple NSAIDs (MNSAID-UA) the most frequently associated clinical entity. A recent genome-wide association study identified the gene encoding the centrosomal protein of 68 KDa (CEP68) as the major locus associated with aspirin intolerance susceptibility in asthmatics. In this study, we aimed to assess the role of this locus in susceptibility to CRI to NSAIDs by examining 53 common gene variants in a total of 635 patients that were classified as MNSAID-UA (n = 399), airway exacerbations (n = 110) or blended pattern (n = 126), and 425 controls. We found in the MNSAID-UA group a number of variants (17) associated (lowest p-value = 1.13×10−6), including the non-synonymous Gly74Ser variant (rs7572857) previously associated with aspirin intolerance susceptibility in asthmatics. Although not being significant in the context of multiple testing, eight of these variants were also associated with exacerbated respiratory disease or blended reactions. Our results suggest that CEP68 gene variants may play an important role in MNSAID-UA susceptibility and, despite the different regulatory mechanisms involved depending on the specific affected organ, in the development of hypersensitivity reactions to NSAIDs. PMID:24618698

  16. Evaluation of the contribution of tannin to the acute pulmonary inflammatory response against inhaled cotton mill dust.

    PubMed Central

    Lauque, D. E.; Hempel, S. L.; Schroeder, M. A.; Hyatt, R. E.; Rohrbach, M. S.

    1988-01-01

    Anesthetized, intubated, and mechanically ventilated rabbits were exposed to aerosolized saline, cotton dust extract (CDE), or tannin for 5 minutes and lavaged 4 hours after exposure. Cell numbers and types present in the bronchoalveolar lavage fluid (BALF) were determined and the concentrations of thromboxane A2 (TxA2) and prostaglandin F2-alpha (PGF2-alpha) in the BALF were also analyzed. The saline control animals had increased numbers and percentage of polymorphonuclear leukocytes (PMN) in the BALF as well as increased levels of TxB2 and PGF2-alpha compared with unexposed animals. Exposure to CDE further increased the number and percentage of PMN and the level of PGF2-alpha but had no effect on TxA2 levels when compared with control animals. Tannin exposure increased PGF2-alpha levels to the same extent as CDE exposure. PMN also increased but to a lesser extent than with CDE. These results indicate that the inflammatory response to CDE is only partially due to the tannin present in CDE. PMID:3177598

  17. Reduction of Acute Inflammatory Effects of Fumed Silica Nanoparticles in the Lung by Adjusting Silanol Display through Calcination and Metal Doping

    PubMed Central

    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

    2015-01-01

    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 (GRAS) for use in food products by the Food and Drug Administration (FDA). 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 (Ti) and aluminum (Al) doping (0–7%), using flame spray pyrolysis (FSP). 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 (BMDMs). Ti- 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

  18. 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

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

    PubMed

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

    2017-04-01

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

  20. Sarcandra glabra combined with lycopene protect rats from lipopolysaccharide induced acute lung injury via reducing inflammatory response.

    PubMed

    Liu, Tian-Yin; Chen, Shi-Biao

    2016-12-01

    Sarcandra glabra (Chinese name, Zhongjiefeng) is an important herb widely used in traditional Chinese medicine. Lycopene has been shown to be a powerful antioxidant. This study aims to test the hypothesis that Sarcandra glabra combined with lycopene protect rats from lipopolysaccharide (LPS) induced acute lung injury (ALI). Metabolomics approach combined with pathological inspection, serum biochemistry examination, enzyme-linked immunosorbent assay and western blotting were used to explore the protective effects of Sarcandra glabra and lycopene on LPS-induced ALI, and to elucidate the underlying mechanisms. Results showed that Sarcandra glabra and lycopene could significantly ameliorate LPS-induced histopathological injuries, improve the anti-oxidative activities of rats, decrease the levels of TNF-α and IL-6, suppress the activations of MAPK and transcription factor NF-κB and reverse the disturbed metabolism towards the normal status. Taken together, this integrated study revealed that Sarcandra glabra combined with lycopene had great potential in protecting rats from LPS-induced ALI, which would be helpful to guide the clinical medication.

  1. 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

  2. Toll-Like Receptor 2 Is Required for Inflammatory Process Development during Leishmania infantum Infection

    PubMed Central

    Sacramento, Laís A.; da Costa, Jéssica L.; de Lima, Mikhael H. F.; Sampaio, Pedro A.; Almeida, Roque P.; Cunha, Fernando Q.; Silva, João S.; Carregaro, Vanessa

    2017-01-01

    Visceral leishmaniasis (VL) is a chronic and fatal disease caused by Leishmania infantum in Brazil. Leukocyte recruitment to infected tissue is a crucial event for the control of infections such as VL. Among inflammatory cells, neutrophils are recruited to the site of Leishmania infection, and these cells may control parasite replication through oxidative or non-oxidative mechanisms. The recruitment, activation and functions of the neutrophils are coordinated by pro-inflammatory cytokines and chemokines during recognition of the parasite by pattern recognition receptors (PRRs). Here, we demonstrated that the Toll-like receptor 2 (TLR2) signaling pathway contributes to the development of the innate immune response during L. infantum infection. The protective mechanism is related to the appropriate recruitment of neutrophils to the inflammatory site. Neutrophil migration is coordinated by DCs that produce CXCL1 and provide a prototypal Th1 and Th17 environment when activated via TLR2. Furthermore, infected TLR2−/− mice failed to induce nitric oxide synthase (iNOS) expression in neutrophils but not in macrophages. In vitro, infected TLR2−/− neutrophils presented deficient iNOS expression, nitric oxide (NO) and TNF-α production, decreased expression of CD11b and reduced L. infantum uptake capacity. The non-responsive state of neutrophils is associated with increased amounts of IL-10. Taken together, these data clarify new mechanisms by which TLR2 functions in promoting the development of the adaptive immune response and effector mechanisms of neutrophils during L. infantum infection. PMID:28280488

  3. The Role of Inflammatory Processes in Occurrence of Left Ventricular Failure in Patients with Chronic Kidney Disease

    PubMed Central

    Shemirani, Hassan; Tavakol, Sara; Atapoor, Abdolamir; Golshahi, Jafar

    2017-01-01

    Background: Recently, the relationship between increased level of inflammatory mediators and occurrence of left ventricular failure in patients with kidney disease has been suggested. The present study attempted to assess relationship between inflammatory mediators and occurrence of left ventricular failure in patients with chronic kidney disease. Materials and Methods: This cross-sectional study was performed at Noor and Hazrat Aliasghar hospital in Isfahan between September 2012 to September 2013 on patients aged >19 years that referred for following their chronic kidney disease. Serum level of inflammatory parameters including C-reactive protein (CRP) and Interleukin-6 (IL-6) was measured using spectrophotometer. All patients were also assessed using M-mode echocardiography to determine left ventricular ejection fraction (LVEF). Results: The group with significant reduced LVEF showed lower GFR when compared to the normal LVEF group (40.73 ± 20.61% versus 44.43 ± 17.98%, P = 0.032). Comparing GFR across the three groups with normal LVEF (>55%), with mild LV dysfunction (LVEF: 45 – 55) those with significant LV dysfunction (LVEF < 45%) showed significantly lower GFR level in latter group compared with normal LVEF and mild LV dysfunction group (P = 0.026). Although the level of serum CRP was significantly higher in patients with significant left ventricular failure than other groups (P = 0.018). Conclusion: Inflammatory processes can potentially affect left ventricular function in patients with chronic kidney disease. In this regard, increased level of CRP may be a main factor for predicting severity of left ventricular failure in these patients. PMID:28299305

  4. Guinea-pig interpubic joint (symphysis pubica) relaxation at parturition: Underlying cellular processes that resemble an inflammatory response

    PubMed Central

    Rodríguez, Horacio A; Ortega, Hugo H; Ramos, Jorge G; Muñoz-de-Toro, Mónica; Luque, Enrique H

    2003-01-01

    Background At term, cervical ripening in coordination with uterine contractions becomes a prerequisite for a normal vaginal delivery. Currently, cervical ripening is considered to occur independently from uterine contractions. Many evidences suggest that cervical ripening resembles an inflammatory process. Comparatively little attention has been paid to the increased flexibility of the pelvic symphysis that occurs in many species to enable safe delivery. The aim of this study was to investigate whether the guinea-pig interpubic joint relaxation process observed during late pregnancy and parturition resembles an inflammatory process. Methods Samples of pubic symphysis were taken from pregnant guinea-pigs sacrificed along gestation, parturition and postpartum. Serial sections of paraffin-embedded tissues were used to measure the interpubic distance on digitalized images, stained with Giemsa to quantify leukocyte infiltration and to describe the vascular area changes, or studied by the picrosirius-polarization method to evaluate collagen remodeling. P4 and E2 serum levels were measured by a sequential immunometric assay. Results Data showed that the pubic relaxation is associated with an increase in collagen remodeling. In addition, a positive correlation between E2 serum levels and the increase in the interpubic distance was found. On the other hand, a leukocyte infiltration in the interpubic tissue around parturition was described, with the presence of almost all inflammatory cells types. At the same time, histological images show an increase in vascular area (angiogenesis). Eosinophils reached their highest level immediately before parturition; whereas for the neutrophilic and mononuclear infiltration higher values were recorded one day after parturition. Correlation analysis showed that eosinophils and mononuclear cells were positively correlated with E2 levels, but only eosinophilic infiltration was associated with collagen remodeling. Additionally, we observed

  5. 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

    2016-03-15

    Acute kidney injury (AKI) is a common complication in sepsis. This study compared the effects of a fish oil-based with a mixed oil fat emulsion on remote renal injury in an antibiotic-treated septic murine model. Mice were randomly assigned to a normal control (NC) group and three septic groups. Sepsis was induced by cecal ligation and puncture (CLP). The antibiotic was injected intraperitoneally (IP) after CLP and then daily till the time of sacrifice. Three hours after antibiotic treatment, one of the septic groups was injected IP with a fish oil-based emulsion (FO), while the other two groups were given either a mixed oil emulsion (MO) or saline (SC). The septic groups were further divided into two separate time groups, with blood and kidneys samples collected at 24 h or 72 h post-CLP. The results showed that sepsis leads to the activation of neutrophils, T helper (Th)1/Th-2/Th-17 and Treg cells (p < 0.05). Plasma NGAL and mRNA expressions of renal MyD88 and TLR4 were also enhanced (p < 0.05). Compared to the SC group, the group given the fish oil-based emulsion had decreased plasma NGAL by 22% and Treg by 33%. Furthermore, renal gene expressions of MyD88 and TLR4 reduced by 46% and 62%, respectively, whereas heat shock protein 70 and peroxisome proliferator-activated receptor-γ increased by 158% and 69%, respectively (p < 0.05), at Day 3 after CLP. These results suggest that administration of a fish oil-based emulsion has favorable effects, maintaining blood T cell percentage, downregulating Treg expression, attenuating systemic and local inflammation and offering renal protection under conditions of antibiotic-treated polymicrobial sepsis.

  6. 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.

  7. An acute inflammatory response alters bone homeostasis, body composition, and the humoral immune response of broiler chickens.

    PubMed

    Mireles, A J; Kim, S M; Klasing, K C

    2005-04-01

    To quantify the effects of an acute phase response in broilers, chicks were injected with 1 mg/kg Escherichia coli lipopolysaccharide (LPS) at 15 and 23 d. Lipopolysaccharide injection increased feed/gain (P = 0.03), increased liver weight (P = 0.09), and decreased tibia calcium (P = 0.05) and breaking strength (P < 0.04) by d 28. In a second experiment, 3 d postinjection of chicks at d 31, LPS decreased BW (P < 0.01), breast weight (P = 0.08), and tibia breaking strength (P = 0.05), and increased liver weight (P < 0.01), mortality (P = 0.05), and titers to bronchitis and Mycoplasma gallisepticum that were induced by vaccination at hatch or by field exposure, respectively (P = 0.04). For experiment 3, chicks were challenged with LPS at 23d and 27d. Lipopolysaccharide-injected chicks had decreased BW (P = 0.06), feed consumption (P = 0.05), tibia weight (P< 0.01), and breaking strength (P < 0.01), and increased feed/gain (P < 0.01), liver weight (P < 0.01), and plasma ionized calcium level (P = 0.08). For experiment 4, chicks were injected with 0, 0.33, 0.66, 1.00, or 4.25 mg of LPS/kg of BW. There was an inverse relationship between LPS level and BW or bone breaking strength. Experiment 5 compared 4 broiler strains. Strain x LPS interactions were found for bone breaking strength (P = 0.01). Mortality before LPS challenge was inversely correlated to liver weight (r2 = 0.95, P = 0.02) and bone breaking strength (r2 = 0.99, P = 0.01) only after an LPS challenge.

  8. Vaginal Heparan Sulfate Linked to Neutrophil Dysfunction in the Acute Inflammatory Response Associated with Experimental Vulvovaginal Candidiasis

    PubMed Central

    Yano, Junko; Noverr, Mairi C.

    2017-01-01

    ABSTRACT Despite acute inflammation by polymorphonuclear neutrophils (PMNs) during vulvovaginal candidiasis (VVC), clearance of Candida fails to occur. The purpose of this study was to uncover the mechanism of vaginal PMN dysfunction. Designs included assessing PMN migration, proinflammatory mediators, and tissue damage (by analysis of the activity of lactate dehydrogenase [LDH]) in mice susceptible (C3H/HeN-C57BL/6) or resistant (CD-1) to chronic VVC (CVVC-S or CVVC-R) and testing morphology-specific Candida albicans strains under conditions of preinduced PMN migration (CVVC-S mice) or PMN depletion (CVVC-R mice). In vitro designs included evaluation of C. albicans killing by elicited vaginal or peritoneal PMNs in standard or vaginal conditioned medium (VCM). Results showed that despite significant migration of PMNs and high levels of vaginal beta interleukin-1 (IL-1β) and alarmin S100A8, CVVC-S mice failed to reduce vaginal fungal burden irrespective of morphology or whether PMNs were present pre- or postinoculation, and had high LDH levels. In contrast, CVVC-R mice had reduced fungal burden and low LDH levels following PMN recruitment and IL-1β/S100A8 production, but maintained colonization in the absence of PMNs. Elicited vaginal and peritoneal PMNs showed substantial killing activity in standard media or VCM from CVVC-R mice but not in VCM from CVVC-S mice. The inhibitory effect of VCM from CVVC-S mice was unaffected by endogenous or exogenous estrogen and was ablated following depletion/neutralization of Mac-1 ligands using Mac-1+/+ PMNs or recombinant Mac-1. Heparan sulfate (HS) was identified as the putative inhibitor as evidenced by the rescue of PMN killing following heparanase treatment of VCM, as well as by inhibition of killing by purified HS. These results suggest that vaginal HS is linked to PMN dysfunction in CVVC-S mice as a competitive ligand for Mac-1. PMID:28292981

  9. Comparative expression profile of NOD1/2 and certain acute inflammatory cytokines in thermal-stressed cell culture model of native and crossbred cattle

    NASA Astrophysics Data System (ADS)

    Bhanuprakash, V.; Singh, Umesh; Sengar, Gyanendra Singh; Raja, T. V.; Sajjanar, Basavraj; Alex, Rani; Kumar, Sushil; Alyethodi, R. R.; Kumar, Ashish; Sharma, Ankur; Kumar, Suresh; Bhusan, Bharat; Deb, Rajib

    2016-11-01

    Thermotolerance depends mainly on the health and immune status of the animals. The variation in the immune status of the animals may alter the level of tolerance of animals exposed to heat or cold stress. The present study was conducted to investigate the expression profile of two important nucleotide binding and oligomerization domain receptors (NLRs) (NOD1 and NOD2) and their central signalling molecule RIP2 gene during in vitro thermal-stressed bovine peripheral blood mononuclear cells (PBMCs) of native (Sahiwal) and crossbred (Sahiwal X HF) cattle. We also examined the differential expression profile of certain acute inflammatory cytokines in in vitro thermal-stressed PBMC culture among native and its crossbred counterparts. Results revealed that the expression profile of NOD1/2 positively correlates with the thermal stress, signalling molecule and cytokines. Present findings also highlighted that the expression patterns during thermal stress were comparatively superior among indigenous compared to crossbred cattle which may add references regarding the better immune adaptability of Zebu cattle.

  10. Early Electrodiagnostic Features of Upper Extremity Sensory Nerves Can Differentiate Axonal Guillain-Barré Syndrome from Acute Inflammatory Demyelinating Polyneuropathy

    PubMed Central

    Koo, Yong Seo; Shin, Ha Young; Kim, Jong Kuk; Nam, Tai-Seung; Shin, Kyong Jin; Bae, Jong-Seok; Suh, Bum Chun; Oh, Jeeyoung; Yoon, Byeol-A

    2016-01-01

    Background and Purpose Serial nerve conduction studies (NCSs) are recommended for differentiating axonal and demyelinating Guillain-Barré syndrome (GBS), but this approach is not suitable for early diagnoses. This study was designed to identify possible NCS parameters for differentiating GBS subtypes. Methods We retrospectively reviewed the medical records of 70 patients with GBS who underwent NCS within 10 days of symptom onset. Patients with axonal GBS and acute inflammatory demyelinating polyneuropathy (AIDP) were selected based on clinical characteristics and serial NCSs. An antiganglioside antibody study was used to increase the diagnostic certainty. Results The amplitudes of median and ulnar nerve sensory nerve action potentials (SNAPs) were significantly smaller in the AIDP group than in the axonal-GBS group. Classification and regression-tree analysis revealed that the distal ulnar sensory nerve SNAP amplitude was the best predictor of axonal GBS. Conclusions Early upper extremity sensory NCS findings are helpful in differentiating axonal-GBS patients with antiganglioside antibodies from AIDP patients. PMID:27819421

  11. Detoxification of Abrus precatorius L. seeds by Ayurvedic Shodhana process and anti-inflammatory potential of the detoxified extract

    PubMed Central

    Dhoble, Sagar B.; Majumdar, Anuradha S.

    2014-01-01

    Background: Abrus precatorius seeds traditionally used for the treatment of sciatica and alopecia contains the toxic protein, abrin, a Type II Ribosome Inactivating Protein. Ayurveda recommends the use of Abrus seeds after the Shodhana process (detoxification). Objective: The current study was aimed at performing the Shodhana process, swedana (boiling) of Abrus precatorius seeds using water as a medium and to evaluate the anti-inflammatory potential of seed extract post detoxification. Materials and Methods: Non-detoxified and detoxified extracts were prepared and subsequently subjected to various in vitro and in vivo assays. In hemagglutination assay, the non-detoxified extract shows higher agglutination of RBCs than detoxified extract indicating riddance of toxic hemagglutinating proteins by Shodhana. This was confirmed by the SDSPAGE analysis of detoxified extract revealing the absence of abrin band in detoxified extract when compared to non-detoxified extract. Results: The cytotoxicity assay in HeLa cell line expresses a higher reduction in growth percentage of the cells with non-detoxified extract as compared to detoxified extract indicating successful detoxification. Brine shrimp lethality test indicated the reduction in toxicity index of detoxified extract as compared to non-detoxified extract. Further, the whole body apoptosis assay in zebrafish revealed that percentage of viable cells were greater for detoxified extract than non-detoxified extract. The anti-inflammatory studies using carrageenan induced paw edema model in rats was carried out on the extracts with doses of 100 mg/kg and 200 mg/kg, per oral, where the detoxified extract exhibited significant inhibition of rat paw edema at both the doses comparable to that of Diclofenac sodium. Conclusion: Absence of toxicity and the retention of the anti-inflammatory activity of detoxified Abrus seed extract confirmed that the Swedana process is effective in carrying out the detoxification without affecting

  12. Lactobacillus acidophilus ATCC 4356 attenuates the atherosclerotic progression through modulation of oxidative stress and inflammatory process.

    PubMed

    Chen, Lihua; Liu, Wenen; Li, Yanming; Luo, San; Liu, Qingxia; Zhong, Yiming; Jian, Zijuan; Bao, Meihua

    2013-09-01

    The aim of this study was to investigate the effect of Lactobacillus (L.) acidophilus ATCC 4356 on the progression of atherosclerosis in Apoliprotein-E knockout (ApoE(-/-)) mice and the underlying mechanisms. Eight week-old ApoE(-/-) mice were treated with L. acidophilus ATCC 4356 daily for 12 weeks. The wild type (WT) mice or ApoE(-/-) mice in the vehicle group were treated with saline only. Body weights, serum lipid levels, aortic atherosclerotic lesions, and tissue oxidative and inflammatory statuses were examined among the groups. As compared to ApoE(-/-) mice in the vehicle group, ApoE(-/-) mice treated with L. acidophilus ATCC 4356 had no changes in body weights and serum lipid profiles, but showed decreased atherosclerotic lesion size in en face aorta. In comparison with WT mice, ApoE(-/-) mice in the vehicle group showed higher levels of serum malondialdehyde (MDA), oxidized low density lipoprotein (oxLDL) and tumor necrosis factor-alpha (TNF-α), but lower levels of interleukin-10 (IL-10) and superoxide dismutase (SOD) activities in serum. Administration of L. acidophilus ATCC 4356 could reverse these trends in a dose-dependent manner in ApoE(-/-) mice. Furthermore, ApoE(-/-) mice treated with L. acidophilus ATCC 4356 showed an inhibition of translocation of NF-κB p65 from cytoplasm to nucleus, suppression of degradation of aortic IκB-α, and improvements of gut microbiota distribution, as compared to ApoE(-/-) mice in the vehicle group. Our findings suggest that administration of L. acidophilus ATCC 4356 can attenuate the development of atherosclerotic lesions in ApoE(-/-) mice through reducing oxidative stress and inflammatory response.

  13. [Influence of immunocorrection on the inflammatory process in the urogenital tract in men with infertility].

    PubMed

    Tsiporenko, S Iu

    2013-01-01

    We studied the concentration of metalloproteinases, pro-and anti-inflammatory cytokines, lymphocyte activation markers in seminal plasma of men with oligosymptomatic forms of chronic inflammation of the urogenital tract complicated with infertility. It was shown that chronic inflammation of the urogenital tract shifts the levels of cytokine profile, reduces the concentration of metalloproteinase-2 (576.4 +/- 89.3 ng/ml, P < 0.001), chemokines - fractalkine (16.3 +/- 1.3 pg/ml, P < 0.001) and chemmmokine regulated by activation, expression and secretion of normal T-cells (RANTES (12.7 +/- 1.0 pg/ ml, P < 0.001). Additionally, we observed a sharp increase in IL-8 (215.5 +/- 7.8 pg/ml, P < 0.01), MCP-1 (926.4 +/- 30.2 pg/ml, P < 0.001) and elevation of the CD25 + / CD95 + ratio. These observations point for alterations in apoptotic mechanisms in pathological forms of the generative cells and their accumulation in the sperm. Prolonged inflammation of the genital area is accompanied by depletion of the local immune system resulting in the development of infertility. The multidirectional shifts in IL-10/IL-12 index have been established: an increase in the group of patients with elevated level of hypercapitated spermatozoa and its reduction in microsomatic morphotype of spermatozoa. These data emphasize the importance of the microenvironment in maturation of gametes. It was shown that an inclusion of alfagin and gepatomax in immunorehabilitation of men with oligosymptomatic forms of urogenital infections improves leukocyte subpopulation content of sperm and concentrations of pro-and anti-inflammatory cytokines, and therefore, results in an increase in fertilizing potential.

  14. Six weeks of voluntary wheel running modulates inflammatory protein (MCP-1, IL-6, and IL-10) and DAMP (Hsp72) responses to acute stress in white adipose tissue of lean rats.

    PubMed

    Speaker, Kristin J; Cox, Stewart S; Paton, Madeline M; Serebrakian, Arman; Maslanik, Thomas; Greenwood, Benjamin N; Fleshner, Monika

    2014-07-01

    To prime local tissues for dealing with potential infection or injury, exposure to an acute, intense stressor evokes increases in circulating and local tissue inflammatory proteins. Regular physical activity facilitates stress-evoked innate reactivity and modulates the expression of inflammatory proteins in immuno-metabolic tissues such as white adipose tissue (WAT). The impact of regular physical activity on stress-evoked inflammatory protein expression in WAT, however, remains unclear. To investigate this question, lean male F344 rats (150-175g) were allowed voluntary access to a running wheel for 6weeks followed by exposure to an acute stressor (100, 1.5mA-5s inescapable tail shocks). Using ELISAs, corticosterone, heat shock protein 72 (Hsp72), macrophage chemoattractant protein (MCP-1), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, and IL-10 concentrations were measured in plasma and subcutaneous, intraperitoneal (epididymal and retroperitoneal WAT depots) and visceral (omental and mesenteric WAT depots) WAT compartments. Acute stress increased plasma concentrations of all proteins except TNF-α and, depending upon the compartment examined, WAT concentrations of MCP-1, IL-1β, IL-6, and IL-10. Exercise ubiquitously increased IL-1β within WAT, potentiated stress-evoked Hsp72 in plasma and WAT, and differentially increased stress-evoked MCP-1, IL-6, and IL-10 within WAT. These data suggest: (a) inflammatory proteins in non-obese WAT may serve compartment-specific immune and metabolic roles important to the acute stress response and; (b) voluntary habitual exercise may optimize stress-induced augmentation of innate immune function through increases in stress-evoked Hsp72, MCP-1, IL-6, and IL-10 and decreases in IL-1β/IL10 and TNF-α/IL10 ratios within white adipose tissue.

  15. Effects of lovastatin and pravastatin on amyloid processing and inflammatory response in TgCRND8 brain.

    PubMed

    Chauhan, Neelima B; Siegel, George J; Feinstein, Douglas L

    2004-10-01

    Previous studies suggest that treatment with statins reduce beta amyloid (Abeta) deposition in brains of mouse models of Alzheimer's disease (AD) and may reduce the prevalence of AD in humans. Since lipophilicity influences the biological efficacy of statins, we compared the effects of lovastatin, a lipophilic statin, to effects of the hydrophilic pravastatin on amyloid processing and inflammatory responses in brain. Three-month old TgCRND8 mice expressing mutant human amyloid precursor protein (mHuAPP) were treated daily with various doses of either statin. After 1 month, levels of cerebral soluble and fibrillar Abeta peptides, soluble sAPPalpha, and inflammatory cytokines were measured. Both statins caused dose-dependent reductions in total Abeta peptides with parallel increases in total sAPPalpha. At all doses, slightly greater effects were observed with lovastatin than with pravastatin. In contrast, only lovastatin significantly increased levels of IL-1beta and of TNFalpha in a dose-dependent manner. Lovastatin, but not pravastatin, decreased succinic dehydrogenase and increased lactate dehydrogenase activities in skeletal muscle and increased TUNEL staining in liver. Our data demonstrate that both statins shift the balance of APP processing from excessive beta-toward the normal alpha-cleavage while reducing the total amyloid burden in TgCRND8 brain and that lovastatin, but not pravastatin, potentiates cerebral inflammation and is associated with liver and muscle histotoxicity in these animals. These data show that pravastatin can reduce amyloid burden without potentiating inflammatory responses in brain and, therefore, may have a wider dose-range of safety than have lipophilic statins in the treatment or prevention of AD.

  16. Differences in the Cellular Response to Acute Spinal Cord Injury between Developing and Mature Rats Highlights the Potential Significance of the Inflammatory Response

    PubMed Central

    Sutherland, Theresa C.; Mathews, Kathryn J.; Mao, Yilin; Nguyen, Tara; Gorrie, Catherine A.

    2017-01-01

    There exists a trend for a better functional recovery from spinal cord injury (SCI) in younger patients compared to adults, which is also reported for animal studies; however, the reasons for this are yet to be elucidated. The post injury tissue microenvironment is a complex milieu of cells and signals that interact on multiple levels. Inflammation has been shown to play a significant role in this post injury microenvironment. Endogenous neural progenitor cells (NPC), in the ependymal layer of the central canal, have also been shown to respond and migrate to the lesion site. This study used a mild contusion injury model to compare adult (9 week), juvenile (5 week) and infant (P7) Sprague-Dawley rats at 24 h, 1, 2, and 6 weeks post-injury (n = 108). The innate cells of the inflammatory response were examined using counts of ED1/IBA1 labeled cells. This found a decreased inflammatory response in the infants, compared to the adult and juvenile animals, demonstrated by a decreased neutrophil infiltration and macrophage and microglial activation at all 4 time points. Two other prominent cellular contributors to the post-injury microenvironment, the reactive astrocytes, which eventually form the glial scar, and the NPC were quantitated using GFAP and Nestin immunohistochemistry. After SCI in all 3 ages there was an obvious increase in Nestin staining in the ependymal layer, with long basal processes extending into the parenchyma. This was consistent between age groups early post injury then deviated at 2 weeks. The GFAP results also showed stark differences between the mature and infant animals. These results point to significant differences in the inflammatory response between infants and adults that may contribute to the better recovery indicated by other researchers, as well as differences in the overall injury progression and cellular responses. This may have important consequences if we are able to mirror and manipulate this response in patients of all ages; however

  17. 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

  18. Neurogenic markers of the inflammatory process in atopic dermatitis: relation to the severity and pruritus

    PubMed Central

    Czarnecka-Operacz, Magdalena; Jenerowicz, Dorota; Silny, Wojciech

    2013-01-01

    Introduction Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease, characterized by eczematous skin lesions and intensive pruritus. Recent studies have shed light on the role of the nervous system in the pathogenesis of AD. It can influence the course of the disease through an altered pattern of cutaneous innervation and abnormal expression of neuropeptides in the lesional skin. Aim The aim of the study was to evaluate plasma concentrations of the nerve growth factor (NGF), substance P (SP) and vasoactive intestinal peptide (VIP) in AD patients in comparison to two control groups (healthy volunteers and patients suffering from psoriasis). Correlations between plasma levels of evaluated parameters, severity of the disease and selected clinical parameters (skin prick tests, total and antigen specific IgE levels) were also analysed. Material and methods Seventy-five patients with AD, 40 patients with psoriasis and 40 healthy volunteers were included into the study. Patients with AD included 52 persons suffering from an extrinsic and 23 from an intrinsic type of the disease. The severity of skin lesions was assessed with SCORAD index. Pruritus was evaluated on the basis of the questionnaire assessing the extent, frequency and intensity of pruritus. Commercial enzyme-linked immunosorbent assays (SP, NGF: R&D Systems; and VIP: Phoenix Pharmaceuticals) were used to assess the neuropeptide and NGF plasma levels. Results Nerve growth factor and VIP plasma concentrations were significantly higher in AD patients compared to psoriatic patients and healthy subjects. Substance P plasma concentrations were elevated in the extrinsic type of AD and psoriasis comparing to healthy volunteers. There were no statistically significant differences in NGF, SP and VIP plasma concentrations between the extrinsic and intrinsic type of AD. There was also no correlation between plasma levels of evaluated parameters (NGF, SP, VIP) and SCORAD index in both types of AD

  19. Effect of acute sleep deprivation and recovery on Insulin-like Growth Factor-I responses and inflammatory gene expression in healthy men.

    PubMed

    Chennaoui, Mounir; Drogou, Catherine; Sauvet, Fabien; Gomez-Merino, Danielle; Scofield, Denis E; Nindl, Bradley C

    2014-01-01

    Acute sleep deprivation in humans has been found to increase inflammatory markers and signaling pathways in the periphery through a possible Toll-like receptor 4 (TLR-4). In addition, short duration sleep has been associated with low circulating total Insulin-like Growth Factor-I (IGF-I) concentrations. We aimed to determine whether a total sleep deprivation (TSD) protocol with recovery altered whole-blood gene expression of the proinflammatory cytokines TNF-α and IL-6, as well as TLR-4 expression, and to examine the relationship with circulating concentrations of the IGF-I system. Twelve healthy men participated in a five-day TSD (two control nights followed by one night of sleep deprivation and one night of recovery). Blood was sampled at 0800, before and after sleep deprivation (D2 and D4), and after recovery (D5). It is shown that 25 h of sleep deprivation (D4) induced significant increases in mRNA levels of TNF-α and its soluble receptor R1 (P<0.01 respectively), as well as TLR-4 (P<0.05), while IL-6 mRNA levels remained unchanged. Circulating concentrations of free IGF-I were decreased at D4 (P<0.001). One night of recovery was sufficient to restore basal expression levels for TNF-α, sTNF-R1, TLR-4 and circulating IGF-I. Changes in TLR-4 mRNA levels during the protocol correlated positively with those of TNF-α and sTNF-R1 (r=0.393 and r=0.490 respectively), and negatively with circulating free IGF-I (r=-0.494). In conclusion, 25 h of sleep deprivation in healthy subjects is sufficient to induce transient and reversible genomic expression of the pro-inflammatory cytokine TNF-α and its R1 receptor, and its mediator TLR-4, with a possible link to IGF-I axis inhibition.

  20. 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

  1. 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

  2. Deferoxamine attenuates lipid peroxidation, blocks interleukin-6 production, ameliorates sepsis inflammatory response syndrome, and confers renoprotection after acute hepatic ischemia in pigs.

    PubMed

    Vlahakos, Demetrios; Arkadopoulos, Nikolaos; Kostopanagiotou, Georgia; Siasiakou, Sofia; Kaklamanis, Loukas; Degiannis, Dimitrios; Demonakou, Maria; Smyrniotis, Vassilios

    2012-04-01

    We have previously shown that deferoxamine (DFO) infusion protected myocardium against reperfusion injury in patients undergoing open heart surgery, and reduced brain edema, intracranial pressure, and lung injury in pigs with acute hepatic ischemia (AHI). The purpose of this research was to study if DFO could attenuate sepsis inflammatory response syndrome (SIRS) and confer renoprotection in the same model of AHI in anesthetized pigs. Fourteen animals were randomly allocated to two groups. In the Group DFO (n=7), 150mg/kg of DFO dissolved in normal saline was continuously infused in animals undergoing hepatic devascularization and portacaval anastomosis. The control group (Group C, n=7) underwent the same surgical procedure and received the same volume of normal saline infusion. Animals were euthanized after 24h. Hematological, biochemical parameters, malondialdehyde (MDA), and cytokines (interleukin [IL]-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α) were determined from sera obtained at baseline, at 12h, and after euthanasia. Hematoxylin-eosin and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling were used to evaluate necrosis and apoptosis, respectively, in kidney sections obtained after euthanasia. A rapid and substantial elevation (more than 100-fold) of serum IL-6 levels was observed in Group C reaching peak at the end of the experiment, associated with increased production of oxygen free radicals and lipid peroxidation (MDA 3.2±0.1nmol/mL at baseline and 5.5±0.9nmol/mL at the end of the experiment, P<0.05) and various manifestations of SIRS and multiple organ dysfunction (MOD), including elevation of high-sensitivity C-reactive protein, severe hypotension, leukocytosis, thrombocytopenia, hypoproteinemia, and increased serum levels of lactate dehydrogenase (fourfold), alkaline phosphatase (fourfold), alanine aminotransferase (14-fold), and ammonia (sevenfold). In sharp contrast, IL-6 production and lipid

  3. Acute lacunar infarcts in CLIPPERS: is the chronic infiltrative lymphocytic perivascular disease process to blame?

    PubMed

    Saigal, Gaurav; Quencer, Robert

    2013-12-01

    CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is a recently described chronic inflammatory disorder involving the brainstem with characteristic imaging findings. Since it was originally described in 2002, only a handful of cases have been reported in the literature. We describe two additional cases of CLIPPERS with characteristic clinical and radiological findings. Besides the previously described MR findings, one of the cases also demonstrated multiple basal ganglia lacunar infarcts, a finding which has not been previously reported. We hypothesize that the lacunar infarcts are caused by this chronic infiltrative perivascular disease process.

  4. Acute Lacunar Infarcts in CLIPPERS: Is the Chronic Infiltrative Lymphocytic Perivascular Disease Process to Blame?

    PubMed Central

    Saigal, Gaurav; Quencer, Robert

    2013-01-01

    Summary CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is a recently described chronic inflammatory disorder involving the brainstem with characteristic imaging findings. Since it was originally described in 2002, only a handful of cases have been reported in the literature. We describe two additional cases of CLIPPERS with characteristic clinical and radiological findings. Besides the previously described MR findings, one of the cases also demonstrated multiple basal ganglia lacunar infarcts, a finding which has not been previously reported. We hypothesize that the lacunar infarcts are caused by this chronic infiltrative perivascular disease process. PMID:24355180

  5. Abarema cochliacarpos extract decreases the inflammatory process and skeletal muscle injury induced by Bothrops leucurus venom.

    PubMed

    Saturnino-Oliveira, Jeison; Santos, Daiana Do Carmo; Guimarães, Adriana Gibara; Santos Dias, Antônio; Tomaz, Marcelo Amorim; Monteiro-Machado, Marcos; Estevam, Charles Santos; De Lucca Júnior, Waldecy; Maria, Durvanei Augusto; Melo, Paulo A; Araújo, Adriano Antunes de Souza; Santos, Márcio Roberto Viana; Almeida, Jackson Roberto Guedes da Silva; Oliveira, Rita de Cássia Meneses; Pereira de Oliveira, Aldeidia; Quintans Júnior, Lucindo José

    2014-01-01

    Snakebites are a public health problem, especially in tropical countries. However, treatment with antivenom has limited effectiveness against venoms' local effects. Here, we investigated the ability of Abarema cochliacarpos hydroethanolic extract (EAc) to protect mice against injection of Bothrops leucurus venom. Swiss mice received perimuscular venom injection and were subsequently treated orally with EAc in different doses. Treatment with EAc 100, 200, and 400 mg/kg reduced the edema induced by B. leucurus in 1%, 13%, and 39%, respectively. Although lower doses showed no antihypernociceptive effect in the Von Frey test, the higher dose significantly reduced hyperalgesia induced by the venom. Antimyotoxic activity of EAc was also observed by microscopy assessment, with treated muscles presenting preserved structures, decreased edema, and inflammatory infiltrate as compared to untreated ones. Finally, on the rotarod test, the treated mice showed better motor function, once muscle fibers were preserved and there were less edema and pain. Treated mice could stand four times more time on the rotating rod than untreated ones. Our results have shown that EAc presented relevant activities against injection of B. leucurus venom in mice, suggesting that it can be considered as an adjuvant in the treatment of envenomation.

  6. Abarema cochliacarpos Extract Decreases the Inflammatory Process and Skeletal Muscle Injury Induced by Bothrops leucurus Venom

    PubMed Central

    Saturnino-Oliveira, Jeison; Santos, Daiana Do Carmo; Guimarães, Adriana Gibara; Santos Dias, Antônio; Tomaz, Marcelo Amorim; Monteiro-Machado, Marcos; Estevam, Charles Santos; Lucca Júnior, Waldecy De; Maria, Durvanei Augusto; Melo, Paulo A.; Araújo, Adriano Antunes de Souza; Santos, Márcio Roberto Viana; Almeida, Jackson Roberto Guedes da Silva; Oliveira, Rita de Cássia Meneses; Pereira de Oliveira, Aldeidia; Quintans Júnior, Lucindo José

    2014-01-01

    Snakebites are a public health problem, especially in tropical countries. However, treatment with antivenom has limited effectiveness against venoms' local effects. Here, we investigated the ability of Abarema cochliacarpos hydroethanolic extract (EAc) to protect mice against injection of Bothrops leucurus venom. Swiss mice received perimuscular venom injection and were subsequently treated orally with EAc in different doses. Treatment with EAc 100, 200, and 400 mg/kg reduced the edema induced by B. leucurus in 1%, 13%, and 39%, respectively. Although lower doses showed no antihypernociceptive effect in the Von Frey test, the higher dose significantly reduced hyperalgesia induced by the venom. Antimyotoxic activity of EAc was also observed by microscopy assessment, with treated muscles presenting preserved structures, decreased edema, and inflammatory infiltrate as compared to untreated ones. Finally, on the rotarod test, the treated mice showed better motor function, once muscle fibers were preserved and there were less edema and pain. Treated mice could stand four times more time on the rotating rod than untreated ones. Our results have shown that EAc presented relevant activities against injection of B. leucurus venom in mice, suggesting that it can be considered as an adjuvant in the treatment of envenomation. PMID:25136627

  7. 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.

  8. Osthole ameliorates acute myocardial infarction in rats by decreasing the expression of inflammatory-related cytokines, diminishing MMP-2 expression and activating p-ERK.

    PubMed

    Duan, Juan; Yang, Yu; Liu, Hong; Dou, Peng-Cheng; Tan, Sheng-Yu

    2016-01-01

    Osthole, the active constituent of Cnidium monnieri extracts, has been shown to have a diverse range of pharmacological properties. In the present study, we aimed to evaluate the cardioprotective effects of osthole in a rat model of acute myocardial infarction (AMI). The rats with AMI were treated with 1, 3 and 10 mg/kg of osthole or the vehicle for 4 weeks. The infarct size of the rats with AMI was measured, and casein kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) activities in the rats with AMI were analyzed using commercially available kits. The nuclear factor-κB (NF-κB), tumor necrosis factor‑α (TNF-α), interleukin (IL)-1β and IL-6 levels in whole blood from rats with AMI were also detected using commercially available kits. The levels of Toll-like receptors 2/4 (TLR2/4) and nucleotide-binding oligomerization domain-containing protein 1/2 (NOD1/2) were also detected by RT-qPCR. Moreover, the protein expression levels of endothelial nitric oxide synthase (eNOS) and mitogen-activated protein kinase (MAPK) cascades, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38, cyclooxygenase-2 (COX-2), as well as matrix metalloproteinase-2 (MMP-2) were all assayed by western blot analysis. Our results revealed that osthole markedly reduced the infarct size, and the levels of CK, CK-MB, LDH and cTnT in the rats with AMI, and that these cardioprotective effects may be associated with the inhibition of inflammatory reactions, the reduction in MMP-2 activity and the activation of MAPK cascades.

  9. Inflammatory processes and antiinflammatory drugs in Alzheimer's disease: a current appraisal.

    PubMed

    Breitner, J C

    1996-01-01

    The study of risk factors and protective influences can yield clues to the pathogenesis of Alzheimer's disease (AD). Intervention on such factors can effect disease prevention or treatment while etiology remains unknown. Most known AD risk factors offer no prospect of prevention, but 14 of 15 relevant publications since 1987 suggest that the symptoms of AD are prevented or attenuated by antiinflammatory treatments. These findings are supported by numerous circumstantial findings suggesting a role for cytokines and acute phase reactants in the pathogenesis of AD. In particular, activated microglia and/or reactive astrocytes, found within or near all AD lesions, are thought to kill target cells by using either free radicals or the classical complement pathway. These mechanisms should be suppressed by glucocorticoids, but the available data suggest that nonsteroidal antiinflammatory drugs (NSAIDs) exert a stronger protective influence than steriods. NSAIDs (but not steroids) suppress the action of cyclooxygenases (COX), which catalyze synthesis of prostaglandins. The latter are intermediaries in the postsynaptic signal transduction cascade of cells with NMDA-type glutamate receptors. They may also potentiate glutamatergic transmission by inhibiting astrocytic reuptake of glutamate. Both mechanisms can potentiate excitotoxic cell death. Further work is needed to clarify whether steroids, NSAIDs, or both prevent or attenuate the symptoms of AD.

  10. Conserved gene regulation during acute inflammation between zebrafish and mammals.

    PubMed

    Forn-Cuní, G; Varela, M; Pereiro, P; Novoa, B; Figueras, A

    2017-02-03

    Zebrafish (Danio rerio), largely used as a model for studying developmental processes, has also emerged as a valuable system for modelling human inflammatory diseases. However, in a context where even mice have been questioned as a valid model for these analysis, a systematic study evaluating the reproducibility of human and mammalian inflammatory diseases in zebrafish is still lacking. In this report, we characterize the transcriptomic regulation to lipopolysaccharide in adult zebrafish kidney, liver, and muscle tissues using microarrays and demonstrate how the zebrafish genomic responses can effectively reproduce the mammalian inflammatory process induced by acute endotoxin stress. We provide evidence that immune signaling pathways and single gene expression is well conserved throughout evolution and that the zebrafish and mammal acute genomic responses after lipopolysaccharide stimulation are highly correlated despite the differential susceptibility between species to that compound. Therefore, we formally confirm that zebrafish inflammatory models are suited to study the basic mechanisms of inflammation in human inflammatory diseases, with great translational impact potential.

  11. Kainic acid-induced neurodegeneration and activation of inflammatory processes in organotypic hippocampal slice cultures: treatment with cyclooxygenase-2 inhibitor does not prevent neuronal death.

    PubMed

    Järvelä, Juha T; Ruohonen, Saku; Kukko-Lukjanov, Tiina-Kaisa; Plysjuk, Anna; Lopez-Picon, Francisco R; Holopainen, Irma E

    2011-06-01

    In the postnatal rodent hippocampus status epilepticus (SE) leads to age- and region-specific excitotoxic neuronal damage, the precise mechanisms of which are still incompletely known. Recent studies suggest that the activation of inflammatory responses together with glial cell reactivity highly contribute to excitotoxic neuronal damage. However, pharmacological tools to attenuate their activation in the postnatal brain are still poorly elucidated. In this study, we investigated the role of inflammatory mediators in kainic acid (KA)-induced neuronal damage in organotypic hippocampal slice cultures (OHCs). A specific cyclooxygenase-2 (COX-2) inhibitor N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398) was used to study whether or not it could ameliorate neuronal death. Our results show that KA treatment (24 h) resulted in a dose-dependent degeneration of CA3a/b pyramidal neurons. Furthermore, COX-2 immunoreactivity was pronouncedly enhanced particularly in CA3c pyramidal neurons, microglial and astrocyte morphology changed from a resting to active appearance, the expression of the microglial specific protein, Iba1, increased, and prostaglandin E₂ (PGE₂) production increased. These indicated the activation of inflammatory processes. However, the expression of neither proinflammatory cytokines, i.e. tumour necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), nor the anti-inflammatory cytokine IL-10 mRNA was significantly altered by KA treatment as studied by real-time PCR. Despite activation of an array of inflammatory processes, neuronal damage could not be rescued either with the combined pre- and co-treatment with a specific COX-2 inhibitor, NS-398. Our results suggest that KA induces activation of a repertoire of inflammatory processes in immature OHCs, and that the timing of anti-inflammatory treatment to achieve neuroprotection is a challenge due to developmental properties and the complexity of inflammatory processes activated by

  12. Bioactive Fraction of Geopropolis from Melipona scutellaris Decreases Neutrophils Migration in the Inflammatory Process: Involvement of Nitric Oxide Pathway

    PubMed Central

    Franchin, Marcelo; da Cunha, Marcos Guilherme; Denny, Carina; Napimoga, Marcelo Henrique; Cunha, Thiago Mattar; Bueno-Silva, Bruno; Matias de Alencar, Severino; Ikegaki, Masaharu; Luiz Rosalen, Pedro

    2013-01-01

    The aim of this study was to evaluate the activity of the ethanolic extract of geopropolis (EEGP) from Melipona scutellaris and its fractions on the modulation of neutrophil migration in the inflammatory process, and the participation of nitric oxide (NO) pathway, as well as to check the chemical profile of the bioactive fraction. EEGP and its aqueous fraction decreased neutrophil migration in the peritoneal cavity and also the interaction of leukocytes (rolling and adhesion) with endothelial cells. The levels of chemokines CXCL1/KC and CXCL2/MIP-2 were not altered after treatment with EEGP and the aqueous fraction. It was found that the injection of NO pathway antagonists abolished the EEGP and the aqueous fraction inhibitory activity on the neutrophil migration. The expression of intercellular adhesion molecule type 1 (ICAM-1) was reduced, and nitrite levels increased after treatment with EEGP and aqueous fraction. In the carrageenan-induced paw edema model, EEGP and the aqueous fraction showed antiedema activity. No pattern of flavonoid and phenolic acid commonly found in propolis samples of Apis mellifera could be detected in the aqueous fraction samples. These data indicate that the aqueous fraction found has promising bioactive substances with anti-inflammatory activity. PMID:23737853

  13. The sterile inflammatory response.

    PubMed

    Rock, Kenneth L; Latz, Eicke; Ontiveros, Fernando; Kono, Hajime

    2010-01-01

    The acute inflammatory response is a double-edged sword. On the one hand, it plays a key role in initial host defense, particularly against many infections. On the other hand, its aim is imprecise, and as a consequence, when it is drawn into battle, it can cause collateral damage in tissues. In situations where the inciting stimulus is sterile, the cost-benefit ratio may be high; because of this, sterile inflammation underlies the pathogenesis of a number of diseases. Although there have been major advances in our understanding of how microbes trigger inflammation, much less has been learned about this process in sterile situations. This review focuses on a subset of the many sterile stimuli that can induce inflammation-specifically dead cells and a variety of irritant particles, including crystals, minerals, and protein aggregates. Although this subset of stimuli is structurally very diverse and might appear to be unrelated, there is accumulating evidence that the innate immune system may recognize them in similar ways and stimulate the sterile inflammatory response via common pathways. Here we review established and emerging data about these responses.

  14. Acute viral myocarditis

    PubMed Central

    Dennert, Robert; Crijns, Harry J.; Heymans, Stephane

    2008-01-01

    Acute myocarditis is one of the most challenging diagnosis in cardiology. At present, no diagnostic gold standard is generally accepted, due to the insensitivity of traditional diagnostic tests. This leads to the need for new diagnostic approaches, which resulted in the emergence of new molecular tests and a more detailed immunohistochemical analysis of endomyocardial biopsies. Recent findings using these new diagnostic tests resulted in increased interest in inflammatory cardiomyopathies and a better understanding of its pathophysiology, the recognition in overlap of virus-mediated damage, inflammation, and autoimmune dysregulation. Novel results also pointed towards a broader spectrum of viral genomes responsible for acute myocarditis, indicating a shift of enterovirus and adenovirus to parvovirus B19 and human herpes virus 6. The present review proposes a general diagnostic approach, focuses on the viral aetiology and associated autoimmune processes, and reviews treatment options for patients with acute viral myocarditis. PMID:18617482

  15. Inflammatory and fibrotic processes are involved in the cardiotoxic effect of sunitinib: Protective role of L-carnitine.

    PubMed

    Blanca, Antonio J; Ruiz-Armenta, María V; Zambrano, Sonia; Miguel-Carrasco, José L; Arias, José L; Arévalo, Miguel; Mate, Alfonso; Aramburu, Oscar; Vázquez, Carmen M

    2016-01-22

    Sunitinib (Su) is currently approved for treatment of several malignances. However, along with the benefits of disease stabilization, cardiovascular toxicities have also been increasingly recognized. The aim of this study was to analyze which mechanisms are involved in the cardiotoxicity caused by Su, as well as to explore the potential cardioprotective effects of l-carnitine (LC). To this end, four groups of Wistar rats were used: (1) control; (2) rats treated with 400mg LC/kg/day; (3) rats treated with 25mg Su/kg/day; and (4) rats treated with LC+Su simultaneously. In addition, cultured rat cardiomyocytes were treated with an inhibitor of nuclear factor kappa B (NF-κB), in order to examine the role of this transcription factor in this process. An elevation in the myocardial expression of pro-inflammatory cytokines, together with an increase in the mRNA expression of NF-κB, was observed in Su-treated rats. These results were accompanied by an increase in the expression of pro-fibrotic factors, nitrotyrosine and NOX 2 subunit of NADPH oxidase; and by a decrease in that of collagen degradation factor. Higher blood pressure and heart rate levels were also found in Su-treated rats. All these alterations were inhibited by co-administration of LC. Furthermore, cardiotoxic effects of Su were blocked by NF-κB inhibition. Our results suggest that: (i) inflammatory and fibrotic processes are involved in the cardiac toxicity observed following treatment with Su; (ii) these processes might be mediated by the transcription factor NF-κB; (iii) LC exerts a protective effect against arterial hypertension, cardiac inflammation and fibrosis, which are all observed after Su treatment.

  16. Effects of Campomanesia xanthocarpa on inflammatory processes, oxidative stress, endothelial dysfunction and lipid biomarkers in hypercholesterolemic individuals.

    PubMed

    Viecili, Paulo Ricardo Nazário; Borges, Diego Olschowsky; Kirsten, Karina; Malheiros, Jênifer; Viecili, Eduardo; Melo, Rodolfo Dahlem; Trevisan, Gabriela; da Silva, Mariane Arnoldi; Bochi, Guilherme Vargas; Moresco, Rafael Noal; Klafke, Jonatas Zeni

    2014-05-01

    In Brazil, the edible plant Campomanesia xanthocarpa Berg. (Myrtaceae), popularly known as "guavirova," has been studied in hypercholesterolemic individuals. The present work investigated the effects of C. xanthocarpa on inflammatory processes, oxidative stress, endothelial dysfunction and lipid biomarkers in hypercholesterolemic individuals. A total of 156 individuals were selected in a double-blind fashion and randomly divided into two groups in accordance with the intervals used in the criteria for hypercholesterolemia: individuals with total cholesterol (TC) levels between 200 and 240 mg/dL (undesirable level individuals - UL) and individuals with TC levels >240 mg/dL (hypercholesterolemic individuals - HL). Both groups had a control group (CG), which received placebo treatment, an encapsulated excipient group (lactose) and an experimental group that received 500 mg (EG 500), 750 mg (EG 750) or 1000 mg (EG 1000) of encapsulated C. xanthocarpa. The inflammatory processes (high-sensitivity C-reactive protein - hs-CRP), oxidative stress (advanced oxidation protein products-AOPPs; ischemia-modified albumin-IMA), endothelial dysfunction (nitric oxide - NOx) and biochemical (TC, triglycerides, high-density lipoprotein - HDL, low-density lipoproteins - LDL, and very low-density lipoprotein - VLDL) parameters were measured before and 90 days after the initiation of treatment. A significant decrease in TC and LDL levels was observed in HL individuals from the EG 500 group (reduction of 29 ± 3% and 41 ± 5% to levels before treatment) compared to the CG group individuals. A significant reduction in oxidative stress and inflammatory process components (reduction of 52 ± 11% in AOPPs, 32 ± 10% in IMA and 57 ± 7% in hs-CRP) and a significant increase in NOx (increase of 84 ± 27%) was observed in HL individuals in the EG 1000 group when compared to the CG group individuals. Treatment with encapsulated C. xanthocarpa reduced blood TC and LDL levels in

  17. Proteinase inhibitors in severe inflammatory processes (septic shock and experimental endotoxaemia): biochemical, pathophysiological and therapeutic aspects.

    PubMed

    Fritz, H

    1979-01-01

    course of a local inflammatory response. Preliminary results indicate that HUSI-I, which is produced by the epithelial cells of mucous membranes, does not belong to any known structural type of acid-stable proteinase inhibitor. The search for other candidates suitable for medication in humans led to the discovery of a potent elastase--cathepsin G inhibitor, called eglin, in the leech Hirudo medicinalis. This acid-stable inhibitor with a molecular weight close to 8100 has an unusual structural property in that the structure of the molecule is not stabilized by any disulphide bridge.

  18. Spray-drying process preserves the protective capacity of a breast milk-derived Bifidobacterium lactis strain on acute and chronic colitis in mice.

    PubMed

    Burns, Patricia; Alard, Jeanne; Hrdỳ, Jiri; Boutillier, Denise; Páez, Roxana; Reinheimer, Jorge; Pot, Bruno; Vinderola, Gabriel; Grangette, Corinne

    2017-02-24

    Gut microbiota dysbiosis plays a central role in the development and perpetuation of chronic inflammation in inflammatory bowel disease (IBD) and therefore is key target for interventions with high quality and functional probiotics. The local production of stable probiotic formulations at limited cost is considered an advantage as it reduces transportation cost and time, thereby increasing the effective period at the consumer side. In the present study, we compared the anti-inflammatory capacities of the Bifidobacterium animalis subsp. lactis (B. lactis) INL1, a probiotic strain isolated in Argentina from human breast milk, with the commercial strain B. animalis subsp. lactis BB12. The impact of spray-drying, a low-cost alternative of bacterial dehydration, on the functionality of both bifidobacteria was also investigated. We showed for both bacteria that the spray-drying process did not impact on bacterial survival nor on their protective capacities against acute and chronic colitis in mice, opening future perspectives for the use of strain INL1 in populations with IBD.

  19. Spray-drying process preserves the protective capacity of a breast milk-derived Bifidobacterium lactis strain on acute and chronic colitis in mice

    PubMed Central

    Burns, Patricia; Alard, Jeanne; Hrdỳ, Jiri; Boutillier, Denise; Páez, Roxana; Reinheimer, Jorge; Pot, Bruno; Vinderola, Gabriel; Grangette, Corinne

    2017-01-01

    Gut microbiota dysbiosis plays a central role in the development and perpetuation of chronic inflammation in inflammatory bowel disease (IBD) and therefore is key target for interventions with high quality and functional probiotics. The local production of stable probiotic formulations at limited cost is considered an advantage as it reduces transportation cost and time, thereby increasing the effective period at the consumer side. In the present study, we compared the anti-inflammatory capacities of the Bifidobacterium animalis subsp. lactis (B. lactis) INL1, a probiotic strain isolated in Argentina from human breast milk, with the commercial strain B. animalis subsp. lactis BB12. The impact of spray-drying, a low-cost alternative of bacterial dehydration, on the functionality of both bifidobacteria was also investigated. We showed for both bacteria that the spray-drying process did not impact on bacterial survival nor on their protective capacities against acute and chronic colitis in mice, opening future perspectives for the use of strain INL1 in populations with IBD. PMID:28233848

  20. Dopaminergic signaling mediates the motivational response underlying the opponent process to chronic but not acute nicotine.

    PubMed

    Grieder, Taryn E; Sellings, Laurie H; Vargas-Perez, Hector; Ting-A-Kee, Ryan; Siu, Eric C; Tyndale, Rachel F; van der Kooy, Derek

    2010-03-01

    The mesolimbic dopamine (DA) system is implicated in the processing of the positive reinforcing effect of all drugs of abuse, including nicotine. It has been suggested that the dopaminergic system is also involved in the aversive motivational response to drug withdrawal, particularly for opiates, however, the role for dopaminergic signaling in the processing of the negative motivational properties of nicotine withdrawal is largely unknown. We hypothesized that signaling at dopaminergic receptors mediates chronic nicotine withdrawal aversions and that dopaminergic signaling would differentially mediate acute vs dependent nicotine motivation. We report that nicotine-dependent rats and mice showed conditioned place aversions to an environment paired with abstinence from chronic nicotine that were blocked by the DA receptor antagonist alpha-flupenthixol (alpha-flu) and in DA D(2) receptor knockout mice. Conversely, alpha-flu pretreatment had no effect on preferences for an environment paired with abstinence from acute nicotine. Taken together, these results suggest that dopaminergic signaling is necessary for the opponent motivational response to nicotine in dependent, but not non-dependent, rodents. Further, signaling at the DA D(2) receptor is critical in mediating withdrawal aversions in nicotine-dependent animals. We suggest that the alleviation of nicotine withdrawal primarily may be driving nicotine motivation in dependent animals.

  1. [Dynamics of interferon production during different phases of the pathological process in children with acute pneumonia and relapsing bronchitis].

    PubMed

    Koval'chuk, O L

    2001-01-01

    With the purpose of gaining further insight into regularities of changes that take place in indices for the interferon status in children with acute pneumonia and current bronchitis depending on the phase of the pathological process, 112 children were examined in whom the level of serum interferon was measured together with production of alpha- and gamma-interferon by leucocytes of the peripheral blood in vitro. It is shown that in the examined patients with acute pneumonia and relapsing bronchitis in the acute period and during the phase of reparation there are differences in functioning of indices for the system of interferon.

  2. Curcumin in inflammatory diseases.

    PubMed

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

    2013-01-01

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

  3. 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

    2016-09-05

    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 that morin exert a potent anti-inflammatory effect on MSU crystal-induced inflammation in rats.

  4. IL-1 family cytokines trigger sterile inflammatory disease

    PubMed Central

    Lukens, John R.; Gross, Jordan M.; Kanneganti, Thirumala-Devi

    2012-01-01

    Inflammation plays vital roles in protective responses against pathogens and tissue repair, however, improper resolution of inflammatory networks is centrally involved in the pathogenesis of many acute and chronic diseases. Extensive advances have been made in recent years to define the inflammatory processes that are required for pathogen clearance, however, in comparison, less is known about the regulation of inflammation in sterile settings. Over the past decade non-communicable chronic diseases that are potentiated by sterile inflammation have replaced infectious diseases as the major threat to global human health. Thus, improved understanding of the sterile inflammatory process has emerged as one of the most important areas of biomedical investigation during our time. In this review we highlight the central role that interleukin-1 family cytokines play in sterile inflammatory diseases. PMID:23087690

  5. [THE PATHOGENIC POTENTIAL OF MORAXELLA CATARRHALIS AND STAPHYLOCOCCUS EPIDERMIDIS UNDER INFLAMMATORY PROCESSES OF UPPER RESPIRATORY TRACTS].

    PubMed

    Kraeva, L A; Burgasova, O A; Kunilova, E S; Petrova, I S; Tseneva, G Ya; Bespalova, G L

    2015-11-01

    The frequent isolation from biological material of Moraxella catarrhalis under bronchitis and pneumonia and Staphilococcus epidermidis under rhinitis and sinusitis requires profound investigation offactors ofpathogenicity ofthe mentioned microorganisms. The genetic and phenotypic markers of virulence of strains M. catarrhalis and S. epidermidis are examined. Their etiologic role in development of infection processes of respiratory tract and middle ear is determined The most of M catarrhalis strains isolated under bronchitis and pneumonia have gene mcaP responsiblefor production ofprotein McaP that provides adhesion to epithelium cell of host and lipolitic activity of bacteria. The strains isolated from patients with pneumonia had the most adhesive activity. The cluster of genes ICA with leading role of gene icaA is responsible for for availability offactors of intercellular adhesion in Staphilococci strains. In the clinical samples from patients with sinusitis this gene is detected 5 times more frequently than from healthy individuals. In phenotypic tests, expression of gene icaA in S. epidermidis isolated from patients is three times higher than in strains isolated from healthy individuals. To establish etiologic role of M. catarrhalis and S. epidermidis and to develop tactic of therapy of patients with bronchitis, pneumonia and sinusitis complex approach is needed, including detection of genetic and phenotypic markers of virulence in isolated microorganisms.

  6. Role of dietary polyphenols and inflammatory processes on disease progression mediated by the gut microbiota.

    PubMed

    Martínez, J Alfredo; Etxeberría, Usune; Galar, Alicia; Milagro, Fermín I

    2013-10-01

    Mendelsohn and Larrick have recently discussed in a recent article in Rejuvenation Research that dietary modifications of the gut microbiota affect the risk for cardiovascular disease. In this context, dietary patterns and single specific nutrients appear to produce singular consequences on the gut microbiota, subsequently impacting on maintenance of well-being and disease onset or evolution, whose intimate influences and mechanisms are now starting to be disentangled. Thus, the consumption of dietary fiber and particular polysaccharides affects colonic fermentation processes involving short-chain fatty acid production, accompanying changes in the environmental pH, inhibiting Bacteroides spp., and rising levels of butyrate-producing Gram-positive bacteria. This scenario may contribute to the design of novel therapeutic approaches to manipulate gut microbiota to treat cardiovascular diseases and obesity. Indeed, cardiovascular risk may be indirectly dependent on pathways associated with microbe-induced obesity or diabetes through inflammation. Diverse components of the diet, including bioactive molecules with bactericidal functions, such as polyphenols, may play a role on intestinal mucosa inflammation and permeability and contribute to explaining the mutual interactions between obesity, diabetes, and adverse cardiovascular events.

  7. Resolvins and omega three polyunsaturated fatty acids: Clinical implications in inflammatory diseases and cancer.

    PubMed

    Moro, Kazuki; Nagahashi, Masayuki; Ramanathan, Rajesh; Takabe, Kazuaki; Wakai, Toshifumi

    2016-07-16

    Inflammation is a central process in several disorders and contributes to cancer progression. Inflammation involves a complex cascade of pro-inflammatory and anti-inflammatory signaling events with protein and lipid mediators. Recent advances in lipid detection have revealed the importance of lipid mediators in inflammation. Omega three polyunsaturated fatty acids (ω-3 PUFA) are found naturally in fish oil and have been extensively studied in multiple inflammatory diseases with improved outcomes. Resolvins are thought to be the active metabolites of ω-3 PUFA, and are responsible for facilitating the resolving phase of acute inflammation. Clinically, resolvins have been associated with resolution of acute kidney injury and acute lung injury, micro and macro vascular response to injury, and inhibition of microglia-activated inflammation in neurodegenerative disorders. In addition to inflammatory diseases, ω-3 PUFA and resolvins appear to modulate cancer progression. ω-3 PUFA intake has been associated with reduced inflammation in colorectal cancer, and favorable phenotype in breast cancer. Resolvins offer promising therapeutic potential as they may modulate inflammation with minimal side-effects, in contrast to currently available anti-inflammatory medications. This review describes the roles of ω-3 PUFA and resolvins in the inflammatory cascade, various inflammatory diseases, and specific cancers. Additionally, it will discuss the clinical therapeutic potential of resolvins as targets in inflammatory diseases and cancers.

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

    PubMed

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

    2014-03-01

    Currently, treatment of muscle injuries represents a challenge in clinical practice. In acute phase, the most employed therapies are cryotherapy and nonsteroidal anti-inflammatory drugs. In the last years, low-level laser therapy (LLLT) has becoming a promising therapeutic agent; however, its effects are not fully known. The aim of this study was to analyze the effects of sodium diclofenac (topical application), cryotherapy, and LLLT on pro-inflammatory cytokine levels after a controlled model of muscle injury. For such, we performed a single trauma in tibialis anterior muscle of rats. After 1 h, animals were treated with sodium diclofenac (11.6 mg/g of solution), cryotherapy (20 min), or LLLT (904 nm; superpulsed; 700 Hz; 60 mW mean output power; 1.67 W/cm(2); 1, 3, 6 or 9 J; 17, 50, 100 or 150 s). Assessment of interleukin-1β and interleukin-6 (IL-1β and IL-6) and tumor necrosis factor-alpha (TNF-α) levels was performed at 6 h after trauma employing enzyme-linked immunosorbent assay method. LLLT with 1 J dose significantly decreased (p < 0.05) IL-1β, IL-6, and TNF-α levels compared to non-treated injured group as well as diclofenac and cryotherapy groups. On the other hand, treatment with diclofenac and cryotherapy does not decrease pro-inflammatory cytokine levels compared to the non-treated injured group. Therefore, we can conclude that 904 nm LLLT with 1 J dose has better effects than topical application of diclofenac or cryotherapy in acute inflammatory phase after muscle trauma.

  9. Structural basis of the anti-inflammatory activity of quercetin: inhibition of the 5-hydroxytryptamine type 2 receptor.

    PubMed

    Rotelli, Alejandra Ester; Aguilar, Carlos Fernando; Pelzer, Lilian Eugenia

    2009-09-01

    The anti-inflammatory activity of quercetin was evaluated through serotonin-induced rat-paw edema. The experiments showed that quercetin had an important effect on acute inflammatory processes. Docking of serotonin and quercetin into the homology model of the 5-Hydroxytryptamine Type 2 Receptor allowed to analyze the structural basis of the anti-inflammatory activity. Results showed that serotonin and quercetin bind in the same region of the active site with a similar binding energy but quercetin has a much bigger inhibition constant. Therefore, it seems possible that quercetin may act as a natural inhibitor of the receptor blocking the acute inflammation generated by serotonin.

  10. Blueprint for Implementing New Processes in Acute Care: Rescuing Adult Patients With Intraosseous Access.

    PubMed

    Chreiman, Kristen M; Kim, Patrick K; Garbovsky, Lyudmila A; Schweickert, William D

    2015-01-01

    The intraosseous (IO) access initiative at an urban university adult level 1 trauma center began from the need for a more expeditious vascular access route to rescue patients in extremis. The goal of this project was a multidisciplinary approach to problem solving to increase access of IO catheters to rescue patients in all care areas. The initiative became a collaborative effort between nursing, physicians, and pharmacy to embark on an acute care endeavor to standardize IO access. This is a descriptive analysis of processes to effectively develop collaborative strategies to navigate hospital systems and successfully implement multilayered initiatives. Administration should empower nurse to advance their practice to include IO for patient rescue. Intraosseous access may expedite resuscitative efforts in patients in extremis who lack venous access or where additional venous access is required for life-saving therapies. Limiting IO dwell time may facilitate timely definitive venous access. Continued education and training by offering IO skill laboratory refreshers and annual e-learning didactic is optimal for maintaining proficiency and knowledge. More research opportunities exist to determine medication safety and efficacy in adult patients in the acute care setting.

  11. ACUTE OZONE-INDUCED INFLAMMATORY GENE EXPRESSION IN THE RAT LUNG IS NOT RELATED TO LEVELS OF ANTIOXIDANTS IN THE LAVAGE FLUID

    EPA Science Inventory

    ABSTRACT BODY: Ozone causes oxidative stress and lung inflammation. We hypothesized that rat strains with or without genetic susceptibility to cardiovascular disease will have different antioxidant levels in alveolar lining, and that ozone induced inflammatory gene expression wil...

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

    PubMed

    Paquette, Stéphane G; Banner, David; Chi, Le Thi Bao; Leόn, Alberto J; Xu, Luoling; Ran, Longsi; Huang, Stephen S H; Farooqui, Amber; Kelvin, David J; Kelvin, Alyson A

    2014-01-05

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

  13. Acute abdomen. Outcomes.

    PubMed

    Madonna, M B; Boswell, W C; Arensman, R M

    1997-05-01

    The outcome for children with common surgical conditions that cause an acute abdomen is discussed. These conditions include appendicitis, intussusception, malrotation, inflammatory bowel disease, intestinal obstructions, and nonorganic pain. Emphasis is placed on surgical intervention and disease processes that significantly affect outcome. The outcome of many of the diseases discussed is strongly influenced by the timing of diagnosis and treatment. These children should have prompt care and intervention to prevent morbidity and mortality. In addition, many children who present with common pediatric surgical emergencies have other medical conditions and are best treated in an environment that has a multidisciplinary team to handle their care and decrease the long-term complications.

  14. Nutrition, Inflammation, and Acute Pancreatitis

    PubMed Central

    Petrov, Max

    2013-01-01

    Acute pancreatitis is acute inflammatory disease of the pancreas. Nutrition has a number of anti-inflammatory effects that could affect outcomes of patients with pancreatitis. Further, it is the most promising nonspecific treatment modality in acute pancreatitis to date. This paper summarizes the best available evidence regarding the use of nutrition with a view of optimising clinical management of patients with acute pancreatitis. PMID:24490104

  15. [Chorioamnionitis and inflammatory disease in the premature newborn infant].

    PubMed

    Vedovato, S; Zanardo, V

    2010-06-01

    Preterm births occurs in 6-12% of all pregnancies, accounts for 75% of neonatal death and causes significant neonatal morbidity. A large number of preterm birth is associated with infection (30%), because of the release of many cytokines. In fact acute chorioamnionitis represents the inflammatory response to extracellular microorganisms that gain access to the gestational sac. Clinical signs of infection compare in the 12% of cases, while the prevalence of positive amniotic fluid cultures is approximately 50% in patients with preterm PROM. Despite the recent studies about the dosage of inflammatory biomarkers in the amniotic fluid or in fetal and maternal blood, placenta histology remains the gold standard for the diagnosis of chorioamnionitis. Histological chorioamnionitis describes the progression of the inflammatory process. Organisms first colonise the chorioamnionic surface. Then, the neutrophils migrates to the chorion (chorionitis) and to the amnion (chorioamnionitis) and, in the last stage, amnionic epithelial cells undergo necrosis (necrotising chorioamnionitis). It represents the mother inflammatory response and it differs from the fetal inflammatory response (funisitis). Funisitis first appears in vessels of the chorionic plate (chorionic vasculitis) or in the umbilical vein (umbilical phlebitis), then in the umbilical artery (umbilical arteritis), and in the Wharton's jelly (umbilical perivasculitis). The fetal inflammatory response has been associated with inflammatory diseases of preterm infants, increasing the risk of neonatal sepsis and meningitis, bronchopulmonary dysplasia and cerebral palsy. We present our experience on the relationship between histological chorioamnionitis, preterm birth and inflammatory diseases of VLBW infants.

  16. Major comorbid disease processes associated with increased incidence of acute kidney injury.

    PubMed

    Farooqi, Salwa; Dickhout, Jeffrey G

    2016-03-06

    Acute kidney injury (AKI) is commonly seen amongst critically ill and hospitalized patients. Individuals with certain co-morbid diseases have an increased risk of developing AKI. Thus, recognizing the co-morbidities that predispose patients to AKI is important in AKI prevention and treatment. Some of the most common co-morbid disease processes that increase the risk of AKI are diabetes, cancer, cardiac surgery and human immunodeficiency virus (HIV) acquired immune deficiency syndrome (AIDS). This review article identifies the increased risk of acquiring AKI with given co-morbid diseases. Furthermore, the pathophysiological mechanisms underlying AKI in relation to co-morbid diseases are discussed to understand how the risk of acquiring AKI is increased. This paper reviews the effects of various co-morbid diseases including: Diabetes, cancer, cardiovascular disease and HIV AIDS, which all exhibit a significant increased risk of developing AKI. Amongst these co-morbid diseases, inflammation, the use of nephrotoxic agents, and hypoperfusion to the kidneys have been shown to be major pathological processes that predisposes individuals to AKI. The pathogenesis of kidney injury is complex, however, effective treatment of the co-morbid disease processes may reduce its risk. Therefore, improved management of co-morbid diseases may prevent some of the underlying pathology that contributes to the increased risk of developing AKI.

  17. Acute aerobic exercise influences the inhibitory process in the go/no-go task in humans.

    PubMed

    Akatsuka, Kosuke; Yamashiro, Koya; Nakazawa, Sho; Mitsuzono, Ryouichi; Maruyama, Atsuo

    2015-07-23

    This study evaluated the influence of acute aerobic exercise on the human inhibitory system. For studies on the neural mechanisms of somato-motor inhibitory processing in humans, the go/no-go task is a useful paradigm for recording event-related potentials. Ten subjects performed somatosensory go/no-go tasks in a control condition and exercise condition. In the control condition, the subjects performed the go/no-go task before and after 20 min of rest. In the exercise condition, the subjects performed the go/no-go task before and after 15 min of treadmill running with the exercise intensity set individually for each subject at 50% of peak oxygen intake. We successfully recorded a clear-cut N140 component under all conditions, and found that the peak amplitude of no-go-N140 at Fz and Cz was significantly enhanced during moderate exercise. In contrast, there were no significant changes in Fz and Cz in the control condition. These results suggest that moderate exercise can affect the amplitude of no-go-N140, which could be interpreted as an index of the human inhibition process in the central nervous system. The human inhibitory system is an important cognitive process, and this system may underlie the hypothetical ability of physical exercise to maintain and improve cognitive performance throughout the lifespan.

  18. Major comorbid disease processes associated with increased incidence of acute kidney injury

    PubMed Central

    Farooqi, Salwa; Dickhout, Jeffrey G

    2016-01-01

    Acute kidney injury (AKI) is commonly seen amongst critically ill and hospitalized patients. Individuals with certain co-morbid diseases have an increased risk of developing AKI. Thus, recognizing the co-morbidities that predispose patients to AKI is important in AKI prevention and treatment. Some of the most common co-morbid disease processes that increase the risk of AKI are diabetes, cancer, cardiac surgery and human immunodeficiency virus (HIV) acquired immune deficiency syndrome (AIDS). This review article identifies the increased risk of acquiring AKI with given co-morbid diseases. Furthermore, the pathophysiological mechanisms underlying AKI in relation to co-morbid diseases are discussed to understand how the risk of acquiring AKI is increased. This paper reviews the effects of various co-morbid diseases including: Diabetes, cancer, cardiovascular disease and HIV AIDS, which all exhibit a significant increased risk of developing AKI. Amongst these co-morbid diseases, inflammation, the use of nephrotoxic agents, and hypoperfusion to the kidneys have been shown to be major pathological processes that predisposes individuals to AKI. The pathogenesis of kidney injury is complex, however, effective treatment of the co-morbid disease processes may reduce its risk. Therefore, improved management of co-morbid diseases may prevent some of the underlying pathology that contributes to the increased risk of developing AKI. PMID:26981437

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

    SciTech Connect

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

    2014-01-05

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

  20. Preliminary Study of Acute Changes in Emotion Processing in Trauma Survivors with PTSD Symptoms

    PubMed Central

    Wang, Xin; Xie, Hong; Cotton, Andrew S.; Duval, Elizabeth R.; Tamburrino, Marijo B.; Brickman, Kristopher R.; Elhai, Jon D.; Ho, S. Shaun; McLean, Samuel A.; Ferguson, Eric J.; Liberzon, Israel

    2016-01-01

    Accumulating evidence suggests traumatic experience can rapidly alter brain activation associated with emotion processing. However, little is known about acute changes in emotion neurocircuits that underlie PTSD symptom development. To examine acute alterations in emotion circuit activation and structure that may be linked to PTSD symptoms, thirty-eight subjects performed a task of appraisal of emotional faces as their brains were functionally and structurally studied with MRI at both two weeks and three months after motor vehicle collision (MVC). As determined by symptoms reported in the PTSD Checklist at three months, sixteen survivors developed probable PTSD, whereas the remaining 22 did not meet criteria for PTSD diagnosis (non-PTSD). The probable PTSD group had greater activation than the non-PTSD group in dorsal and ventral medial prefrontal cortex (dmPFC and vmPFC) while appraising fearful faces within two weeks after MVC and in left insular cortex (IC) three months after MVC. dmPFC activation at two weeks significantly positively correlated with PTSD symptom severity at two weeks (R = 0.462, P = 0.006) and three months (R = 0.418, p = 0.012). Changes over time in dmPFC activation and in PTSD symptom severity were also significantly positively correlated in the probable PTSD group (R = 0.641, P = 0.018). A significant time by group interaction was found for volume changes in left superior frontal gyrus (SFG, F = 6.048, p = 0.019) that partially overlapped dmPFC active region. Between two weeks and three months, left SFG volume decreased in probable PTSD survivors. These findings identify alterations in frontal cortical activity and structure during the early post-trauma period that appear to be associated with development of PTSD symptoms. PMID:27415431

  1. The relationship between business process re-engineering and Internet usage: survey of acute care hospitals in the United States.

    PubMed

    Hatcher, M

    1999-12-01

    The data from a national survey of acute care hospitals was used for analysis. Hatcher discusses the complete questionnaire, data collection procedure, and sample selection. The relationship between business process re-engineering, total quality management, innovation system approaches, and Internet usage and potential usage will be reported and discussed.

  2. Social Work Discharge Planning in Acute Care Hospitals in Israel: Clients' Evaluation of the Discharge Planning Process and Adequacy

    ERIC Educational Resources Information Center

    Soskolne, Varda; Kaplan, Giora; Ben-Shahar, Ilana; Stanger, Varda; Auslander, Gail. K.

    2010-01-01

    Objective: To examine the associations of patients' characteristics, hospitalization factors, and the patients' or family assessment of the discharge planning process, with their evaluation of adequacy of the discharge plan. Method: A prospective study. Social workers from 11 acute care hospitals in Israel provided data on 1426 discharged…

  3. [Acute-phase proteins in the saliva of workers engaged in processing natural gas and condensate high in hydrogen sulfide].

    PubMed

    Boĭko, V I; Dotsenko, Iu I; Boĭko, O V

    2011-06-01

    The paper considers current methods for assessing the workers' health status. It shows it possible to identify increased quantities of acute-phase serum proteins upon exposure to the negative factors characteristic of the Astrakhan gas processing plant. A wider range of tests for acute-phase tissue and serum proteins is proposed to be included in order to gain a fuller insight into the influence of unfavorable industrial factors on man and to make monitoring that enables the existing health risks and the efficiency of preventive measures to be controlled.

  4. In Vitro TNF-α Inhibitory Activity of Brazilian Plants and Anti-Inflammatory Effect of Stryphnodendron adstringens in an Acute Arthritis Model

    PubMed Central

    Henriques, Bárbara O.; Corrêa, Olívia; Azevedo, Elaine Patrícia C.; Pádua, Rodrigo M.; de Oliveira, Vívian Louise S.; Oliveira, Thiago Henrique C.; Boff, Daiane; Dias, Ana Carolina F.; Amaral, Flávio A.; Castilho, Rachel O.

    2016-01-01

    Stryphnodendron species, popularly named “barbatimão,” are traditionally used in Brazil as anti-inflammatory agents. This study aimed to investigate the effect of barbatimão and 11 other species on the production of tumor necrosis factor-alpha (TNF-α) in lipopolysaccharide- (LPS-) stimulated THP-1 cells, as well as their anti-arthritis activity. The extracts of Stryphnodendron adstringens, Stryphnodendron obovatum, Campomanesia lineatifolia, and Terminalia glabrescens promoted a concentration-dependent inhibition of TNF-α. Mice injected with LPS in the knee joint were treated per os with fractions from the selected extracts. Both the organic (SAO) and the aqueous (SAA) fractions of S. adstringens promoted a dose-dependent reduction of leukocyte migration and neutrophil accumulation into the joint, but none of them reduced CXCL1 concentration in the periarticular tissue. In contrast, treatment with C. lineatifolia and T. glabrescens fractions did not ameliorate the inflammatory parameters. Analyses of SAO by Ultra Performance Liquid Chromatography (UPLC) coupled to electrospray ionization mass spectrometry (ESI-MS) led to the identification of gallic acid along with 11 prodelphinidins, characterized as monomers and dimers of the B-type. Our findings contribute to some extent to corroborating the traditional use of S. adstringens as an anti-inflammatory agent. This activity is probably related to a decrease of leukocyte migration into the inflammatory site. Polyphenols like gallic acid and prodelphinidins, identified in the active fraction, may contribute to the observed activity. PMID:27867403

  5. Inflammatory response to trauma: Implications for coagulation and resuscitation

    PubMed Central

    Pierce, Albert; Pittet, Jean-François

    2014-01-01

    Purpose of this review Recent studies have changed our understanding of the timing and interactions of the inflammatory processes and coagulation cascade following severe trauma. This review highlights this information and correlates its impact on the current clinical approach for fluid resuscitation and treatment of coagulopathy for trauma patients. Recent findings Severe trauma is associated with a failure of multiple biologic emergency response systems that includes imbalanced inflammatory response, acute coagulopathy of trauma (ACOT), and endovascular glycocalyx degradation with microcirculatory compromise. These abnormalities are all inter-linked and related. Recent observations show that after severe trauma: 1) pro-inflammatory and anti-inflammatory responses are concomitant, not sequential and 2) resolution of the inflammatory response is an active process, not a passive one. Understanding these interrelated processes is considered extremely important for the development of future therapies for severe trauma in humans. Summary Traumatic injuries continue to be a significant cause of mortality worldwide. Recent advances in understanding the mechanisms of end-organ failure, and modulation of the inflammatory response has important clinical implications regarding fluid resuscitation and treatment of coagulopathy. PMID:24419158

  6. Effects of some natural carotenoids on TRPA1- and TRPV1-induced neurogenic inflammatory processes in vivo in the mouse skin.

    PubMed

    Horváth, Györgyi; Kemény, Ágnes; Barthó, Loránd; Molnár, Péter; Deli, József; Szente, Lajos; Bozó, Tamás; Pál, Szilárd; Sándor, Katalin; Szőke, Éva; Szolcsányi, János; Helyes, Zsuzsanna

    2015-05-01

    Mechanisms of the potent anti-inflammatory actions of carotenoids are unknown. Since carotenoids are incorporated into membranes, they might modulate transient receptor potential ankyrin 1 and vanilloid 1 (TRPA1 and TRPV1) activation predominantly on peptidergic sensory nerves. We therefore investigated the effects of three carotenoids (β-carotene, lutein and lycopene) on cutaneous neurogenic inflammation. Acute neurogenic edema and inflammatory cell recruitment were induced by smearing the TRPA1 agonist mustard oil (5%) or the TRPV1 activator capsaicin (2.5%) on the mouse ear. Ear thickness was then determined by micrometry, microcirculation by laser Doppler imaging and neutrophil accumulation by histopathology and spectrophotometric determination of myeloperoxidase activity. The effects of lutein on the stimulatory action of the TRPA1 agonist mustard oil were also tested on the guinea-pig small intestine, in isolated organ experiments. Mustard oil evoked 50-55% ear edema and granulocyte influx, as shown by histology and myeloperoxidase activity. Swelling was significantly reduced between 2 and 4 h after administration of lutein or β-carotene (100 mg/kg subcutane three times during 24 h). Lutein also decreased neutrophil accumulation induced by TRPA1 activation, but did not affect mustard oil-evoked intestinal contraction. Lycopene had no effect on any of these parameters. None of the three carotenoids altered capsaicin-evoked inflammation. It is proposed that the dihydroxycarotenoid lutein selectively inhibits TRPA1 activation and consequent neurogenic inflammation, possibly by modulating lipid rafts.

  7. [Changes in the chromatin structure of lymphoid cells under the influence of low-intensity extremely high-frequency electromagnetic radiation against the background of inflammatory process].

    PubMed

    Gapeev, A B; Romanova, N A; Chemeris, N K

    2011-01-01

    Using the alkaline single cell gel electrophoresis technique (comet assay), changes in chromatin structure of peripheral blood leukocytes and peritoneal neutrophils have been studied in mice exposed to low-intensity extremely high-frequency electromagnetic radiation (42.2 GHz, 0.1 mW/cm2, 20 min at 1 h after induction of inflammation) against the background of the systemic inflammatory process. It was revealed that the exposure of mice with the developing inflammation leads to a pronounced decrease in the level of DNA damage to peripheral blood leukocytes and peritoneal neutrophils. It is supposed that the changes in the chromatin structure of lymphoid cells have a genoprotective character in the inflammatory process and can underlie the mechanisms of realization of antiinflammatory effects of the electromagnetic radiation.

  8. Tannic acid NPs - synthesis and immobilization onto a solid surface in a one-step process and their antibacterial and anti-inflammatory properties.

    PubMed

    Perelshtein, Ilana; Ruderman, Elena; Francesko, Antonio; Fernandes, Margarida M; Tzanov, Tzanko; Gedanken, Aharon

    2014-11-01

    Tannic acid nanoparticles were synthesized from an aqueous solution without the use of stabilizers via a sonochemical process. In order to avoid the dissolution of the formed nanoparticles, the sonochemical reaction was performed in the presence of a cotton fabric: following their formation, the tannic acid nanoparticles were embedded into the cotton substrate in a one-step process. The bioactive properties of the tannic acid coated surface were examined towards the inhibition of myeloperoxidase and collagenase, two major enzymes related with inflammatory processes. In addition, the antibacterial activity of the tannic acid nanoparticles coated textiles was evaluated against Staphylococcus aureus and Pseudomonas aeruginosa.

  9. Acute toxicity evaluation for quinolone antibiotics and their chlorination disinfection processes.

    PubMed

    Li, Min; Wei, Dongbin; Du, Yuguo

    2014-09-01

    Acute toxicity of 21 quinolone antibiotics was monitored using photobacterium Vibrio fischeri assay. The minimum IC20 (inhibitory concentration for 20% luminescence elimination) was obtained at the least 18.86μmol/L for the tested quinolones. A quantitative structure-activity relationship model was established to investigate the possible mechanism for the acute toxicity. The critical physicochemical descriptors, describing σ and π atom electronegativity, implied that the electron transfer might occur between the quinolones and photobacterium V. fischeri. Although the quinolones exhibited limited acute toxicity to photobacterium, toxicity elevation was detected after their chlorination. Hence, chlorination disinfection treatment of quinolone-containing water should be of concerns.

  10. Oral processing effort, appetite and acute energy intake in lean and obese adults.

    PubMed

    Mattes, Richard D; Considine, Robert V

    2013-08-15

    Chewing reportedly contributes to satiation and satiety signals. Attempts to document and quantify this have led to small and inconsistent effects. The present trial manipulated oral processing effort though required chewing of gums of different hardness and measured appetitive sensations, energy intake, gastric emptying, GI transit time, and concentrations of glucose, insulin, GLP-1, ghrelin and pancreatic polypeptide. Sixty adults classified by sex and BMI (15 each of lean females, obese females, lean males and obese males) were tested in a randomized, controlled, cross-over trial with three arms. They chewed nothing, soft gum or hard gum for 15 min while sipping grape juice (10% of individual energy needs) containing acetaminophen and lactulose on one day each separated by 7 days. Electromyographic recordings and self-reports were obtained during and after chewing to quantify oral processing effort. Blood was sampled through an indwelling catheter and appetite ratings were obtained at baseline and at 0, 15, 30, 45, 60, 90, 120, 180 and 240 min after chewing initiation. Breath samples were collected at 10 min intervals for the first 2h and at 30 min intervals for the next 2h. No effects of chewing were observed for appetitive sensations or gut peptide concentrations. Energy intake tended to decline in lean and increase in obese participants so that daily energy intake differed significantly between the two groups when chewing either gum, while no difference was observed on the non-chewing day. Serum glucose and insulin were significantly lower at selected time points 90-240 min after chewing compared to baseline and the non-chewing day. These data indicate chewing effort does not affect appetitive sensations or gut peptide secretion, but may exert a small differential effect on acute energy intake in lean and obese individuals and lead to greater post-prandial declines of serum glucose and insulin. The efficacy of gum chewing as a substitute for eating for weight

  11. Acute effects of the ampakine farampator on memory and information processing in healthy elderly volunteers.

    PubMed

    Wezenberg, Elke; Verkes, Robert Jan; Ruigt, Ge S F; Hulstijn, Wouter; Sabbe, Bernard G C

    2007-06-01

    Ampakines act as positive allosteric modulators of AMPA-type glutamate receptors and facilitate hippocampal long-term potentiation (LTP), a mechanism associated with memory storage and consolidation. The present study investigated the acute effects of farampator, 1-(benzofurazan-5-ylcarbonyl) piperidine, on memory and information processes in healthy elderly volunteers. A double-blind, placebo-controlled, randomized, cross-over study was performed in 16 healthy, elderly volunteers (eight male, eight female; mean age 66.1, SD 4.5 years). All subjects received farampator (500 mg) and placebo. Testing took place 1 h after drug intake, which was around Tmax for farampator. Subjects performed tasks assessing episodic memory (wordlist learning and picture memory), working and short-term memory (N-back, symbol recall) and motor learning (maze task, pursuit rotor). Information processing was assessed with a tangled lines task, the symbol digit substitution test (SDST) and the continuous trail making test (CTMT). Farampator (500 mg) unequivocally improved short-term memory but appeared to impair episodic memory. Furthermore, it tended to decrease the number of switching errors in the CTMT. Drug-induced side effects (SEs) included headache, somnolence and nausea. Subjects with SEs had significantly higher plasma levels of farampator than subjects without SEs. Additional analyses revealed that in the farampator condition the group without SEs showed a significantly superior memory performance relative to the group with SEs. The positive results on short-term memory and the favorable trends in the trail making test (CTMT) are interesting in view of the development of ampakines in the treatment of Alzheimer's disease and schizophrenia.

  12. Cerebrospinal Fluid Neopterin Analysis in Neuropediatric Patients: Establishment of a New Cut Off-Value for the Identification of Inflammatory-Immune Mediated Processes

    PubMed Central

    Molero-Luis, Marta; Fernández-Ureña, Sergio; Jordán, Iolanda; Serrano, Mercedes; Ormazábal, Aida; Garcia-Cazorla, Àngels; Artuch, Rafael

    2013-01-01

    Objective A high level of cerebrospinal fluid (CSF) neopterin is a marker of central nervous system inflammatory-immune mediated processes. We aimed to assess data from 606 neuropediatric patients, describing the clinical and biochemical features of those neurological disorders presenting CSF neopterin values above a new cut-off value that was defined in our laboratory. Methods To establish the new CSF neopterin cut-off value, we studied two groups of patients: Group 1 comprised 68 patients with meningoencephalitis, and Group 2 comprised 52 children with a confirmed peripheral infection and no central nervous system involvement. We studied 606 CSF samples from neuropediatric patients who were classified into 3 groups: genetic diagnosis (A), acquired/unknown etiologic neurologic diseases (B) and inflammatory-immune mediated processes (C). Results The CSF neopterin cut-off value was 61 nmol/L. Out of 606 cases, 56 presented a CSF neopterin level above this value. Group C had significantly higher CSF neopterin, protein and leukocyte values than the other groups. Sixteen of twenty-three patients in this group had a CSF neopterin level above the cut-off, whereas three and seven patients presented increased leukocyte and protein values, respectively. A significant association was found among CSF neopterin, proteins and leukocytes in the 606 patients. White matter disturbances were associated with high CSF neopterin concentrations. Conclusions Although children with inflammatory-immune mediated processes presented higher CSF neopterin values, patients with other neurological disorders also showed increased CSF neopterin concentrations. These results stress the importance of CSF neopterin analysis for the identification of inflammatory-immune mediated processes. PMID:24367586

  13. Effects of acute alcohol consumption and processing of emotion in faces: Implications for understanding alcohol-related aggression.

    PubMed

    Attwood, Angela S; Munafò, Marcus R

    2014-08-01

    The negative consequences of chronic alcohol abuse are well known, but heavy episodic consumption ("binge drinking") is also associated with significant personal and societal harms. Aggressive tendencies are increased after alcohol but the mechanisms underlying these changes are not fully understood. While effects on behavioural control are likely to be important, other effects may be involved given the widespread action of alcohol. Altered processing of social signals is associated with changes in social behaviours, including aggression, but until recently there has been little research investigating the effects of acute alcohol consumption on these outcomes. Recent work investigating the effects of acute alcohol on emotional face processing has suggested reduced sensitivity to submissive signals (sad faces) and increased perceptual bias towards provocative signals (angry faces) after alcohol consumption, which may play a role in alcohol-related aggression. Here we discuss a putative mechanism that may explain how alcohol consumption influences emotional processing and subsequent aggressive responding, via disruption of orbitofrontal cortex (OFC)-amygdala connectivity. While the importance of emotional processing on social behaviours is well established, research into acute alcohol consumption and emotional processing is still in its infancy. Further research is needed and we outline a research agenda to address gaps in the literature.

  14. Variable Effects of Non-steroidal Anti-inflammatory Drugs (NSAIDs) on Selected Biochemical Processes Mediated by Soil Microorganisms

    PubMed Central

    Cycoń, Mariusz; Borymski, Sławomir; Żołnierczyk, Bartłomiej; Piotrowska-Seget, Zofia

    2016-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently used group of pharmaceuticals. The high consumption and the uncontrolled disposal of unused drugs into municipal waste or their deposit in landfills can result in an increased concentration of these compounds in soils. Moreover, these drugs can affect the microbial activity. However, there is a lack of knowledge about these effects or it is very limited. Therefore, the objective of this study was to compare the impact of selected commercially available NSAIDs, i.e., diclofenac (DCF), naproxen (NPX), ibuprofen (IBF) and ketoprofen (KTP), applied at concentrations of 1 and 10 mg/kg soil, on the activity of soil microorganisms during the 90-day experiment. To ascertain this impact, substrate-induced respiration (SIR), soil enzyme activities, i.e., dehydrogenase (DHA), acid and alkaline phosphatases (PHOS-H and PHOS-OH) and urease (URE) as well as changes in the rates of nitrification and ammonification processes were determined. In addition, the number of culturable bacteria and fungi were enumerated. In general, the obtained data showed a significant stimulatory effect of NSAIDs on the microbial activity. Higher concentrations of NSAIDs caused a greater effect, which was observed for SIR, PHOS-H, PHOS-OH, URE, N-NO3- and N-NH4+, even during the whole incubation period. Moreover, the number of heterotrophic bacteria and fungi increased significantly during the experiment, which was probably a consequence of the evolution of specific microorganisms that were capable of degrading NSAIDs and used them as an additional source of carbon and energy. However, an inhibitory effect of NPX, IBF or KTP for SIR, DHA, on both phosphatases and culturable bacteria and fungi was observed at the beginning of the experiment. At lower concentrations of NSAIDs, in turn, the effects were negligible or transient. In conclusion, the application of NSAIDs altered the biochemical and microbial activity of soil what may

  15. Radiological Followup of the Evolution of Inflammatory Process in Sacroiliac Joint with Magnetic Resonance Imaging: A Case with Pyogenic Sacroiliitis

    PubMed Central

    Cinar, Muhammet; Sanal, Hatice Tugba; Yilmaz, Sedat; Simsek, Ismail; Erdem, Hakan; Pay, Salih; Dinc, Ayhan

    2012-01-01

    Pyogenic sacroiliitis (PS) is an acute form of sacroiliitis that mostly starts with very painful buttock pain. Here in this case, the followup magnetic resonance (MR) images of a 49-year-old male patient with PS is displayed. After his sacroiliitis was documented by MR images, he was treated with the combination of rifampicin plus streptomycin and moxifloxacin. Serial MR investigations were done to disclose acute and subsequent imaging changes concerning sacroiliac joint and surrounding bone structures. Although after treatment all the symptoms were completely resolved, 20 months later changes suggesting active sacroiliitis on MR images were continuing. PMID:23050188

  16. The opposing effects of ghrelin on hypothalamic and systemic inflammatory processes are modulated by its acylation status and food intake in male rats.

    PubMed

    García-Cáceres, Cristina; Fuente-Martín, Esther; Díaz, Francisca; Granado, Miriam; Argente-Arizón, Pilar; Frago, Laura M; Freire-Regatillo, Alejandra; Barrios, Vicente; Argente, Jesús; Chowen, Julie A

    2014-08-01

    Ghrelin is an endogenous hormone that stimulates appetite and adipose tissue accrual. Both the acylated (AG) and non-acylated (DAG) isoforms of this hormone are also reported to exert anti-inflammatory and protective effects systemically and in the central nervous system. As inflammatory processes have been implicated in obesity-associated secondary complications, we hypothesized that this natural appetite stimulator may protect against negative consequences resulting from excessive food intake. Adult male Wistar rats were treated icv (5 μg/day) with AG, DAG, the ghrelin mimetic GH-releasing peptide (GHRP)-6, AG, and pair-fed with controls (AG-pf) or saline for 14 days. Regardless of food intake AG increased visceral adipose tissue (VAT) and decreased circulating cytokine levels. However, AG reduced cytokine production in VAT only in rats fed ad libitum. Hypothalamic cytokine production was increased in AG-treated rats fed ad libitum and by DAG, but intracellular inflammatory signaling pathways associated with insulin and leptin resistance were unaffected. Gliosis was not observed in response to any treatment as glial markers were either reduced or unaffected. AG, DAG, and GHRP-6 stimulated production of hypothalamic insulin like-growth factor I that is involved in cell protective mechanisms. In hypothalamic astrocyte cell cultures AG decreased tumor necrosis factorα and DAG decreased interleukin-1β mRNA levels, suggesting direct anti-inflammatory effects on astrocytes. Thus, whereas ghrelin stimulates food intake and weight gain, it may also induce mechanisms of cell protection that help to detour or delay systemic inflammatory responses and hypothalamic gliosis due to excess weight gain, as well as its associated pathologies.

  17. Comparative effectiveness research on patients with acute ischemic stroke using Markov decision processes

    PubMed Central

    2012-01-01

    Background Several methodological issues with non-randomized comparative clinical studies have been raised, one of which is whether the methods used can adequately identify uncertainties that evolve dynamically with time in real-world systems. The objective of this study is to compare the effectiveness of different combinations of Traditional Chinese Medicine (TCM) treatments and combinations of TCM and Western medicine interventions in patients with acute ischemic stroke (AIS) by using Markov decision process (MDP) theory. MDP theory appears to be a promising new method for use in comparative effectiveness research. Methods The electronic health records (EHR) of patients with AIS hospitalized at the 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine between May 2005 and July 2008 were collected. Each record was portioned into two "state-action-reward" stages divided by three time points: the first, third, and last day of hospital stay. We used the well-developed optimality technique in MDP theory with the finite horizon criterion to make the dynamic comparison of different treatment combinations. Results A total of 1504 records with a primary diagnosis of AIS were identified. Only states with more than 10 (including 10) patients' information were included, which gave 960 records to be enrolled in the MDP model. Optimal combinations were obtained for 30 types of patient condition. Conclusion MDP theory makes it possible to dynamically compare the effectiveness of different combinations of treatments. However, the optimal interventions obtained by the MDP theory here require further validation in clinical practice. Further exploratory studies with MDP theory in other areas in which complex interventions are common would be worthwhile. PMID:22400712

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

    PubMed

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

    2016-10-01

    Long-term exposure to inorganic arsenic (iAs) through drinking water has been associated with cognitive impairment in children and adults; however, the related pathogenic mechanisms have not been completely described. Increased or chronic inflammation in the brain is linked to impaired cognition and neurodegeneration; iAs induces strong inflammatory responses in several cells, but this effect has been poorly evaluated in central nervous system (CNS) cells. Because astrocytes are the most abundant cells in the CNS and play a critical role in brain homeostasis, including regulation of the inflammatory response, any functional impairment in them can be deleterious for the brain. We propose that iAs could induce cognitive impairment through inflammatory response activation in astrocytes. In the present work, rat cortical astrocytes were acutely exposed in vitro to the monomethylated metabolite of iAs (MMA(III)), which accumulates in glial cells without compromising cell viability. MMA(III) LD50 in astrocytes was 10.52 μM, however, exposure to sub-toxic MMA(III) concentrations (50-1000 nM) significantly increased IL-1β, IL-6, TNF-α, COX-2, and MIF-1 gene expression. These effects were consistent with amyloid precursor protein (APP) and β-secretase (BACE-1) increased gene expression, mainly for those MMA(III) concentrations that also induced TNF-α over-expression. Other effects of MMA(III) on cortical astrocytes included increased proliferative and metabolic activity. All tested MMA(III) concentrations led to an inhibition of intracellular lactate dehydrogenase (LDH) activity. Results suggest that MMA(III) induces important metabolic and functional changes in astrocytes that may affect brain homeostasis and that inflammation may play a major role in cognitive impairment-related pathogenicity in As-exposed populations.

  19. Hormonal regulation of pro-inflammatory and lipid peroxidation processes in liver of old ovariectomized female rats.

    PubMed

    Kireev, R A; Tresguerres, A C F; Garcia, C; Borras, C; Ariznavarreta, C; Vara, E; Vina, J; Tresguerres, J A F

    2010-04-01

    There is now a large body of evidence suggesting that the decline in ovarian function with menopause is associated with spontaneous increases in pro-inflammatory cytokines. On the other hand, oxidative stress has been implicated in the pathogenesis of several alterations due to menopause, and can arise through the increased production of lipid peroxides (LPO) and/or a deficiency of antioxidant defense. The aim of the present study was to investigate the effect of aging and ovariectomy on various physiological parameters related to inflammation and oxidative stress in livers obtained from old female rats and the influence of chronic exogenous administration of estrogens, phytoestrogens and growth hormone on these. Thirty-six female Wistar rats of 22 months of age were used in the present study. Twelve of them remained intact, and the other 24 had been ovariectomized at 12 months of age. Intact animals were divided into two groups and treated for 10 weeks with GH or saline, and ovariectomized animals were divided into four groups and treated for the same time with GH, estrogens, phytoestrogens or saline. A group of 2 month old intact female rats was used as young control. Protein expression of iNOS, HO-1, IL-6, TNFalpha, and IL-1beta were determined by Western blot analysis. The levels of NO( x ), LPO, TNFalpha, IL-1beta, IL-6 and IL-10 were determined in different fractions of the liver. Levels of LPO in the liver homogenates as well as iNOS protein expression and NO( x ) levels were increased in old rats as compared to young animals; this effect was more evident in ovariectomized animals. Pro-inflammatory cytokines TNF-alpha, IL-1beta and IL-6 were significantly increased and anti-inflammatory IL-10 decreased during ageing and after ovariectomy. Aging also significantly increased expression of HO-1 protein and ovariectomized rats showed an additional increase. Hormonal administration to the ovariectomized groups decreased NO( x ), LPO levels and pro-inflammatory

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

    PubMed

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

    2016-08-01

    Mammalian heat-shock-protein (HSP) 90α rapidly responses to environmental insults. We examined the hypothesis that not only serum HSP72 but also HSP90α is increased in the systemic inflammatory response syndrome (SIRS), severe-sepsis (SS), and/or sepsis (S) compared to healthy children (H); we assessed HSP90α relation to (a) multiple organ system failure (MOSF) and (b) inflammatory-metabolic response and severity of illness.A total of 65 children with S, SS, or SIRS and 25 H were included. ELISA was used to evaluate extracellular HSP90α and HSP72, chemiluminescence interleukins (ILs), flow-cytometry neutrophil-CD64 (nCD64)-expression.HSP90α, along with HSP72, were dramatically increased among MOSF patients. Patients in septic groups and SIRS had elevated HSP90α compared to H (P < 0.01). HSP90α was independently related to predicted death rate and severity of illness; positively to HSP72, nCD64, ILs, length of stay, days on ventilator, and fever; negatively to HDL and LDL (P < 0.05). The HSP72 was increased in SS/S and related negatively to HDL and LDL (P < 0.05).Serum HSP90α is markedly elevated in children with severe sepsis and is associated with MOSF. Better than the HSP72, also increased in SS, SIRS, and MOSF, HSP90α is related to the inflammatory stress, fever, outcome endpoints, and predicted mortality and inversely related to the low-LDL/low-HDL stress metabolic pattern.

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

    PubMed

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

    2017-01-01

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

  2. The PPAR-γ agonist, darglitazone, restores acute inflammatory responses to cerebral hypoxia–ischemia in the diabetic ob/ob mouse

    PubMed Central

    Kumari, Rashmi; Willing, Lisa B; Patel, Shyama D; Krady, J Kyle; Zavadoski, William J; Gibbs, E Michael; Vannucci, Susan J; Simpson, Ian A

    2010-01-01

    Diabetes is an increased risk factor for stroke and results in increased brain damage in experimental animals and humans. The precise mechanisms are unclear, but our earlier studies in the db/db mice suggested that the cerebral inflammatory response initiating recovery was both delayed and diminished in the diabetic mice compared with the nondiabetic db/+ mice. In this study, we investigated the actions of the peroxisome proliferator-activated receptor (PPAR)-γ agonist darglitazone in treating diabetes and promoting recovery after a hypoxic-ischemic (H/I) insult in the diabetic ob/ob mouse. Male ob/+ and ob/ob mice received darglitazone (1 mg/kg) for 7 days before induction of H/I. Darglitazone restored euglycemia and normalized elevated corticosterone, triglycerides, and very-low-density lipoprotein levels. Darglitazone dramatically reduced the infarct size in the ob/ob mice at 24 h of recovery compared with the untreated group (30±13% to 3.3±1.6%, n=6 to 8) but did not show any significant effect in the ob/+ mice. Microglial and astrocytic activation monitored by cytokine expression (interleukin-1β and tumor necrosis factor-α) and in situ hybridization studies (bfl1 and glial fibrillary acidic protein) suggest a biphasic inflammatory response, with darglitazone restoring the compromised proinflammatory response(s) in the diabetic mouse at 4 h but suppressing subsequent inflammatory responses at 8 and 24 h in both control and diabetic mice. PMID:19861974

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

    PubMed Central

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

    2016-01-01

    Abstract Mammalian heat-shock-protein (HSP) 90α rapidly responses to environmental insults. We examined the hypothesis that not only serum HSP72 but also HSP90α is increased in the systemic inflammatory response syndrome (SIRS), severe-sepsis (SS), and/or sepsis (S) compared to healthy children (H); we assessed HSP90α relation to (a) multiple organ system failure (MOSF) and (b) inflammatory-metabolic response and severity of illness. A total of 65 children with S, SS, or SIRS and 25 H were included. ELISA was used to evaluate extracellular HSP90α and HSP72, chemiluminescence interleukins (ILs), flow-cytometry neutrophil-CD64 (nCD64)-expression. HSP90α, along with HSP72, were dramatically increased among MOSF patients. Patients in septic groups and SIRS had elevated HSP90α compared to H (P < 0.01). HSP90α was independently related to predicted death rate and severity of illness; positively to HSP72, nCD64, ILs, length of stay, days on ventilator, and fever; negatively to HDL and LDL (P < 0.05). The HSP72 was increased in SS/S and related negatively to HDL and LDL (P < 0.05). Serum HSP90α is markedly elevated in children with severe sepsis and is associated with MOSF. Better than the HSP72, also increased in SS, SIRS, and MOSF, HSP90α is related to the inflammatory stress, fever, outcome endpoints, and predicted mortality and inversely related to the low-LDL/low-HDL stress metabolic pattern. PMID:27583886

  4. Potentiation of indomethacin-induced anti-inflammatory response by pioglitazone in carrageenan-induced acute inflammation in rats: Role of PPARγ receptors.

    PubMed

    Houshmand, Gholamreza; Mansouri, Mohammad Taghi; Naghizadeh, Bahareh; Hemmati, Ali Asghar; Hashemitabar, Mahmoud

    2016-09-01

    This study aimed to assess the interaction between anti-inflammatory effects of pioglitazone (peroxysome proliferator activated receptor-gamma (PPARγ) agonist, PGL), and indomethacin (cyclooxygenase (COX) inhibitor, IND) and to evaluate the possible underlying mechanisms. Paw edema induced by carrageenan was used to induce inflammation. Different doses of IND (0.3-10mg/kg) and PGL (1-20mg/kg) alone or in combination were administered intraperitoneally to rats. Paw tissue levels of PPARγ, COX-2, and prostaglandin E2 and serum levels of TNF-α and IL-10 were also estimated. Doses of IND and PGL showed a statistically significant anti-inflammatory effect. Combination of a non-effective dose of IND (0.3mg/kg) with increasing doses of PGL (1-10mg/kg) resulted in potentiated anti-inflammation and vise versa. IND, PGL and the combination were able to reduce the COX-2, PGE2 contents and TNF-α level. Moreover, all these treatments caused elevation in PPARγ levels and IL-10 levels. However, when the rats were pre-treated with GW-9662 (a selective PPARγ antagonist), all the anti-inflammation and alterations in the biochemical factors were antagonized. These results showed that PGL markedly enhanced the anti-inflammatory activity of IND and this effect mediated partly at least, through PPARγ. Possible mechanisms of the interaction were that PGL stimulates the PPARγ and inhibits COX-2 by those cytokines that trigger the PPARγ and also inhibit COX-2. This study suggests that combination therapy with pioglitazone and indomethacin may provide an alternative for the clinical control of inflammation especially in patients with diabetes.

  5. Anti-inflammatory and antioxidant effects of curcumin on acute lung injury in a rodent model of intestinal ischemia reperfusion by inhibiting the pathway of NF-Kb

    PubMed Central

    Fan, Zhe; Yao, Jihong; Li, Yang; Hu, Xiaowei; Shao, Huizhu; Tian, Xiaofeng

    2015-01-01

    Objective: To investigate the anti-inflammatory and antioxidant effect of curcumin on lung lesion induced by intestinal ischemia reperfusion injury (IIR). Methods: Rats were divided into four groups: sham, intestinal IIR (IIR), 1 mg/kg of curcumin treatment group (1 mg/kg), and 5 mg/kg of curcumin treatment group (5 mg/kg). Curcumin was given respectively (1 mg/kg and 5 mg/kg) following the above doses. IIR was produced by 1 h of intestinal ischemia followed by 2 h of reperfusion. Rats were sacrificed at the end of reperfusion and lung tissues were collected for biochemical and histopathological examination in 4 groups. Lung tissues histology and bronchoalveolar lavage fluid (BALF) protein were assayed. Serum IL-6, lung superoxide dismutase (SOD) and myeloperoxidase (MPO) were measured. The expression level of NF-κB and ICAM-1 (including immunohistochemical analysis and western blot analysis) were also measured. Results: Lung tissue injury induced by IIR was obviously observed through pathology and BALF protein. MPO activity, IL-6 level and ICAM-1 expression were significantly increased with the elevation of NF-κB, simultaneously, SOD activity was decreased. With Treatment of curcumin, pathology and BALF protein of lung tissue were improved clearly. Inflammatory indexes (MPO activity, IL-6 level and ICAM-1) were improved and antioxidant index (SOD activity) was enhanced paralleled with NF-κB. Conclusion: Using curcumin effectively prevented IIR-induced lung injury. Anti-inflammatory and antioxidant effects of curcumin could be observed by inhibiting the pathway of NF-κB. PMID:26097529

  6. Acute intradialytic cardiac function and inflammatory cytokine changes during high-efficiency online hemodiafiltration with acetate-free and standard dialysis solutions.

    PubMed

    Tiranathanagul, Khajohn; Tangvoraphonkchai, Kamonwan; Srisawat, Nattachai; Susantitaphong, Paweena; Tungsanga, Kriang; Praditpornsilpa, Kearkiat; Eiam-Ong, Somchai

    2015-06-01

    Acetate in standard acetate-containing bicarbonate (AC) dialysis fluid could induce peripheral vasodilatation, suppression of myocardial function, and inflammatory cytokine production, resulting in intradialytic hypotension in conventional hemodialysis (HD) patients. Online hemodiafiltration (HDF) provides superior hemodynamic stability over HD. The potentially additive hemodynamic benefits of the novel acetate-free bicarbonate (AF) dialysis fluid in online HDF have never been explored before. The present randomized, double-blind, crossover study was conducted in 22 online HDF patients to investigate the impact of AF dialysis fluid on hemodynamic and cytokine changes compared with AC dialysis fluid in online HDF. The results demonstrated the comparable changes of arterial pressure between AF and AC online HDF. During the study periods, the incidences of composite intradialytic hypotension and other adverse events were not different. The baseline and hourly changes of cardiac index, cardiac output, and peripheral vascular resistance during dialysis were comparable (P=0.534, 0.199, and 0.641, respectively). The percent reductions of NT-proBNP and cTnT were not significantly different (72.6 ± 12.3 vs. 72.6 ± 12.8%, P=0.99 and 35.2 ± 12.8 vs. 36.7 ± 12.0%, P=0.51). The changes of all pro-inflammatory cytokines (IL-2β, IL-6, IL-8, and TNF-α) and anti-inflammatory cytokine (IL-10) during dialysis were comparable between both groups. In conclusion, AF dialysis solution does not offer additional hemodynamic benefit for stable online HDF patients. The hemodynamic stability provided by online HDF might protect the adverse effects of acetate.

  7. Inflammatory cytokine kinetics to single bouts of acute moderate and intense aerobic exercise in women with active and inactive systemic lupus erythematosus.

    PubMed

    Perandini, L A; Sales-de-Oliveira, D; Mello, Sbv; Camara, N O; Benatti, F B; Lima, F R; Borba, E; Bonfa, E; Roschel, H; Sá-Pinto, A L; Gualano, B

    2015-01-01

    The aim of this study was to evaluate changes in the cytokines INF-γ, IL-10, IL-6, TNF-α and soluble TNF receptors (sTNFR1 and sTNFR2) in response to single bouts of acute moderate and intense exercise in systemic lupus erythematosus women with active (SLE(ACTIVE)) and inactive (SLE(INACTIVE)) disease. Twelve SLE(INACTIVE) women (age: 35.3 ± 5.7 yrs; BMI: 25.6±3.4 kg/m2), eleven SLE(ACTIVE) women (age: 30.4 ± 4.5 yrs; BMI: 26.1±4.8 kg/m2), and 10 age- and BMI-matched healthy control women (HC) performed 30 minutes of acute moderate (~50% of VO(2)peak) and intense (~70% of VO(2)peak) exercise bout. Cytokines and soluble TNF receptors were assessed at baseline, immediately after, every 30 minutes up to three hours, and 24 hours after both acute exercise bouts. In response to acute moderate exercise, cytokines and soluble TNF receptors levels remained unchanged in all groups (P>0.05), except for a reduction in IL-6 levels in the SLE(ACTIVE) group at the 60th and 180th minutes of recovery (P<0.05), and a reduction in sTNFR1 levels in the HC group at the 90th, 120th, 150th, 180th minutes of recovery (P<0.05). The SLE(INACTIVE) group showed higher levels of TNF-α, sTNFR1, and sTNFR2 at all time points when compared with the HC group (P<0.05). Also, the SLE(ACTIVE) group showed higher levels of IL-6 at the 60th minute of recovery (P<0.05) when compared with the HC group. After intense exercise, sTNFR1 levels were reduced at the 150th (P=0.041) and 180th (P=0.034) minutes of recovery in the SLE(INACTIVE) group, whereas the other cytokines and sTNFR2 levels remained unchanged (P>0.05). In the HC group, IL-10, TNF-α, sTNFR1, and sTNFR2 levels did not change, whilst INF-γ levels decreased (P=0.05) and IL-6 levels increased immediately after the exercise (P=0.028), returning to baseline levels 24 hours later (P > 0.05). When compared with the HC group, the SLE(INACTIVE) group showed higher levels of TNF-α and sTNFR2 in all time points, and higher levels of sTNFR1 at

  8. [Acute respiratory distress syndrome].

    PubMed

    Matĕjovic, M; Novák, I; Srámek, V; Rokyta, R; Hora, P; Nalos, M

    1999-04-26

    Acute respiratory distress syndrome (ARDS) is the general term used for severe acute respiratory failure of diverse aetiology. It is associated with a high morbidity, mortality (50-70%), and financial costs. Regardless of aetiology, the basic pathogenesis of ARDS is a systemic inflammatory response leading to a diffuse inflammatory process that involves both lungs, thus causing diffuse alveolar and endothelial damage with increased pulmonary capillary permeability and excessive extravascular lung water accumulation. ARDS is commonly associated with sepsis and multiple organ failure. The clinical picture involves progressive hypoxaemia, radiographic evidence of pulmonary oedema, decreased lung compliance and pulmonary hypertension. Despite the scientific and technological progress in critical care medicine, there is no specific ARDS therapy available at the moment and its management remains supportive. Therapeutic goals include resolution of underlying conditions, maintenance of acceptable gas exchange and tissue oxygenation and prevention of iatrogenic lung injury. Many new specific therapeutic strategies have been developed, however, most of them require further scientific evaluation. The paper reviews definition, basic pathogenesis and pathophysiology of ARDS and discusses current concepts of therapeutic possibilities of ARDS.

  9. [Quality indicators in the acute coronary syndrome for the analysis of the pre- and in-hospital care process].

    PubMed

    Felices-Abad, F; Latour-Pérez, J; Fuset-Cabanes, M P; Ruano-Marco, M; Cuñat-de la Hoz, J; del Nogal-Sáez, F

    2010-01-01

    We present a map of 27 indicators to measure the care quality given to patients with acute coronary syndrome attended in the pre- and hospital area. This includes technical process indicators (registration of care intervals, performance of electrocardiogram, monitoring and vein access, assessment of prognostic risk, hemorrhage and in-hospital mortality, use of reperfusion techniques and performance of echocardiograph), pharmacological process indicators (platelet receptors inhibition, anticoagulation, thrombolysis, beta-blockers, angiotensin converting inhibitors and lipid lowering drugs) and outcomes indicators (quality scales of the care given and mortality).

  10. Hydrogen sulfide (H2S) attenuates uranium-induced acute nephrotoxicity through oxidative stress and inflammatory response via Nrf2-NF-κB pathways.

    PubMed

    Zheng, Jifang; Zhao, Tingting; Yuan, Yan; Hu, Nan; Tang, Xiaoqing

    2015-12-05

    As an endogenous gaseous mediator, H2S exerts anti-oxidative, anti-inflammatory and cytoprotective effects in kidneys. This study was designed to investigate the protective effect of H2S against uranium-induced nephrotoxicity in adult SD male rats after in vivo effect of uranium on endogenous H2S formation was explored in kidneys. The levels of endogenous H2S and H2S-producing enzymes (CBS and CSE) were measured in renal homogenates from rats intoxicated by an intraperitoneally (i.p.) injection of uranyl acetate at a single dose of 2.5, 5 or 10 mg/kg. In rats injected i.p. with uranyl acetate (5 mg/kg) or NaHS (an H2S donor, 28 or 56 μmol/kg) alone or in combination, we determined biochemical parameters and histopathological alteration to assess kidney function, examined oxidative stress markers, and investigated Nrf2 and NF-κB pathways in kidney homogenates. The results suggest that uranium intoxication in rats decreased endogenous H2S generation as well as CBS and CSE protein expression. NaHS administration in uranium-intoxicated rats ameliorated the renal biochemical indices and histopathological effects, lowered MDA accumulation, and restored GSH level and anti-oxidative enzymes activities like SOD, CAT, GPx and GST. NaHS treatment in uranium-intoxicated rats activated uranium-inhibited protein expression and nuclear translocation of transcription factor Nrf2, which increased protein expression of downstream target-Nrf2 genes HO-1, NQO-1, GCLC, and TXNRD-1. NaHS administration in uranium-intoxicated rats inhibited uranium-induced nuclear translocation and phosphorylation of transcription factor κB/p65, which decreased protein expression of target-p65 inflammatory genes TNF-α, iNOS, and COX-2. Taken together, these data implicate that H2S can afford protection to rat kidneys against uranium-induced adverse effects through induction of antioxidant defense by activating Nrf2 pathway and reduction of inflammatory response by suppressing NF-κB pathway.

  11. Dihydro-Resveratrol Ameliorates Lung Injury in Rats with Cerulein-Induced Acute Pancreatitis.

    PubMed

    Lin, Ze-Si; Ku, Chuen Fai; Guan, Yi-Fu; Xiao, Hai-Tao; Shi, Xiao-Ke; Wang, Hong-Qi; Bian, Zhao-Xiang; Tsang, Siu Wai; Zhang, Hong-Jie

    2016-04-01