H₂S and substance P in inflammation.

PubMed

Bhatia, Madhav

2015-01-01

Hydrogen sulfide (H2S) and substance P play a key role in inflammation. Using animal models of inflammation of different etiologies such as acute pancreatitis, sepsis, burns, and joint inflammation, studies have recently shown an important role of the proinflammatory action of H2S and substance P. Also, H2S contributes to inflammation in different conditions via substance P. This chapter reviews methods and key data that have led to our current understanding of the role of H2S and substance P in inflammation. © 2015 Elsevier Inc. All rights reserved.

G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling

PubMed Central

Bajrami, Besnik; Zhu, Haiyan; Zhang, Yu C.

2016-01-01

Cytokine-induced neutrophil mobilization from the bone marrow to circulation is a critical event in acute inflammation, but how it is accurately controlled remains poorly understood. In this study, we report that CXCR2 ligands are responsible for rapid neutrophil mobilization during early-stage acute inflammation. Nevertheless, although serum CXCR2 ligand concentrations increased during inflammation, neutrophil mobilization slowed after an initial acute fast phase, suggesting a suppression of neutrophil response to CXCR2 ligands after the acute phase. We demonstrate that granulocyte colony-stimulating factor (G-CSF), usually considered a prototypical neutrophil-mobilizing cytokine, was expressed later in the acute inflammatory response and unexpectedly impeded CXCR2-induced neutrophil mobilization by negatively regulating CXCR2-mediated intracellular signaling. Blocking G-CSF in vivo paradoxically elevated peripheral blood neutrophil counts in mice injected intraperitoneally with Escherichia coli and sequestered large numbers of neutrophils in the lungs, leading to sterile pulmonary inflammation. In a lipopolysaccharide-induced acute lung injury model, the homeostatic imbalance caused by G-CSF blockade enhanced neutrophil accumulation, edema, and inflammation in the lungs and ultimately led to significant lung damage. Thus, physiologically produced G-CSF not only acts as a neutrophil mobilizer at the relatively late stage of acute inflammation, but also prevents exaggerated neutrophil mobilization and the associated inflammation-induced tissue damage during early-phase infection and inflammation. PMID:27551153

Reversal of acute and chronic synovial inflammation by anti-transforming growth factor beta.

PubMed

Wahl, S M; Allen, J B; Costa, G L; Wong, H L; Dasch, J R

1993-01-01

Transforming growth factor beta (TGF-beta) induces leukocyte recruitment and activation, events central to an inflammatory response. In this study, we demonstrate that antagonism of TGF-beta with a neutralizing antibody not only blocks inflammatory cell accumulation, but also tissue pathology in an experimental model of chronic erosive polyarthritis. Intraarticular injection of monoclonal antibody 1D11.16, which inhibits both TGF-beta 1 and TGF-beta 2 bioactivity, into animals receiving an arthropathic dose of bacterial cell walls significantly inhibits arthritis. Inhibition was observed with a single injection of 50 micrograms antibody, and a 1-mg injection blocked acute inflammation > 75% compared with the contralateral joints injected with an irrelevant isotype control antibody (MOPC21) as quantitated by an articular index (AI = 0.93 +/- 0.23 for 1D11.16, and AI = 4.0 +/- 0 on day 4; p < 0.001). Moreover, suppression of the acute arthritis achieved with a single injection of antibody was sustained into the chronic, destructive phase of the disease (on day 18, AI = 0.93 +/- 0.07 vs. AI = 2.6 +/- 0.5; p < 0.01). The decreased inflammatory index associated with anti-TGF-beta treatment was consistent with histopathologic and radiologic evidence of a therapeutic response. These data implicate TGF-beta as a profound agonist not only in the early events responsible for synovial inflammation, but also in the chronicity of streptococcal cell wall fragment-induced inflammation culminating in destructive pathology. Interrupting the cycle of leukocyte recruitment and activation with TGF-beta antagonists may provide a mechanism for resolution of chronic destructive lesions.

Reversal of acute and chronic synovial inflammation by anti- transforming growth factor beta

PubMed Central

1993-01-01

Transforming growth factor beta (TGF-beta) induces leukocyte recruitment and activation, events central to an inflammatory response. In this study, we demonstrate that antagonism of TGF-beta with a neutralizing antibody not only blocks inflammatory cell accumulation, but also tissue pathology in an experimental model of chronic erosive polyarthritis. Intraarticular injection of monoclonal antibody 1D11.16, which inhibits both TGF-beta 1 and TGF-beta 2 bioactivity, into animals receiving an arthropathic dose of bacterial cell walls significantly inhibits arthritis. Inhibition was observed with a single injection of 50 micrograms antibody, and a 1-mg injection blocked acute inflammation > 75% compared with the contralateral joints injected with an irrelevant isotype control antibody (MOPC21) as quantitated by an articular index (AI = 0.93 +/- 0.23 for 1D11.16, and AI = 4.0 +/- 0 on day 4; p < 0.001). Moreover, suppression of the acute arthritis achieved with a single injection of antibody was sustained into the chronic, destructive phase of the disease (on day 18, AI = 0.93 +/- 0.07 vs. AI = 2.6 +/- 0.5; p < 0.01). The decreased inflammatory index associated with anti-TGF-beta treatment was consistent with histopathologic and radiologic evidence of a therapeutic response. These data implicate TGF-beta as a profound agonist not only in the early events responsible for synovial inflammation, but also in the chronicity of streptococcal cell wall fragment-induced inflammation culminating in destructive pathology. Interrupting the cycle of leukocyte recruitment and activation with TGF-beta antagonists may provide a mechanism for resolution of chronic destructive lesions. PMID:8418203

Tenascin-C levels in synovial fluid are elevated after injury to the human and canine joint and correlate with markers of inflammation and matrix degradation.

PubMed

Chockalingam, P S; Glasson, S S; Lohmander, L S

2013-02-01

We have previously shown the capacity of tenascin-C (TN-C) to induce inflammatory mediators and matrix degradation in vitro in human articular cartilage. The objective of the present study was to follow TN-C release into knee synovial fluid after acute joint injury or in joint disease, and to correlate TN-C levels with markers of cartilage matrix degradation and inflammation. Human knee synovial fluid samples (n = 164) were from a cross-sectional convenience cohort. Diagnostic groups were knee healthy reference, knee anterior cruciate ligament rupture, with or without concomitant meniscus lesions, isolated knee meniscus injury, acute inflammatory arthritis (AIA) and knee osteoarthritis (OA). TN-C was measured in synovial fluid samples using an enzyme-linked immunosorbent assay (ELISA) and results correlated to other cartilage markers. TN-C release was also monitored in joints of dogs that underwent knee instability surgery. Statistically significantly higher levels of TN-C compared to reference subjects were observed in the joint fluid of all human disease groups and in the dogs that underwent knee instability surgery. Statistically significant correlations were observed between the TN-C levels in the synovial fluid of the human patients and the levels of aggrecanase-dependent Ala-Arg-Gly-aggrecan (ARG-aggrecan) fragments and matrix metalloproteinases 1 and 3. We find highly elevated levels of TN-C in human knee joints after injury, AIA or OA that correlated with markers of cartilage degradation and inflammation. TN-C in synovial fluid may serve dual roles as a marker of joint damage and a stimulant of further joint degradation. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Intraspinal release of immunoreactive calcitonin gene-related peptide during development of inflammation in the joint in vivo--a study with antibody microprobes in cat and rat.

PubMed

Schaible, H G; Freudenberger, U; Neugebauer, V; Stiller, R U

1994-10-01

This study addressed the intraspinal release of immunoreactive calcitonin gene-related peptide in vivo during mechanical stimulation of the normal joint and during the development of an acute experimental inflammation in the knee joint in the anaesthetized cat (spinalized) and rat (not spinalized). Release was assessed using microprobes coated with antibody to calcitonin gene-related peptide; inhibition of binding of [125I]calcitonin gene-related peptide to these probes following insertion into the spinal cord is equated with intraspinal release of the endogenous (unlabelled) peptide. Probes inserted prior to inflammation showed marked basal release of immunoreactive calcitonin gene-related peptide in the dorsal horn with a maximum in the superficial dorsal horn in the absence of intentional stimulation. The pattern of binding of [125I]calcitonin gene-related peptide was not or only minimally changed by innocuous mechanical stimuli (flexion of and innocuous pressure to the knee in the cat and innocuous pressure to the knee of the rat) but was significantly altered by electrical stimulation of the tibial nerve in the cat (sufficient to excite unmyelinated afferent fibres), indicating release of the peptide by the latter stimulus. During the first hours of the development of an experimental inflammation in the knee joint induced by intra-articular injections of kaolin and carrageenan, the pattern of binding of [125I]calcitonin gene-related peptide changed. In the cat, the level of immunoreactive calcitonin gene-related peptide showed a persistent increase in the gray matter and up to the surface of the cord and release was slightly increased by innocuous stimuli. In the rat, increased levels of immunoreactive calcitonin gene-related peptide were mainly seen in the superficial and deep dorsal horn during innocuous pressure (this stimulus did not evoke release of the peptide prior to inflammation) and noxious pressure applied to the injected knee, whereas increased

Monitoring inflammation (including fever) in acute brain injury.

PubMed

Provencio, J Javier; Badjatia, Neeraj

2014-12-01

Inflammation is an important part of the normal physiologic response to acute brain injury (ABI). How inflammation is manifest determines if it augments or hinders the resolution of ABI. Monitoring body temperature, the cellular arm of the inflammatory cascade, and inflammatory proteins may help guide therapy. This summary will address the utility of inflammation monitoring in brain-injured adults. An electronic literature search was conducted for English language articles describing the testing, utility, and optimal methods to measure inflammation in ABI. Ninety-four articles were included in this review. Current evidence suggests that control of inflammation after ABI may hold promise for advances in good outcomes. However, our understanding of how much inflammation is good and how much is deleterious is not yet clear. Several important concepts emerge form our review. First, while continuous temperature monitoring of core body temperature is recommended, temperature pattern alone is not useful in distinguishing infectious from noninfectious fever. Second, when targeted temperature management is used, shivering should be monitored at least hourly. Finally, white blood cell levels and protein markers of inflammation may have a limited role in distinguishing infectious from noninfectious fever. Our understanding of optimal use of inflammation monitoring after ABI is limited currently but is an area of active investigation.

Vinpocetine Inhibits NF-κB-Dependent Inflammation in Acute Ischemic Stroke Patients.

PubMed

Zhang, Fang; Yan, Chen; Wei, Changjuan; Yao, Yang; Ma, Xiaofeng; Gong, Zhongying; Liu, Shoufeng; Zang, Dawei; Chen, Jieli; Shi, Fu-Dong; Hao, Junwei

2018-04-01

Immunity and inflammation play critical roles in the pathogenesis of acute ischemic stroke. Therefore, immune intervention, as a new therapeutic strategy, is worthy of exploration. Here, we tested the inflammation modulator, vinpocetine, for its effect on the outcomes of stroke. For this multi-center study, we recruited 60 patients with anterior cerebral circulation occlusion and onset of stroke that had exceeded 4.5 h but lasted less than 48 h. These patients, after random division into two groups, received either standard management alone (controls) or standard management plus vinpocetine (30 mg per day intravenously for 14 consecutive days, Gedeon Richter Plc., Hungary). Vinpocetine treatment did not change the lymphocyte count; however, nuclear factor kappa-light-chain-enhancer of activated B cell activation was inhibited as seen not only by the increased transcription of IκBα mRNA but also by the impeded phosphorylation and degradation of IκBα and subsequent induction of pro-inflammatory mediators. These effects led to significantly reduced secondary lesion enlargement and an attenuated inflammation reaction. Compared to controls, patients treated with vinpocetine had a better recovery of neurological function and improved clinical outcomes during the acute phase and at 3-month follow-up. These findings identify vinpocetine as an inflammation modulator that could improve clinical outcomes after acute ischemic stroke. This study also indicated the important role of immunity and inflammation in the pathogenesis of acute ischemic stroke and the significance of immunomodulatory treatment. www.clinicaltrials.gov . Identifier: NCT02878772.

Age-related ventricular-vascular coupling during acute inflammation in humans: Effect of physical activity.

PubMed

Lane, Abbi D; Kappus, Rebecca M; Bunsawat, Kanokwan; Ranadive, Sushant M; Yan, Huimin; Phillips, Shane; Baynard, Tracy; Woods, Jeffrey A; Motl, Robert; Fernhall, Bo

2015-07-01

Aging is commonly accompanied by increased arterial and ventricular stiffness (determined by arterial elastance (Ea) and ventricular elastance (Elv)), augmented ventricular-vascular coupling ratios (Ea/Elv) and systemic inflammation. Acute inflammation may impact ventricular-vascular coupling and predispose older adults to cardiovascular events. However, physically active older adults have more compliant large arteries and left ventricles and lower inflammation than sedentary older adults. We hypothesized that acute inflammation would alter Ea, Elv, and Ea/Elv more in older versus younger adults but that higher levels of physical activity would attenuate inflammation-induced changes. End-systolic and central blood pressures were obtained using applanation tonometry before and at 24 and 48 h post-influenza vaccination in 24 older and 38 younger adults. Ultrasonography was used to measure ventricular volumes and other indices of cardiac performance. Physical activity was measured with accelerometry. Ea and Ea/Elv were maintained (p > 0.05), but Elv was reduced (p < 0.05) 24 h post-inflammation. Other indices of systolic performance were reduced in older but not younger adults; diastolic performance was attenuated in both groups 24 h post-inflammation (p < 0.05 for all). Older, but not younger, adults decreased central pressure during inflammation (p < 0.05). When controlled for age, physical activity was not related to the inflammation-induced changes in elastance (p > 0.05) except in the most active group of seniors (p < 0.05). Aging did not affect the elastance responses but did affect central blood pressure and other ventricular systolic responses to acute inflammation. Aging, not physical activity, appears to modulate cardiovascular responses to acute inflammation, except in the most active older adults. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Sulforaphane Modulates Joint Inflammation in a Murine Model of Complete Freund's Adjuvant-Induced Mono-Arthritis.

PubMed

Silva Rodrigues, João Francisco; Silva E Silva, Cristiane; França Muniz, Thayanne; de Aquino, Alana Fernanda; Neuza da Silva Nina, Larissa; Fialho Sousa, Nagila Caroline; Nascimento da Silva, Luis Claudio; de Souza, Breno Glaessner Gomes Fernandes; da Penha, Tatiana Aranha; Abreu-Silva, Ana Lúcia; de Sá, Joicy Cortez; Soares Fernandes, Elizabeth; Grisotto, Marcos Augusto Grigolin

2018-04-24

Rheumatoid arthritis (RA) is characterized by inflammation of one or more joints, and affects ~1% of the adult population worldwide. Sulforaphane (SFN) is a natural compound that has been suggested as an antioxidant. Here, SFN’s effects were evaluated in a murine mono-arthritis model. Mono-arthritis was induced in mice by a single intra-articular injection of Complete Freund’s Adjuvant (CFA-10 µg/joint, in 10 µL) into the ipsilateral joint. The contralateral joint received an equal volume of PBS. On the 4th day post-joint inflammation induction, animals received either SFN (10 mg/kg) or vehicle (3% DMSO in saline), intraperitoneally (i.p.), twice a day for 3 days. Joint swelling and secondary mechanical allodynia and hyperalgesia were evaluated over 7 days post-CFA. After this period, animals were culled and their blood and synovial fluid samples were collected for analysis of cell populations, cytokine release and thioredoxin reductase (TrxR) activity. Knee joint samples were also collected for histology. SFN reduced joint swelling and damage whilst increasing the recruitment of Ly6C⁺ and Ly6G⁺ cells to CFA-injected joints. SFN-treated animals presented down-regulation of CD11b and CD62L on synovial fluid Ly6G⁺ cells. Synovial fluid samples obtained from CFA-injected joints and plasma samples of SFN-treated mice presented higher levels of IL-6 and increased activity of TrxR, in comparison with controls. These results indicate that SFN reduces knee joint damage by modulating cell activation/migration to the joints, cytokine production and increasing the activity of TrxR, and therefore, may represent an alternative treatment to joint inflammation.

Influence of fitness and age on the endothelial response to acute inflammation.

PubMed

Schroeder, Elizabeth C; Lane-Cordova, Abbi D; Ranadive, Sushant M; Baynard, Tracy; Fernhall, Bo

2018-06-01

What is the central question of the study? What are the effects of age and fitness on the vascular response to acute inflammation in younger and older adults? What is the main finding and its importance? In older adults, cardiorespiratory fitness level has a differential impact on endothelial function after acute inflammation. Compared with older adults with low fitness, older, moderately fit adults have a greater decrease in endothelial function, similar to that of younger adults. These findings have important implications in support of the beneficial effects of higher cardiorespiratory fitness in maintaining vascular reactivity and the ability to respond to stressors. Inflammation is associated with greater risk of cardiovascular events and reduced vascular function with ageing. Higher cardiorespiratory fitness is associated with lower risk of cardiovascular events and better vascular function. We evaluated the role of fitness in the vascular response to acute inflammation in 26 younger adults (YA) and 62 older adults (OA). We used an influenza vaccine to induce acute inflammation. Blood pressure, flow-mediated dilatation (FMD), augmentation index, carotid elastic modulus and inflammatory markers were measured before and 24 h after vaccination. Peak oxygen uptake was measured via a treadmill test. 'Fit' was defined as a peak oxygen uptake greater than the age- and sex-determined 50th percentile according to the American College of Sports Medicine. An interaction effect existed for the FMD response during acute inflammation (P < 0.05). The YA (low fit, from 11.5 ± 1.8 to 9.2 ± 1.3%; moderately fit, from 11.9 ± 0.8 to 9.0 ± 0.8%) and moderately fit OA (from 7.5 ± 1.0 to 3.9 ± 0.8%) had similar reductions in FMD at 24 h (P < 0.05). Low-fit OA did not reduce FMD at 24 h (from 5.5 ± 0.4 to 5.2 ± 0.5%, P > 0.05). The reduction in FMD in YA was similar between fitness groups (P > 0.05). All groups had similar reductions in mean

Smoking Is Associated with Acute and Chronic Prostatic Inflammation: Results from the REDUCE Study.

PubMed

Moreira, Daniel M; Nickel, J Curtis; Gerber, Leah; Muller, Roberto L; Andriole, Gerald L; Castro-Santamaria, Ramiro; Freedland, Stephen J

2015-04-01

Both anti- and proinflammatory effects of cigarette smoking have been described. As prostate inflammation is common, we hypothesized smoking could contribute to prostate inflammation. Thus, we evaluated the association of smoking status with acute and chronic inflammation within the prostate of men undergoing prostate biopsy. We retrospectively analyzed 8,190 men ages 50 to 75 years with PSA levels between 2.5 and 10 ng/mL enrolled in the Reduction by Dutasteride of Prostate Cancer Events study. Smoking status was self-defined as never, former, or current. Prostate inflammation was assessed by systematic central review blinded to smoking status. The association of smoking with inflammation in the baseline, 2-year, and 4-year biopsies was evaluated with univariable and multivariable logistic regressions. At study enrollment, 1,233 (15%), 3,203 (39%), and 3,754 (46%) men were current, former, and never smokers, respectively. Current smokers were significantly younger and had smaller prostates than former and never smokers (all P < 0.05). Former smokers were significantly heavier than current and never smokers (P < 0.001). Acute and chronic prostate inflammations were identified in 1,261 (15%) and 6,352 (78%) baseline biopsies, respectively. In univariable analysis, current smokers were more likely to have acute inflammation than former (OR, 1.35; P, 0.001) and never smokers (OR, 1.36; P, 0.001). The results were unchanged at 2- and 4-year biopsies. In contrast, current smoking was linked with chronic inflammation in the baseline biopsy, but not at 2- and 4-year biopsies. In conclusion, among men undergoing prostate biopsy, current smoking was independently associated with acute and possibly chronic prostate inflammations. ©2015 American Association for Cancer Research.

Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis

PubMed Central

Philpott, Holly T.; O'Brien, Melissa; McDougall, Jason J.

2017-01-01

Abstract Osteoarthritis (OA) is a multifactorial joint disease, which includes joint degeneration, intermittent inflammation, and peripheral neuropathy. Cannabidiol (CBD) is a noneuphoria producing constituent of cannabis that has the potential to relieve pain. The aim of this study was to determine whether CBD is anti-nociceptive in OA, and whether inhibition of inflammation by CBD could prevent the development of OA pain and joint neuropathy. Osteoarthritis was induced in male Wistar rats (150-175 g) by intra-articular injection of sodium monoiodoacetate (MIA; 3 mg). On day 14 (end-stage OA), joint afferent mechanosensitivity was assessed using in vivo electrophysiology, whereas pain behaviour was measured by von Frey hair algesiometry and dynamic incapacitance. To investigate acute joint inflammation, blood flow and leukocyte trafficking were measured on day 1 after MIA. Joint nerve myelination was calculated by G-ratio analysis. The therapeutic and prophylactic effects of peripheral CBD (100-300 μg) were assessed. In end-stage OA, CBD dose-dependently decreased joint afferent firing rate, and increased withdrawal threshold and weight bearing (P < 0.0001; n = 8). Acute, transient joint inflammation was reduced by local CBD treatment (P < 0.0001; n = 6). Prophylactic administration of CBD prevented the development of MIA-induced joint pain at later time points (P < 0.0001; n = 8), and was also found to be neuroprotective (P < 0.05; n = 6-8). The data presented here indicate that local administration of CBD blocked OA pain. Prophylactic CBD treatment prevented the later development of pain and nerve damage in these OA joints. These findings suggest that CBD may be a safe, useful therapeutic for treating OA joint neuropathic pain. PMID:28885454

Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis.

PubMed

Philpott, Holly T; OʼBrien, Melissa; McDougall, Jason J

2017-12-01

Osteoarthritis (OA) is a multifactorial joint disease, which includes joint degeneration, intermittent inflammation, and peripheral neuropathy. Cannabidiol (CBD) is a noneuphoria producing constituent of cannabis that has the potential to relieve pain. The aim of this study was to determine whether CBD is anti-nociceptive in OA, and whether inhibition of inflammation by CBD could prevent the development of OA pain and joint neuropathy. Osteoarthritis was induced in male Wistar rats (150-175 g) by intra-articular injection of sodium monoiodoacetate (MIA; 3 mg). On day 14 (end-stage OA), joint afferent mechanosensitivity was assessed using in vivo electrophysiology, whereas pain behaviour was measured by von Frey hair algesiometry and dynamic incapacitance. To investigate acute joint inflammation, blood flow and leukocyte trafficking were measured on day 1 after MIA. Joint nerve myelination was calculated by G-ratio analysis. The therapeutic and prophylactic effects of peripheral CBD (100-300 μg) were assessed. In end-stage OA, CBD dose-dependently decreased joint afferent firing rate, and increased withdrawal threshold and weight bearing (P < 0.0001; n = 8). Acute, transient joint inflammation was reduced by local CBD treatment (P < 0.0001; n = 6). Prophylactic administration of CBD prevented the development of MIA-induced joint pain at later time points (P < 0.0001; n = 8), and was also found to be neuroprotective (P < 0.05; n = 6-8). The data presented here indicate that local administration of CBD blocked OA pain. Prophylactic CBD treatment prevented the later development of pain and nerve damage in these OA joints. These findings suggest that CBD may be a safe, useful therapeutic for treating OA joint neuropathic pain.

Quantification of joint inflammation in rheumatoid arthritis by time-resolved diffuse optical spectroscopy and tracer kinetic modeling

NASA Astrophysics Data System (ADS)

Ioussoufovitch, Seva; Morrison, Laura B.; Lee, Ting-Yim; St. Lawrence, Keith; Diop, Mamadou

2015-03-01

Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation, which can cause progressive joint damage and disability. Diffuse optical spectroscopy (DOS) and imaging have the potential to become potent monitoring tools for RA. We devised a method that combined time-resolved DOS and tracer kinetics modeling to rapidly and reliably quantify blood flow in the joint. Preliminary results obtained from two animals show that the technique can detect joint inflammation as early as 5 days after onset.

Requirements for flare reactions of joint inflammation induced in mice by cloned MT4+, Lyt-2- T cells.

PubMed

Klasen, I S; Ladestein, R M; van den Berg, W B; Benner, R

1989-03-01

Joint inflammation was induced in C57B1/6 mice by injection of cloned MT4+, Lyt-2- T cells specific for the antigen methylated bovine serum albumin (mBSA), together with mBSA. In this model, after waning of the inflammation, flare reactions can be induced by a rechallenge with the specific antigen. Herein we show that such flare reactions can still be induced several weeks after waning of the joint inflammation, as was demonstrated both in normal C57B1/6 mice and in athymic C57B1 nude mice. The results in the latter group indicate that T cells of the recipient mice are not necessary for the elicitation of flare reactions. On histologic examination, the inflammatory infiltrates in the knee joints of the nude mice appeared to be mainly granulocytic. The cloned T cells persisted and remained functionally reactive in the knee joint for at least 2 weeks in the absence of the antigen, and thus, in the absence of inflammation. In view of the similarities between induced joint inflammation in mice and rheumatoid arthritis in humans, these data may be relevant to our understanding of the processes involved in the latter disease.

Possible Involvement of Liver Resident Macrophages (Kupffer Cells) in the Pathogenesis of Both Intrahepatic and Extrahepatic Inflammation

PubMed Central

Kakinuma, Yuki; Kimura, Takuya

2017-01-01

Liver resident macrophages designated Kupffer cells (KCs) form the largest subpopulation of tissue macrophages. KCs are involved in the pathogenesis of liver inflammation. However, the role of KCs in the systemic inflammation is still elusive. In this study, we examined whether KCs are involved in not only intrahepatic inflammation but also extrahepatic systemic inflammation. Administration of clodronate liposomes resulted in the KC deletion and in the suppression of liver injury in T cell-mediated hepatitis by ConA as a local acute inflammation model, while the treatment did not influence dextran sulfate sodium- (DSS-) induced colitis featured by weight loss, intestinal shrink, and pathological observation as an ectopic local acute inflammation model. In contrast, KC deletion inhibited collagen-induced arthritis as a model of extrahepatic, systemic chronical inflammation. KC deleted mice showed weaker arthritic scores, less joint swelling, and more joint space compared to arthritis-induced control mice. These results strongly suggest that KCs are involved in not only intrahepatic inflammatory response but also systemic (especially) chronic inflammation. PMID:28804705

Possible Involvement of Liver Resident Macrophages (Kupffer Cells) in the Pathogenesis of Both Intrahepatic and Extrahepatic Inflammation.

PubMed

Kakinuma, Yuki; Kimura, Takuya; Watanabe, Yoshifumi

2017-01-01

Liver resident macrophages designated Kupffer cells (KCs) form the largest subpopulation of tissue macrophages. KCs are involved in the pathogenesis of liver inflammation. However, the role of KCs in the systemic inflammation is still elusive. In this study, we examined whether KCs are involved in not only intrahepatic inflammation but also extrahepatic systemic inflammation. Administration of clodronate liposomes resulted in the KC deletion and in the suppression of liver injury in T cell-mediated hepatitis by ConA as a local acute inflammation model, while the treatment did not influence dextran sulfate sodium- (DSS-) induced colitis featured by weight loss, intestinal shrink, and pathological observation as an ectopic local acute inflammation model. In contrast, KC deletion inhibited collagen-induced arthritis as a model of extrahepatic, systemic chronical inflammation. KC deleted mice showed weaker arthritic scores, less joint swelling, and more joint space compared to arthritis-induced control mice. These results strongly suggest that KCs are involved in not only intrahepatic inflammatory response but also systemic (especially) chronic inflammation.

Dioscin relieves endotoxemia induced acute neuro-inflammation and protect neurogenesis via improving 5-HT metabolism

PubMed Central

Yang, Rui; Chen, Wei; Lu, Ye; Li, Yingke; Du, Hongli; Gao, Songyan; Dong, Xin; Yuan, Hongbin

2017-01-01

Sepsis, in addition to causing fatality, is an independent risk factor for cognitive impairment among sepsis survivors. The pathologic mechanism of endotoxemia induced acute neuro-inflammation still has not been fully understood. For the first time, we found the disruption of neurotransmitters 5-HT, impaired neurogenesis and activation of astrocytes coupled with concomitant neuro-inflammation were the potential pathogenesis of endotoxemia induced acute neuro-inflammation in sepsis survivors. In addition, dioscin a natural steroidal saponin isolated from Chinese medicinal herbs, enhanced the serotonergic system and produced anti-depressant effect by enhancing 5-HT levels in hippocampus. What is more, this finding was verified by metabolic analyses of hippocampus, indicating 5-HT related metabolic pathway was involved in the pathogenesis of endotoxemia induced acute neuro-inflammation. Moreover, neuro-inflammation and neurogenesis within hippocampus were indexed using quantitative immunofluorescence analysis of GFAP DCX and Ki67, as well as real-time RT-PCR analysis of some gene expression levels in hippocampus. Our in vivo and in vitro studies show dioscin protects hippocampus from endotoxemia induced cascade neuro-inflammation through neurotransmitter 5-HT and HMGB-1/TLR4 signaling pathway, which accounts for the dioscin therapeutic effect in behavioral tests. Therefore, the current findings suggest that dioscin could be a potential approach for the therapy of endotoxemia induced acute neuro-inflammation. PMID:28059131

Vocal exercise may attenuate acute vocal fold inflammation

PubMed Central

Abbott, Katherine Verdolini; Li, Nicole Y.K.; Branski, Ryan C.; Rosen, Clark A.; Grillo, Elizabeth; Steinhauer, Kimberly; Hebda, Patricia A.

2012-01-01

Objectives/Hypotheses The objective was to assess the utility of selected “resonant voice” exercises for the reduction of acute vocal fold inflammation. The hypothesis was that relatively large-amplitude, low-impact exercises associated with resonant voice would reduce inflammation more than spontaneous speech and possibly more than voice rest. Study Design The study design was prospective, randomized, double-blind. Methods Nine vocally healthy adults underwent a 1-hr vocal loading procedure, followed by randomization to (a) a spontaneous speech condition, (b) a vocal rest condition, or (c) a resonant voice exercise condition. Treatments were monitored in clinic for 4 hr, and continued extra-clinically until the next morning. At baseline, immediately following loading, after the 4-hr in-clinic treatment, and 24 hr post baseline, secretions were suctioned from the vocal folds bilaterally and submitted to enzyme-linked immunosorbent assay (ELISA) to estimate concentrations of key markers of tissue injury and inflammation: IL-1β, IL-6, IL-8, TNF-α, MMP-8, and IL-10. Results Complete data sets were obtained for 3 markers -- IL-1β, IL-6, and MMP-8 -- for one subject in each treatment condition. For those markers, results were poorest at 24-hr follow-up in the spontaneous speech condition, sharply improved in the voice rest condition, and best in the resonant voice condition. Average results for all markers, for all responsive subjects with normal baseline mediator concentrations, revealed an almost identical pattern. Conclusions Some forms of tissue mobilization may be useful to attenuate acute vocal fold inflammation. PMID:23177745

Relationship of HS CRP and Sacroiliac Joint Inflammation in Undifferentiated Spondyloarthritis.

PubMed

Liu, Te-Jung; Chang, Cheng-Chiang; Chen, Liang-Cheng; Chu, Heng-Yi; Hsu, Chun-Sheng; Chang, Shin-Tsu

2018-01-01

Elevation of serum high sensitivity C-reactive protein (hs-CRP) level has been demonstrated as a risk factor for varying diseases, as well as a biomarker for predicting recovery after operation of lumber disc herniation. Our objective was to investigate the relationship between serum hs-CRP and sacroiliac (SI) joint inflammation in patients with undifferentiated spondyloarthritis (uSpA). In this retrospective study, we enrolled patients with uSpA who underwent hs-CRP testing between January 2007 and September 2013. Serum hs-CRP was analyzed at our central laboratory. All enrolled patients underwent skeletal scintigraphic scan with quantitative sacroiliac measurement. A total of 29 patients were enrolled with mean age 32.27 years and female:male ratio of 6:23. Pearson's correlation coefficient showed a significant difference between hs-CRP in serum and SI/S ratio in uSpA, particularly the middle part of the sacroiliac joint, either right side or left side. The significantly high concentration of serum hs-CRP might indicate a systemic inflammatory response to flare-up of the SI joint and might be an indicator of SI inflammation in uSpA.

Relationship of HS CRP and Sacroiliac Joint Inflammation in Undifferentiated Spondyloarthritis

PubMed Central

Liu, Te-Jung; Chang, Cheng-Chiang; Chen, Liang-Cheng; Chu, Heng-Yi; Hsu, Chun-Sheng; Chang, Shin-Tsu

2018-01-01

Abstract Objective Elevation of serum high sensitivity C-reactive protein (hs-CRP) level has been demonstrated as a risk factor for varying diseases, as well as a biomarker for predicting recovery after operation of lumber disc herniation. Our objective was to investigate the relationship between serum hs-CRP and sacroiliac (SI) joint inflammation in patients with undifferentiated spondyloarthritis (uSpA). Methods In this retrospective study, we enrolled patients with uSpA who underwent hs-CRP testing between January 2007 and September 2013. Serum hs-CRP was analyzed at our central laboratory. All enrolled patients underwent skeletal scintigraphic scan with quantitative sacroiliac measurement. Results A total of 29 patients were enrolled with mean age 32.27 years and female:male ratio of 6:23. Pearson’s correlation coefficient showed a significant difference between hs-CRP in serum and SI/S ratio in uSpA, particularly the middle part of the sacroiliac joint, either right side or left side. The significantly high concentration of serum hs-CRP might indicate a systemic inflammatory response to flare-up of the SI joint and might be an indicator of SI inflammation in uSpA. PMID:29785410

Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms.

PubMed

Skelly, Donal T; Griffin, Éadaoin W; Murray, Carol L; Harney, Sarah; O'Boyle, Conor; Hennessy, Edel; Dansereau, Marc-Andre; Nazmi, Arshed; Tortorelli, Lucas; Rawlins, J Nicholas; Bannerman, David M; Cunningham, Colm

2018-06-06

Systemic inflammation can impair cognition with relevance to dementia, delirium and post-operative cognitive dysfunction. Episodes of delirium also contribute to rates of long-term cognitive decline, implying that these acute events induce injury. Whether systemic inflammation-induced acute dysfunction and acute brain injury occur by overlapping or discrete mechanisms remains unexplored. Here we show that systemic inflammation, induced by bacterial LPS, produces both working-memory deficits and acute brain injury in the degenerating brain and that these occur by dissociable IL-1-dependent processes. In normal C57BL/6 mice, LPS (100 µg/kg) did not affect working memory but impaired long-term memory consoliodation. However prior hippocampal synaptic loss left mice selectively vulnerable to LPS-induced working memory deficits. Systemically administered IL-1 receptor antagonist (IL-1RA) was protective against, and systemic IL-1β replicated, these working memory deficits. Dexamethasone abolished systemic cytokine synthesis and was protective against working memory deficits, without blocking brain IL-1β synthesis. Direct application of IL-1β to ex vivo hippocampal slices induced non-synaptic depolarisation and irrevesible loss of membrane potential in CA1 neurons from diseased animals and systemic LPS increased apoptosis in the degenerating brain, in an IL-1RI -/- -dependent fashion. The data suggest that LPS induces working memory dysfunction via circulating IL-1β but direct hippocampal action of IL-1β causes neuronal dysfunction and may drive neuronal death. The data suggest that acute systemic inflammation produces both reversible cognitive deficits, resembling delirium, and acute brain injury contributing to long-term cognitive impairment but that these events are mechanistically dissociable. These data have significant implications for management of cognitive dysfunction during acute illness.

In vivo effects of CB2 receptor-selective cannabinoids on the vasculature of normal and arthritic rat knee joints

PubMed Central

McDougall, J J; Yu, V; Thomson, J

2007-01-01

Background and purpose: Cannabinoids (CBs) are known to be vasoactive and to regulate tissue inflammation. The present study examined the in vivo vasomotor effects of the CB2 receptor agonists JWH015 and JWH133 in rat knee joints. The effect of acute and chronic joint inflammation on CB2 receptor-mediated responses was also tested. Experimental approach: Blood flow was assessed in rat knee joints by laser Doppler imaging both before and following topical administration of CB2 receptor agonists. Vasoactivity was measured in normal, acute kaolin/carrageenan inflamed and Freund's complete adjuvant chronically inflamed knees. Key results: In normal animals, JWH015 and JWH133 caused a concentration-dependent increase in synovial blood flow which in the case of JWH133 was blocked by the selective CB2 receptor antagonist AM630 as well as the transient receptor potential vanilloid-1 (TRPV1) antagonist SB366791. The vasodilator effect of JWH133 was significantly attenuated in both acute and chronically inflamed knees. Given alone, AM630 had no effect on joint blood flow. Conclusion and implications: In normal joints, the cannabinomimetic JWH133 causes hyperaemia via a CB2 and TRPV1 receptor mechanism. During acute and chronic inflammation, however, this vasodilatatory response is significantly attenuated. PMID:17982474

Joint mobilization acutely improves landing kinematics in chronic ankle instability.

PubMed

Delahunt, Eamonn; Cusack, Kim; Wilson, Laura; Doherty, Cailbhe

2013-03-01

The objective of this study is to examine the acute effect of ankle joint mobilizations akin to those performed in everyday clinical practice on sagittal plane ankle joint kinematics during a single-leg drop landing in participants with chronic ankle instability (CAI). Fifteen participants with self-reported CAI (defined as <24 on the Cumberland Ankle Instability Tool) performed three single-leg drop landings under two different conditions: 1) premobilization and, 2) immediately, postmobilization. The mobilizations performed included Mulligan talocrural joint dorsiflexion mobilization with movement, Mulligan inferior tibiofibular joint mobilization, and Maitland anteroposterior talocrural joint mobilization. Three CODA cx1 units (Charnwood Dynamics Ltd., Leicestershire, UK) were used to provide information on ankle joint sagittal plane angular displacement. The dependent variable under investigation was the angle of ankle joint plantarflexion at the point of initial contact during the drop landing. There was a statistically significant acute decrease in the angle of ankle joint plantarflexion from premobilization (34.89° ± 4.18°) to postmobilization (31.90° ± 5.89°), t(14) = 2.62, P < 0.05 (two-tailed). The mean decrease in the angle of ankle joint plantarflexion as a result of the ankle joint mobilization was 2.98° with a 95% confidence interval ranging from 0.54 to 5.43. The eta squared statistic (0.32) indicated a large effect size. These results indicate that mobilization acted to acutely reduce the angle of ankle joint plantarflexion at initial contact during a single-leg drop landing. Mobilization applied to participants with CAI has a mechanical effect on the ankle joint, thus facilitating a more favorable positioning of the ankle joint when landing from a jump.

Intra-articular implantation of gentamicin impregnated collagen sponge causes joint inflammation and impaired renal function in dogs.

PubMed

Hayes, Galina; Gibson, Tom; Moens, Noel M M; Nykamp, Stephanie; Wood, Darren; Foster, Robert; Lerer, Asaf

2016-01-01

Gentamicin impregnated collagen sponge (GICS) can be used to treat intra-articular surgical site infections. High local concentrations of gentamicin can be reached for short periods; however the collagen vehicle may persist for much longer periods. We wished to determine the effect of sponge implantation on joint inflammation and renal function. Eighteen medium sized mixed breed research dogs of hound type were randomized to two groups; arthroscopic implantation of GICS at gentamicin dose = 6 mg/kg (n = 9) or sham operation (n = 9). Endpoints consisted of joint inflammation measured by synovial fluid cell counts and cytokine concentrations; lameness measured by force plate asymmetry indices; and renal function measured by glomerular filtration rate (GFR) study. The prevalence of lesions associated with aminoglycoside nephrotoxicity was assessed by renal biopsy and transmission electron microscopy. Gentamicin impregnated collagen sponge implantation caused joint inflammation (p <0.01), lameness (p = 0.04), and decreased GFR (p = 0.04). No difference was observed in the prevalence of renal lesions on biopsy between the treatment and control groups (p = 0.49). Gentamicin impregnated collagen sponge implantation causes joint inflammation and lameness as well as GFR reductions at the dose assessed. Gentamicin impregnated collagen sponge are not recommended for intra-articular implantation in dogs.

Gait Analysis in Rats with Single Joint Inflammation: Influence of Experimental Factors

PubMed Central

Ängeby Möller, Kristina; Kinert, Susanne; Størkson, Rolf; Berge, Odd-Geir

2012-01-01

Disability and movement-related pain are major symptoms of joint disease, motivating the development of methods to quantify motor behaviour in rodent joint pain models. We used observational scoring and automated methods to compare weight bearing during locomotion and during standing after single joint inflammation induced by Freund's complete adjuvant (0.12–8.0 mg/mL) or carrageenan (0.47–30 mg/mL). Automated gait analysis was based on video capture of prints generated by light projected into the long edge of the floor of a walkway, producing an illuminated image of the contact area of each paw with light intensity reflecting the contact pressure. Weight bearing was calculated as an area-integrated paw pressure, that is, the light intensity of all pixels activated during the contact phase of a paw placement. Automated static weight bearing was measured with the Incapacitance tester. Pharmacological sensitivity of weight-bearing during locomotion was tested in carrageenan-induced monoarthritis by administration of the commonly used analgesics diclofenac, ibuprofen, and naproxen, as well as oxycodone and paracetamol. Observational scoring and automated quantification yielded similar results. We found that the window between control rats and monoarthritic rats was greater during locomotion. The response was more pronounced for inflammation in the ankle as compared to the knee, suggesting a methodological advantage of using this injection site. The effects of both Freund's complete adjuvant and carrageenan were concentration related, but Freund's incomplete adjuvant was found to be as effective as lower, commonly used concentrations of the complete adjuvant. The results show that gait analysis can be an effective method to quantify behavioural effects of single joint inflammation in the rat, sensitive to analgesic treatment. PMID:23071540

Management of acute unstable acromioclavicular joint injuries.

PubMed

Cisneros, Luis Natera; Reiriz, Juan Sarasquete

2016-12-01

Surgical management of acute unstable acromioclavicular joint injuries should be focused on realigning the torn ends of the ligaments to allow for healing potential. The most widely utilized treatment methods incorporate the use of metal hardware, which can alter the biomechanics of the acromioclavicular joint. This leads to a second surgical procedure for hardware removal once the ligaments have healed. Patients with unstable acromioclavicular joint injuries managed with arthroscopy-assisted procedures have shown good and excellent clinical outcomes, without the need for a second operation. These procedures incorporate a coracoclavicular suspension device aimed to function as an internal brace, narrowing the coracoclavicular space thus allowing for healing of the torn coracoclavicular ligaments. The lesser morbidity of a minimally invasive approach and the possibility to diagnose and treat concomitant intraarticular injuries; no obligatory implant removal, and the possibility of having a straight visualization of the inferior aspect of the base of the coracoid (convenient when placing coracoclavicular fixation systems) are the main advantages of the arthroscopic approach over classic open procedures. This article consists on a narrative review of the literature in regard to the management of acute acromioclavicular joint instability.

MRI evidence of persistent joint inflammation and progressive joint damage despite clinical remission during treatment of early rheumatoid arthritis.

PubMed

Forslind, K; Svensson, B

2016-01-01

To determine the value of magnetic resonance imaging (MRI) of bones and joints in patients with recent-onset rheumatoid arthritis (RA) treated for 2 years from diagnosis with disease-modifying anti-rheumatic drugs (DMARDs) and glucocorticoids. Thirteen patients with early RA were treated according to clinical practice and followed with MRI, radiographs, and Disease Activity Score calculated on 28 joints (DAS28) at inclusion (baseline) and after 1, 4, 7, 13, and 25 months. MRI of the dominant wrist and metacarpophalangeal (MCP) joints were assessed for synovitis, bone oedema, and erosions using the RA MRI Score (RAMRIS) and for tenosynovitis by an MRI tenosynovitis scoring method. Radiographs were assessed by the van der Heijde modified Sharp score (SHS). Clinical remission was defined by a DAS28 < 2.6. MRI at baseline detected inflammation in joints and tendons in all patients as well as erosions in 10 out of 13 patients. Over time, the erosion score increased while the synovitis and tenosynovitis scores remained almost unchanged. Bone oedema strongly correlated with synovitis. Synovitis and tenosynovitis correlated well with the erosion score at baseline but not thereafter. The MRI changes showed that joint damage started early and continued in the presence of persistent synovial and tenosynovial inflammation. The observations made in this small study suggest that the treatment goal of 'clinical remission' should be supplemented by a 'joint remission' goal. To this end, MRI is an appropriate tool. Further studies are needed to evaluate the optimal use of MRI in early RA.

Contributions of transferrin to acute inflammation in the goldfish, C. auratus.

PubMed

Trites, M J; Barreda, D R

2017-02-01

Transferrin is an evolutionary conserved protein that in addition to having a critical role in iron transport also has been shown to have a crucial role in host defence, by depriving iron from invading pathogens. Recently cleaved transferrin products was shown to activate macrophages in vitro. We now use an in vivo model of self-resolving peritonitis in goldfish, coupled with gene expression and protein analysis to evaluate the contributions of cleaved transferrin to acute inflammation. We show, for the first time, that cleaved transferrin products are produced in vivo early during an acute inflammatory response. These cleaved transferrin fragments were produced during pathogen-induced, but not sterile, inflammation. Both macrophages and neutrophils were able to contribute to transferrin cleavage. However, only macrophages contributed to this innate process through inducible expression of transferrin. The appearance of transferrin cleavage products in vivo correlated with the influx of leukocytes but did not necessarily correlate the induction of robust respiratory burst and nitric oxide responses. Overall, this study adds to a growing body of work highlighting the role of transferrin as an immune regulator during acute inflammation. Given the significant conservation of this and related molecules, these findings have potentially broad implications for host defences and inflammation control across evolution. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of an acute bout of moderate-intensity exercise on postprandial lipemia and airway inflammation.

PubMed

Johnson, Ariel M; Kurti, Stephanie P; Smith, Joshua R; Rosenkranz, Sara K; Harms, Craig A

2016-03-01

A high-fat meal (HFM) induces an increase in blood lipids (postprandial lipemia; PPL), systemic inflammation, and acute airway inflammation. While acute exercise has been shown to have anti-inflammatory and lipid-lowering effects, it is unknown whether exercise prior to an HFM will translate to reduced airway inflammation post-HFM. Our purpose was to determine the effects of an acute bout of exercise on airway inflammation post-HFM and to identify whether any protective effect of exercise on airway inflammation was associated with a reduction in PPL or systemic inflammation. In a randomized cross-over study, 12 healthy, 18- to 29-year-old men (age, 23.0 ± 3.2 years; height, 178.9 ± 5.5 cm; weight, 78.5 ± 11.7 kg) consumed an HFM (1 g fat/1 kg body weight) 12 h following exercise (EX; 60 min at 60% maximal oxygen uptake) or without exercise (CON). Fractional exhaled nitric oxide (FENO; measure of airway inflammation), triglycerides (TG), and inflammatory markers (high-sensitivity C-reactive protein, tumor-necrosis factor-alpha, and interleukin-6) were measured while fasted at 2 h and 4 h post-HFM. FENO increased over time (2 h: CON, p = 0.001; EX, p = 0.002, but not by condition (p = 0.991). TG significantly increased 2 and 4 h post-HFM (p < 0.001), but was not significant between conditions (p = 0.256). Inflammatory markers did not significantly increase by time or condition (p > 0.05). There were no relationships between FENO and TG or systemic inflammatory markers for any time point or condition (p > 0.05). In summary, an acute bout of moderate-intensity exercise performed 12 h prior to an HFM did not change postprandial airway inflammation or lipemia in healthy, 18- to 29-year-old men.

Novel lipid mediators promote resolution of acute inflammation: impact of aspirin and statins

PubMed Central

Spite, Matthew; Serhan, Charles N.

2010-01-01

The resolution of acute inflammation is a process that allows for inflamed tissues to return to homeostasis. Resolution was held to be a passive process, a concept now overturned with new evidence demonstrating that resolution is actively orchestrated by distinct cellular events and endogenous chemical mediators. Among these, lipid mediators, such as the lipoxins, resolvins, protectins and newly identified maresins, have emerged as a novel genus of potent and stereoselective players that counter-regulate excessive acute inflammation and stimulate molecular and cellular events that define resolution. Given that uncontrolled, chronic inflammation is associated with many cardiovascular pathologies, an appreciation of the endogenous pathways and mediators that control timely resolution can open new terrain for therapeutic approaches targeted at stimulating resolution of local inflammation, as well as correcting the impact of chronic inflammation in cardiovascular disorders. Here, we overview and update the biosynthesis and actions of pro-resolving lipid mediators, highlighting their diverse protective roles relevant to vascular systems and their relation to aspirin and statin therapies. PMID:21071715

Arthroscopic treatment of acute acromioclavicular joint dislocation by coracoclavicular ligament augmentation.

PubMed

Liu, Xudong; Huangfu, Xiaoqiao; Zhao, Jinzhong

2015-05-01

Coracoclavicular (CC) ligament augmentation has been a method to treat acromioclavicular (AC) joint dislocation in recent years. The purpose of this paper is to describe our arthroscopic CC ligament augmentation technique in treating type III and V acute AC joint dislocations and to report the early clinical and radiological results. From 2010 to 2011, twelve patients suffering from acute type III or V AC joint dislocations were arthroscopically treated in our department, by CC ligament augmentation after AC joint reduction. The post-operative outcomes were assessed through physical examination, radiographic examination and the Constant-Murley Shoulder Score. All patients post-operatively experienced anatomical reduction in their AC joint dislocation. No intraoperative complications occurred. At a mean follow-up at 24 months (ranging from 18 to 32 months), the mean Constant-Murley Shoulder Score significantly improved from 24.3 pre-operatively to 91.1 post-operatively. No neurovascular complications or secondary degenerative changes of the AC joint were detected in any of the patients. In one case, a second dislocation occurred 1 month post-operation because the patient had had another traumatic injury. This patient accepted a revision operation, but his AC joint eventually fixated into a subluxated position after his second injury. Based on the resultant successful repair in all cases, the arthroscopic CC ligament augmentation method has thus far proven to be a safe and reliable technique for treatment of acute type III or V AC joint dislocation. The arthroscopic CC ligament augmentation with a flip button/polyethylene belt repair is an efficient method to treat acute type III and V AC joint dislocations which should be popularized. IV.

Impact of lipopolysaccharide-induced acute inflammation on baroreflex-controlled sympathetic arterial pressure regulation

PubMed Central

Tohyama, Takeshi; Kawada, Toru; Kishi, Takuya; Yoshida, Keimei; Nishikawa, Takuya; Mannoji, Hiroshi; Kamada, Kazuhiro; Sunagawa, Kenji; Tsutsui, Hiroyuki

2018-01-01

Background Lipopolysaccharide (LPS) induces acute inflammation, activates sympathetic nerve activity (SNA) and alters hemodynamics. Since the arterial baroreflex is a negative feedback system to stabilize arterial pressure (AP), examining the arterial baroreflex function is a prerequisite to understanding complex hemodynamics under LPS challenge. We investigated the impact of LPS-induced acute inflammation on SNA and AP regulation by performing baroreflex open-loop analysis. Methods Ten anesthetized Sprague-Dawley rats were used. Acute inflammation was induced by an intravenous injection of LPS (60 μg/kg). We isolated the carotid sinuses from the systemic circulation and controlled carotid sinus pressure (CSP) by a servo-controlled piston pump. We matched CSP to AP to establish the baroreflex closed-loop condition, whereas we decoupled CSP from AP to establish the baroreflex open-loop condition and changed CSP stepwise to evaluate the baroreflex open-loop function. We recorded splanchnic SNA and hemodynamic parameters under baroreflex open- and closed-loop conditions at baseline and at 60 and 120 min after LPS injection. Results In the baroreflex closed-loop condition, SNA continued to increase after LPS injection, reaching three-fold the baseline value at 120 min (baseline: 94.7 ± 3.6 vs. 120 min: 283.9 ± 31.9 a.u.). In contrast, AP increased initially (until 75 min), then declined to the baseline level. In the baroreflex open-loop condition, LPS reset the neural arc (CSP-SNA relationship) upward to higher SNA, while shifted the peripheral arc (SNA-AP relationship) downward at 120 min after the injection. As a result, the operating point determined by the intersection between function curves of neural arc and peripheral arc showed marked sympatho-excitation without substantial changes in AP. Conclusions LPS-induced acute inflammation markedly increased SNA via resetting of the baroreflex neural arc, and suppressed the peripheral arc. The balance between the

Impact of lipopolysaccharide-induced acute inflammation on baroreflex-controlled sympathetic arterial pressure regulation.

PubMed

Tohyama, Takeshi; Saku, Keita; Kawada, Toru; Kishi, Takuya; Yoshida, Keimei; Nishikawa, Takuya; Mannoji, Hiroshi; Kamada, Kazuhiro; Sunagawa, Kenji; Tsutsui, Hiroyuki

2018-01-01

Lipopolysaccharide (LPS) induces acute inflammation, activates sympathetic nerve activity (SNA) and alters hemodynamics. Since the arterial baroreflex is a negative feedback system to stabilize arterial pressure (AP), examining the arterial baroreflex function is a prerequisite to understanding complex hemodynamics under LPS challenge. We investigated the impact of LPS-induced acute inflammation on SNA and AP regulation by performing baroreflex open-loop analysis. Ten anesthetized Sprague-Dawley rats were used. Acute inflammation was induced by an intravenous injection of LPS (60 μg/kg). We isolated the carotid sinuses from the systemic circulation and controlled carotid sinus pressure (CSP) by a servo-controlled piston pump. We matched CSP to AP to establish the baroreflex closed-loop condition, whereas we decoupled CSP from AP to establish the baroreflex open-loop condition and changed CSP stepwise to evaluate the baroreflex open-loop function. We recorded splanchnic SNA and hemodynamic parameters under baroreflex open- and closed-loop conditions at baseline and at 60 and 120 min after LPS injection. In the baroreflex closed-loop condition, SNA continued to increase after LPS injection, reaching three-fold the baseline value at 120 min (baseline: 94.7 ± 3.6 vs. 120 min: 283.9 ± 31.9 a.u.). In contrast, AP increased initially (until 75 min), then declined to the baseline level. In the baroreflex open-loop condition, LPS reset the neural arc (CSP-SNA relationship) upward to higher SNA, while shifted the peripheral arc (SNA-AP relationship) downward at 120 min after the injection. As a result, the operating point determined by the intersection between function curves of neural arc and peripheral arc showed marked sympatho-excitation without substantial changes in AP. LPS-induced acute inflammation markedly increased SNA via resetting of the baroreflex neural arc, and suppressed the peripheral arc. The balance between the augmented neural arc and suppressed

[Clinical features and management of acute myositis in idiopathic orbital inflammation].

PubMed

Halimi, E; Rosenberg, R; Wavreille, O; Bouckehove, S; Franquet, N; Labalette, P

2013-09-01

Acute myositis is the second most common component of non-specific orbital inflammation. We will describe its clinical features and natural history. This is a retrospective study of 10 cases. The diagnosis of acute myositis was based on clinical and imaging criteria. Our study includes five men and five women. The average age was 35.8 years (17-59 years). Clinical symptoms were: pain increased on eye movement (10/10), diplopia (4/10), proptosis (6/10), visual loss (3/10), lid edema (6/10), conjunctival hyperemia (7/10), anterior scleritis (2/10), episcleritis (2/10), chemosis (4/10), upper lid retraction (1/10), limitation of eye movement (3/10), fundus abnormalities (2/10). Imaging showed thickening of one or more extraocular muscles (10/10). Recovery was complete with anti-inflammatory therapy in six patients. Three patients experienced recurrence, and one patient had a clinical rebound upon tapering the treatment. Acute myositis can be defined by pain on eye movement, signs of inflammation, and extraocular muscle thickening on imaging. If the clinical presentation is typical, histopathological analysis can be deferred but remains necessary in cases of poor response to treatment, chronic duration or suspicion of tumor infiltration. The diagnosis of acute myositis may be suspected in the presence of consistent, well-defined clinical signs. Contiguous inflammation is often associated. Treatment is based on steroids or non-steroidal treatment anti-inflammatory therapy, administered alone or consecutively. Recurrences are frequent but do not alter the final prognosis. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Treatment of rheumatoid joint inflammation with intrasynovial triamcinolone hexacetonide.

PubMed

McCarty, D J; Harman, J G; Grassanovich, J L; Qian, C

1995-09-01

To determine the effectiveness of intrasynovial triamcinolone hexacetonide coupled with joint rest (3 weeks upper extremity; 6 weeks lower extremity) in the treatment of joint and tendon sheath inflammation in patients with seropositive rheumatoid arthritis (RA). The medical records of 169 patients with seropositive RA treated by a single rheumatologist for at least one year between 1974 and 1992 were abstracted. Nine hundred fifty-six injections were given to 140 patients; approximately 75% of injected synovial structures remained in remission during a mean followup 7 years; 218 injections were given into previously treated structures. The injection rate was about 2 per patient in the first year, half of which were given at the time of the first visit. The rate then approximated 0.6 injections per patient-year for the next 15 years. Joints in the right upper extremity were injected significantly (p = 0.01) more frequently than those on the left. Intrasynovial triamcinolone hexacetonide followed by rest is a very useful adjunctive modality in the treatment of seropositive rheumatoid arthritis.

Systemic metabolic signaling in acute and chronic gastrointestinal inflammation of inflammatory bowel diseases.

PubMed

Karrasch, T; Obermeier, F; Straub, R H

2014-06-01

Acute and chronic intestinal inflammation stimulates innate and adaptive immune systems, thereby increasing energy demand of activated immune cells. Energy regulation by systemically released mediators is of critical importance for homeostasis. We wanted to find out how systemic metabolic mediators are affected during intestinal inflammation. A total of 123 patients suffering from Crohn's disease (CD), 76 patients with ulcerative colitis (UC), and 21 healthy controls were recruited. Patients receiving systemic steroids or therapy regimens including biologicals (anti-TNF) were excluded from the study. Serum levels of IL-6, CRP, insulin, glucose, free fatty acid, and RBP-4 were measured by ELISA and RIA. Intestinal inflammation was accompanied by elevated systemic inflammatory para-meters such as IL-6 and CRP in UC and CD and, concomitantly, with elevated insulin levels and increased insulin/glucose ratio in patients with UC. This indicates insulin resistance in liver, muscle, and fat. In addition, intestinal inflammation was associated with elevated levels of circulating free fatty acids in UC and CD, indicating an activation of the organism's appeal for energy-rich substrates (energy appeal reaction). RBP-4 serum levels were also high in acute and chronic intestinal inflammation in UC and CD, which can support insulin resistance. The organism's "energy appeal reaction" in response to acute and chronic inflammation provides free energy in the circulation, which is needed by inflammatory cells. A major mechanism of the redirection program is insulin resistance. New therapeutic strategies might be developed in the future, directly impacting on the storage and utilization of energy-rich fuels. © Georg Thieme Verlag KG Stuttgart · New York.

Regulatory cells induced by acute toxoplasmosis prevent the development of allergic lung inflammation.

PubMed

Fenoy, Ignacio M; Sanchez, Vanesa R; Soto, Ariadna S; Picchio, Mariano S; Maglioco, Andrea; Corigliano, Mariana G; Dran, Graciela I; Martin, Valentina; Goldman, Alejandra

2015-05-01

The increased prevalence of allergies in developed countries has been attributed to a reduction of some infections. Supporting epidemiological studies, we previously showed that both acute and chronic Toxoplasma gondii infection can diminish allergic airway inflammation in BALB/c mice. The mechanisms involved when sensitization occurs during acute phase would be related to the strong Th1 response induced by the parasite. Here, we further investigated the mechanisms involved in T. gondii allergy protection in mice sensitized during acute T. gondii infection. Adoptive transference assays and ex vivo co-cultures experiments showed that not only thoracic lymph node cells from infected and sensitized mice but also from non-sensitized infected animals diminished both allergic lung inflammation and the proliferation of effector T cells from allergic mice. This ability was found to be contact-independent and correlated with high levels of CD4(+)FoxP3(+) cells. IL-10 would not be involved in allergy suppression since IL-10-deficient mice behaved similar to wild type mice. Our results extend earlier work and show that, in addition to immune deviation, acute T. gondii infection can suppress allergic airway inflammation through immune suppression. Copyright © 2014 Elsevier GmbH. All rights reserved.

Role of inflammation and its mediators in acute ischemic stroke

PubMed Central

Jin, Rong; Liu, Lin; Zhang, Shihao; Nanda, Anil; Li, Guohong

2013-01-01

Inflammation plays an important role in the pathogenesis of ischemic stroke and other forms of ischemic brain injury. Increasing evidence suggests that inflammatory response is a double-edged sword, as it not only exacerbates secondary brain injury in the acute stage of stroke but also beneficially contributes to brain recovery after stroke. In this article, we provide an overview on the role of inflammation and its mediators in acute ischemic stroke. We discuss various pro-inflammatory and anti-inflammatory responses in different phases after ischemic stroke and the possible reasons for their failures in clinical trials. Undoubtedly, there is still much to be done in order to translate promising pre-clinical findings into clinical practice. A better understanding of the dynamic balance between pro- and anti-inflammatory responses and identifying the discrepancies between pre-clinical studies and clinical trials may serve as a basis for designing effective therapies. PMID:24006091

Effect of simvastatin injections on temporomandibular joint inflammation in growing rats.

PubMed

George, Mark D; Owen, Callista M; Reinhardt, Adam L; Giannini, Peter J; Marx, David B; Reinhardt, Richard A

2013-05-01

Juvenile idiopathic arthritis often affects the temporomandibular joint (TMJ), resulting in facial deformities, and intra-articular injections of anti-inflammatory steroids used in treatment may inhibit bone growth in the developing condyle. The purpose of this pilot study was to evaluate the anti-inflammatory properties of simvastatin (SIM), a bone anabolic drug, compared with the common steroid triamcinolone hexacetonide (TH) in experimental TMJ arthritis of growing rats. Joint inflammation was induced by injecting complete Freund's adjuvant (CFA) into the TMJs of 32 growing (4-week-old) Sprague-Dawley rats while simultaneously receiving 1) ethanol drug carrier, 2) 0.1 mg of SIM, 3) 0.5 mg of SIM, or 4) 0.15 mg of TH. Six rats had no treatment to the TMJ. Animals were euthanized 28 days later, and TMJs were decalcified and stained with hematoxylin-eosin. Histopathologic TMJ results showed that CFA injection along with drug carrier induced increased thickness of the articular layer on the head of the condyle and inflammation of the retrodiscal area (CFA and ethanol). Although both TH and SIM reduced the articular layer thickness, 0.5 mg of SIM was more effective at reducing subsynovial inflammation. Intra-articular simvastatin showed anti-inflammatory properties in this TMJ model, prompting its further study in the growing TMJ, where bone anabolic properties would be important. Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Protective effect of Clerodendrum colebrookianum Walp., on acute and chronic inflammation in rats

PubMed Central

Deb, Lokesh; Dey, Amitabha; Sakthivel, G.; Bhattamishra, Subrat Kumar; Dutta, Amitsankar

2013-01-01

Aim: To evaluate antioxidant, anti-inflammatory potential of the aqueous extracts and its aqueous, n-butanol, ethyl-acetate, and chloroform fractions of Clerodendrum colebrookianum Walp. leaves. Materials and Methods: In this present study, all the test samples were evaluated on in-vivo inflammatory model such as carrageenan and histamine-induced acute-inflammation and cotton pellet induced granuloma formation in albino male rats. Test samples were also employed in in-vitro assays like DPPH* free radical scavenging activity and COX inhibition assay. Results: The test samples at the dose of 200mg/kg/p.o. were found to cause significant inhibition of carrageenan and histamine-induced inflammation and cotton pallet-induced granuloma formation on acute and chronic inflammation in rats. The test samples, except n-butanol fraction, exhibited inhibitory effect for both COX-1 and COX-2, in in-vitro assay but their percentage of inhibition values differs from each other. The test samples (aqueous extracts, aqueous, n-butanol, ethyl-acetate, and chloroform fractions) at 100 μg concentration exhibits 54.37%, 33.88%, 62.85%, 56.28%, and 57.48% DPPH* radical-scavenging effect respectively in in-vitro antioxidant study. Conclusion: These observations established the anti-inflammatory effect of C. colebrookianum leaves in acute and chronic stages of inflammation by free radical scavenging and inhibition of COX-1 and COX-2. PMID:24014914

Inflammation and Cardiovascular Disease Risk: A Case Study of HIV and Inflammatory Joint Disease.

PubMed

Rahman, Faisal; Martin, Seth S; Whelton, Seamus P; Mody, Freny V; Vaishnav, Joban; McEvoy, John William

2018-04-01

The epidemiologic data associating infection and inflammation with increased risk of cardiovascular disease is well established. Patients with chronically upregulated inflammatory pathways, such as those with HIV and inflammatory joint diseases, often have a risk of future cardiovascular risk that is similar to or higher than patients with diabetes. Thus, it is of heightened importance for clinicians to consider the cardiovascular risk of patients with these conditions. HIV and inflammatory joint diseases are archetypal examples of how inflammatory disorders contribute to vascular disease and provide illustrative lessons that can be leveraged in the prevention of cardiovascular disease. Managing chronic inflammatory diseases calls for a multifaceted approach to evaluation and treatment of suboptimal lifestyle habits, accurate estimation of cardiovascular disease risk with potential upwards recalibration due to chronic inflammation, and more intensive treatment of risk factors because current tools often underestimate the risk in this population. This approach is further supported by the recently published CANTOS trial demonstrating that reducing inflammation can serve as a therapeutic target among persons with residual inflammatory risk for cardiovascular disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of Ergothioneine on Acute Lung Injury and Inflammation in Cytokine Insufflated Rats

PubMed Central

Repine, John E.; Elkins, Nancy D.

2012-01-01

Objective The Acute Respiratory Distress Syndrome (ARDS), the most severe form of Acute Lung Injury (ALI), is a highly-fatal, diffuse non-cardiogenic edematous lung disorder. The pathogenesis of ARDS is unknown but lung inflammation and lung oxidative stress are likely contributing factors. Since no specific pharmacologic intervention exists for ARDS, our objective was to determine the effect of treatment with ergothioneine---a safe agent with multiple anti-inflammatory and antioxidant properties on the development of lung injury and inflammation in rats insufflated with cytokines found in lung lavages of ARDS patients. Method Sprague-Dawley rats (3-10/group) were given 15 mg/kg or 150 mg/kg L-ergothioneine intravenously 1 hour before or 18 hours after cytokine (IL-1 and IFNγ) insufflation. Lung injury (lavage LDH levels) and lung inflammation (lavage neutrophil numbers) were measured 24 hours after cytokine insufflation. Results Ergothioneine pre- and post- treatment generally decreased lung injury and lung inflammation in cytokine insufflated rats. Conclusion Ergothioneine should be considered for additional testing as a potential therapy for treating and preventing ARDS. PMID:22197759

Chronic, not acute, skin-specific inflammation promotes thrombosis in psoriasis murine models.

PubMed

Golden, Jackelyn B; Wang, Yunmei; Fritz, Yi; Diaconu, Doina; Zhang, Xiufen; Debanne, Sara M; Simon, Daniel I; McCormick, Thomas S; Ward, Nicole L

2015-12-16

Psoriasis patients exhibit an increased risk of atherothrombotic events, including myocardial infarction and stroke. Clinical evidence suggests that psoriasis patients with early onset and more severe disease have the highest risk for these co-morbidities, perhaps due to the extent of body surface involvement, subsequent levels of systemic inflammation, or chronicity of disease. We sought to determine whether acute or chronic skin-specific inflammation was sufficient to promote thrombosis. We used two experimental mouse models of skin-specific inflammation generated in either an acute (topical Aldara application onto wild-type C57Bl/6 mice for 5 days) or chronic (a genetically engineered K5-IL-17C mouse model of psoriasiform skin inflammation) manner. Arterial thrombosis was induced using carotid artery photochemical injury (Rose Bengal-green light laser) and carotid artery diameters were measured post-clot formation. We also examined measures of clot formation including prothrombin (PT) and activated partial thromboplastin time (aPTT). Skin inflammation was examined histologically and we profiled plasma-derived lipids. The number of skin-draining lymph-node (SDLN) and splenic derived CD11b(+)Ly6C(high) pro-inflammatory monocytes and CD11b(+)Ly6G(+) neutrophils was quantified using multi-color flow cytometry. Mice treated with topical Aldara for 5 days had similar carotid artery thrombotic occlusion times to mice treated with vehicle cream (32.2 ± 3.0 vs. 31.4 ± 2.5 min, p = 0.97); in contrast, K5-IL-17C mice had accelerated occlusion times compared to littermate controls (15.7 ± 2.1 vs. 26.5 ± 3.5 min, p < 0.01) while carotid artery diameters were similar between all mice. Acanthosis, a surrogate measure of inflammation, was increased in both Aldara-treated and K5-IL-17C mice compared to their respective controls. Monocytosis, defined as elevated SDLN and/or splenic CD11b(+)Ly6C(high) cells, was significantly increased in both Aldara-treated (SDLN: 3.8-fold, p

Low-Grade Inflammation and Ambulatory Cortisol in Adolescents: Interaction Between Interviewer-Rated Versus Self-Rated Acute Stress and Chronic Stress.

PubMed

Schreier, Hannah M C; Chen, Edith

To determine whether the association between self-rated or interviewer-rated recent acute stress exposures and low-grade inflammation and daily cortisol production in adolescents is moderated by chronic stress ratings. Acute and chronic stress exposures were assessed in 261 adolescents aged 13 to 16 years using a semistructured life stress interview. The negative impact of acute stressors was independently rated by both adolescents (self-rated) and interviewers (interviewer-rated). Markers of inflammation (interleukin (IL)-6, IL-1ra, C-reactive protein) were measured from peripheral blood samples obtained via antecubital venipuncture. Participants collected 4 saliva samples at home on each of 6 consecutive days for the analysis of diurnal salivary cortisol profiles. There were no main effects of acute stressors (self- and interviewer-rated) and chronic family or peer stress on adolescent inflammation markers and cortisol (p values > .10). However, the interaction between interviewer-rated acute stress and chronic family stress was significantly associated with adolescent inflammation markers (IL-6, IL-1ra). Specifically, as chronic family stress increased, the association between acute stressor impact (interviewer-rated) and inflammation markers became more positive (IL-6 (B = .054, SE = .023, p = .022); IL-1ra (B = .030, SE = .014, p = .034)). Interactions between self-rated acute stress and chronic family stress were not associated with any biological measures (p values > .10). Interactions between acute stressor impact (both self- and interviewer-rated) and chronic peer stress were also not significantly associated with any biological measures (p values > .05). Among adolescents, interviewer-based ratings of acute stressor impact may allow for better prediction of health-relevant inflammation markers than adolescents' own ratings.

Low-Grade Inflammation and Ambulatory Cortisol in Adolescents: Interaction between Interviewer-rated versus Self-rated Acute Stress and Chronic Stress

PubMed Central

Schreier, Hannah M. C.; Chen, Edith

2016-01-01

Objective To determine whether the association between self-rated or interviewer-rated recent acute stress exposures and low-grade inflammation and daily cortisol production in adolescents is moderated by chronic stress ratings. Methods Acute and chronic stress exposures were assessed in 261 adolescents aged 13-16 using a semi-structured life stress interview. The negative impact of acute stressors was independently rated by both adolescents (self-rated) and interviewers (interviewer-rated). Markers of inflammation (IL-6, IL-1ra, CRP) were measured from peripheral blood samples obtained via antecubital venipuncture. Participants collected 4 saliva samples at home on each of six consecutive days for the analysis of diurnal salivary cortisol profiles. Results There were no main effects of acute stressors (self- and interviewer-rated) and chronic family or peer stress on adolescent inflammation markers and cortisol (ps > .10). However, the interaction between interviewer-rated acute stress and chronic family stress was significantly associated with adolescent inflammation markers (IL-6, IL-1ra). Specifically, as chronic family stress increased, the association between acute stressor impact (interviewer-rated) and inflammation markers became more positive (IL-6 (B = .054, SE = .023, p = .022); IL-1ra (B = .030, SE = .014, p = .034)). Interactions between self-rated acute stress and chronic family stress were not associated with any biological measures (ps > .10). Interactions between acute stressor impact (both self- and interviewer-rated) and chronic peer stress were also not significantly associated with any biological measures (ps > .05). Conclusions Among adolescents, interviewer-based ratings of acute stressor impact may allow for better prediction of health-relevant inflammation markers than adolescents’ own ratings. PMID:27490853

Effects of acute systemic inflammation on the interplay between sad mood and affective cognition.

PubMed

Benson, Sven; Brinkhoff, Alexandra; Lueg, Larissa; Roderigo, Till; Kribben, Andreas; Wilde, Benjamin; Witzke, Oliver; Engler, Harald; Schedlowski, Manfred; Elsenbruch, Sigrid

2017-12-11

Experimental endotoxemia is a translational model to study inflammatory mechanisms involved in the pathophysiology of mood disorders including depression. Disturbed affective cognition constitutes a core aspect in depression, but has never been studied in the context of inflammation. We combined experimental endotoxemia with an established experimental mood induction procedure to assess the interaction between acute inflammation and sad mood and their effects on affective cognition. In this randomized cross-over study, N = 15 healthy males received endotoxin (0.8 ng/kg lipopolysaccharide iv) on one study day and placebo an otherwise identical study day. The affective Go/Nogo task was conducted after experimental induction of neutral and sad mood. Inflammatory markers were assessed hourly. Endotoxin application induced a transient systemic inflammation, characterized by increased leukocyte counts, TNF-alpha and interleukin-6 plasma concentrations (all p < 0.01, interaction effects). Mood induction led to greater sadness ratings, with highest ratings when sad mood was induced during inflammation (p < 0.05, interaction effect). Based on a 2 (endotoxin vs. placebo) × 2 (sad vs. neutral mood) × 2 (sad vs. happy Go/Nogo target words) factorial design, we observed a significant target × endotoxin condition interaction (p < 0.01) reflecting slower responses to sad targets during endotoxemia. Additionally, we found a valence × mood interaction (p < 0.05), reflecting slower reaction times to sad targets in sad mood. In summary, acute inflammation and sad mood are risk factors for disturbed affective cognition. The results may reflect a mood-congruency effect, with prolonged and sustained processing of mood-congruent information during acute inflammation, which may contribute to depression risk.

Chikungunya Arthritis: Implications of Acute and Chronic Inflammation Mechanisms on Disease Management.

PubMed

Zaid, Ali; Gérardin, Patrick; Taylor, Adam; Mostafavi, Helen; Malvy, Denis; Mahalingam, Suresh

2018-04-01

In the past decade, arboviruses-arthropod-borne viruses-have been the focus of public health institutions worldwide following a spate of devastating outbreaks. Chikungunya virus, an arbovirus that belongs to the alphavirus genus, is a reemerging arthritogenic virus that has caused explosive outbreaks since 2006, notably on Réunion Island, and more recently in the Caribbean, South America, India, and Southeast Asia. The severity of arthritic disease caused by chikungunya virus has prompted public health authorities in affected countries to develop specific guidelines to tackle this pathogen. Chikungunya virus disease manifests first as an acute stage of severe joint inflammation and febrile illness, which later progresses to a chronic stage, during which patients may experience debilitating and persisting articular pain for extended periods. This review aims to provide a broad perspective on current knowledge of chikungunya virus pathogenesis by identifying key clinical and experimental studies that have contributed to our understanding of chikungunya virus to date. In addition, the review explores the practical aspects of treatment and management of both acute and chronic chikungunya virus based on clinical experience during chikungunya virus outbreaks. Finally, recent findings on potential therapeutic solutions-from antiviral agents to immunomodulators-are reviewed to provide both viral immunologists and clinical rheumatologists with a balanced perspective on the nature of a reemerging arboviral disease of significant public health concern, and insight into future therapeutic approaches to better address the treatment and management of chikungunya virus. © 2017, American College of Rheumatology.

Bovine Intestinal Alkaline Phosphatase Reduces Inflammation After Induction of Acute Myocardial Infarction in Mice.

PubMed

Fiechter, Danielle; Kats, Suzanne; Brands, Ruud; van Middelaar, Ben; Pasterkamp, Gerard; de Kleijn, Dominique; Seinen, Willem

2011-10-01

There has been increasing evidence suggesting that lipopolysaccharide or endotoxin may be an important activator of the innate immune system after acute myocardial infarction. Bovine intestinal alkaline phosphatase reduces inflammation in several endotoxin mediated diseases by dephosphorylation of the lipid A moiety of lipopolysaccharide. The aim of this study was to investigate the effect of bovine intestinal alkaline phosphatase on reducing inflammation after acute myocardial infarction. Just before permanent ligation of the left anterior descending coronary (LAD) artery to induce acute myocardial infarction in Balb/c mice, bovine intestinal alkaline phosphatase (bIAP) was administrated intravenously. After 4 hours, mice were sacrificed and the inflammatory response was assessed. Acute myocardial infarction induced the production of different cytokines, which were measured in blood. Treatment with bovine intestinal alkaline phosphatase resulted in a significant reduction of the pro-inflammatory cytokines IL-6, IL-1β and the chymase mouse mast cell protease-1. No difference in the production of the anti-inflammatory cytokine IL-10 was observed between the control group and the bovine intestinal alkaline phosphatase treated group. In a mouse model of permanent LAD coronary artery ligation, bIAP diminishes the pro-inflammatory responses but does not have an effect on the anti-inflammatory response in the acute phase after acute myocardial infarction.

Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation.

PubMed

Zhang, Da-Gang; Zhang, Cheng; Wang, Jun-Xian; Wang, Bi-Wei; Wang, Hua; Zhang, Zhi-Hui; Chen, Yuan-Hua; Lu, Yan; Tao, Li; Wang, Jian-Qing; Chen, Xi; Xu, De-Xiang

2017-01-01

The farnesoid X receptor (FXR) is a ligand-activated transcription factor that plays important roles in regulating bile acid homeostasis. The aim of the present study was to investigate the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, carbon tetrachloride (CCl 4 )-induced acute liver injury. Mice were intraperitoneally injected with CCl 4 (0.15ml/kg). In CCl 4 +OCA group, mice were orally with OCA (5mg/kg) 48, 24 and 1h before CCl 4 . As expected, hepatic FXR was activated by OCA. Interestingly, OCA pretreatment alleviated CCl 4 -induced elevation of serum ALT and hepatic necrosis. Moreover, OCA pretreatment inhibited CCl 4 -induced hepatocyte apoptosis. Additional experiment showed that OCA inhibits CCl 4 -induced hepatic chemokine gene Mcp-1, Mip-2 and Kc. Moreover, OCA inhibits CCl 4 -induced hepatic pro-inflammatory gene Tnf-α and Il-1β. By contrast, OCA pretreatment elevated hepatic anti-inflammatory gene Il-4. Further analysis showed that OCA pretreatment inhibited hepatic IκB phosphorylation and blocked nuclear translocation of NF-κB p65 and p50 subunits during CCl 4 -induced acute liver injury. In addition, OCA pretreatment inhibited hepatic Akt, ERK and p38 phosphorylation in CCl 4 -induced acute liver injury. These results suggest that OCA protects against CCl 4 -induced acute liver injury and inflammation. Synthetic FXR agonists may be effective antidotes for hepatic inflammation during acute liver injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Temporomandibular joint involvement caused by Borrelia Burgdorferi.

PubMed

Lesnicar, Gorazd; Zerdoner, Danijel

2007-12-01

Lyme borreliosis is an endemic disease in Slovenia with an incidence of around 150 patients per 100,000 inhabitants. Although the large joints are most typically affected in Lyme borreliosis, there are also periods of disease activity with arthritis or arthralgias involving smaller joints, including the temporo-mandibular joint. During the years between 2000 and 2003, two patients with Lyme borreliosis affecting the temporo-mandibular joints were treated. The patients presented with fatigue and pain in diverse muscle groups accompanied by arthralgia, which was most pronounced in the temporomandibular joint area. None of the patients were febrile or had joint effusions. Both patients were examined by means of biochemical and serological examinations for Borrelia burgdorferi using ELISA assay and Western blot test (both for IgM and IgG), plain radiographs, MR and CT scans, and scinti-scan of the temporo-mandibular joints They both had positive serum markers for an acute B. burgdorferi infection and were treated with intravenous ceftriaxone. None of the patients had clinical or laboratory signs of chronic Lyme disease activity two and four years following therapy, respectively. Roentgenographic and nuclear magnetic resonance imaging of the temporo-mandibular joints had not shown any persistent sign of acute inflammation. There are only few reports of patients with manifest temporo-mandibular joint involvement of Lyme borreliosis in the literature. This report emphasizes the importance of differential diagnosis of acute temporo-mandibular joint arthralgia, of early diagnosis of Lyme borreliosis, and of the necessity for prompt antibiotic treatment.

Extraction, characterization and evaluation of Kaempferia galanga L. (Zingiberaceae) rhizome extracts against acute and chronic inflammation in rats.

PubMed

Jagadish, Puralae Channabasavaiah; Latha, Kotehal Parameshwarappa; Mudgal, Jayesh; Nampurath, Gopalan Kutty

2016-12-24

The rhizomes of an acaulescent perennial herb, Kaempferia galanga Linn (Family: Zingiberaceae), used as traditional ayurvedic herb to get relief from indigestion, swelling, pain, high blood pressure and dyslipidemia. To prepare and characterize various extracts of Kaempferia galanga (K. galanga) for their comparative evaluation for the identification of the most efficacious extract and its possible pharmacological implication in acute and chronic inflammatory paradigm. Dried and powdered rhizome of K. galanga was subjected to alcoholic extraction as well as successive extractions with various solvents. After phytochemical characterization, all the extracts were standardized for the presence of ethyl-p-methoxycinnamate. The extracts, and the isolated compound, were tested against carrageenan-induced acute inflammation in rats. The most promising extract was tested against adjuvant-induced chronic inflammation in rats. Further, local myeloperoxidase (MPO) levels were investigated to establish the possible mechanism of action. Among the extracts, petroleum ether extract (SKG-1) and crude alcoholic extract (KG) had the maximum quantity of ethyl-p-methoxycinnamate. SKG-1 (300mg/kg) was found effective against acute inflammation in rats. Further, SKG-1 (100mg/kg) reversed the inflammation and elevated MPO levels found in the chronic model. The results suggest that among all the extracts of K. galanga, SKG-1 effectively suppresses the progression of acute and chronic inflammation in rats by inhibition of neutrophil infiltration. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Dichotomous versus semi-quantitative scoring of ultrasound joint inflammation in rheumatoid arthritis using novel individualized joint selection methods.

PubMed

Tan, York Kiat; Allen, John C; Lye, Weng Kit; Conaghan, Philip G; Chew, Li-Ching; Thumboo, Julian

2017-05-01

The aim of the study is to compare the responsiveness of two joint inflammation scoring systems (dichotomous scoring (DS) versus semi-quantitative scoring (SQS)) using novel individualized ultrasound joint selection methods and existing ultrasound joint selection methods. Responsiveness measured by the standardized response means (SRMs) using the DS and the SQS system (for both the novel and existing ultrasound joint selection methods) was derived using the baseline and the 3-month total inflammatory scores from 20 rheumatoid arthritis patients. The relative SRM gain ratios (SRM-Gains) for both scoring system (DS and SQS) comparing the novel to the existing methods were computed. Both scoring systems (DS and SQS) demonstrated substantial SRM-Gains (ranged from 3.31 to 5.67 for the DS system and ranged from 1.82 to 3.26 for the SQS system). The SRMs using the novel methods ranged from 0.94 to 1.36 for the DS system and ranged from 0.89 to 1.11 for the SQS system. The SRMs using the existing methods ranged from 0.24 to 0.32 for the DS system and ranged from 0.34 to 0.49 for the SQS system. The DS system appears to achieve high responsiveness comparable to SQS for the novel individualized ultrasound joint selection methods.

Obeticholic acid protects against carbon tetrachloride-induced acute liver injury and inflammation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Da-Gang

The farnesoid X receptor (FXR) is a ligand-activated transcription factor that plays important roles in regulating bile acid homeostasis. The aim of the present study was to investigate the effects of obeticholic acid (OCA), a novel synthetic FXR agonist, carbon tetrachloride (CCl{sub 4})-induced acute liver injury. Mice were intraperitoneally injected with CCl{sub 4} (0.15 ml/kg). In CCl{sub 4} + OCA group, mice were orally with OCA (5 mg/kg) 48, 24 and 1 h before CCl{sub 4}. As expected, hepatic FXR was activated by OCA. Interestingly, OCA pretreatment alleviated CCl{sub 4}-induced elevation of serum ALT and hepatic necrosis. Moreover, OCA pretreatmentmore » inhibited CCl{sub 4}-induced hepatocyte apoptosis. Additional experiment showed that OCA inhibits CCl{sub 4}-induced hepatic chemokine gene Mcp-1, Mip-2 and Kc. Moreover, OCA inhibits CCl{sub 4}-induced hepatic pro-inflammatory gene Tnf-α and Il-1β. By contrast, OCA pretreatment elevated hepatic anti-inflammatory gene Il-4. Further analysis showed that OCA pretreatment inhibited hepatic IκB phosphorylation and blocked nuclear translocation of NF-κB p65 and p50 subunits during CCl{sub 4}-induced acute liver injury. In addition, OCA pretreatment inhibited hepatic Akt, ERK and p38 phosphorylation in CCl{sub 4}-induced acute liver injury. These results suggest that OCA protects against CCl{sub 4}-induced acute liver injury and inflammation. Synthetic FXR agonists may be effective antidotes for hepatic inflammation during acute liver injury. - Highlights: • OCA pretreatment activates hepatic FXR. • FXR activation protects against CCl{sub 4}-induced acute liver injury. • FXR activation inhibits hepatocyte apoptosis during CCl{sub 4}-induced liver injury. • FXR activation differentially regulates hepatic inflammatory genes. • Synthetic FXR agonists are effective antidotes for acute liver injury.« less

Flaxseed lignans enriched in secoisolariciresinol diglucoside prevent acute asbestos-induced peritoneal inflammation in mice

PubMed Central

Pietrofesa, Ralph A.; Velalopoulou, Anastasia; Arguiri, Evguenia; Menges, Craig W.; Testa, Joseph R.; Hwang, Wei-Ting; Albelda, Steven M.

2016-01-01

Malignant mesothelioma (MM), linked to asbestos exposure, is a highly lethal form of thoracic cancer with a long latency period, high mortality and poor treatment options. Chronic inflammation and oxidative tissue damage caused by asbestos fibers are linked to MM development. Flaxseed lignans, enriched in secoisolariciresinol diglucoside (SDG), have antioxidant, anti-inflammatory and cancer chemopreventive properties. As a prelude to chronic chemoprevention studies for MM development, we tested the ability of flaxseed lignan component (FLC) to prevent acute asbestos-induced inflammation in MM-prone Nf2+/mu mice. Mice (n = 16–17 per group) were placed on control (CTL) or FLC-supplemented diets initiated 7 days prior to a single intraperitoneal bolus of 400 µg of crocidolite asbestos. Three days post asbestos exposure, mice were evaluated for abdominal inflammation, proinflammatory/profibrogenic cytokine release, WBC gene expression changes and oxidative and nitrosative stress in peritoneal lavage fluid (PLF). Asbestos-exposed mice fed CTL diet developed acute inflammation, with significant (P < 0.0001) elevations in WBCs and proinflammatory/profibrogenic cytokines (IL-1ß, IL-6, TNFα, HMGB1 and active TGFß1) relative to baseline (BL) levels. Alternatively, asbestos-exposed FLC-fed mice had a significant (P < 0.0001) decrease in PLF WBCs and proinflammatory/profibrogenic cytokine levels relative to CTL-fed mice. Importantly, PLF WBC gene expression of cytokines (IL-1ß, IL-6, TNFα, HMGB1 and TGFß1) and cytokine receptors (TNFαR1 and TGFßR1) were also downregulated by FLC. FLC also significantly (P < 0.0001) blunted asbestos-induced nitrosative and oxidative stress. FLC reduces acute asbestos-induced peritoneal inflammation, nitrosative and oxidative stress and may thus prove to be a promising agent in the chemoprevention of MM. PMID:26678224

Double-button Fixation System for Management of Acute Acromioclavicular Joint Dislocation

PubMed Central

Torkaman, Ali; Bagherifard, Abolfazl; Mokhatri, Tahmineh; Haghighi, Mohammad Hossein Shabanpour; Monshizadeh, Siamak; Taraz, Hamid; Hasanvand, Amin

2016-01-01

Background: Surgical treatments for acromioclavicular (AC) joint dislocation present with some complications. The present study was designed to evaluate the double-button fixation system in the management of acute acromioclavicular joint dislocation. Methods: This cross sectional study, done between February 2011 to June 2014, consisted of 28 patients who underwent surgical management by the double-button fixation system for acute AC joint dislocation. Age, sex, injury mechanism, dominant hand, side with injury, length of follow up, time before surgery, shoulder and hand (DASH), constant and visual analogue scale (VAS) scores, and all complications of the cases during the follow up were recorded. Results: The mean age of patients was 33.23±6.7 years. Twenty four patients (85.71%) were male and four (14.28%) were female. The significant differences were observed between pre-operation VAS, constant shoulder scores and post-operation measurements. There were not any significant differences between right and left coracoclavicular, but two cases of heterotrophic ossifications were recorded. The mean follow-up time was 16.17±4.38 months. Conclusion: According to the results, the double-button fixation system for management of acute acromioclavicular joint dislocation has suitable results and minimal damage to the soft tissues surrounding the coracoclavicular ligaments. PMID:26894217

A "multi-hit" model of neonatal white matter injury: cumulative contributions of chronic placental inflammation, acute fetal inflammation and postnatal inflammatory events.

PubMed

Korzeniewski, Steven J; Romero, Roberto; Cortez, Josepf; Pappas, Athina; Schwartz, Alyse G; Kim, Chong Jai; Kim, Jung-Sun; Kim, Yeon Mee; Yoon, Bo Hyun; Chaiworapongsa, Tinnakorn; Hassan, Sonia S

2014-11-01

We sought to determine whether cumulative evidence of perinatal inflammation was associated with increased risk in a "multi-hit" model of neonatal white matter injury (WMI). This retrospective cohort study included very preterm (gestational ages at delivery <32 weeks) live-born singleton neonates delivered at Hutzel Women's Hospital, Detroit, MI, from 2006 to 2011. Four pathologists blinded to clinical diagnoses and outcomes performed histological examinations according to standardized protocols. Neurosonography was obtained per routine clinical care. The primary indicator of WMI was ventriculomegaly (VE). Neonatal inflammation-initiating illnesses included bacteremia, surgical necrotizing enterocolitis, other infections, and those requiring mechanical ventilation. A total of 425 live-born singleton neonates delivered before the 32nd week of gestation were included. Newborns delivered of pregnancies affected by chronic chorioamnionitis who had histologic evidence of an acute fetal inflammatory response were at increased risk of VE, unlike those without funisitis, relative to referent newborns without either condition, adjusting for gestational age [odds ratio (OR) 4.7; 95% confidence interval (CI) 1.4-15.8 vs. OR 1.3; 95% CI 0.7-2.6]. Similarly, newborns with funisitis who developed neonatal inflammation-initiating illness were at increased risk of VE, unlike those who did not develop such illness, compared to the referent group without either condition [OR 3.6 (95% CI 1.5-8.3) vs. OR 1.7 (95% CI 0.5-5.5)]. The greater the number of these three types of inflammation documented, the higher the risk of VE (P<0.0001). Chronic placental inflammation, acute fetal inflammation, and neonatal inflammation-initiating illness seem to interact in contributing risk information and/or directly damaging the developing brain of newborns delivered very preterm.

Bovine Intestinal Alkaline Phosphatase Reduces Inflammation After Induction of Acute Myocardial Infarction in Mice

PubMed Central

Fiechter, Danielle; Kats, Suzanne; Brands, Ruud; van Middelaar, Ben; Pasterkamp, Gerard; de Kleijn, Dominique; Seinen, Willem

2011-01-01

Background There has been increasing evidence suggesting that lipopolysaccharide or endotoxin may be an important activator of the innate immune system after acute myocardial infarction. Bovine intestinal alkaline phosphatase reduces inflammation in several endotoxin mediated diseases by dephosphorylation of the lipid A moiety of lipopolysaccharide. The aim of this study was to investigate the effect of bovine intestinal alkaline phosphatase on reducing inflammation after acute myocardial infarction. Methods Just before permanent ligation of the left anterior descending coronary (LAD) artery to induce acute myocardial infarction in Balb/c mice, bovine intestinal alkaline phosphatase (bIAP) was administrated intravenously. After 4 hours, mice were sacrificed and the inflammatory response was assessed. Acute myocardial infarction induced the production of different cytokines, which were measured in blood. Results Treatment with bovine intestinal alkaline phosphatase resulted in a significant reduction of the pro-inflammatory cytokines IL-6, IL-1β and the chymase mouse mast cell protease-1. No difference in the production of the anti-inflammatory cytokine IL-10 was observed between the control group and the bovine intestinal alkaline phosphatase treated group. Conclusion In a mouse model of permanent LAD coronary artery ligation, bIAP diminishes the pro-inflammatory responses but does not have an effect on the anti-inflammatory response in the acute phase after acute myocardial infarction. PMID:28357012

The central role of hypothalamic inflammation in the acute illness response and cachexia.

PubMed

Burfeind, Kevin G; Michaelis, Katherine A; Marks, Daniel L

2016-06-01

When challenged with a variety of inflammatory threats, multiple systems across the body undergo physiological responses to promote defense and survival. The constellation of fever, anorexia, and fatigue is known as the acute illness response, and represents an adaptive behavioral and physiological reaction to stimuli such as infection. On the other end of the spectrum, cachexia is a deadly and clinically challenging syndrome involving anorexia, fatigue, and muscle wasting. Both of these processes are governed by inflammatory mediators including cytokines, chemokines, and immune cells. Though the effects of cachexia can be partially explained by direct effects of disease processes on wasting tissues, a growing body of evidence shows the central nervous system (CNS) also plays an essential mechanistic role in cachexia. In the context of inflammatory stress, the hypothalamus integrates signals from peripheral systems, which it translates into neuroendocrine perturbations, altered neuronal signaling, and global metabolic derangements. Therefore, we will discuss how hypothalamic inflammation is an essential driver of both the acute illness response and cachexia, and why this organ is uniquely equipped to generate and maintain chronic inflammation. First, we will focus on the role of the hypothalamus in acute responses to dietary and infectious stimuli. Next, we will discuss the role of cytokines in driving homeostatic disequilibrium, resulting in muscle wasting, anorexia, and weight loss. Finally, we will address mechanisms and mediators of chronic hypothalamic inflammation, including endothelial cells, chemokines, and peripheral leukocytes. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effects of acute inflammation on cognitive functioning and emotional processing in humans: A systematic review of experimental studies.

PubMed

Bollen, Jessica; Trick, Leanne; Llewellyn, David; Dickens, Chris

2017-03-01

The cognitive neuropsychological model of depression proposes that negative biases in the processing of emotionally salient information have a central role in the development and maintenance of depression. We have conducted a systematic review to determine whether acute experimental inflammation is associated with changes to cognitive and emotional processing that are thought to cause and maintain depression. We identified experimental studies in which healthy individuals were administered an acute inflammatory challenge (bacterial endotoxin/vaccination) and standardised tests of cognitive function were performed. Fourteen references were identified, reporting findings from 12 independent studies on 345 participants. Methodological quality was rated strong or moderate for 11 studies. Acute experimental inflammation was triggered using a variety of agents (including endotoxin from E. coli, S. typhi, S. abortus Equi and Hepatitis B vaccine) and cognition was assessed over hours to months, using cognitive tests of i) attention/executive functioning, ii) memory and iii) social/emotional processing. Studies found mixed evidence that acute experimental inflammation caused changes to attention/executive functioning (2 of 6 studies showed improvements in attention executive function compared to control), changes in memory (3 of 5 studies; improved reaction time: reduced memory for object proximity: poorer immediate and delayed memory) and changes to social/emotional processing (4 of 5 studies; reduced perception of emotions, increased avoidance of punishment/loss experiences, and increased social disconnectedness). Acute experimental inflammation causes negative biases in social and emotional processing that could explain observed associations between inflammation and depression. Copyright © 2017 Elsevier Inc. All rights reserved.

[Acute injuries of lateral ankle joint ligaments].

PubMed

Lacko, M; Sidor, Z; Stolfa, S; Cellár, R; Vasko, G

2010-08-01

Acute injuries of the lateral ankle ligaments are one of the most common form of injury involving the musculoskeletal apparatus. Treatment usually range from cast immobilisation or acute surgical repair to functional rehabilitation. The aim of our study was to evaluate the incidence of different grades of acute injuries of lateral ligaments of the ankle joint in our patients group and to compare the results of non surgical versus surgical treatment of third grade injuries. 3148 patients were treated for acute lateral ankle sprain in a period of 5 years at our department. Each patient had stress X-ray of the ankle for evaluation of instability at the first visit. From the 234 patients with third grade injury, 39 were enrolled in our study with non surgical treatment and 18 with surgical treatment. Each group was divided regarding to the age in two subgroups. Functional outcome was evaluated 12 and 24 months after injury with AOFAS clinical rating scale and Sports Ankle Rating System--Single Assessment Numeric Evaluation. Statistical analysis was done with Pearson's Chi quadrate test with P < 0.05. First grade injury was present in 62%, second grade in 31% and only 7% of the patients had third grade injury of the lateral ankle ligaments. Further only third grade injuries were studied. Statistically significant better results were seen in patients under the age of 25, in the patient group with surgical treatment compared to patients over 25 years of age. Also statistically significant better results were seen in patient with surgical treatment to non surgical treatment in each age group. No significant difference was observed in the non surgical treatment group regarding to age. Although the injuries of the ankle ligaments belong to the most common injuries of the musculoskeletal system, there is no consensus in the treatment of such disorders. Our experiences and the results of our study show, that surgical treatment in indicated cases provides better results in

A ‘Multi-Hit’ Model of Neonatal White Matter Injury: Cumulative Contributions of Chronic Placental Inflammation, Acute Fetal Inflammation and Postnatal Inflammatory Events

PubMed Central

Korzeniewski, SJ; Romero, R; Cortez, J; Pappas, A; Schwartz, AG; Kim, CJ; Kim, JS; Kim, YM; Yoon, BH; Chaiworapongsa, T; Hassan, SS

2018-01-01

Objective We sought to determine whether cumulative evidence of perinatal inflammation was associated with increased risk in a ‘multi-hit’ model of neonatal white matter injury. Methods This retrospective cohort study included very preterm (gestational ages at delivery <32 weeks) liveborn singleton neonates delivered at Hutzel Women’s Hospital, Detroit, MI, from 2006–2011. Four pathologists blinded to clinical diagnoses and outcomes performed histological examinations according to standardized protocols. Neurosonography was obtained per routine clinical care. The primary indicator of WMI was ventriculomegaly (VE). Neonatal inflammation-initiating illnesses included bacteremia, surgical necrotizing enterocolitis, other infections, and those requiring mechanical ventilation. Results A total of 425 liveborn singleton neonates delivered before the 32nd week of gestation were included. Newborns delivered of pregnancies affected by chronic chorioamnionitis who had histologic evidence of an acute fetal inflammatory response were at increased risk of VE, unlike those without funisitis, relative to referent newborns without either condition, adjusting for gestational age [OR 4.7; 95%CI 1.4–15.8 vs. OR 1.3; 95%CI 0.7–2.6]. Similarly, newborns with funisitis who developed neonatal inflammation initiating illness were at increased risk of VE, unlike those who did not develop such illness, compared to the referent group without either condition [OR 3.6; 95%CI 1.5–8.3 vs. OR 1.7; 95%CI 0.5–5.5]. The greater the number of these three types of inflammation documented, the higher the risk of VE (p<0.0001). Conclusion Chronic placental inflammation, acute fetal inflammation and neonatal inflammation-initiating illness seem to interact in contributing risk information and/or directly damaging the developing brain of newborns delivered very preterm. PMID:25205706

Fingerprint of Lung Fluid Ultrafine Particles, a Novel Marker of Acute Lung Inflammation.

PubMed

Bar-Shai, Amir; Alcalay, Yifat; Sagiv, Adi; Rotem, Michal; Feigelson, Sara W; Alon, Ronen; Fireman, Elizabeth

2015-01-01

Acute lung inflammation can be monitored by various biochemical readouts of bronchoalveolar lavage fluid (BALF). To analyze the BALF content of ultrafine particles (UFP; <100 nm) as an inflammatory biomarker in early diagnosis of acute and chronic lung diseases. Mice were exposed to different stress conditions and inflammatory insults (acute lipopolysaccharide inhalation, tobacco smoke and lethal dose of total body irradiation, i.e. 950 rad). After centrifugation, the cellular pellet was assessed while cytokines and ultrafine particles were measured in the soluble fraction of the BALF. A characteristic UFP distribution with a D50 (i.e. the dimension of the 50th UFP percentile) was shared by all tested mouse strains in the BALF of resting lungs. All tested inflammatory insults similarly shifted this size distribution, resulting in a unique UFP fingerprint with an averaged D50 of 58.6 nm, compared with the mean UFP D50 of 23.7 nm for resting BALF (p < 0.0001). This UFP profile was highly reproducible and independent of the intensity or duration of the inflammatory trigger. It returned to baseline after resolution of the inflammation. Neither total body irradiation nor induction of acute cough induced this fingerprint. The UFP fingerprint in the BALF of resting and inflamed lungs can serve as a binary biomarker of healthy and acutely inflamed lungs. This marker can be used as a novel readout for the onset of inflammatory lung diseases and for complete lung recovery from different insults.

Small RNA-seq during acute maximal exercise reveal RNAs involved in vascular inflammation and cardiometabolic health: brief report.

PubMed

Shah, Ravi; Yeri, Ashish; Das, Avash; Courtright-Lim, Amanda; Ziegler, Olivia; Gervino, Ernest; Ocel, Jeffrey; Quintero-Pinzon, Pablo; Wooster, Luke; Bailey, Cole Shields; Tanriverdi, Kahraman; Beaulieu, Lea M; Freedman, Jane E; Ghiran, Ionita; Lewis, Gregory D; Van Keuren-Jensen, Kendall; Das, Saumya

2017-12-01

Exercise improves cardiometabolic and vascular function, although the mechanisms remain unclear. Our objective was to demonstrate the diversity of circulating extracellular RNA (ex-RNA) release during acute exercise in humans and its relevance to exercise-mediated benefits on vascular inflammation. We performed plasma small RNA sequencing in 26 individuals undergoing symptom-limited maximal treadmill exercise, with replication of our top candidate miRNA in a separate cohort of 59 individuals undergoing bicycle ergometry. We found changes in miRNAs and other ex-RNAs with exercise (e.g., Y RNAs and tRNAs) implicated in cardiovascular disease. In two independent cohorts of acute maximal exercise, we identified miR-181b-5p as a key ex-RNA increased in plasma after exercise, with validation in a separate cohort. In a mouse model of acute exercise, we found significant increases in miR-181b-5p expression in skeletal muscle after acute exercise in young (but not older) mice. Previous work revealed a strong role for miR-181b-5p in vascular inflammation in obesity, insulin resistance, sepsis, and cardiovascular disease. We conclude that circulating ex-RNAs were altered in plasma after acute exercise target pathways involved in inflammation, including miR-181b-5p. Further investigation into the role of known (e.g., miRNA) and novel (e.g., Y RNAs) RNAs is warranted to uncover new mechanisms of vascular inflammation on exercise-mediated benefits on health. NEW & NOTEWORTHY How exercise provides benefits to cardiometabolic health remains unclear. We performed RNA sequencing in plasma during exercise to identify the landscape of small noncoding circulating transcriptional changes. Our results suggest a link between inflammation and exercise, providing rich data on circulating noncoding RNAs for future studies by the scientific community. Copyright © 2017 the American Physiological Society.

[Effects of balneotherapy on the reactants of acute inflammation phase in ankylosing spondylitis].

PubMed

2009-01-01

Ankylosing spondylitis (AS) is a chronic inflammatory disease that affects sacroiliac joints, spinal column and peripheral joints. Beside medication therapy, physical and balneotherapy play an important role in its complex treatment. The aim of the research was to establish serum concentrations of C-reactive protein (CRP), alpha 1-acid glycoprotein (alpha 1-AGP), ceruloplasmine (CP) and erythrocyte sedimentation rate (SE) before and after the balneotherapy in ankylosing spondylitis. The research included 50 AS patients according to the revised New York criteria, of mean age 43 years, who were treated for 14 days on the average at the Clinic for Rheumatology of the Institute "Niska Banja". All the patients received medications and balneotherapy (radioactive oligomineral baths, peloid, massage, kinesitherapy); the serum concentrations of CRP, al-AGP, CP and SE were measured before and after balneotherapy. Serum proteins were determined using original Nor Partigen plates Boehringer. Erythrocyte sedimentation rate was measured by Westergreen method. Balneotherapy was applied individually, intensively or mildly, depending on the AS stage and activity phase. After dosed balneotherapy, a significant decrease in the concentrations of CP (p < 0.05), alpha1-AGP (p < 0.01) and CRP (p < 0.05) was registered in the serums of AS patients. ESR was not significantly reduced. The research proved that alpha 1-acid glycoprotein, ceruloplasmine and C-reactive protein represent more sensitive inflammation markers as compared to erythrocyte sedimentation rate. The identification of acute phase reactants is important in the evaluation of dosed balneotherapy efficiency in the treatment of ankylosing spondylitis.

Deciphering the complexity of acute inflammation using mathematical models.

PubMed

Vodovotz, Yoram

2006-01-01

Various stresses elicit an acute, complex inflammatory response, leading to healing but sometimes also to organ dysfunction and death. We constructed both equation-based models (EBM) and agent-based models (ABM) of various degrees of granularity--which encompass the dynamics of relevant cells, cytokines, and the resulting global tissue dysfunction--in order to begin to unravel these inflammatory interactions. The EBMs describe and predict various features of septic shock and trauma/hemorrhage (including the response to anthrax, preconditioning phenomena, and irreversible hemorrhage) and were used to simulate anti-inflammatory strategies in clinical trials. The ABMs that describe the interrelationship between inflammation and wound healing yielded insights into intestinal healing in necrotizing enterocolitis, vocal fold healing during phonotrauma, and skin healing in the setting of diabetic foot ulcers. Modeling may help in understanding the complex interactions among the components of inflammation and response to stress, and therefore aid in the development of novel therapies and diagnostics.

Fetal inflammation associated with minimal acute morbidity in moderate/late preterm infants.

PubMed

Gisslen, Tate; Alvarez, Manuel; Wells, Casey; Soo, Man-Ting; Lambers, Donna S; Knox, Christine L; Meinzen-Derr, Jareen K; Chougnet, Claire A; Jobe, Alan H; Kallapur, Suhas G

2016-03-23

To determine whether exposure to acute chorioamnionitis and fetal inflammation caused short-term adverse outcomes. This is a prospective observational study: subjects were mothers delivering at 32-36 weeks gestation and their preterm infants at a large urban tertiary level III perinatal unit (N=477 infants). Placentae and fetal membranes were scored for acute histological chorioamnionitis based on the Redline criteria. Fetal inflammation was characterised by histological diagnosis of funisitis (umbilical cord inflammation), increased cord blood cytokines measured by ELISA, and activation of the inflammatory cells infiltrating the placenta and fetal membranes measured by immunohistology. Maternal and infant data were collected. Twenty-four per cent of 32-36-week infants were exposed to histological chorioamnionitis and 6.9% had funisitis. Immunostaining for leucocyte subsets showed selective infiltration of the placenta and fetal membranes with activated neutrophils and macrophages with chorioamnionitis. Interleukin (IL) 6, IL-8 and granulocyte colony-stimulating factor were selectively increased in the cord blood of preterm infants with funisitis. Compared with infants without chorioamnionitis, funisitis was associated with increased ventilation support during resuscitation (43.8% vs 15.4%) and more respiratory distress syndrome postnatally (27.3% vs 10.2%) in univariate analysis. However, these associations disappeared after adjusting for prematurity. Despite fetal exposure to funisitis, increased cord blood cytokines and activated placental inflammatory cells, we could not demonstrate neonatal morbidity specifically attributable to fetal inflammation after adjusting for gestational age in moderate and late preterm infants. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Prevalence and pattern of glenohumeral injuries among acute high-grade acromioclavicular joint instabilities.

PubMed

Pauly, Stephan; Kraus, Natascha; Greiner, Stefan; Scheibel, Markus

2013-06-01

With increasing numbers of arthroscopically assisted acromioclavicular (AC) joint stabilization procedures has come an increase in reports of concomitant glenohumeral injuries among AC joint separations. The aim of the present study was to evaluate the prevalence, pattern, and cause of glenohumeral pathologies among a large patient population with acute high-grade AC joint instability. A total of 125 patients (13 women, 112 men) with high-grade AC joint dislocation (6 Rockwood II; 119 Rockwood V) underwent diagnostic glenohumeral arthroscopy before AC joint repair. Pathologic lesions were evaluated for acute or degenerative origin and, if considered relevant, treated all-arthroscopically. Concomitant glenohumeral pathologies were found in 38 of 125 patients (30.4%). Analysis of pathogenesis distinguished different patterns of accompanying injuries: acute intra-articular lesions, related to the recent shoulder trauma, were found in 9 patients (7.2%), degenerative lesions, considered to be unrelated to the recent trauma, were found in 18 (14.4%), and 11 (8.8%) had an unclear traumatic correlation (intermediate group). Within the acute and the degenerative group, affected structures were predominantly partial, articular-sided tears of the anterosuperior rotator cuff, including instabilities of the pulley complex, followed by pathologies of the long head of the biceps and superior labrum anteroposterior lesions. The intermediate group presented mainly with articular-sided partial tears of the subscapularis tendon. This prospective study showed a high prevalence (30%) of concomitant glenohumeral pathologies, of which some indicate additional surgical therapy and could be missed by an isolated open AC repair. Hence, the arthroscopic approach for AC joint stabilization allows for the diagnosis and treatment of associated intra-articular pathologies. Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

The dynamics of acute inflammation

NASA Astrophysics Data System (ADS)

Kumar, Rukmini

The acute inflammatory response is the non-specific and immediate reaction of the body to pathogenic organisms, tissue trauma and unregulated cell growth. An imbalance in this response could lead to a condition commonly known as "shock" or "sepsis". This thesis is an attempt to elucidate the dynamics of acute inflammatory response to infection and contribute to its systemic understanding through mathematical modeling and analysis. The models of immunity discussed use Ordinary Differential Equations (ODEs) to model the variation of concentration in time of the various interacting species. Chapter 2 discusses three such models of increasing complexity. Sections 2.1 and 2.2 discuss smaller models that capture the core features of inflammation and offer general predictions concerning the design of the system. Phase-space and bifurcation analyses have been used to examine the behavior at various parameter regimes. Section 2.3 discusses a global physiological model that includes several equations modeling the concentration (or numbers) of cells, cytokines and other mediators. The conclusions drawn from the reduced and detailed models about the qualitative effects of the parameters are very similar and these similarities have also been discussed. In Chapter 3, the specific applications of the biologically detailed model are discussed in greater detail. These include a simulation of anthrax infection and an in silico simulation of a clinical trial. Such simulations are very useful to biologists and could prove to be invaluable tools in drug design. Finally, Chapter 4 discusses the general problem of extinction of populations modeled as continuous variables in ODES is discussed. The average time to extinction and threshold are estimated based on analyzing the equivalent stochastic processes.

Mind-body interactions in the regulation of airway inflammation in asthma: A PET study of acute and chronic stress

PubMed Central

Rosenkranz, Melissa A.; Esnault, Stephane; Christian, Bradley T.; Crisafi, Gina; Gresham, Lauren K.; Higgins, Andrew T.; Moore, Mollie N.; Moore, Sarah M.; Weng, Helen Y.; Salk, Rachel H.; Busse, William W.; Davidson, Richard J.

2016-01-01

Background Psychological stress has long been recognized as a contributing factor to asthma symptom expression and disease progression. Yet, the neural mechanisms that underlie this relationship have been largely unexplored in research addressing the pathophysiology and management of asthma. Studies that have examined the mechanisms of this relationship in the periphery suggest that it is the superimposition of acute stress on top of chronic stress that is of greatest concern for airway inflammation. Methods We compared asthmatic individuals with high and low levels of chronic life stress in their neural and peripheral physiological responses to the Trier Social Stress Test and a matched control task. We used FDG-PET to measure neural activity during performance of the two tasks. We used both circulating and airway-specific markers of asthma-related inflammation to assess the impact of acute stress in these two groups. Results Asthmatics under chronic stress had a larger HPA-axis response to an acute stressor, which failed to show the suppressive effects on inflammatory markers observed in those with low chronic stress. Moreover, our PET data suggest that greater activity in the anterior insula during acute stress may reflect regulation of the effect of stress on inflammation. In contrast, greater activity in the mid-insula and perigenual anterior cingulate seems to reflect greater reactivity and was associated with greater airway inflammation, a more robust alpha amylase response, and a greater stress-induced increase in proinflammatory cytokine mRNA expression in airway cells. Conclusions Acute stress is associated with increases in markers of airway inflammation in asthmatics under chronic stress. This relationship may be mediated by interactions between the insula and anterior cingulate cortex, that determine the salience of environmental cues, as well as descending regulatory influence of inflammatory pathways in the periphery. PMID:27039241

Mind-body interactions in the regulation of airway inflammation in asthma: A PET study of acute and chronic stress.

PubMed

Rosenkranz, Melissa A; Esnault, Stephane; Christian, Bradley T; Crisafi, Gina; Gresham, Lauren K; Higgins, Andrew T; Moore, Mollie N; Moore, Sarah M; Weng, Helen Y; Salk, Rachel H; Busse, William W; Davidson, Richard J

2016-11-01

Psychological stress has long been recognized as a contributing factor to asthma symptom expression and disease progression. Yet, the neural mechanisms that underlie this relationship have been largely unexplored in research addressing the pathophysiology and management of asthma. Studies that have examined the mechanisms of this relationship in the periphery suggest that it is the superimposition of acute stress on top of chronic stress that is of greatest concern for airway inflammation. We compared asthmatic individuals with high and low levels of chronic life stress in their neural and peripheral physiological responses to the Trier Social Stress Test and a matched control task. We used FDG-PET to measure neural activity during performance of the two tasks. We used both circulating and airway-specific markers of asthma-related inflammation to assess the impact of acute stress in these two groups. Asthmatics under chronic stress had a larger HPA-axis response to an acute stressor, which failed to show the suppressive effects on inflammatory markers observed in those with low chronic stress. Moreover, our PET data suggest that greater activity in the anterior insula during acute stress may reflect regulation of the effect of stress on inflammation. In contrast, greater activity in the mid-insula and perigenual anterior cingulate seems to reflect greater reactivity and was associated with greater airway inflammation, a more robust alpha amylase response, and a greater stress-induced increase in proinflammatory cytokine mRNA expression in airway cells. Acute stress is associated with increases in markers of airway inflammation in asthmatics under chronic stress. This relationship may be mediated by interactions between the insula and anterior cingulate cortex, that determine the salience of environmental cues, as well as descending regulatory influence of inflammatory pathways in the periphery. Copyright © 2016 Elsevier Inc. All rights reserved.

S100A8/A9, a potent serum and molecular imaging biomarker for synovial inflammation and joint destruction in seronegative experimental arthritis.

PubMed

Geven, Edwin J W; van den Bosch, Martijn H J; Di Ceglie, Irene; Ascone, Giuliana; Abdollahi-Roodsaz, Shahla; Sloetjes, Annet W; Hermann, Sven; Schäfers, Michael; van de Loo, Fons A J; van der Kraan, Peter M; Koenders, Marije I; Foell, Dirk; Roth, Johannes; Vogl, Thomas; van Lent, Peter L E M

2016-10-24

Seronegative joint diseases are characterized by a lack of well-defined biomarkers since autoantibodies are not elevated. Calprotectin (S100A8/A9) is a damage-associated molecular pattern (DAMP) which is released by activated phagocytes, and high levels are found in seronegative arthritides. In this study, we investigated the biomarker potential of systemic and local levels of these S100 proteins to assess joint inflammation and joint destruction in an experimental model for seronegative arthritis. Serum levels of S100A8/A9 and various cytokines were monitored during disease development in interleukin-1 receptor antagonist (IL-1Ra) -/- mice using ELISA and multiplex bead-based immunoassay, and were correlated to macroscopic and microscopic parameters for joint inflammation, bone erosion, and cartilage damage. Local expression of S100A8 and S100A9 and matrix metalloproteinase (MMP)-mediated cartilage damage in the ankle joints were investigated by immunohistochemistry. In addition, local S100A8 and activated MMPs were monitored in vivo by optical imaging using anti-S100A8-Cy7 and AF489-Cy5.5, a specific tracer for activated MMPs. Serum levels of S100A8/A9 were significantly increased in IL-1Ra -/- mice and correlated with macroscopic joint swelling and histological inflammation, while serum levels of pro-inflammatory cytokines did not correlate with joint swelling. In addition, early serum S100A8/A9 levels were prognostic for disease outcome at a later stage. The increased serum S100A8/A9 levels were reflected by an increased expression of S100A8 and S100A9 within the ankle joint, as visualized by molecular imaging. Next to inflammatory processes, serum S100A8/A9 also correlated with histological parameters for bone erosion and cartilage damage. In addition, arthritic IL-1Ra -/- mice with increased synovial S100A8 and S100A9 expression showed increased cartilage damage that coincided with MMP-mediated neoepitope expression and in vivo imaging of activated MMPs

Autoantibodies to citrullinated proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism

PubMed Central

Wigerblad, Gustaf; Bas, Duygu B; Fernades-Cerqueira, Cátia; Krishnamurthy, Akilan; Rogoz, Katarzyna; Kato, Jungo; Sandor, Katalin; Su, Jie; Jimenez–Andrade, Juan Miguel; Finn, Anja; Bersellini Farinotti, Alex; Amara, Khaled; Lundberg, Karin; Holmdahl, Rikard; Jakobsson, Per-Johan; Malmström, Vivianne; Catrina, Anca I; Klareskog, Lars; Svensson, Camilla I

2016-01-01

Objective An interesting and so far unexplained feature of chronic pain in autoimmune disease is the frequent disconnect between pain and inflammation. This is illustrated well in rheumatoid arthritis (RA) where pain in joints (arthralgia) may precede joint inflammation and persist even after successful anti-inflammatory treatment. In the present study, we have addressed the possibility that autoantibodies against citrullinated proteins (ACPA), present in RA, may be directly responsible for the induction of pain, independent of inflammation. Methods Antibodies purified from human patients with RA, healthy donors and murinised monoclonal ACPA were injected into mice. Pain-like behaviour was monitored for up to 28 days, and tissues were analysed for signs of pathology. Mouse osteoclasts were cultured and stimulated with antibodies, and supernatants analysed for release of factors. Mice were treated with CXCR1/2 (interleukin (IL) 8 receptor) antagonist reparixin. Results Mice injected with either human or murinised ACPA developed long-lasting pronounced pain-like behaviour in the absence of inflammation, while non-ACPA IgG from patients with RA or control monoclonal IgG were without pronociceptive effect. This effect was coupled to ACPA-mediated activation of osteoclasts and release of the nociceptive chemokine CXCL1 (analogue to human IL-8). ACPA-induced pain-like behaviour was reversed with reparixin. Conclusions The data suggest that CXCL1/IL-8, released from osteoclasts in an autoantibody-dependent manner, produces pain by activating sensory neurons. The identification of this new pain pathway may open new avenues for pain treatment in RA and also in other painful diseases associated with autoantibody production and/or osteoclast activation. PMID:26613766

Baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation and oxidative stress in rat

PubMed Central

Chen, Huaguo; Xu, Yongfu; Wang, Jianzhong; Zhao, Wei; Ruan, Huihui

2015-01-01

Baicalin belongs to glucuronic acid glycosides and after hydrolysisbaicalein and glucuronic acid come into being. It has such effects as clearing heat and removing toxicity, anti-inflammation, choleresis, bringing high blood pressure down, diuresis, anti-allergic reaction and so on. In this study, we investigated whether baicalin ameliorates isoproterenol-induced acute myocardial infarction and its mechanism. Rat model of acute myocardial infarction was induced by isoproterenol. Casein kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH), cardiac troponin T (cTnT) and infarct size measurement were used to measure the protective effect of baicalin on isoproterenol-induced acute myocardial infarction. iNOS protein expression in rat was analyzed using western blot analysis. Tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), malondialdehyde (MDA) and superoxide dismutase (SOD) and caspase-3 activation levels were explored using commercial ELISA kits. In the acute myocardial infarction experiment, baicalin effectively ameliorates the level of CK, CK-MB, LDH and cTnT, reduced infarct size in acute myocardial infarction rat model. Meanwhile, treatment with baicalin effectively decreased the iNOS protein expression, inflammatory factors and oxidative stresses in a rat model of acute myocardial infarction. However, baicalin emerged that anti-apoptosis activity and suppressed the activation of caspase-3 in a rat model of acute myocardial infarction. The data suggest that the protective effect of baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation and oxidative stress in rat. PMID:26617721

Myeloid-related proteins S100A8/S100A9 regulate joint inflammation and cartilage destruction during antigen-induced arthritis.

PubMed

van Lent, P L E M; Grevers, L; Blom, A B; Sloetjes, A; Mort, J S; Vogl, T; Nacken, W; van den Berg, W B; Roth, J

2008-12-01

To study the active involvement of Myeloid-related proteins S100A8 and S100A9 in joint inflammation and cartilage destruction during antigen-induced arthritis (AIA). Joint inflammation and cartilage destruction was measured with 99mTc uptake and histology. The role of S100A8/A9 was investigated by inducing AIA in S100A9-/- mice that also lack S100A8 at protein level, or after intra-articular injection of rS100A8 in mouse knee joints. Cartilage destruction was measured using immunolocalisation of the neoepitope VDIPEN or NITEGE. mRNA levels of matrix metalloproteinases (MMPs) and cytokines were measured using reverse transcriptase (RT)-PCR. Immunisation of S100A9-/- mice with the antigen mBSA induced normal cellular and humoral responses, not different from wild type (WT) controls. However, joint swelling measured at day 3 and 7 after AIA induction was significantly lower (36 and 70%, respectively). Histologically, at day 7 AIA, cellular mass was much lower (63-80%) and proteoglycan depletion from cartilage layers was significantly reduced (between 50-95%). Cartilage destruction mediated by MMPs was absent in S100A9-/- mice but clearly present in controls. MMP3, 9 and 13 mRNA levels were significantly lowered in arthritic synovia of S100A9-/-. In vitro stimulation of macrophages by the heterodimer S100A8/A9 or S100A8 elevated mRNA levels of MMP3, 9 and in particular MMP13. Intra-articular injection of S100A8 caused prominent joint inflammation and depletion of proteoglycans at day 1. Significant upregulation of mRNA levels of S100A8/A9, cytokines (interleukin 1 (IL1)), MMPs (MMP3, MMP13 and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4) was found in the synovium and correlated with strong upregulation of NITEGE neoepitopes within the cartilage layers. S100A8/A9 regulate joint inflammation and cartilage destruction during antigen-induced arthritis.

A modified surgical technique for reconstruction of an acute acromioclavicular joint dislocation

PubMed Central

Marchie, Anthony; Kumar, Arun; Catre, Melanio

2009-01-01

We report a modified surgical technique for reconstruction of coracoclavicular and acromioclavicular ligaments after acute dislocation of acromioclavicular joint using suture anchors. We have repaired 3 consecutive type III acromioclavicular dislocations with good results. This technique is simple and safe and allows anatomical reconstruction of the ligaments in acute dislocations. PMID:20671868

Analysis of adrenocortical secretory responses during acute an prolonged immune stimulation in inflammation-susceptible and -resistant rat strains.

PubMed

Andersson, I M; Lorentzen, J C; Ericsson-Dahlstrand, A

2000-11-01

Endogenous corticosterone secreted during immune challenge restricts the inflammatory process and genetic variations in this neuroendocrine-immune dialogue have been suggested to influence an individuals sensitivity to develop chronic inflammatory disorders. We have tested inflammation-susceptible Dark Agouti (DA) rats and resistant, MHC-identical, PVG.1AV1 rats for their abilities to secrete corticosterone in response to acute challenge with bacterial lipopolysaccharide (LPS) or a prolonged activation of the nonspecific immune system with arthritogenic yeast beta-glucan. Intravenous injection of LPS triggered equipotent secretion of corticosterone in both rat strains. Interestingly, peak concentrations of corticosterone did not differ significantly between the strains. Intradermal injection of beta-glucan caused severe, monophasic, polyarthritis in DA rats while PVG.1AV1 responded with significantly milder joint inflammation. Importantly, serial sampling of plasma from glucan-injected DA and PVG.1AV1 rats did not reveal elevated concentrations of plasma corticosterone at any time from days 1-30 postinjection compared to preinjection values, in spite of the ongoing inflammatory process. Interestingly, adrenalectomized, beta-glucan-challenged DA rats responded with an aggravated arthritic process, indicating an anti-inflammatory role for the basal levels of corticosterone that were detected in intact DA rats challenged with beta-glucan. Moreover, substitution with subcutaneous corticosterone-secreting pellets, yielding moderate stress-levels, significantly attenuated the arthritic response. In contrast, adrenalectomized and glucan-challenged PVG.1AV1 rats did not respond with an elevated arthritic response, suggesting that these rats contain the arthritic process via corticosterone-independent mechanisms. In conclusion, the hypothalamic-pituitary-adrenal axis in both rat strains exhibited strong activation after challenge with LPS. This contrasted to the basal

Pro-Resolving lipid mediators and Mechanisms in the resolution of acute inflammation

PubMed Central

Buckley, Christopher D.; Gilroy, Derek W.; Serhan, Charles N.

2014-01-01

SUMMARY Inflammatory responses, like all biological cascades, are shaped by a delicate balance between positive and negative feedback loops. It is now clear that in addition to positive and negative checkpoints, the inflammatory cascade rather unexpectedly boasts an additional checkpoint, a family of chemicals that actively promote resolution and tissue repair without compromising host defence. Indeed the resolution phase of inflammation is just as actively orchestrated and carefully choreographed as its induction and inhibition. In this review we explore the immunological consequences of these omega-3-derived specialized pro-resolving mediators (SPMs) and discuss their place within what is currently understood of the role of the arachidonic acid-derived prostaglandins, lipoxins and their natural C15-epimers. We propose that treatment of inflammation should not be restricted to the use of inhibitors of the acute cascade (antagonism) but broadened to take account of the enormous therapeutic potential of inducers (agonists) of the resolution phase of inflammation. PMID:24656045

Autoantibodies to citrullinated proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism.

PubMed

Wigerblad, Gustaf; Bas, Duygu B; Fernades-Cerqueira, Cátia; Krishnamurthy, Akilan; Nandakumar, Kutty Selva; Rogoz, Katarzyna; Kato, Jungo; Sandor, Katalin; Su, Jie; Jimenez-Andrade, Juan Miguel; Finn, Anja; Bersellini Farinotti, Alex; Amara, Khaled; Lundberg, Karin; Holmdahl, Rikard; Jakobsson, Per-Johan; Malmström, Vivianne; Catrina, Anca I; Klareskog, Lars; Svensson, Camilla I

2016-04-01

An interesting and so far unexplained feature of chronic pain in autoimmune disease is the frequent disconnect between pain and inflammation. This is illustrated well in rheumatoid arthritis (RA) where pain in joints (arthralgia) may precede joint inflammation and persist even after successful anti-inflammatory treatment. In the present study, we have addressed the possibility that autoantibodies against citrullinated proteins (ACPA), present in RA, may be directly responsible for the induction of pain, independent of inflammation. Antibodies purified from human patients with RA, healthy donors and murinised monoclonal ACPA were injected into mice. Pain-like behaviour was monitored for up to 28 days, and tissues were analysed for signs of pathology. Mouse osteoclasts were cultured and stimulated with antibodies, and supernatants analysed for release of factors. Mice were treated with CXCR1/2 (interleukin (IL) 8 receptor) antagonist reparixin. Mice injected with either human or murinised ACPA developed long-lasting pronounced pain-like behaviour in the absence of inflammation, while non-ACPA IgG from patients with RA or control monoclonal IgG were without pronociceptive effect. This effect was coupled to ACPA-mediated activation of osteoclasts and release of the nociceptive chemokine CXCL1 (analogue to human IL-8). ACPA-induced pain-like behaviour was reversed with reparixin. The data suggest that CXCL1/IL-8, released from osteoclasts in an autoantibody-dependent manner, produces pain by activating sensory neurons. The identification of this new pain pathway may open new avenues for pain treatment in RA and also in other painful diseases associated with autoantibody production and/or osteoclast activation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Quantification of structural changes in acute inflammation by fractal dimension, angular second moment and correlation.

PubMed

Stankovic, Marija; Pantic, Igor; De Luka, Silvio R; Puskas, Nela; Zaletel, Ivan; Milutinovic-Smiljanic, Sanja; Pantic, Senka; Trbovich, Alexander M

2016-03-01

The aim of the study was to examine alteration and possible application of fractal dimension, angular second moment, and correlation for quantification of structural changes in acutely inflamed tissue. Acute inflammation was induced by injection of turpentine oil into the right and left hind limb muscles of mice, whereas control animals received intramuscular saline injection. After 12 h, animals were anesthetised and treated muscles collected. The tissue was stained by hematoxylin and eosin, digital micrographs produced, enabling determination of fractal dimension of the cells, angular second moment and correlation of studied tissue. Histopathological analysis showed presence of inflammatory infiltrate and tissue damage in inflammatory group, whereas tissue structure in control group was preserved, devoid of inflammatory infiltrate. Fractal dimension of the cells, angular second moment and correlation of treated tissue in inflammatory group decreased in comparison to the control group. In this study, we were first to observe and report that fractal dimension of the cells, angular second moment, and correlation were reduced in acutely inflamed tissue, indicating loss of overall complexity of the cells in the tissue, the tissue uniformity and structure regularity. Fractal dimension, angular second moment and correlation could be useful methods for quantification of structural changes in acute inflammation. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

Corosolic acid ameliorates acute inflammation through inhibition of IRAK-1 phosphorylation in macrophages

PubMed Central

Kim, Seung-Jae; Cha, Ji-Young; Kang, Hye Suk; Lee, Jae-Ho; Lee, Ji Yoon; Park, Jae-Hyung; Bae, Jae-Hoon; Song, Dae-Kyu; Im, Seung-Soon

2016-01-01

Corosolic acid (CA), a triterpenoid compound isolated from Lagerstroemia speciosa L. (Banaba) leaves, exerts anti-inflammatory effects by regulating phosphorylation of interleukin receptor- associated kinase (IRAK)-2 via the NF-κB cascade. However, the protective effect of CA against endotoxic shock has not been reported. LPS (200 ng/mL, 30 min) induced phosphorylation of IRAK-1 and treatment with CA (10 μM) significantly attenuated this effect. In addition, CA also reduced protein levels of NLRP3 and ASC which are the main components of the inflammasome in BMDMs. LPS-induced inflammasome assembly through activation of IRAK-1 was down-regulated by CA challenge. Treatment with Bay11-7082, an inhibitor of IκB-α, had no effect on CA-mediated inhibition of IRAK-1 activation, indicating that CA-mediated attenuation of IRAK-1 phosphorylation was independent of NF-κB signaling. These results demonstrate that CA ameliorates acute inflammation in mouse BMDMs and CA may be useful as a pharmacological agent to prevent acute inflammation. [BMB Reports 2016; 49(5): 276-281] PMID:26615974

Low triiodothyronine: A new facet of inflammation in acute ischemic stroke.

PubMed

Ma, Lili; Zhu, Dongliang; Jiang, Ying; Liu, Yingying; Ma, Xiaomeng; Liu, Mei; Chen, Xiaohong

2016-07-01

Patients with acute ischemic stroke (AIS) frequently experience low free triiodothyronine (fT3) concentrations. Inflammation is recognized as a key contributor to the pathophysiology of stroke. Previous studies, however, did not simultaneously evaluate fT3 and inflammation biomarkers in AIS patients. Markers of inflammation, including serum concentrations of C-reactive protein (CRP) and albumin, and fT3 were assessed retrospectively in 117 patients. Stroke severity was measured on the National Institutes of Health Stroke Scale (NIHSS). Regression analyses were performed to adjust for confounders. Serum fT3 concentrations were significantly lower in moderate AIS patients than those in mild AIS patients (P<0.001). fT3 concentration also positively correlated with serum albumin concentration (r=0.358, P<0.001) and negatively correlated with log10CRP concentration (r=-0.341, P<0.001), NIHSS score (r=-0.384, P<0.001). Multiple regression analysis showed that CRP, albumin concentrations and NIHSS score were independently correlated with fT3 concentration. Binary logistic regression analysis showed that fT3 concentration was an independent factor correlated with NIHSS score, the area under the receiver operating characteristic curve was 0.712 (95% CI, 0.618-0.805). Low fT3 concentrations may be involved in the pathogenic pathway linking inflammation to stroke severity in AIS patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Matrix Metalloproteinase-8 Inactivates Macrophage Inflammatory Protein-1α to Reduce Acute Lung Inflammation and Injury in Mice

PubMed Central

Quintero, Pablo A.; Knolle, Martin D.; Cala, Luisa F.; Zhuang, Yuehong; Owen, Caroline A.

2010-01-01

To determine the role of matrix metalloproteinase-8 (MMP-8) in acute lung injury (ALI), we delivered LPS or bleomycin by the intratracheal route to MMP-8−/− mice versus WT mice or subjected the mice to hyperoxia (95% O2) and measured lung inflammation and injury at intervals. MMP-8−/− mice with ALI had greater increases in lung PMN and macrophage counts, measures of alveolar capillary barrier injury, lung elastance, and mortality than WT mice with ALI. Bronchoalveolar lavage fluid (BALF) from LPS-treated MMP-8−/− mice had more macrophage inflammatory protein-1α (MIP-1α) than BALF from LPS-treated WT mice, but similar levels of other pro- and anti-inflammatory mediators. MIP-1α−/− mice with ALI had less acute lung inflammation and injury than WT mice with ALI, confirming that MIP-1α promotes acute lung inflammation and injury in mice. Genetically deleting MIP-1α in MMP-8−/− mice abrogated the increased lung inflammation and injury and mortality in MMP-8−/− mice with ALI. Soluble MMP-8 cleaved and inactivated MIP-1α in vitro, but membrane-bound MMP-8 on activated PMNs had greater MIP-1α-degrading activity than soluble MMP-8. High levels of membrane-bound MMP-8 were detected on lung PMNs from LPS-treated WT mice, but soluble, active MMP-8 was not detected in BALF samples. Thus, MMP-8 has novel roles in restraining lung inflammation and in limiting alveolar capillary barrier injury during ALI in mice by inactivating MIP-1α. In addition, membrane-bound MMP-8 on activated lung PMNs is likely to be the key bioactive form of the enzyme that limits lung inflammation and alveolar capillary barrier injury during ALI. PMID:20042585

Involvement of prostaglandins and histamine in nickel wire-induced acute inflammation in mice.

PubMed

Hirasawa, Noriyasu; Goi, Yoshiaki; Tanaka, Rina; Ishihara, Kenji; Ohtsu, Hiroshi; Ohuchi, Kazuo

2010-06-15

The irritancy of Nickel (Ni) ions has been well documented clinically. However, the chemical mediators involved in the acute inflammation induced by solid Ni are not fully understood. We used the Ni wire-implantation model in mice and examined roles of prostaglandins and histamine in plasma leakage in the acute phase. The subcutaneous implantation of a Ni wire into the back of mice induced plasma leakage from 8 to 24 h and tissue necrosis around the wire at 3 days, whereas the implantation of an aluminum wire induced no such inflammatory responses. An increase in the mRNA for cyclooxygenase (COX)-2 and HDC in cells around the Ni wire was detected 4 h after the implantation. The leakage of plasma at 8 h was inhibited by indomethacin in a dose-dependent manner. Dexamethasone and the p38 MAP kinase inhibitor SB203580 also inhibited the exudation of plasma consistent with the inhibition of the expression of COX-2 mRNA. Furthermore, plasma leakage was partially but siginificantly reduced in histamine H1 receptor knockout mice and histidine decarboxylase (HDC) knockout mice but not in H2 receptor knockout mice. These results suggested that the Ni ions released from the wire induced the expression of COX-2 and HDC, resulting in an increase in vascular permeability during the acute phase of inflammation. (c) 2009 Wiley Periodicals, Inc.

Effects of hydrogen sulfide on inflammation in caerulein-induced acute pancreatitis

PubMed Central

2009-01-01

Background Hydrogen sulfide (H2S), a gaseous mediator plays an important role in a wide range of physiological and pathological processes. H2S has been extensively studied for its various roles in cardiovascular and neurological disorders. However, the role of H2S in inflammation is still controversial. The current study was aimed to investigate the therapeutic potential of sodium hydrosulfide (NaHS), an H2S donor in in vivo model of acute pancreatitis in mice. Methods Acute pancreatitis was induced in mice by hourly caerulein injections (50 μg/kg) for 10 hours. Mice were treated with different dosages of NaHS (5 mg/kg, 10 mg/kg or 15 mg/kg) or with vehicle, distilled water (DW). NaHS or DW was administered 1 h before induction of pancreatitis. Mice were sacrificed 1 h after the last caerulein injection. Blood, pancreas and lung tissues were collected and were processed to measure the plasma amylase, myeloperoxidase (MPO) activities in pancreas and lung and chemokines and adhesion molecules in pancreas and lung. Results It was revealed that significant reduction of inflammation, both in pancreas and lung was associated with NaHS 10 mg/kg. Further the anti-inflammatory effects of NaHS 10 mg/kg were associated with reduction of pancreatic and pulmonary inflammatory chemokines and adhesion molecules. NaHS 5 mg/kg did not cause significant improvement on inflammation in pancreas and associated lung injury and NaHS 15 mg/kg did not further enhance the beneficial effects seen with NaHS 10 mg/kg. Conclusion In conclusion, these data provide evidence for anti-inflammatory effects of H2S based on its dosage used. PMID:20040116

Baicalin Inhibits IL-17-Mediated Joint Inflammation in Murine Adjuvant-Induced Arthritis

PubMed Central

Yang, Xue; Yang, Ji; Zou, Hejian

2013-01-01

T-helper-17 (Th17) cells are implicated in a number of inflammatory disorders including rheumatoid arthritis. Antagonism of Th17 cells is a treatment option for arthritis. Here, we report that Baicalin, a compound isolated from the Chinese herb Huangqin (Scutellaria baicalensis Georgi), relieved ankle swelling and protected the joint against inflammatory destruction in a murine adjuvant-induced arthritis model. Baicalin inhibited splenic Th17 cell population expansion in vivo. Baicalin prevented interleukin- (IL-) 17-mediated lymphocyte adhesion to cultured synoviocytes. Baicalin also blocked IL-17-induced intercellular adhesion molecule 1, vascular cell adhesion molecule 1, IL-6, and tumor necrosis factor-alpha mRNA expression in cultured synoviocytes. Collectively, these findings suggest that Baicalin downregulates the joint inflammation caused by IL-17, which is likely produced by an expanded population of splenic Th17 cells in experimental arthritis. Baicalin might be a promising novel therapeutic agent for treating rheumatoid arthritis in humans. PMID:23840239

Acute phase response, inflammation and metabolic syndrome biomarkers of Libby asbestos exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shannahan, Jonathan H.; Alzate, Oscar; Winnik, Witold M.

Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. In four experiments spanning varied protocols and temporality, healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic syndrome (MetS), and the acute phase response (APR) were analyzed. All rat strains exhibited acute increases inmore » α-2-macroglobulin, and α1-acid glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH and SHHF and osteopontin only in WKY after LA exposure. While rat strain- and age-related changes were apparent in MetS biomarkers, no LA effects were evident. The cancer marker mesothelin was increased only slightly at 1 month in WKY in one of the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 day or 4 weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. Those included serine protease inhibitor, apolipoprotein E, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1 day after last LA exposure. All changes were reversible after a short recovery regardless of the acute or long-term exposures. Thus, LA exposure induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA. -- Highlights: ► Biomarkers of asbestos exposure are required for disease diagnosis. ► Libby amphibole exposure is associated with increased human mortality. ► Libby amphibole increases circulating proteins

UP-REGULATION OF IL-6, IL-8 AND CCL2 GENE EXPRESSION AFTER ACUTE INFLAMMATION: CORRELATION TO CLINICAL PAIN

PubMed Central

Wang, Xiao-Min; Hamza, May; Wu, Tai-Xia; Dionne, Raymond A.

2012-01-01

Tissue injury initiates a cascade of inflammatory mediators and hyperalgesic substances including prostaglandins, cytokines and chemokines. Using microarray and qRT-PCR gene expression analyses, the present study evaluated changes in gene expression of a cascade of cytokines following acute inflammation and the correlation between the changes in the gene expression level and pain intensity in the oral surgery clinical model of acute inflammation. Tissue injury resulted in a significant up-regulation in the gene expression of Interleukin-6 (IL-6; 63.3-fold), IL-8 (8.1-fold), chemokine (C-C motif) ligand 2 (CCL2; 8.9-fold), chemokine (C-X-C motif) ligand 1 (CXCL1; 30.5-fold), chemokine (C-X-C motif) ligand 2 (CXCL2; 26-fold) and annexin A1 (ANXA1; 12-fold). The up-regulation of IL-6 gene expression was significantly correlated to the up-regulation on the gene expression of IL-8, CCL2, CXCL1 and CXCL2. Interestingly, the tissue injury induced up-regulation of IL-6 gene expression, IL-8 and CCL2 were positively correlated to pain intensity at 3 hours post-surgery, the onset of acute inflammatory pain. However, ketorolac treatment did not have a significant effect on the gene expression of IL-6, IL-8, CCL2, CXCL2 and ANXA1 at the same time point of acute inflammation. These results demonstrate that up-regulation of IL-6, IL-8 and CCL2 gene expression contributes to the development of acute inflammation and inflammatory pain. The lack of effect for ketorolac on the expression of these gene products may be related to the ceiling analgesic effects of non-steroidal anti-inflammatory drugs. PMID:19233564

Acute hyperglycaemia and inflammation in patients with ST segment elevation myocardial infarction.

PubMed

Terlecki, Michał; Bednarek, Agnieszka; Kawecka-Jaszcz, Kalina; Czarnecka, Danuta; Bryniarski, Leszek

2013-01-01

Acute hyperglycaemia in patients with acute coronary syndromes (ACS) is associated with increased cardiovascular (CV) risk among both diabetic and non-diabetic patients although the mechanisms underlying this association are not clearly understood. Acute hyperglycaemia in patients with ACS may be associated with increased systemic inflammation. Leukocytes are the major cellular mediators of inflammation and their elevated count is associated with higher CV event rate in ACS patients. Thus, it is possible that there is a relationship between acute hyperglycaemia and high leukocyte count and concomitant presence of these two conditions may contribute to increased CV risk among patients with ST segment elevation myocardial infarction (STEMI). To investigate the relationship between acute hyperglycaemia and high leukocyte count and to evaluate its association with outcomes in patients with STEMI. Glucose level and leukocyte count on admission were measured in 246 patients with STEMI admitted in 2004- -2007 to the First Department of Cardiology and Hypertension at the University Hospital in Cracow who were treated with an early invasive management strategy. Patients were divided into two groups, with acute hyperglycaemia (glycaemia on admission ≥ 7.8 mmol/L) and with normoglycaemia (glycaemia on admission < 7.8 mmol/L). Leukocyte count was defined as high when it was greater than or equal to the median in the overall study group. Acute hyperglycaemia was noted in 136 (55.3%) patients. Median leukocyte count on admission in the overall study group was 10.8 × 103/mm3 (interquartile range: 8.5-13.0). Significantly higher in-hospital mortality (11.8% vs. 1.8%, p = 0.0029) and higher rates of cardiogenic shock (10.3% vs. 0.9%, p = 0.0022), Killip class > 1 heart failure (HF; 44.1% vs. 20.0%, p < 0.0001), atrial fibrillation (11.0% vs. 3.6%, p = 0.0308), ventricular fibrillation (5.9% vs. 0.9%, p = 0.0389), repeated percutaneous coronary angioplasty (5.2% vs. 0.0%, p = 0

Conserved gene regulation during acute inflammation between zebrafish and mammals

PubMed Central

Forn-Cuní, G.; Varela, M.; Pereiro, P.; Novoa, B.; Figueras, A.

2017-01-01

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. PMID:28157230

Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide

PubMed Central

Bengtson, Stefan; Knudsen, Kristina B.; Kyjovska, Zdenka O.; Berthing, Trine; Skaug, Vidar; Levin, Marcus; Koponen, Ismo K.; Shivayogimath, Abhay; Booth, Timothy J.; Alonso, Beatriz; Pesquera, Amaia; Zurutuza, Amaia; Thomsen, Birthe L.; Troelsen, Jesper T.; Jacobsen, Nicklas R.

2017-01-01

We investigated toxicity of 2–3 layered >1 μm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addition, we assessed exposure levels of particulate matter emitted during production of graphene in a clean room and in a normal industrial environment using chemical vapour deposition. Toxicity was evaluated at day 1, 3, 28 and 90 days (18, 54 and 162 μg/mouse), except for GO exposed mice at day 28 and 90 where only the lowest dose was evaluated. GO induced a strong acute inflammatory response together with a pulmonary (Serum-Amyloid A, Saa3) and hepatic (Saa1) acute phase response. rGO induced less acute, but a constant and prolonged inflammation up to day 90. Lung histopathology showed particle agglomerates at day 90 without signs of fibrosis. In addition, DNA damage in BAL cells was observed across time points and doses for both GO and rGO. In conclusion, pulmonary exposure to GO and rGO induced inflammation, acute phase response and genotoxicity but no fibrosis. PMID:28570647

Non-terminal animal model of post-traumatic osteoarthritis induced by acute joint injury

PubMed Central

Boyce, Mary K.; Trumble, Troy N.; Carlson, Cathy S.; Groschen, Donna M.; Merritt, Kelly A.; Brown, Murray P.

2013-01-01

Objective Develop a non-terminal animal model of acute joint injury that demonstrates clinical and morphological evidence of early post-traumatic osteoarthritis (PTOA). Methods An osteochondral (OC) fragment was created arthroscopically in one metacarpophalangeal (MCP) joint of 11 horses and the contralateral joint was sham operated. Eleven additional horses served as unoperated controls. Every 2 weeks, force plate analysis, flexion response, joint circumference, and synovial effusion scores were recorded. At weeks 0 and 16, radiographs (all horses) and arthroscopic videos (OC injured and sham joints) were graded. At week 16, synovium and cartilage biopsies were taken arthroscopically from OC injured and sham joints for histologic evaluation and the OC fragment was removed. Results Osteochondral fragments were successfully created and horses were free of clinical lameness after fragment removal. Forelimb gait asymmetry was observed at week 2 (P=0.0012), while joint circumference (P<0.0001) and effusion scores (P<0.0001) were increased in injured limbs compared to baseline from weeks 2 to 16. Positive flexion response of injured limbs was noted at multiple time points. Capsular enthesophytes were seen radiographically in injured limbs. Articular cartilage damage was demonstrated arthroscopically as mild wear-lines and histologically as superficial zone chondrocyte death accompanied by mild proliferation. Synovial hyperemia and fibrosis were present at the site of OC injury. Conclusion Acute OC injury to the MCP joint resulted in clinical, imaging, and histologic changes in cartilage and synovium characteristic of early PTOA. This model will be useful for defining biomarkers of early osteoarthritis and for monitoring response to therapy and surgery. PMID:23467035

Attenuation of acute lung inflammation induced by cigarette smoke in CXCR3 knockout mice.

PubMed

Nie, Li; Xiang, Ruolan; Zhou, Weixun; Lu, Bao; Cheng, Deyun; Gao, Jinming

2008-12-16

CD8+ T cells may participate in cigarette smoke (CS) induced-lung inflammation in mice. CXCL10/IP-10 (IFNgamma-inducible protein 10) and CXCL9/Mig (monokine induced by IFN-gamma) are up-regulated in CS-induced lung injury and may attract T-cell recruitment to the lung. These chemokines together with CXCL11/ITAC (IFN-inducible T-cell alpha chemoattractant) are ligands for the chemokine receptor CXCR3 which is preferentially expressed chiefly in activated CD8+ T cells. The purpose of this investigation was to study the contribution of CXCR3 to acute lung inflammation induced by CS using CXCR3 knockout (KO) mice. Mice (n = 8 per group) were placed in a closed plastic box connected to a smoke generator and were exposed whole body to the tobacco smoke of five cigarettes four times a day for three days. Lung pathological changes, expression of inflammatory mediators in bronchoalveolar lavage (BAL) fluid and lungs at mRNA and protein levels, and lung infiltration of CD8+ T cells were compared between CXCR3-/- mice and wild type (WT) mice. Compared with the WT littermates, CXCR3 KO mice showed less CS-induced lung inflammation as evidenced by less infiltration of inflammatory cells in airways and lung tissue, particularly fewer CD8+ T cells, lower levels of IFNgamma and CXCR3 ligands (particularly CXCL10). Our findings show that CXCR3 is important in promoting CD8+ T cell recruitment and in initiating IFNgamma and CXCL10 release following CS exposure. CXCR3 may represent a promising therapeutic target for acute lung inflammation induced by CS.

Attenuation of acute lung inflammation induced by cigarette smoke in CXCR3 knockout mice

PubMed Central

Nie, Li; Xiang, Ruolan; Zhou, Weixun; Lu, Bao; Cheng, Deyun; Gao, Jinming

2008-01-01

Background CD8+ T cells may participate in cigarette smoke (CS) induced-lung inflammation in mice. CXCL10/IP-10 (IFNγ-inducible protein 10) and CXCL9/Mig (monokine induced by IFN-γ) are up-regulated in CS-induced lung injury and may attract T-cell recruitment to the lung. These chemokines together with CXCL11/ITAC (IFN-inducible T-cell alpha chemoattractant) are ligands for the chemokine receptor CXCR3 which is preferentially expressed chiefly in activated CD8+ T cells. The purpose of this investigation was to study the contribution of CXCR3 to acute lung inflammation induced by CS using CXCR3 knockout (KO) mice. Methods Mice (n = 8 per group) were placed in a closed plastic box connected to a smoke generator and were exposed whole body to the tobacco smoke of five cigarettes four times a day for three days. Lung pathological changes, expression of inflammatory mediators in bronchoalveolar lavage (BAL) fluid and lungs at mRNA and protein levels, and lung infiltration of CD8+ T cells were compared between CXCR3-/- mice and wild type (WT) mice. Results Compared with the WT littermates, CXCR3 KO mice showed less CS-induced lung inflammation as evidenced by less infiltration of inflammatory cells in airways and lung tissue, particularly fewer CD8+ T cells, lower levels of IFNγ and CXCR3 ligands (particularly CXCL10). Conclusion Our findings show that CXCR3 is important in promoting CD8+ T cell recruitment and in initiating IFNγ and CXCL10 release following CS exposure. CXCR3 may represent a promising therapeutic target for acute lung inflammation induced by CS. PMID:19087279

Intra-Articular Blockade of P2X7 Receptor Reduces the Articular Hyperalgesia and Inflammation in the Knee Joint Synovitis Especially in Female Rats.

PubMed

Teixeira, Juliana Maia; Dias, Elayne Vieira; Parada, Carlos Amílcar; Tambeli, Cláudia Herrera

2017-02-01

Synovitis is a key factor in joint disease pathophysiology, which affects a greater proportion of women than men. P2X7 receptor activation contributes to arthritis, but whether it plays a role in articular inflammatory pain in a sex-dependent manner is unknown. We investigated whether the P2X7 receptor blockade in the knee joint of male and female rats reduces the articular hyperalgesia and inflammation induced by a carrageenan knee joint synovitis model. Articular hyperalgesia was quantified using the rat knee joint incapacitation test and the knee joint inflammation, characterized by the concentration of cytokines tumor necrosis factor-α, interleukin-1β, interleukin-6, and cytokine-induced neutrophil chemoattractant-1, and by neutrophil migration, was quantified using enzyme-linked immunosorbent assay and by myeloperoxidase enzyme activity measurement, respectively. P2X7 receptor blockade by the articular coadministration of selective P2X7 receptor antagonist A740003 with carrageenan significantly reduced articular hyperalgesia, pro-inflammatory cytokine concentrations, and myeloperoxidase activity induced by carrageenan injection into the knee joint of male and estrus female rats. However, a lower dose of P2X7 receptor antagonist was sufficient to significantly induce the antihyperalgesic and anti-inflammatory effects in estrus female but not in male rats. These results suggest that P2X7 receptor activation by endogenous adenosine 5'-triphosphate is essential to articular hyperalgesia and inflammation development in the knee joint of male and female rats. However, female rats are more responsive than male rats to the antihyperalgesic and anti-inflammatory effects induced by P2X7 receptor blockade. P2X7 receptors could be promising therapeutic targets in the treatment of knee joint disease symptoms, especially in women, who are more affected than men by these conditions. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Non-terminal animal model of post-traumatic osteoarthritis induced by acute joint injury.

PubMed

Boyce, M K; Trumble, T N; Carlson, C S; Groschen, D M; Merritt, K A; Brown, M P

2013-05-01

Develop a non-terminal animal model of acute joint injury that demonstrates clinical and morphological evidence of early post-traumatic osteoarthritis (PTOA). An osteochondral (OC) fragment was created arthroscopically in one metacarpophalangeal (MCP) joint of 11 horses and the contralateral joint was sham operated. Eleven additional horses served as unoperated controls. Every 2 weeks, force plate analysis, flexion response, joint circumference, and synovial effusion scores were recorded. At weeks 0 and 16, radiographs (all horses) and arthroscopic videos (OC injured and sham joints) were graded. At week 16, synovium and cartilage biopsies were taken arthroscopically from OC injured and sham joints for histologic evaluation and the OC fragment was removed. OC fragments were successfully created and horses were free of clinical lameness after fragment removal. Forelimb gait asymmetry was observed at week 2 (P = 0.0012), while joint circumference (P < 0.0001) and effusion scores (P < 0.0001) were increased in injured limbs compared to baseline from weeks 2 to 16. Positive flexion response of injured limbs was noted at multiple time points. Capsular enthesophytes were seen radiographically in injured limbs. Articular cartilage damage was demonstrated arthroscopically as mild wear-lines and histologically as superficial zone chondrocyte death accompanied by mild proliferation. Synovial hyperemia and fibrosis were present at the site of OC injury. Acute OC injury to the MCP joint resulted in clinical, imaging, and histologic changes in cartilage and synovium characteristic of early PTOA. This model will be useful for defining biomarkers of early osteoarthritis and for monitoring response to therapy and surgery. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

ASEPTIC INFLAMMATION IN THE LUNGS IN ACUTE RADIATION SICKNESS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ivanov, A.E.

1963-09-01

Inflammation in the lungs of irradiated rabbits at the site of turpentine injection has much in common with the inflammatory changes arising in other tissues and organs during local irradiation or acute radiation sickness. The fact that the inflammatory changes under different conditions of irradiation are similar in type regardless of the character of the inflammatory agent suggests that the phenomenon has a common mechanism. The absence of polymorphonuclear (eosinophtlic) leukocytes from inflammatory foci in irradiated rabbits is due not only to the developing leukopenia, but also to a disturbance of the leukocyte emigration process into the inflammatory focus. Inmore » irradiated rabbits in cortrast to the controls, the normal arrangement of the fibrous structures is preserved in the necrotic lung tissue at the site of turpentine injection. In animals with severe acute radiation sickness induced by external irradiation in sublethal doses, the ability of the organism to respond to introduction of an inflammatory agent by an increase in the number of leukocytes in the blood and by a rise of the body temperature is to some extent preserved. (auth)« less

Surgical treatment of acute acromioclavicular joint dislocations: hook plate versus minimally invasive reconstruction.

PubMed

Metzlaff, S; Rosslenbroich, S; Forkel, P H; Schliemann, B; Arshad, H; Raschke, M; Petersen, W

2016-06-01

This study was performed to compare the clinical results of a minimally invasive technique for acute acromioclavicular (AC) joint dislocation repair with the traditional hook plate fixation. Forty-four patients with an acute (within 2 weeks after trauma) complete AC joint separation (35 male, nine female; median age 36.2 years, range 18-56) underwent surgical repair with either a minimally invasive AC joint repair or a conventional hook plate. Functional outcome was evaluated using the Constant-Murley Score (CMS), the TAFT score and the AC joint instability score (ACJI). Radiographic evaluation was performed with bilateral anterior-posterior (a.p.) stress and Alexander views. All patients were available after a median follow-up of 32 months (range 24-51). There were no significant differences in the mean CMS, Taft score and the ACJI between the two groups. The radiological assessment revealed no significant difference in the coracoclavicular distance. In both groups, a slight loss of reduction was observed. Periarticular ossification was seen in 11 patients of the minimally invasive AC joint repair and eight patients of the hook plate group but this did not affect the final outcome. Hook plates were removed after a median interval of 11.9 weeks (range 10-13). Good clinical results can be achieved with both minimally invasive AC joint repair and hook plate fixation. However, in the hook plate group a second operation is mandatory for plate removal. III.

Mast cells and histamine are triggering the NF-κB-mediated reactions of adult and aged perilymphatic mesenteric tissues to acute inflammation

PubMed Central

Nizamutdinova, Irina Tsoy; Dusio, Giuseppina F.; Gasheva, Olga Yu.; Skoog, Hunter; Tobin, Richard; Peddaboina, Chander; Meininger, Cynthia J.; Zawieja, David C.; Newell-Rogers, M. Karen; Gashev, Anatoliy A.

2016-01-01

This study aimed to establish mechanistic links between the aging-associated changes in the functional status of mast cells and the altered responses of mesenteric tissue and mesenteric lymphatic vessels (MLVs) to acute inflammation. We used an in vivo model of acute peritoneal inflammation induced by lipopolysaccharide treatment of adult (9-month) and aged (24-month) F-344 rats. We analyzed contractility of isolated MLVs, mast cell activation, activation of nuclear factor-κB (NF-κB) without and with stabilization of mast cells by cromolyn or blockade of all types of histamine receptors and production of 27 major pro-inflammatory cytokines in adult and aged perilymphatic mesenteric tissues and blood. We found that the reactivity of aged contracting lymphatic vessels to LPS-induced acute inflammation was abolished and that activated mast cells trigger NF-κB signaling in the mesentery through release of histamine. The aging-associated basal activation of mesenteric mast cells limits acute inflammatory NF-κB activation in aged mesentery. We conclude that proper functioning of the mast cell/histamine/NF-κB axis is necessary for reactions of the lymphatic vessels to acute inflammatory stimuli as well as for interaction and trafficking of immune cells near and within the collecting lymphatics. PMID:27875806

Melatonin attenuates inflammation of acute pulpitis subjected to dental pulp injury

PubMed Central

Li, Ji-Guo; Lin, Jia-Ji; Wang, Zhao-Ling; Cai, Wen-Ke; Wang, Pei-Na; Jia, Qian; Zhang, An-Sheng; Wu, Gao-Yi; Zhu, Guo-Xiong; Ni, Long-Xing

2015-01-01

Acute pulpitis (AP), one of the most common diseases in the endodontics, usually causes severe pain to the patients, which makes the search for therapeutic target of AP essential in clinic. Toll-like receptor 4 (TLR4) signaling is widely involved in the mechanism of pulp inflammation, while melatonin has been reported to have an inhibition for a various kinds of inflammation. We hereby studied whether melatonin can regulate the expression of TLR4/NF-ĸB signaling in the pulp tissue of AP and in human dental pulp cells (HDPCs). Two left dental pulps of the adult rat were drilled open to establish the AP model, and the serum levels of melatonin and pro-inflammatory cytokines, including interleukin 1β (IL-1β), interleukin 18 (IL-18) and tumor necrosis factor α (TNF-α), were assessed at 1, 3 and 5 d post injury. At the same time points, the expression of TLR4 signaling in the pulp was explored by quantitative real-time PCR and immunohistochemistry. The AP rats were administered an abdominal injection of melatonin to assess whether melatonin rescued AP and TLR4/NF-ĸB signaling. Dental pulp injury led to an approximately five-day period acute pulp inflammation and necrosis in the pulp and a significant up-regulation of IL-1β, IL-18 and TNF-α in the serum. ELISA results showed that the level of melatonin in the serum decreased due to AP, while an abdominal injection of melatonin suppressed the increase in serum cytokines and the percentage of necrosis at the 5 d of the injured pulp. Consistent with the inflammation in AP rats, TLR4, NF-ĸB, TNF-α and IL-1β in the pulp were increased post AP compared with the baseline expression. And melatonin showed an inhibition on TLR4/NF-ĸB signaling as well as IL-1β and TNF-α production in the pulp of AP rats. Furthermore, melatonin could also regulate the expression of TLR4/NF-ĸB signaling in LPS-stimulated HDPCs. These data suggested that dental pulp injury induced AP and reduced the serum level of melatonin and that

Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury.

PubMed

Ribeiro, A; Almeida, V I; Costola-de-Souza, C; Ferraz-de-Paula, V; Pinheiro, M L; Vitoretti, L B; Gimenes-Junior, J A; Akamine, A T; Crippa, J A; Tavares-de-Lima, W; Palermo-Neto, J

2015-02-01

We have previously shown that the prophylactic treatment with cannabidiol (CBD) reduces inflammation in a model of acute lung injury (ALI). In this work we analyzed the effects of the therapeutic treatment with CBD in mice subjected to the model of lipopolysaccharide (LPS)-induced ALI on pulmonary mechanics and inflammation. CBD (20 and 80 mg/kg) was administered (i.p.) to mice 6 h after LPS-induced lung inflammation. One day (24 h) after the induction of inflammation the assessment of pulmonary mechanics and inflammation were analyzed. The results show that CBD decreased total lung resistance and elastance, leukocyte migration into the lungs, myeloperoxidase activity in the lung tissue, protein concentration and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) in the bronchoalveolar lavage supernatant. Thus, we conclude that CBD administered therapeutically, i.e. during an ongoing inflammatory process, has a potent anti-inflammatory effect and also improves the lung function in mice submitted to LPS-induced ALI. Therefore the present and previous data suggest that in the future cannabidiol might become a useful therapeutic tool for the attenuation and treatment of inflammatory lung diseases.

Fecal markers of inflammation, protein loss, and microbial changes in dogs with the acute hemorrhagic diarrhea syndrome (AHDS).

PubMed

Heilmann, Romy M; Guard, Melissa M; Steiner, Jörg M; Suchodolski, Jan S; Unterer, Stefan

2017-09-01

Idiopathic acute hemorrhagic diarrhea syndrome (AHDS) is characterized by acute onset of bloody diarrhea, severe dehydration, and increased vascular and intestinal mucosal permeability. Markers of gastrointestinal inflammation, protein loss, and changes in the intestinal microbiota have not been studied extensively in dogs with AHDS. For 3 consecutive days, feces were collected from dogs with AHDS, and assayed for calprotectin and S100A12 (both markers of inflammation), α 1 -proteinase inhibitor (a marker of gastrointestinal protein loss), and the presence of selected species of bacteria. Concentrations of all assayed markers were significantly greater than the institutional reference intervals at the time of presentation, and all decreased significantly by Day 3 of treatment. Abundances of selected bacterial groups (Ruminococcaceae, Faecalibacterium spp., Bifidobacterium spp., and Proteobacteria) at the time of diagnosis were consistent with an intestinal bacterial dysbiosis. No differences in the abundance of bacterial groups over time was seen, except for a mild but significant decrease in Ruminococcaceae at Day 3. These results suggest that canine AHDS is associated with a significant but transient gastrointestinal loss of protein and intestinal inflammation. The intestinal bacterial dysbiosis appears to outlast the protein loss and inflammation. © Veterinary Emergency and Critical Care Society 2017.

Acute inflammation induces segmental, bilateral, supraspinally mediated opioid release in the rat spinal cord, as measured by μ-opioid receptor internalization

PubMed Central

Chen, Wenling; Marvizón, Juan Carlos G.

2009-01-01

The objective of this study was to measure opioid release in the spinal cord during acute and long-term inflammation using μ-opioid receptor (MOR) internalization. In particular, we determined whether opioid release occurs in the segments receiving the noxious signals or in the entire spinal cord, and whether it involves supraspinal signals. Internalization of neurokinin 1 receptors (NK1Rs) was measured to track the intensity of the noxious stimulus. Rats received peptidase inhibitors intrathecally to protect opioids from degradation. Acute inflammation of the hindpaw with formalin induced moderate MOR internalization in the L5 segment bilaterally, whereas NK1R internalization occurred only ipsilaterally. MOR internalization was restricted to the lumbar spinal cord, regardless of whether the peptidase inhibitors were injected in a lumbar or thoracic site. Formalin-induced MOR internalization was substantially reduced by isoflurane anesthesia. It was also markedly reduced by a lidocaine block of the cervical-thoracic spinal cord (which did not affect the evoked NK1R internalization) indicating that spinal opioid release is mediated supraspinally. In the absence of peptidase inhibitors, formalin and hindpaw clamp induced a small amount of MOR internalization, which was significantly higher than in controls. To study spinal opioid release during chronic inflammation, we injected Complete Freund's Adjuvant (CFA) in the hindpaw and peptidase inhibitors intrathecally. Two days later, no MOR or NK1R internalization was detected. Furthermore, CFA inflammation decreased MOR internalization induced by clamping the inflamed hindpaw. These results show that acute inflammation, but not chronic inflammation, induce segmental opioid release in the spinal cord that involves supraspinal signals. PMID:19298846

Acute inflammation induces segmental, bilateral, supraspinally mediated opioid release in the rat spinal cord, as measured by mu-opioid receptor internalization.

PubMed

Chen, W; Marvizón, J C G

2009-06-16

The objective of this study was to measure opioid release in the spinal cord during acute and long-term inflammation using mu-opioid receptor (MOR) internalization. In particular, we determined whether opioid release occurs in the segments receiving the noxious signals or in the entire spinal cord, and whether it involves supraspinal signals. Internalization of neurokinin 1 receptors (NK1Rs) was measured to track the intensity of the noxious stimulus. Rats received peptidase inhibitors intrathecally to protect opioids from degradation. Acute inflammation of the hind paw with formalin induced moderate MOR internalization in the L5 segment bilaterally, whereas NK1R internalization occurred only ipsilaterally. MOR internalization was restricted to the lumbar spinal cord, regardless of whether the peptidase inhibitors were injected in a lumbar or thoracic site. Formalin-induced MOR internalization was substantially reduced by isoflurane anesthesia. It was also markedly reduced by a lidocaine block of the cervical-thoracic spinal cord (which did not affect the evoked NK1R internalization) indicating that spinal opioid release is mediated supraspinally. In the absence of peptidase inhibitors, formalin and hind paw clamp induced a small amount of MOR internalization, which was significantly higher than in controls. To study spinal opioid release during chronic inflammation, we injected complete Freund's adjuvant (CFA) in the hind paw and peptidase inhibitors intrathecally. Two days later, no MOR or NK1R internalization was detected. Furthermore, CFA inflammation decreased MOR internalization induced by clamping the inflamed hind paw. These results show that acute inflammation, but not chronic inflammation, induces segmental opioid release in the spinal cord that involves supraspinal signals.

Medial joint line bone bruising at MRI complicating acute ankle inversion injury: what is its clinical significance?

PubMed

Chan, V O; Moran, D E; Shine, S; Eustace, S J

2013-10-01

To assess the incidence and clinical significance of medial joint line bone bruising following acute ankle inversion injury. Forty-five patients who underwent ankle magnetic resonance imaging (MRI) within 2 weeks of acute ankle inversion injury were included in this prospective study. Integrity of the lateral collateral ligament complex, presence of medial joint line bone bruising, tibio-talar joint effusion, and soft-tissue swelling were documented. Clinical follow-up at 6 months was carried out to determine the impact of injury on length of time out of work, delay in return to normal walking, delay in return to sports activity, and persistence of medial joint line pain. Thirty-seven patients had tears of the anterior talofibular ligament (ATFL). Twenty-six patients had medial joint line bone bruising with altered marrow signal at the medial aspect of the talus and congruent surface of the medial malleolus. A complete ATFL tear was seen in 92% of the patients with medial joint line bone bruising (p = 0.05). Patients with an ATFL tear and medial joint line bone bruising had a longer delay in return to normal walking (p = 0.0002), longer delay in return to sports activity (p = 0.0001), and persistent medial joint line pain (p = 0.0003). There was no statistically significant difference in outcome for the eight patients without ATFL tears. Medial joint line bone bruising following an acute ankle inversion injury was significantly associated with a complete ATFL tear, longer delay in the return to normal walking and sports activity, as well as persistent medial joint line pain. Its presence should prompt detailed assessment of the lateral collateral ligament complex, particularly the ATFL. Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Local injections of corticotropin releasing factor reduce doxorubicin-induced acute inflammation in the eyelid.

PubMed

McLoon, L K; Wirtschafter, J

1997-04-01

Doxorubicin chemomyectomy is an effective alternative treatment option for patients with blepharospasm and hemifacial spasm. One side effect of the use of doxorubicin in localized injections is the development of acute inflammation and skin injury at the injection site. Corticotropin releasing factor (CRF) was reported to reduce inflammation after acute inflammatory injuries due to other causes and at other sites. This study was performed to assess the potential of CRF to prevent the development of skin injury and eyelid soreness after local doxorubicin injection. Rabbits received lower eyelid injections of either 75 or 150 micrograms CRF followed by injection of either 0.5, 1, or 2 mg doxorubicin or doxorubicin alone. Eyelids were assessed for changes in acute inflammation by immunohistochemical localization of macrophages and monocytes using anti-CD11, an antibody specific for these cell types. Short-term alterations in vascular permeability were assessed using an Evans blue assay. Additional eyelids were followed daily for changes in the skin over the injection site to determine day of onset of skin injury and the total duration of skin injury. After 1 month, the eyelids were processed histologically for morphometric analysis of muscle fiber loss. Monkey eyelids also were examined for the effect of CRF and doxorubicin injections. Doxorubicin alone produced an acute inflammatory reaction in the treated eyelids, with a large influx of macrophages and monocytes throughout the connective tissue at 1 and 2 days. Corticotropin releasing factor pretreatment significantly reduced this influx of inflammatory cells into the connective tissue. Doxorubicin produced a large increase in vascular permeability in the treated eyelids, with resultant edema. Corticotropin releasing factor did not alter this change in vascular permeability, indicating that CRF appears to have a specific effect on migration of inflammatory cells rather than just a generalized effect on vascular

Salivary Markers of Inflammation in Response to Acute Stress

PubMed Central

Slavish, Danica C.; Graham-Engeland, Jennifer E.; Smyth, Joshua M.; Engeland, Christopher G.

2014-01-01

There is burgeoning interest in the ability to detect inflammatory markers in response to stress within naturally occurring social contexts and/or across multiple time points per day within individuals. Salivary collection is a less invasive process than current methods of blood collection and enables intensive naturalistic methodologies, such as those involving extensive repeated measures per day over time. Yet the reliability and validity of saliva-based to blood-based inflammatory biomarkers in response to stress remains unclear. We review and synthesize the published studies that have examined salivary markers of inflammation following exposure to an acute laboratory stressor. Results from each study are reviewed by analyte (IL-1β, TNF-α, IL-6, IL-2, IL-4, IL-10, IL-12, CRP) and stress type (social-cognitive and exercise-physical), after which methodological issues and limitations are addressed. Although the literature is limited, several inflammatory markers (including IL-1β, TNF-α, and IL-6) have been reliably determined from saliva and have increased significantly in response to stress across multiple studies, with effect sizes ranging from very small to very large. Although CRP from saliva has been associated with CRP in circulating blood more consistently than other biomarkers have been associated with their counterparts in blood, evidence demonstrating it reliably responds to acute stress is absent. Although the current literature is presently too limited to allow broad assertion that inflammatory biomarkers determined from saliva are valuable for examining acute stress responses, this review suggests that specific targets may be valid and highlights specific areas of need for future research. PMID:25205395

Modified immunoglobulin G glycosylation pattern during turpentine-induced acute inflammation in rats.

PubMed

Canellada, Andrea; Margni, Ricardo A

2002-01-01

Alterations in the pattern of protein glycosylation have been described during inflammation. In chronic parasitic and tumoral diseases we have reported an increase in the proportion of serum Immunoglobulin G (IgG) molecules possessing an altered Fab glycosylation pattern designated asymmetric antibodies. The alteration results in augmented concanavalin A affinity and functional univalence of the antibody. In addition, Fc agalactosylation has been described as occurring in chronically autoimmune diseases. Therefore, the aim of this paper was to evaluate by analyzing sera whether during an acute inflammatory response in rats produced by subcutaneous inoculation of turpentine oil, there was an alteration in the synthesis and glycosylation of IgG (as revealed by concanavalin A binding). We found that during acute inflammation there was a decrease in the synthesis of IgG which was not affected by prior oral administration of dexamethasone; however, the turpentine-induced increase in IgG binding to concanavalin A was found to be inhibited upon prior administration of the anti-inflammatory agent. As with turpentine, the corticoid used induced an increase in the interleukin-6 levels detected in sera by ELISA. Although we have described an improvement in asymmetric antibody synthesis by low dose of interleukin-6 previously, here we found no correlation between the observed glycosylation pattern of IgG and interleukin-6 concentration assessed in sera of treated rats, probably due to a different dexamethasone mediated pathway.

Joint distraction attenuates osteoarthritis by reducing secondary inflammation, cartilage degeneration and subchondral bone aberrant change.

PubMed

Chen, Y; Sun, Y; Pan, X; Ho, K; Li, G

2015-10-01

Osteoarthritis (OA) is a progressive joint disorder. To date, there is not effective medical therapy. Joint distraction has given us hope for slowing down the OA progression. In this study, we investigated the benefits of joint distraction in OA rat model and the probable underlying mechanisms. OA was induced in the right knee joint of rats through anterior cruciate ligament transaction (ACLT) plus medial meniscus resection. The animals were randomized into three groups: two groups were treated with an external fixator for a subsequent 3 weeks, one with and one without joint distraction; and one group without external fixator as OA control. Serum interleukin-1β level was evaluated by ELISA; cartilage quality was assessed by histology examinations (gross appearance, Safranin-O/Fast green stain) and immunohistochemistry examinations (MMP13, Col X); subchondral bone aberrant changes was analyzed by micro-CT and immunohistochemistry (Nestin, Osterix) examinations. Characters of OA were present in the OA group, contrary to in general less severe damage after distraction treatment: firstly, IL-1β level was significantly decreased; secondly, cartilage degeneration was attenuated with lower histologic damage scores and the lower percentage of MMP13 or Col X positive chondrocytes; finally, subchondral bone abnormal change was attenuated, with reduced bone mineral density (BMD) and bone volume/total tissue volume (BV/TV) and the number of Nestin or Osterix positive cells in the subchondral bone. In the present study, we demonstrated that joint distraction reduced the level of secondary inflammation, cartilage degeneration and subchondral bone aberrant change, joint distraction may be a strategy for slowing OA progression. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Circuit resistance training attenuates acute exertion-induced reductions in arterial function but not inflammation in obese women.

PubMed

Franklin, Nina C; Robinson, Austin T; Bian, Jing-Tan; Ali, Mohamed M; Norkeviciute, Edita; McGinty, Patrick; Phillips, Shane A

2015-06-01

Cardiovascular disease (CVD) is a leading cause of preventable death among young women in the United States. Habitual resistance exercise training is known to have beneficial effects on endothelial function and CVD risk factors, including obesity; however, previous studies show that acute resistance exercise impairs endothelial function in obese adults who are sedentary, a response that may be linked to inflammation. We sought to determine if circuit-based resistance training (CRT) attenuates acute resistance exercise-induced reductions in endothelial function in a population of young, obese, sedentary women and whether or not inflammation plays a role in this response. Eighteen obese [body mass index (BMI) 30.0-40.0 kg · m(-2)] young premenopausal women were randomly assigned to either a CRT group or a no-exercise control group (CON). Conduit artery endothelial function was assessed using brachial artery flow-mediated dilation (FMD) determined by ultrasound before and after a single bout of strenuous weightlifting (SWL). In addition, circulating inflammatory mediators (tumor necrosis factor-α and C-reactive protein), blood pressure, fasting blood lipids, glucose, waist circumference, body composition, and aerobic capacity were assessed. Among participants randomized to the CRT group, 8 weeks of training led to considerable increases in FMD after SWL (P=0.001) compared to the CON group. However, no significant differences between the groups were observed in circulating inflammatory mediators, blood pressure, fasting blood lipids, or other physical and physiological characteristics. This study shows that CRT alleviates acute exertion-induced reductions in endothelial function among obese sedentary women in the absence of changes in inflammation.

Inhibition of the signalling kinase JAK3 alleviates inflammation in monoarthritic rats

PubMed Central

Kim, Byung-Hak; Kim, Myunghwan; Yin, Chang-Hong; Jee, Jun-Goo; Sandoval, Claudio; Lee, Hyejung; Bach, Erika A; Hahm, Dae-Hyun; Baeg, Gyeong-Hun

2011-01-01

BACKGROUND AND PURPOSE Many cytokines associated with autoimmune disorders and inflammation have been shown to activate the signalling kinase JAK3, implying that JAK3 plays key roles in the pathogenesis of these diseases. Therefore, investigating the alterations of JAK3 activity and the efficacy of selective JAK3 antagonists in animal models of such disorders is essential to a better understanding of the biology of JAK3 and to assess the potential clinical benefits of JAK3 inhibitors. EXPERIMENTAL APPROACH Through high-throughput cell-based screening using the NCI compound library, we identified NSC163088 (berberine chloride) as a novel inhibitor of JAK3. Specificity and efficacy of this compound were investigated in both cellular and animal models. KEY RESULTS We show that berberine chloride has selectivity for JAK3 over other JAK kinase members, as well as over other oncogenic kinases such as Src, in various cellular assays. Biochemical and modelling studies strongly suggested that berberine chloride bound directly to the kinase domain of JAK3. Also phospho-JAK3 levels were significantly increased in the synovial tissues of rat joints with acute inflammation, and the treatment of these rats with berberine chloride decreased JAK3 phosphorylation and suppressed the inflammatory responses. CONCLUSIONS AND IMPLICATIONS The up-regulation of JAK3/STATs was closely correlated with acute arthritic inflammation and that inhibition of JAK3 activity by JAK3 antagonists, such as berberine chloride, alleviated the inflammation in vivo. PMID:21434883

Acute cardiovascular toxicity of sterilizers, PHMG, and PGH: severe inflammation in human cells and heart failure in zebrafish.

PubMed

Kim, Jae-Yong; Kim, Hak Hyeon; Cho, Kyung-Hyun

2013-06-01

In 2011, dozens of children and pregnant women in Korea died by exposure to sterilizer for household humidifier, such as Oxy(®) and Cefu(®). Until now, however, it remains unknown how the sterilizer affect the human health to cause the acute deaths. To find its toxicity for organ, we investigated the putative toxicity of the sterilizer in the cardiovascular system. The sterilizers, polyhexamethylene guanidine phosphate (PHMG, Cefu(®)), and oligo-[2-(2-ethoxy)-ethoxyethyl)-guanidinium-chloride (PGH, Oxy(®)) were treated to human lipoproteins, macrophages, and dermal fibroblast cells. The PGH and PHMG at normal dosages caused severe atherogenic process in human macrophages, cytotoxic effect, and aging in human dermal cell. Zebrafish embryos, which were exposed to the sterilizer, showed early death with acute inflammation and attenuated developmental speed. All zebrafish exposed to the working concentration of PHMG (final 0.3 %) and PGH (final 10 mM) died within 70 min and displayed acute increases in serum triacylglycerol level and fatty liver induction. The dead zebrafish showed severe accumulation of fibrous collagen in the bulbous artery of the heart with elevation of reactive oxygen species. In conclusion, the sterilizers showed acute toxic effect in blood circulation system, causing by severe inflammation, atherogenesis, and aging, with embryo toxicity.

Management of acute calcific tendinitis around the hip joint.

PubMed

Park, Sang-Min; Baek, Ji-Hoon; Ko, Young-Bong; Lee, Han-Jun; Park, Ki Jeong; Ha, Yong-Chan

2014-11-01

Although the natural history of calcific tendinitis within the rotator cuff of the shoulder is established, the natural history of calcific tendinitis around the hip joint remains unknown. To examine the duration of symptoms including pain, the location of calcific tendinitis around the hip joint, the radiologic course of calcium phosphate crystals, and the proportion of patients who required surgical treatment. Case series; Level of evidence, 4. Thirty hips (29 patients) with acute calcific tendinitis were treated between January 2010 and December 2012. Level of subjective hip pain using the visual analog scale pain score, radiologic type, and the location and size of calcium deposits were measured during a follow-up period of 12 to 32 months. The 29 patients included 7 men (24%) and 22 women (76%) with a mean age of 51.5 years (range, 28-78 years). All visual analog scale pain scores significantly improved from a mean of 7.1 to 0.8 at the latest follow-up (P < .001). The most common site of calcium deposition was the tendon of the gluteus medius. During follow-up, calcium deposition completely resolved in 5 of 20 hips. Symptoms in 23 patients (24 hips) responded to nonoperative treatment. Two patients (2 hips) were treated with ultrasound-guided local anesthetic and steroid injection. Four patients (4 hips) with long duration (>3 months) of severe pain, solid type, and large size (range, 96-416 mm(2)) were treated with arthroscopic excision. Nonoperative treatment in patients with acute calcific tendinitis of the hip joint might be successful in most patients. Surgical treatment is of value for patients experiencing prolonged severe pain, solid type, and large size. © 2014 The Author(s).

Medicare Program; Comprehensive Care for Joint Replacement Payment Model for Acute Care Hospitals Furnishing Lower Extremity Joint Replacement Services. Final rule.

PubMed

2015-11-24

This final rule implements a new Medicare Part A and B payment model under section 1115A of the Social Security Act, called the Comprehensive Care for Joint Replacement (CJR) model, in which acute care hospitals in certain selected geographic areas will receive retrospective bundled payments for episodes of care for lower extremity joint replacement (LEJR) or reattachment of a lower extremity. All related care within 90 days of hospital discharge from the joint replacement procedure will be included in the episode of care. We believe this model will further our goals in improving the efficiency and quality of care for Medicare beneficiaries with these common medical procedures.

Preoperative Anemia Is Associated With Failure of Open Debridement Polyethylene Exchange in Acute and Acute Hematogenous Prosthetic Joint Infection.

PubMed

Swenson, Richard D; Butterfield, James A; Irwin, Timothy J; Zurlo, John J; Davis, Charles M

2018-06-01

Acute and acute hematogenous prosthetic joint infections (PJIs) are often treated with open debridement and polyethylene exchange (ODPE) in an effort to save the prosthesis, decrease morbidity, and reduce costs. However, failure of ODPE may compromise a subsequent 2-stage treatment. The purpose of this study is to identify patient factors that impact the success of ODPE for acute and acute hematogenous PJIs. A retrospective review examined comorbidities, preoperative laboratory values, and patient history for patients with successful and failed ODPE treatment for acute perioperative or acute hematogenous periprosthetic hip or knee joint infections. Successful treatment was defined as retaining a well-fixed implant without the need for additional surgery for a minimum of 6-month follow-up with or without lifelong oral maintenance antibiotics. Fifty-three of 72 patients (73.6%) underwent successful ODPE. Of the 19 failures, 14 completed 2-stage revision with one subsequent known failure for recurrent infection. Patients with a Staphylococcus aureus infection were more likely to fail ODPE (48.3% vs 11.6%, P = .0012, odds ratio 7.1, 95% confidence interval 2.3-25.3). Patients with a preoperative hematocrit ≤32.1 were also more likely to fail ODPE (55% vs 16%, P = .0013, odds ratio 6.7, 95% confidence interval 2.2-22.4). When neither risk factor was present, 97.1% of PJIs were successfully treated with ODPE. S aureus infection and preoperative hematocrit ≤32.1 are independent risk factors for ODPE failure. ODPE is a safe alternative to 2-stage revision in patients without preoperative anemia and without S aureus infection. Two-thirds of patients with a failed ODPE were successfully treated with a 2-stage reimplantation. Copyright © 2018 Elsevier Inc. All rights reserved.

Central autonomic network mediates cardiovascular responses to acute inflammation: Relevance to increased cardiovascular risk in depression?

PubMed Central

Harrison, Neil A.; Cooper, Ella; Voon, Valerie; Miles, Ken; Critchley, Hugo D.

2013-01-01

Inflammation is a risk factor for both depression and cardiovascular disease. Depressed mood is also a cardiovascular risk factor. To date, research into mechanisms through which inflammation impacts cardiovascular health rarely takes into account central effects on autonomic cardiovascular control, instead emphasizing direct effects of peripheral inflammatory responses on endothelial reactivity and myocardial function. However, brain responses to inflammation engage neural systems for motivational and homeostatic control and are expressed through depressed mood state and changes in autonomic cardiovascular regulation. Here we combined an inflammatory challenge, known to evoke an acute reduction in mood, with neuroimaging to identify the functional brain substrates underlying potentially detrimental changes in autonomic cardiovascular control. We first demonstrated that alterations in the balance of low to high frequency (LF/HF) changes in heart rate variability (a measure of baroreflex sensitivity) could account for some of the inflammation-evoked changes in diastolic blood pressure, indicating a central (rather than solely local endothelial) origin. Accompanying alterations in regional brain metabolism (measured using 18FDG-PET) were analysed to localise central mechanisms of inflammation-induced changes in cardiovascular state: three discrete regions previously implicated in stressor-evoked blood pressure reactivity, the dorsal anterior and posterior cingulate and pons, strongly mediated the relationship between inflammation and blood pressure. Moreover, activity changes within each region predicted the inflammation-induced shift in LF/HF balance. These data are consistent with a centrally-driven component originating within brain areas supporting stressor evoked blood pressure reactivity. Together our findings highlight mechanisms binding psychological and physiological well-being and their perturbation by peripheral inflammation. PMID:23416033

Circulating Cell-Free DNA Differentiates Severity of Inflammation.

PubMed

Frank, Mayu O

2016-10-01

As the U.S. population ages, the incidence of chronic disease will rise. Chronic diseases have been linked to chronic inflammation. The purpose of this review is to summarize the literature on cell-free DNA (cfDNA) in relation to inflammation. PubMed, EMBASE, and Web of Science were searched. Inclusion criteria were noninterventional studies on acute and chronic inflammation, autoimmunity, and infection published in English after 2000, conducted in humans using the fluorescence method of quantifying DNA. Of the 442 articles retrieved, 83 were identified for full-text review and 13 remained after application of inclusion criteria. Of the reviewed studies, three involved acute inflammation, six involved chronic inflammation, and four involved infection. Healthy controls with interpretable results were included in six studies, three of which used the Quant-iT high-sensitivity DNA kit and found cfDNA quantities near 800 ng/ml, while the other three used other fluorescence methods and found quantities below 100 ng/ml. All 13 studies compared groups, and all but 1 found statistically significant differences between them. Among studies using the Quant-iT reagent, levels were higher in infection than in chronic inflammation. Among studies that used other reagents, levels increased from chronic to acute inflammation to severe infection. CfDNA levels were associated with mortality and with clinical outcomes in acute inflammation and infection. Most studies assessed cfDNA's correlation with other inflammation biomarkers and found inconclusive results. There appears to be an association between inflammation and cfDNA. Further research is necessary before cfDNA can be used clinically as a measure of inflammation. © The Author(s) 2016.

Ablating spinal NK1-bearing neurons eliminates the development of pain & reduces spinal neuronal hyperexcitability & inflammation from mechanical joint injury in the rat

PubMed Central

Weisshaar, Christine L.; Winkelstein, Beth A.

2014-01-01

The facet joint is a common source of pain especially from mechanical injury. Although chronic pain is associated with altered spinal glial and neuronal responses, the contribution of specific spinal cells to joint pain are not understood. This study used the neurotoxin [Sar9,Met(O2)11]-substance P-saporin (SSP-SAP) to selectively eliminate spinal cells expressing neurokinin-1 receptor (NK1R) in a rat model of painful facet joint injury to determine the role of those spinal neurons in pain from facet injury. Following spinal administration of SSP-SAP or its control (blank-SAP), a cervical facet injury was imposed and behavioral sensitivity assessed. Spinal extracellular recordings were made on day 7 to classify neurons and quantify evoked firing. Spinal glial activation and IL1α expression also were evaluated. SSP-SAP prevented the development of mechanical hyperalgesia that is induced by joint injury and reduced NK1R expression and mechanically-evoked neuronal firing in the dorsal horn. SSP-SAP also prevented a shift toward wide dynamic range neurons that is seen after injury. Spinal astrocytic activation and IL1α expression were reduced to sham levels with SSP-SAP treatment. These results suggest that spinal NK1R-bearing cells are critical in initiating spinal nociception and inflammation associated with a painful mechanical joint injury. Perspective Results demonstrate that cells expressing NK1R in the spinal cord are critical for the development of joint pain and spinal neuroplasticity and inflammation after trauma to the joint. These findings have utility for understanding mechanisms of joint pain and developing potential targets to treat pain. PMID:24389017

Oxidative stress and inflammation: liver responses and adaptations to acute and regular exercise.

PubMed

Pillon Barcelos, Rômulo; Freire Royes, Luiz Fernando; Gonzalez-Gallego, Javier; Bresciani, Guilherme

2017-02-01

The liver is remarkably important during exercise outcomes due to its contribution to detoxification, synthesis, and release of biomolecules, and energy supply to the exercising muscles. Recently, liver has been also shown to play an important role in redox status and inflammatory modulation during exercise. However, while several studies have described the adaptations of skeletal muscles to acute and chronic exercise, hepatic changes are still scarcely investigated. Indeed, acute intense exercise challenges the liver with increased reactive oxygen species (ROS) and inflammation onset, whereas regular training induces hepatic antioxidant and anti-inflammatory improvements. Acute and regular exercise protocols in combination with antioxidant and anti-inflammatory supplementation have been also tested to verify hepatic adaptations to exercise. Although positive results have been reported in some acute models, several studies have shown an increased exercise-related stress upon liver. A similar trend has been observed during training: while synergistic effects of training and antioxidant/anti-inflammatory supplementations have been occasionally found, others reported a blunting of relevant adaptations to exercise, following the patterns described in skeletal muscles. This review discusses current data regarding liver responses and adaptation to acute and regular exercise protocols alone or combined with antioxidant and anti-inflammatory supplementation. The understanding of the mechanisms behind these modulations is of interest for both exercise-related health and performance outcomes.

Circuit Resistance Training Attenuates Acute Exertion-Induced Reductions in Arterial Function but Not Inflammation in Obese Women

PubMed Central

Franklin, Nina C.; Robinson, Austin T.; Bian, Jing-Tan; Ali, Mohamed M.; Norkeviciute, Edita; McGinty, Patrick

2015-01-01

Abstract Background: Cardiovascular disease (CVD) is a leading cause of preventable death among young women in the United States. Habitual resistance exercise training is known to have beneficial effects on endothelial function and CVD risk factors, including obesity; however, previous studies show that acute resistance exercise impairs endothelial function in obese adults who are sedentary, a response that may be linked to inflammation. We sought to determine if circuit-based resistance training (CRT) attenuates acute resistance exercise-induced reductions in endothelial function in a population of young, obese, sedentary women and whether or not inflammation plays a role in this response. Methods: Eighteen obese [body mass index (BMI) 30.0–40.0 kg·m−2] young premenopausal women were randomly assigned to either a CRT group or a no-exercise control group (CON). Conduit artery endothelial function was assessed using brachial artery flow-mediated dilation (FMD) determined by ultrasound before and after a single bout of strenuous weightlifting (SWL). In addition, circulating inflammatory mediators (tumor necrosis factor-α and C-reactive protein), blood pressure, fasting blood lipids, glucose, waist circumference, body composition, and aerobic capacity were assessed. Results: Among participants randomized to the CRT group, 8 weeks of training led to considerable increases in FMD after SWL (P=0.001) compared to the CON group. However, no significant differences between the groups were observed in circulating inflammatory mediators, blood pressure, fasting blood lipids, or other physical and physiological characteristics. Conclusions: This study shows that CRT alleviates acute exertion-induced reductions in endothelial function among obese sedentary women in the absence of changes in inflammation. PMID:25844686

DO ACUTE PHASE PROTEINS REFLECT SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?

EPA Science Inventory

Title: DO ACUTE PHASE PROTEINS REFLECT THE SEVERITY OF INFLAMMATION IN RAT MODELS OF POLLUTANT-INDUCED LUNG INJURY?

M. C. Schladweiler, BS 1, P. S. Gilmour, PhD 2, D. L. Andrews, BS 1, D. L. Costa, ScD 1, A. D. Ledbetter, BS 1, K. E. Pinkerton, PhD 3 and U. P. Kodavanti, ...

Efficacy of knee joint aspiration in patients with acute ACL injury in the emergency department.

PubMed

Wang, Joon Ho; Lee, Jin Hyuck; Cho, Youngsuk; Shin, Jung Min; Lee, Byung Hoon

2016-08-01

To evaluate the influence of joint aspiration on the sensitivity of physical examination for diagnosing acute anterior cruciate ligament (ACL) lesion in the second outpatient-department (OPD) follow-up referred from emergency department (ED). This retrospective study included sixty patients underwent ACL reconstruction with initial visit at ED. They were divided into two groups based on the presence or absence of joint aspiration at ED. All participants were referred to second OPD follow-up within 7-14days after the injury. Clinical manifestation (including visual analogue scale (VAS) for pain, range of motion (ROM), and severity of knee effusion) and physical examination (Lachman test and pivot shift test) were checked in ED and the second OPD follow-up. The group of patients with joint aspiration (G1) showed substantial decreases in mean values of VAS for pain (p=0.005), ROM (p=0.001), and effusion level (p<0.001), even higher VAS and effusion level and lower ROM at the initial visit of ED than the other group (G2). The sensitivity of positive Lachman and pivot shift test was significantly (p<0.05) increased following knee joint aspiration. Positive Lachman test was recorded at 76.5% in the second follow-up in G1, which was significantly (p=0.047) higher than that (47.6%) in G2. The percentage of positive pivot shift test was recorded at 76.5% in the second follow-up in G1, which as significantly (p<0.001) higher than that (31.0%) in G2. Knee joint aspiration in acute ACL injury with suspected hemarthrosis could be considered as a diagnostic procedure. Joint aspiration in early medical attendance might be able to lower pain scores or raise the sensitivity of physical examination for diagnosing acute ACL injury at follow up visit in orthopedic outpatient department. Retrospective cohort study III. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inflammation and Rupture of a Congenital Pericardial Cyst Manifesting Itself as an Acute Chest Pain Syndrome.

PubMed

Aertker, Robert A; Cheong, Benjamin Y C; Lufschanowski, Roberto

2016-12-01

We present the case of a 63-year-old woman with a remote history of supraventricular tachycardia and hyperlipidemia, who presented with recurrent episodes of acute-onset chest pain. An electrocardiogram showed no evidence of acute coronary syndrome. A chest radiograph revealed a prominent right-sided heart border. A suspected congenital pericardial cyst was identified on a computed tomographic chest scan, and stranding was noted around the cyst. The patient was treated with nonsteroidal anti-inflammatory drugs, and the pain initially abated. Another flare-up was treated similarly. Cardiac magnetic resonance imaging was then performed after symptoms had resolved, and no evidence of the cyst was seen. The suspected cause of the patient's chest pain was acute inflammation of a congenital pericardial cyst with subsequent rupture and resolution of symptoms.

Evaluation of orally administered robenacoxib versus ketoprofen for treatment of acute pain and inflammation associated with musculoskeletal disorders in cats.

PubMed

Giraudel, Jerome M; Gruet, Philippe; Alexander, Debbie G; Seewald, Wolfgang; King, Jonathan N

2010-07-01

To evaluate the efficacy and tolerability of oral administration of robenacoxib for treatment of acute pain and inflammation associated with musculoskeletal disorders in cats. 155 cats requiring relief of signs of pain and inflammation associated with acute musculoskeletal disorders. The study was a multicenter, prospective, randomized, masked, noninferiority field trial. Cats were allocated randomly to 1 of 3 treatment groups: group 1 (1.0 to 2.4 mg of robenacoxib/kg, q 24 h), group 2 (1.0 to 2.4 mg of robenacoxib/kg, q 12 h [daily dosage, 2.0 to 4.8 mg/kg]), and group 3 (ketoprofen [mean dosage, 1 mg/kg, q 24 h]). All cats were administered tablets PO for 5 or 6 days. The primary efficacy endpoint was the investigator global assessment score, which was the sum of scores of signs of pain, inflammation, and mobility assessed in a masked manner by veterinary investigators at baseline, day 2, and day 4 or 5. Cat owners monitored in a nonmasked manner secondary responses by observation of cats' activity, behavior, appetite, and interactions. Safety was assessed by monitoring adverse events, clinical signs, and hematologic and plasma biochemical variables (before and after treatment). No significant differences were detected among the 3 treatment groups for any primary or secondary efficacy endpoints or for tolerability variables. Robenacoxib tablets administered once daily were significantly more palatable than ketoprofen tablets. Robenacoxib tablets administered once daily had noninferior efficacy and tolerability, and superior palatability, compared with the active control drug, ketoprofen, for the treatment of signs of acute pain and inflammation associated with musculoskeletal disorders in cats.

Changing glucocorticoid action: 11β-Hydroxysteroid dehydrogenase type 1 in acute and chronic inflammation

PubMed Central

Chapman, Karen E.; Coutinho, Agnes E.; Zhang, Zhenguang; Kipari, Tiina; Savill, John S.; Seckl, Jonathan R.

2013-01-01

Since the discovery of cortisone in the 1940s and its early success in treatment of rheumatoid arthritis, glucocorticoids have remained the mainstay of anti-inflammatory therapies. However, cortisone itself is intrinsically inert. To be effective, it requires conversion to cortisol, the active glucocorticoid, by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Despite the identification of 11β-HSD in liver in 1953 (which we now know to be 11β-HSD1), its physiological role has been little explored until recently. Over the past decade, however, it has become apparent that 11β-HSD1 plays an important role in shaping endogenous glucocorticoid action. Acute inflammation is more severe with 11β-HSD1-deficiency or inhibition, yet in some inflammatory settings such as obesity or diabetes, 11β-HSD1-deficiency/inhibition is beneficial, reducing inflammation. Current evidence suggests both beneficial and detrimental effects may result from 11β-HSD1 inhibition in chronic inflammatory disease. Here we review recent evidence pertaining to the role of 11β-HSD1 in inflammation. This article is part of a Special Issue entitled ‘CSR 2013’. PMID:23435016

Concomitant glenohumeral pathologies associated with acute and chronic grade III and grade V acromioclavicular joint injuries.

PubMed

Jensen, Gunnar; Millett, Peter J; Tahal, Dimitri S; Al Ibadi, Mireille; Lill, Helmut; Katthagen, Jan Christoph

2017-08-01

The purpose of this study was to identify the risk of concomitant glenohumeral pathologies with acromioclavicular joint injuries grade III and V. Patients who underwent arthroscopically-assisted stabilization of acromioclavicular joint injuries grade III or grade V between 01/2007 and 12/2015 were identified in the patient databases of two surgical centres. Gender, age at index surgery, grade of acromioclavicular joint injury (Rockwood III or Rockwood V), and duration between injury and index surgery (classified as acute or chronic) were of interest. Concomitant glenohumeral pathologies were noted and their treatment was classified as debridement or reconstructive procedure. A total of 376 patients (336 male, 40 female) were included. Mean age at time of arthroscopic acromioclavicular joint reconstruction surgery was 42.1 ± 14.0 years. Overall, 201 patients (53%) had one or more concomitant glenohumeral pathologies. Lesions of the biceps tendon complex and rotator cuff were the most common. Forty-five patients (12.0%) had concomitant glenohumeral pathologies that required an additional repair. The remaining 156 patients (41.5%) received a debridement of their concomitant pathologies. Rockwood grade V compared to Rockwood grade III (p = 0.013; odds ratio 1.7), and chronic compared to acute injury were significantly associated with having a concomitant glenohumeral pathology (p = 0.019; odds ratio 1.7). The probability of having a concomitant glenohumeral pathology was also significantly associated with increasing age (p < 0.0001). Concomitant glenohumeral pathologies were observed in 53% of surgically treated patients with an acute or chronic acromioclavicular joint injury of either grade III or V. Twenty-two percent of these patients with concomitant glenohumeral pathologies received an additional dedicated repair procedure. Although a significant difference in occurrence of concomitant glenohumeral pathologies was seen between Rockwood grades III and V

The expression and activation of the AIM2 inflammasome correlates with inflammation and disease severity in patients with acute pancreatitis.

PubMed

Algaba-Chueca, Francisco; de-Madaria, Enrique; Lozano-Ruiz, Beatriz; Martínez-Cardona, Claudia; Quesada-Vázquez, Noé; Bachiller, Victoria; Tarín, Fabián; Such, José; Francés, Rubén; Zapater, Pedro; González-Navajas, José M

Acute pancreatitis is an inflammatory disorder of the pancreas that is responsible for significant morbidity and mortality. The inflammasome pathway has acquired significant relevance in the pathogenesis of many inflammatory disorders, but its role in patients with acute pancreatitis still awaits clarification. We performed a prospective study in which 27 patients with acute pancreatitis and 16 healthy controls were included. We isolated peripheral blood mononuclear cells (PBMCs) and we assessed the expression and activation of different inflammasomes as well as their association with the clinical course of the disease. Our results show that PBMCs from patients with acute pancreatitis have elevated expression of several components of the inflammasome complex, including the inflammasome-forming receptor absent in melanoma 2 (AIM2), early during the onset of the disease. Activation of the AIM2 or NLRP3 inflammasomes in PBMCs from patients with acute pancreatitis results in exacerbated IL-1β and IL-18 production compared with PBMCs from healthy controls. Furthermore, both AIM2 mRNA expression and AIM2-mediated production of IL-1β by PBMCs correlated with increased systemic inflammation in these patients. Last, AIM2 expression was further increased in those patients that developed transient or persistent organ failure (moderate or severe acute pancreatitis). Our data demonstrates that AIM2 inflammasome expression and activation is increased early during the course of acute pancreatitis, and suggests that AIM2 activation may affect systemic inflammation and organ failure in these patients. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Adjuvant-induced joint inflammation causes very rapid transcription of beta-preprotachykinin and alpha-CGRP genes in innervating sensory ganglia.

PubMed

Bulling, D G; Kelly, D; Bond, S; McQueen, D S; Seckl, J R

2001-04-01

Neuropeptides synthesized in dorsal root ganglia (DRG) have been implicated in neurogenic inflammation and nociception in experimental and clinical inflammatory arthritis. We examined the very early changes in response to adjuvant injection in a rat model of unilateral tibio-tarsal joint inflammation and subsequent monoarthritis. Within 30 min of adjuvant injection ipsilateral swelling and hyperalgesia were apparent, and marked increases in beta-preprotachykinin-A (beta-PPT-A) and alpha-calcitonin gene-related peptide (CGRP)-encoding mRNAs were observed in small-diameter L5 DRG neurones innervating the affected joint. This response was augmented by recruitment of additional small-diameter DRG neurones expressing beta-PPT-A and CGRP transcripts. The increased mRNA was paralleled by initial increases in L5 DRG content of the protein products, substance P and calcitonin gene-related peptide. Within 15 min of adjuvant injection there were increases in electrical activity in sensory nerves innervating a joint. Blockade of this activity prevented the rapid induction in beta-PPT-A and CGRP mRNA expression in DRG neurones. Increased expression of heteronuclear (intron E) beta-PPT-A RNA suggests that increases in beta-PPT-A mRNA levels were, at least in part, due to transcription. Pre-treatment with the protein synthesis inhibitor cycloheximide had no effect upon the early rise in neuropeptide mRNAS: This and the rapid time course of these changes suggest that increased sensory neural discharge and activation of a latent modulator of transcription are involved.

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

PubMed

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

2014-11-01

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

Intratracheal IL-6 protects against lung inflammation in direct, but not indirect, causes of acute lung injury in mice.

PubMed

Bhargava, Rhea; Janssen, William; Altmann, Christopher; Andrés-Hernando, Ana; Okamura, Kayo; Vandivier, R William; Ahuja, Nilesh; Faubel, Sarah

2013-01-01

Serum and bronchoalveolar fluid IL-6 are increased in patients with acute respiratory distress syndrome (ARDS) and predict prolonged mechanical ventilation and poor outcomes, although the role of intra-alveolar IL-6 in indirect lung injury is unknown. We investigated the role of endogenous and exogenous intra-alveolar IL-6 in AKI-mediated lung injury (indirect lung injury), intraperitoneal (IP) endotoxin administration (indirect lung injury) and, for comparison, intratracheal (IT) endotoxin administration (direct lung injury) with the hypothesis that IL-6 would exert a pro-inflammatory effect in these causes of acute lung inflammation. Bronchoalveolar cytokines (IL-6, CXCL1, TNF-α, IL-1β, and IL-10), BAL fluid neutrophils, lung inflammation (lung cytokines, MPO activity [a biochemical marker of neutrophil infiltration]), and serum cytokines were determined in adult male C57Bl/6 mice with no intervention or 4 hours after ischemic AKI (22 minutes of renal pedicle clamping), IP endotoxin (10 µg), or IT endotoxin (80 µg) with and without intratracheal (IT) IL-6 (25 ng or 200 ng) treatment. Lung inflammation was similar after AKI, IP endotoxin, and IT endotoxin. BAL fluid IL-6 was markedly increased after IT endotoxin, and not increased after AKI or IP endotoxin. Unexpectedly, IT IL-6 exerted an anti-inflammatory effect in healthy mice characterized by reduced BAL fluid cytokines. IT IL-6 also exerted an anti-inflammatory effect in IT endotoxin characterized by reduced BAL fluid cytokines and lung inflammation; IT IL-6 had no effect on lung inflammation in AKI or IP endotoxin. IL-6 exerts an anti-inflammatory effect in direct lung injury from IT endotoxin, yet has no role in the pathogenesis or treatment of indirect lung injury from AKI or IP endotoxin. Since intra-alveolar inflammation is important in the pathogenesis of direct, but not indirect, causes of lung inflammation, IT anti-inflammatory treatments may have a role in direct, but not indirect, causes of ARDS.

N-Arachidonoyl Dopamine Modulates Acute Systemic Inflammation via Nonhematopoietic TRPV1

PubMed Central

Lawton, Samira K.; Xu, Fengyun; Tran, Alphonso; Wong, Erika; Schumacher, Mark; Wilhelmsen, Kevin

2017-01-01

N-Arachidonoyl dopamine (NADA) is an endogenous lipid that potently activates the transient receptor potential vanilloid 1 (TRPV1), which mediates pain and thermosensation. NADA is also an agonist of cannabinoid receptors 1 and 2. We have reported that NADA reduces the activation of cultured human endothelial cells by LPS and TNF-α. Thus far, in vivo studies using NADA have focused on its neurologic and behavioral roles. In this article, we show that NADA potently decreases in vivo systemic inflammatory responses and levels of the coagulation intermediary plasminogen activator inhibitor 1 in three mouse models of inflammation: LPS, bacterial lipopeptide, and polymicrobial intra-abdominal sepsis. We also found that the administration of NADA increases survival in endotoxemic mice. Additionally, NADA reduces blood levels of the neuropeptide calcitonin gene-related peptide but increases the neuropeptide substance P in LPS-treated mice. We demonstrate that the anti-inflammatory effects of NADA are mediated by TRPV1 expressed by nonhematopoietic cells and provide data suggesting that neuronal TRPV1 may mediate NADA’s anti-inflammatory effects. These results indicate that NADA has novel TRPV1-dependent anti-inflammatory properties and suggest that the endovanilloid system might be targeted therapeutically in acute inflammation. PMID:28701511

Anatomy of a Joint: Comparing Self-Reported and Actual Dose of Cannabis and Tobacco in a Joint, and How These Are Influenced by Controlled Acute Administration.

PubMed

Hindocha, Chandni; Freeman, Tom P; Curran, H Valerie

2017-01-01

Introduction: Major gaps exist in the measurement of cannabis exposure. The accuracy of self-reported cannabis and tobacco dose per joint is poorly characterized and has never been investigated following acute cannabis/tobacco exposure. Using an innovative "Roll a Joint" paradigm, this study aims to (1) compare estimated and actual dose of cannabis and tobacco per joint at baseline and (2) examine the acute effects of cannabis and/or tobacco on estimated and actual dose. Materials and Methods: We investigated this by using a randomized, double-blind, placebo-controlled crossover 2 (active cannabis, placebo cannabis)×2 (active tobacco, placebo tobacco) design in a laboratory setting. Participants were 24 recreational cousers of cannabis and tobacco. At baseline, they were asked to measure out the amount of cannabis and tobacco they would put in an average joint for themselves (dose per joint). Then, on each of four drug administration sessions, participants were again asked to do this for a joint they would want to smoke "right now." Self-reported and actual amount was recorded (g). Results: At baseline, the estimated amount of cannabis per joint (0.28±0.23 g) was double the actual amount (0.14±0.12 g) ( p =0.003, d =0.723). No difference emerged between estimated (0.43±0.25 g) and actual (0.35±0.15 g) ( p =0.125) amount of tobacco per joint. Compared to placebo, active cannabis reduced the actual dose of both cannabis ( p =0.035) and tobacco ( p <0.001) they put in a joint. Participants accurately estimated this reduction for tobacco ( p =0.014), but not for cannabis ( p =0.680). Conclusions: Self-reported dose per joint is accurate for tobacco but dramatically overestimates cannabis exposure and therefore should be viewed with caution. Cannabis administration reduced the amount of cannabis and tobacco added to joints, suggesting a reduction in dose during a smoking session. The "Roll A Joint" paradigm should be implemented for better accuracy in

Tumor Necrosis Factor Alpha Signaling in Trigeminal Ganglion Contributes to Mechanical Hypersensitivity in Masseter Muscle During Temporomandibular Joint Inflammation.

PubMed

Ito, Reio; Shinoda, Masamichi; Honda, Kuniya; Urata, Kentaro; Lee, Jun; Maruno, Mitsuru; Soma, Kumi; Okada, Shinji; Gionhaku, Nobuhito; Iwata, Koichi

To determine the involvement of tumor necrosis factor alpha (TNFα) signaling in the trigeminal ganglion (TG) in the mechanical hypersensitivity of the masseter muscle during temporomandibular joint (TMJ) inflammation. A total of 55 male Sprague-Dawley rats were used. Following injection of Complete Freund's Adjuvant into the TMJ, the mechanical sensitivities of the masseter muscle and the overlying facial skin were measured. Satellite glial cell (SGC) activation and TNFα expression in the TG were investigated immunohistochemically, and the effects of their inhibition on the mechanical hypersensitivity of the masseter muscle were also examined. Student t test or two-way repeated-measures analysis of variance followed by Bonferroni multiple comparisons test were used for statistical analyses. P < .05 was considered to reflect statistical significance. Mechanical allodynia in the masseter muscle was induced without any inflammatory cell infiltration in the muscle after TMJ inflammation. SGC activation and an increased number of TNFα-immunoreactive cells were induced in the TG following TMJ inflammation. Intra-TG administration of an inhibitor of SGC activity or of TNFα-neutralizing antibody depressed both the increased number of TG cells encircled by activated SGCs and the mechanical hypersensitivity of the masseter following TMJ inflammation. These findings suggest that persistent masseter hypersensitivity associated with TMJ inflammation was mediated by SGC-TG neuron interactions via TNFα signaling in the TG.

Inter- and intraobserver reliability of the Rockwood classification in acute acromioclavicular joint dislocations.

PubMed

Schneider, M M; Balke, M; Koenen, P; Fröhlich, M; Wafaisade, A; Bouillon, B; Banerjee, M

2016-07-01

The reliability of the Rockwood classification, the gold standard for acute acromioclavicular (AC) joint separations, has not yet been tested. The purpose of this study was to investigate the reliability of visual and measured AC joint lesion grades according to the Rockwood classification. Four investigators (two shoulder specialists and two second-year residents) examined radiographs (bilateral panoramic stress and axial views) in 58 patients and graded the injury according to the Rockwood classification using the following sequence: (1) visual classification of the AC joint lesion, (2) digital measurement of the coracoclavicular distance (CCD) and the horizontal dislocation (HD) with Osirix Dicom Viewer (Pixmeo, Switzerland), (3) classification of the AC joint lesion according to the measurements and (4) repetition of (1) and (2) after repeated anonymization by an independent physician. Visual and measured Rockwood grades as well as the CCD and HD of every patient were documented, and a CC index was calculated (CCD injured/CCD healthy). All records were then used to evaluate intra- and interobserver reliability. The disagreement between visual and measured diagnosis ranged from 6.9 to 27.6 %. Interobserver reliability for visual diagnosis was good (0.72-0.74) and excellent (0.85-0.93) for measured Rockwood grades. Intraobserver reliability was good to excellent (0.67-0.93) for visual diagnosis and excellent for measured diagnosis (0.90-0.97). The correlations between measurements of the axial view varied from 0.68 to 0.98 (good to excellent) for interobserver reliability and from 0.90 to 0.97 (excellent) for intraobserver reliability. Bilateral panoramic stress and axial radiographs are reliable examinations for grading AC joint injuries according to Rockwood's classification. Clinicians of all experience levels can precisely classify AC joint lesions according to the Rockwood classification. We recommend to grade acute ACG lesions by performing a digital

Neutrophil-derived JAML Inhibits Repair of Intestinal Epithelial Injury During Acute Inflammation

PubMed Central

Weber, Dominique A.; Sumagin, Ronen; McCall, Ingrid C.; Leoni, Giovanna; Neumann, Philipp A.; Andargachew, Rakieb; Brazil, Jennifer C.; Medina-Contreras, Oscar; Denning, Timothy L.; Nusrat, Asma; Parkos, Charles A.

2014-01-01

Neutrophil transepithelial migration (TEM) during acute inflammation is associated with mucosal injury. Using models of acute mucosal injury in-vitro and in-vivo, we describe a new mechanism by which neutrophils infiltrating the intestinal mucosa disrupt epithelial homeostasis. We report that junctional adhesion molecule-like protein (JAML) is cleaved from neutrophil surface by zinc-metalloproteases during TEM. Neutrophil-derived soluble JAML bound to the epithelial tight junction protein coxsackie-adenovirus receptor (CAR) resulting in compromised barrier and inhibition of wound repair, through decreased epithelial proliferation. The deleterious effects of JAML on barrier and wound repair were reversed with an anti-JAML mAb that inhibits JAML-CAR binding. Thus, JAML released from transmigrating neutrophils across inflamed epithelia can promote recruitment of leukocytes and aid in clearance of invading microorganisms. However, sustained release of JAML under pathologic conditions associated with persistence of large numbers of infiltrated neutrophil would compromise intestinal barrier and inhibit mucosal healing. Targeting JAML-CAR interactions may thus improve mucosal healing responses under conditions of dysregulated neutrophil recruitment. PMID:24621992

STRETCHING IMPACTS INFLAMMATION RESOLUTION IN CONNECTIVE TISSUE

PubMed Central

Berrueta, Lisbeth; Muskaj, Igla; Olenich, Sara; Butler, Taylor; Badger, Gary J.; Colas, Romain A.; Spite, Matthew; Serhan, Charles N.; Langevin, Helene M.

2016-01-01

Acute inflammation is accompanied from its outset by the release of specialized pro-resolving mediators (SPMs), including resolvins, that orchestrate the resolution of local inflammation. We showed earlier that, in rats with subcutaneous inflammation of the back induced by carrageenan, stretching for 10 minutes twice daily reduced inflammation and improved pain, two weeks after carrageenan injection. In this study, we hypothesized that stretching of connective tissue activates local pro-resolving mechanisms within the tissue in the acute phase of inflammation. In rats injected with carrageenan and randomized to stretch vs. no stretch for 48 hours, stretching reduced inflammatory lesion thickness and neutrophil count, and increased resolvin (RvD1) concentrations within lesions. Furthermore, subcutaneous resolvin injection mimicked the effect of stretching. In ex vivo experiments, stretching of connective tissue reduced the migration of neutrophils and increased tissue RvD1 concentration. These results demonstrate a direct mechanical impact of stretching on inflammation-regulation mechanisms within connective tissue. PMID:26588184

Where Does Inflammation Fit?

PubMed

Biasucci, Luigi M; La Rosa, Giulio; Pedicino, Daniela; D'Aiello, Alessia; Galli, Mattia; Liuzzo, Giovanna

2017-09-01

This review focuses on the complex relationship between inflammation and the onset of acute coronary syndrome and heart failure. In the last few years, two important lines of research brought new and essential information to light in the pathogenesis of acute coronary syndrome: a) the understanding of the immune mediate mechanisms of inflammation in Ischemic Heart Disease (IHD) and b) evidence that the inflammatory mechanisms associated with atherosclerosis and its complications can be modulated by anti-inflammatory molecules. A large amount of data also suggests that inflammation is a major component in the development and exacerbation of heart failure (HF), in a symbiotic relationship. In particular, recent evidence underlies peculiar aspects of the phenomenon: oxidative stress and autophagy; DAMPS and TLR-4 signaling activation; different macrophages lineage and the contribution of NLRP-3 inflammasome; adaptive immune system. A possible explanation that could unify the pathogenic mechanism of these different conditions is the rising evidence that increased bowel permeability may allow translation of gut microbioma product into the circulation. These findings clearly establish the role of inflammation as the great trigger for two of the major cardiovascular causes of death and morbidity. Further studies are needed, to better clarify the issue and to define more targeted approaches to reduce pathological inflammation while preserving the physiological one.

Calycophyllum spruceanum BENTH ameliorates acute inflammation in mice.

PubMed

da Silva, Ana Paula Azevedo Barros; Amorim, Renata Morais Ferreira; de Freitas Lopes, Roberta; Mota, Mário Rogério Lima; da Silva, Felipe Moura Araújo; Koolen, Hector Henrique Ferreira; Lima, Emerson Silva; Assreuy, Ana Maria S; da Cunha, Renildo Moura

2018-06-12

Calycophyllum spruceanum (Benth.) Hook. F. ex K. Schum. is widely distributed in the Amazonian region of Brazil, where it is popularly known as "mulateiro", "pau-mulato", "pau-mulato-de-várzea", "escorrega-macaco" or "pau-marfim". Preparations of C. spruceanum barks are used in the form of tea, poultice or skin patches to treat stomach diseases, skin inflammation and uterus tumors. To investigate in vivo the antinociceptive and anti-inflammatory activities of the hydroalcoholic extract of Calycophyllum spruceanum barks (HECSb) in order to validate its popular usage in inflammatory conditions. Chemical analysis of HECSb was performed using the UHPLC-MS system. Mice were treated per oral with HECSb (5-5000 mg/kg) and evaluated for acute toxicity (during 15 days); motor activity (Rota rod test); body weight (up to 72 h); antinociceptive activity: writhes induced by 0.8% acetic acid; paw licking induced by 2.5% formalin; paw withdrawal (von Frey test) induced by carrageenan (300 μg) or PGE2 (100 ng); anti-inflammatory (paw edema model). For histopathological analysis subplantar tissue fragments were collected 1 h after paw edema induction. HECSb chemical analysis revealed the presence of caffeoylquinic derivatives, small organic acids, and phenolic compounds. HECSb showed antinociceptive effect, reducing the number of acetic acid-induced writhes by 72% at 120 mg/kg, paw licking (phase 2- Formalin test) by 33% at 60 mg/kg and 49% at 120 mg/kg; and paw withdrawal elicited by carrageenan (53% at 120 mg/kg) and PGE2 (120 mg/kg) at 0.5 h (48%) and 1 h (45%). HECSb (120 mg/kg) also inhibited the paw edema elicited both by carrageenan (48%) and PGE2 (92%). Histopathological analysis (leukocyte infiltration, edema, focal areas of hemorrhage, vascular congestion) of HECSb treatment at 120 mg/kg demonstrated normal morphology [median 0 (0,1)] compared to PGE2, showing severe alterations [median 3 (2,3); p = 0,0035]. HECSb did not induce acute

S100A8/A9 as a biomarker for synovial inflammation and joint damage in patients with rheumatoid arthritis.

PubMed

Kang, Kwi Young; Woo, Jung-Won; Park, Sung-Hwan

2014-01-01

S100A8 and S100A9 are major leukocyte proteins, known as damage-associated molecular patterns, found at high concentrations in the synovial fluid of patients with rheumatoid arthritis (RA). A heterodimeric complex of S100A8/A9 is secreted by activated leukocytes and binds to Toll-like receptor 4, which mediates downstream signaling and promotes inflammation and autoimmunity. Serum and synovial fluid levels of S100A8/A9 are markedly higher in patients with RA than in patients with osteoarthritis or miscellaneous inflammatory arthritis. Serum levels of S100A8/A9 are significantly correlated with clinical and laboratory markers of inflammation, such as C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and the Disease Activity Score for 28 joints. Significant correlations have also been found between S100A8/A9 and radiographic and clinical assessments of joint damage, such as hand radiographs and the Rheumatoid Arthritis Articular Damage score. In addition, among known inflammatory markers, S100A8/A9 has the strongest correlation with total sum scores of ultrasonography assessment. Furthermore, baseline levels of S100A8/A9 are independently associated with progression of joint destruction in longitudinal studies and are responsive to change during conventional and biologic treatments. These findings suggest S100A8/A9 to be a valuable diagnostic and prognostic biomarker for RA.

Does Regional Lung Strain Correlate With Regional Inflammation in Acute Respiratory Distress Syndrome During Nonprotective Ventilation? An Experimental Porcine Study.

PubMed

Retamal, Jaime; Hurtado, Daniel; Villarroel, Nicolás; Bruhn, Alejandro; Bugedo, Guillermo; Amato, Marcelo Britto Passos; Costa, Eduardo Leite Vieira; Hedenstierna, Göran; Larsson, Anders; Borges, João Batista

2018-06-01

It is known that ventilator-induced lung injury causes increased pulmonary inflammation. It has been suggested that one of the underlying mechanisms may be strain. The aim of this study was to investigate whether lung regional strain correlates with regional inflammation in a porcine model of acute respiratory distress syndrome. Retrospective analysis of CT images and positron emission tomography images using [F]fluoro-2-deoxy-D-glucose. University animal research laboratory. Seven piglets subjected to experimental acute respiratory distress syndrome and five ventilated controls. Acute respiratory distress syndrome was induced by repeated lung lavages, followed by 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressures (mean, 4 cm H2O) and high inspiratory pressures (mean plateau pressure, 45 cm H2O). All animals were subsequently studied with CT scans acquired at end-expiration and end-inspiration, to obtain maps of volumetric strain (inspiratory volume - expiratory volume)/expiratory volume, and dynamic positron emission tomography imaging. Strain maps and positron emission tomography images were divided into 10 isogravitational horizontal regions-of-interest, from which spatial correlation was calculated for each animal. The acute respiratory distress syndrome model resulted in a decrease in respiratory system compliance (20.3 ± 3.4 to 14.0 ± 4.9 mL/cm H2O; p < 0.05) and oxygenation (PaO2/FIO2, 489 ± 80 to 92 ± 59; p < 0.05), whereas the control animals did not exhibit changes. In the acute respiratory distress syndrome group, strain maps showed a heterogeneous distribution with a greater concentration in the intermediate gravitational regions, which was similar to the distribution of [F]fluoro-2-deoxy-D-glucose uptake observed in the positron emission tomography images, resulting in a positive spatial correlation between both variables (median R = 0.71 [0.02-0.84]; p < 0.05 in five of seven animals

Development of a Lubricant Therapy to Prevent Development of Osteoarthritis after Acute Injury of Synovial Joints

DTIC Science & Technology

2015-10-01

AD______________ AWARD NUMBER: W81XWH-14-1-0562 TITLE: Development of a Lubricant Therapy to Prevent Development of Osteoarthritis after Acute...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Development of a Lubricant Therapy to Prevent Development of Osteoarthritis after Acute Injury of Synovial...early-onset osteoarthritis after traumatic joint injury remains a clinical challenge and may be associated with the poor lubricant quality of the

Inhibiting glycogen synthase kinase-3 reduces endotoxaemic acute renal failure by down-regulating inflammation and renal cell apoptosis

PubMed Central

Wang, Y; Huang, WC; Wang, CY; Tsai, CC; Chen, CL; Chang, YT; Kai, JI; Lin, CF

2009-01-01

Background and purpose: Excessive inflammation and apoptosis are pathological features of endotoxaemic acute renal failure. Activation of glycogen synthase kinase-3 (GSK-3) is involved in inflammation and apoptosis. We investigated the effects of inhibiting GSK-3 on lipopolysaccharide (LPS)-induced acute renal failure, nuclear factor-κB (NF-κB), inflammation and apoptosis. Experimental approach: The effects of inhibiting GSK-3 with inhibitors, including lithium chloride (LiCl) and 6-bromo-indirubin-3′-oxime (BIO), on LPS-treated (15 mg·kg−1) C3H/HeN mice (LiCl, 40 mg·kg−1 and BIO, 2 mg·kg−1) and LPS-treated (1 µg·mL−1) renal epithelial cells (LiCl, 20 mM and BIO, 5 µM) were studied. Mouse survival was monitored and renal function was analysed by histological and serological examination. Cytokine and chemokine production, and cell apoptosis were measured by enzyme-linked immunosorbent assay and terminal deoxynucleotidyl transferase-mediated dUTP–biotin nick-end labelling staining, respectively. Activation of NF-κB and GSK-3 was determined by immunostaining and Western blotting, respectively. Key results: Mice treated with GSK-3 inhibitors showed decreased mortality, renal tubular dilatation, vacuolization and sloughing, blood urea nitrogen, creatinine and renal cell apoptosis in response to endotoxaemia. Inhibiting GSK-3 reduced LPS-induced tumour necrosis factor-α (TNF-α) and CCL5/RANTES (released upon activation of normal T-cells) in vivo in mice and in vitro in murine kidney cortical collecting duct epithelial M1 cells. Inhibiting GSK-3 did not block TNF-α-induced cytotoxicity in rat kidney proximal tubular epithelial NRK52E or in M1 cells. Conclusions and implications: These results suggest that GSK-3 inhibition protects against endotoxaemic acute renal failure mainly by down-regulating pro-inflammatory TNF-α and RANTES. PMID:19508392

Effects of Liver × receptor agonist treatment on signal transduction pathways in acute lung inflammation

PubMed Central

2010-01-01

Background Liver × receptor α (LXRα) and β (LXRβ) are members of the nuclear receptor super family of ligand-activated transcription factors, a super family which includes the perhaps better known glucocorticoid receptor, estrogen receptor, thyroid receptor, and peroxisome proliferator-activated receptors. There is limited evidence that LXL activation may reduces acute lung inflammation. The aim of this study was to investigate the effects of T0901317, a potent LXR receptor ligand, in a mouse model of carrageenan-induced pleurisy. Methods Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterized by: accumulation of fluid containing a large number of neutrophils (PMNs) in the pleural cavity, infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate (NOx), tumor necrosis factor-α, (TNF-α) and interleukin-1β (IL-1β). Furthermore, carrageenan induced the expression of iNOS, nitrotyrosine and PARP, as well as induced apoptosis (TUNEL staining and Bax and Bcl-2 expression) in the lung tissues. Results Administration of T0901317, 30 min after the challenge with carrageenan, caused a significant reduction in a dose dependent manner of all the parameters of inflammation measured. Conclusions Thus, based on these findings we propose that LXR ligand such as T0901317, may be useful in the treatment of various inflammatory diseases. PMID:20175894

Non-steroidal Anti-inflammatory Drugs Attenuate Hyperalgesia and Block Upregulation of Trigeminal Ganglionic Sodium Channel 1.7 after Induction of Temporomandibular Joint Inflammation in Rats.

PubMed

Bi, Rui Yun; Ding, Yun; Gan, Ye Hua

2016-03-01

To investigate the association between the analgesic effect of non-steroidal antiinflammatory drugs (NSAIDs) and sodium channel 1.7 (Nav1.7) expression in the trigeminal ganglion (TG). Temporomandibular joint (TMJ) inflammation was induced by complete Freund's adjuvant (CFA) in female rats. Ibuprofen, diclofenac sodium and meloxicam were given intragastrically before induction of TMJ inflammation. Histopathological evaluation and scoring of TMJ inflammation was used to evaluate the level of inflammation. The head withdrawal threshold and food intake were measured to evaluate TMJ nociceptive responses. The mRNA and protein expression of trigeminal ganglionic Nav1.7 was examined using real-time polymerase chain reaction and western blot. Twenty-four hours after the injection of CFA into the TMJs, NSAIDs attenuated hyperalgesia of inflamed TMJ and simultaneously blocked inflammation-induced upregulation of Nav1.7 mRNA and protein expression in the TG. However, ibuprofen and diclofenac sodium slightly attenuated TMJ inflammation and meloxicam did not affect TMJ inflammation. Attenuation of hyperalgesia of inflamed TMJ by NSAIDs might be associated with their role in blocking upregulation of trigeminal ganglionic Nav1.7.

In utero and postnatal exposure to a phytoestrogen-enriched diet increases parameters of acute inflammation in a rat model of TNBS-induced colitis.

PubMed

Seibel, Jan; Molzberger, Almut F; Hertrampf, Torsten; Laudenbach-Leschowski, Ute; Degen, Gisela H; Diel, Patrick

2008-12-01

Inflammatory bowel disease (IBD) is very common in Europe and USA. Its incidence in East Asia has been traditionally low, albeit the risk of IBD increases in Asian immigrants adopting western lifestyles, suggesting a strong role of environmental/dietary factors in IBD. A lifelong exposure to phytoestrogen-rich diets has been associated with a decreased risk of developing breast cancer and might also be protective against IBD. We studied the influence of in utero and postnatal exposure to a phytoestrogen (PE)-rich diet on acute inflammation in an animal model of TNBS-induced colitis. Wistar rats were exposed in utero and postnatally to high (genistein: 240 microg/g feed; daidzein: 232 microg/g feed) or very low levels (genistein and daidzein <10 microg/g feed) of phytoestrogen isoflavones fed to pregnant dams with the diet and throughout nursing. After weaning, the offspring had free access to these diets. At the age of 11 weeks, colitis was induced with an enema of TNBS. After 3 days, animals were sacrificed and tissues were collected for histological evaluation and analysis of molecular markers of inflammation. Animals kept on a PE-rich diet (PRD) had higher colon weights than animals on low PE-levels (PDD), suggesting enhanced acute inflammation by phytoestrogens. This result was supported by histological findings and by analysis of myeloperoxidase activity. Interestingly, relative mRNA and protein expression of cyclooxygenase-2 (COX-2) were modulated in rats on PRD, providing evidence that COX-2, the inducible isoform of the enzyme, is involved in the management of colonic inflammation. Our results suggest that early-in-life exposure to PE might not protect against the development of IBD but enhances the extent of acute inflammation.

HDL cholesterol transport during inflammation.

PubMed

van der Westhuyzen, Deneys R; de Beer, Frederick C; Webb, Nancy R

2007-04-01

The aim of this article is to review recent advances made towards understanding how inflammation and acute phase proteins, particularly serum amyloid A and group IIa secretory phospholipase A2, may alter reverse cholesterol transport by HDL during inflammation and the acute phase response. Findings suggest that the decreased apoA-I content and markedly increased serum amyloid A content in HDL during the acute phase response result from reciprocal and coordinate transcriptional regulation of these proteins as well as HDL remodeling by group IIa secretory phospholipase A2. Serum amyloid A functions efficiently in a lipid-free or lipid-poor form to promote cholesterol efflux by ATP binding cassette protein ABCA1, evidently by functioning directly as an acceptor for cholesterol efflux as well as by increasing the availability of cellular free cholesterol. Serum amyloid A increases the ability of acute phase HDL to serve as an acceptor for SR-BI-dependent cellular cholesterol efflux. Altered remodeling of HDL by group IIa secretory phospholipase A2 in concert with cholesterol ester transfer protein may contribute to the generation of lipid-poor apoA-I and serum amyloid A acceptors for cholesterol efflux. Current data support a model for the acute phase response in which serum amyloid A and sPLA2-IIa, present at sites of inflammation and tissue damage, play a protective role by enhancing cellular cholesterol efflux, thereby promoting the removal of excess cholesterol from macrophages.

Inter-joint coordination strategies during unilateral stance following first-time, acute lateral ankle sprain: A brief report.

PubMed

Doherty, Cailbhe; Bleakley, Chris; Hertel, Jay; Caulfield, Brian; Ryan, John; Sweeney, Kevin; Delahunt, Eamonn

2015-07-01

This investigation combined measures of inter-joint coordination and stabilometry to evaluate eyes-open (condition 1) and eyes-closed (condition 2) static unilateral stance performance in a group of participants with an acute, first-time lateral ankle sprain injury in comparison to a control group. Sixty-six participants with an acute first-time lateral ankle sprain and 19 non-injured controls completed three 20-second unilateral stance task trials in conditions 1 and 2. An adjusted coefficient of multiple determination statistic was used to compare stance limb 3-D kinematic data for similarity in the aim of establishing patterns of inter-joint coordination for these groups. Between-group analyses revealed significant differences in stance limb inter-joint coordination strategies for conditions 1 and 2. Injured participants displayed increases in ankle-hip linked coordination compared to controls in condition 1 (sagittal/frontal plane: 0.12 [0.09] vs 0.06 [0.04]; η(2)=.16) and condition 2 (sagittal/frontal plane: 0.18 [0.13] vs 0.08 [0.06]; η(2)=0.37). Participants with acute first-time lateral ankle sprain exhibit a hip-dominant coordination strategy for static unilateral stance compared to non-injured controls. Copyright © 2015 Elsevier Ltd. All rights reserved.

Autophagy and kidney inflammation.

PubMed

Kimura, Tomonori; Isaka, Yoshitaka; Yoshimori, Tamotsu

2017-06-03

Inflammation plays a pivotal role in pathophysiological processes of kidney diseases. Macroautophagy/autophagy plays multiple roles in inflammatory responses, and the regulation of inflammation by autophagy has great potential as a treatment for damaged kidneys. A growing body of evidence suggests autophagy protects kidney from versatile kidney inflammatory insults, including those that are acute, chronic, metabolic, and aging-related. It is noteworthy that, in kidney, mitophagy is active, and damaged lysosomes are removed by autophagy. In this mode, autophagy suppresses inflammation to protect the kidney. Systemic inflammation also affects the kidney via pro-inflammatory cytokines and infiltration of inflammatory cells, and autophagy also has a regulatory role in systemic inflammation. This review focuses on the roles of autophagy in kidney diseases and aging through inflammation, and discusses the potential usage of autophagy as an inflammatory modulator for the treatment of kidney diseases.

Increased expression of damage-associated molecular patterns (DAMPs) in osteoarthritis of human knee joint compared to hip joint.

PubMed

Rosenberg, John H; Rai, Vikrant; Dilisio, Matthew F; Sekundiak, Todd D; Agrawal, Devendra K

2017-12-01

Osteoarthritis (OA) is a degenerative disease characterized by the destruction of cartilage. The greatest risk factors for the development of OA include age and obesity. Recent studies suggest the role of inflammation in the pathogenesis of OA. The two most common locations for OA to occur are in the knee and hip joints. The knee joint experiences more mechanical stress, cartilage degeneration, and inflammation than the hip joint. This could contribute to the increased incidence of OA in the knee joint. Damage-associated molecular patterns (DAMPs), including high-mobility group box-1, receptor for advanced glycation end products, and alarmins (S100A8 and S100A9), are released in the joint in response to stress-mediated chondrocyte and cartilage damage. This facilitates increased cartilage degradation and inflammation in the joint. Studies have documented the role of DAMPs in the pathogenesis of OA; however, the comparison of DAMPs and its influence on OA has not been discussed. In this study, we compared the DAMPs between OA knee and hip joints and found a significant difference in the levels of DAMPs expressed in the knee joint compared to the hip joint. The increased levels of DAMPs suggest a difference in the underlying pathogenesis of OA in the knee and the hip and highlights DAMPs as potential therapeutic targets for OA in the future.

Underlying chronic inflammation alters the profile and mechanisms of acute neutrophil recruitment.

PubMed

Ma, Bin; Whiteford, James R; Nourshargh, Sussan; Woodfin, Abigail

2016-11-01

Chronically inflamed tissues show altered characteristics that include persistent populations of inflammatory leukocytes and remodelling of the vascular network. As the majority of studies on leukocyte recruitment have been carried out in normal healthy tissues, the impact of underlying chronic inflammation on ongoing leukocyte recruitment is largely unknown. Here, we investigate the profile and mechanisms of acute inflammatory responses in chronically inflamed and angiogenic tissues, and consider the implications for chronic inflammatory disorders. We have developed a novel model of chronic ischaemia of the mouse cremaster muscle that is characterized by a persistent population of monocyte-derived cells (MDCs), and capillary angiogenesis. These tissues also show elevated acute neutrophil recruitment in response to locally administered inflammatory stimuli. We determined that Gr1 low MDCs, which are widely considered to have anti-inflammatory and reparative functions, amplified acute inflammatory reactions via the generation of additional proinflammatory signals, changing both the profile and magnitude of the tissue response. Similar vascular and inflammatory responses, including activation of MDCs by transient ischaemia-reperfusion, were observed in mouse hindlimbs subjected to chronic ischaemia. This response demonstrates the relevance of the findings to peripheral arterial disease, in which patients experience transient exercise-induced ischaemia known as claudication.These findings demonstrate that chronically inflamed tissues show an altered profile and altered mechanisms of acute inflammatory responses, and identify tissue-resident MDCs as potential therapeutic targets. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Global Gene Expression Differences in Joints of Mice with Divergent Post Traumatic Osteoarthritis Phenotypes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kibui, J.

Osteoarthritis (OA) is a debilitating joint disease characterized by cartilage degradation which prompts pain, stiffness and swelling. Contributing factors include age, genetics, obesity, injury and overuse of joints. OA is defined by an acute phase and a chronic phase whereby inflammation and degeneration of articular cartilage and other tissues is followed by joint pain and limited mobility. Patients remain asymptomatic until substantial joint damage has occurred and therefore rely on long term surgical joint replacement and pain management as their sole treatment options. For this reason, there is an increasing need to identify early stage osteoarthritis biomarkers. Our study aimedmore » to identify and characterize gene expression variances in 3 different mouse strains (STR/ort, C57BL/6 and MRL/MpJ) with different susceptibility to post traumatic osteoarthritis (PTOA). Through RNA sequence analysis of whole knee joint RNA, we identified differentially expressed genes associated with the initial stages of PTOA in relation to mice with divergent phenotypes. These results will help elucidate potential mechanisms responsible for PTOA outcomes.« less

Predictors of Inflammation in a Cohort of Bolivian Infants and Toddlers.

PubMed

Burke, Rachel M; Suchdev, Parminder S; Rebolledo, Paulina A; de Aceituno, Anna M Fabiszewski; Revollo, Rita; Iñiguez, Volga; Klein, Mitchel; Drews-Botsch, Carolyn; Leon, Juan S

2016-10-05

Inflammation has been associated with cardiovascular disease and other health outcomes in children and adults, yet few longitudinal data are available on prevalence and predictors of inflammation in infants. We aimed to identify the prevalence of inflammation in a cohort of Bolivian infants and estimate its association with acute (recent illnesses) and chronic (overweight, stunting) morbidities and potential pathogen exposure (represented by water, sanitation, and hygiene [WASH] resources). We measured plasma concentrations of two acute phase proteins (C-reactive protein [CRP], marking acute inflammation, and alpha(1)-acid-glycoprotein [AGP], marking chronic inflammation) at three time points (target 2, 6-8, and 12-18 months). Of 451 singleton infants enrolled in the parent study, 272 had the first blood draw and complete data. Anthropometry and sociodemographic and recent illness data (2-week recall of cough, diarrhea, and fever) were collected at each visit. Inflammation was defined as CRP > 5 mg/L or AGP > 1 g/L. The prevalence of inflammation increased from early infancy (3% at first blood draw) to later infancy (15-22% at later blood draws). Recent cough, recent fever, and age in months were significantly associated with relative increases in CRP (7-44%) and AGP (5-23%), whereas recent diarrhea was only significantly associated with an increase in CRP (48%). Neither anthropometry nor WASH was significantly associated with inflammation. Results confirm the role of recent acute illness in inflammation in infants, and indicate that adiposity and WASH are not as important to inflammation in this age category. © The American Society of Tropical Medicine and Hygiene.

Temporal Role for MyD88 in a Model of Brucella-Induced Arthritis and Musculoskeletal Inflammation

PubMed Central

Lacey, Carolyn A.; Mitchell, William J.; Brown, Charles R.

2017-01-01

ABSTRACT Brucella spp. are facultative intracellular Gram-negative bacteria that cause the zoonotic disease brucellosis, one of the most common global zoonoses. Osteomyelitis, arthritis, and musculoskeletal inflammation are common focal complications of brucellosis in humans; however, wild-type (WT) mice infected systemically with conventional doses of Brucella do not develop these complications. Here we report C57BL/6 WT mice infected via the footpad with 103 to 106 CFU of Brucella spp. display neutrophil and monocyte infiltration of the joint space and surrounding musculoskeletal tissue. Joint inflammation is detectable as early as 1 day postinfection and peaks 1 to 2 weeks later, after which WT mice are able to slowly resolve inflammation. B and T cells were dispensable for the onset of swelling but required for resolution of joint inflammation and infection. At early time points, MyD88−/− mice display decreased joint inflammation, swelling, and proinflammatory cytokine levels relative to WT mice. Subsequently, swelling of MyD88−/− joints surpassed WT joint swelling, and resolution of joint inflammation was prolonged. Joint bacterial loads in MyD88−/− mice were significantly greater than those in WT mice by day 3 postinfection and at all time points thereafter. In addition, MyD88−/− joint inflammatory cytokine levels on day 3 and beyond were similar to WT levels. Collectively these data demonstrate MyD88 signaling mediates early inflammatory responses in the joint but also contributes to subsequent clearance of Brucella and resolution of inflammation. This work also establishes a mouse model for studying Brucella-induced arthritis, musculoskeletal complications, and systemic responses, which will lead to a better understanding of focal complications of brucellosis. PMID:28069819

Temporal Role for MyD88 in a Model of Brucella-Induced Arthritis and Musculoskeletal Inflammation.

PubMed

Lacey, Carolyn A; Mitchell, William J; Brown, Charles R; Skyberg, Jerod A

2017-03-01

Brucella spp. are facultative intracellular Gram-negative bacteria that cause the zoonotic disease brucellosis, one of the most common global zoonoses. Osteomyelitis, arthritis, and musculoskeletal inflammation are common focal complications of brucellosis in humans; however, wild-type (WT) mice infected systemically with conventional doses of Brucella do not develop these complications. Here we report C57BL/6 WT mice infected via the footpad with 10 3 to 10 6 CFU of Brucella spp. display neutrophil and monocyte infiltration of the joint space and surrounding musculoskeletal tissue. Joint inflammation is detectable as early as 1 day postinfection and peaks 1 to 2 weeks later, after which WT mice are able to slowly resolve inflammation. B and T cells were dispensable for the onset of swelling but required for resolution of joint inflammation and infection. At early time points, MyD88 -/- mice display decreased joint inflammation, swelling, and proinflammatory cytokine levels relative to WT mice. Subsequently, swelling of MyD88 -/- joints surpassed WT joint swelling, and resolution of joint inflammation was prolonged. Joint bacterial loads in MyD88 -/- mice were significantly greater than those in WT mice by day 3 postinfection and at all time points thereafter. In addition, MyD88 -/- joint inflammatory cytokine levels on day 3 and beyond were similar to WT levels. Collectively these data demonstrate MyD88 signaling mediates early inflammatory responses in the joint but also contributes to subsequent clearance of Brucella and resolution of inflammation. This work also establishes a mouse model for studying Brucella -induced arthritis, musculoskeletal complications, and systemic responses, which will lead to a better understanding of focal complications of brucellosis. Copyright © 2017 American Society for Microbiology.

Inflammation, Fracture and Bone Repair

PubMed Central

Loi, Florence; Córdova, Luis A.; Pajarinen, Jukka; Lin, Tzu-hua; Yao, Zhenyu; Goodman, Stuart B.

2016-01-01

The reconstitution of lost bone is a subject that is germane to many orthopaedic conditions including fractures and non-unions, infection, inflammatory arthritis, osteoporosis, osteonecrosis, metabolic bone disease, tumors, and periprosthetic particle-associated osteolysis. In this regard, the processes of acute and chronic inflammation play an integral role. Acute inflammation is initiated by endogenous or exogenous adverse stimuli, and can become chronic in nature if not resolved by normal homeostatic mechanisms. Dysregulated inflammation leads to increased bone resorption and suppressed bone formation. Crosstalk amongst inflammatory cells (polymorphonuclear leukocytes and cells of the monocyte-macrophage-osteoclast lineage) and cells related to bone healing (cells of the mesenchymal stem cell-osteoblast lineage and vascular lineage) is essential to the formation, repair and remodeling of bone. In this review, the authors provide a comprehensive summary of the literature related to inflammation and bone repair. Special emphasis is placed on the underlying cellular and molecular mechanisms, and potential interventions that can favorably modulate the outcome of clinical conditions that involve bone repair. PMID:26946132

Distribution of pericellular matrix molecules in the temporomandibular joint and their chondroprotective effects against inflammation

PubMed Central

Chu, Wern Cui; Zhang, Shipin; Sng, Timothy J; Ong, Yu Jie; Tan, Wen-Li; Ang, Vivien Y; Foldager, Casper B; Toh, Wei Seong

2017-01-01

The objectives of this study were to (1) determine the distribution and synthesis of pericellular matrix (PCM) molecules (collagen VI, collagen IV and laminin) in rat temporomandibular joint (TMJ) and (2) investigate the effects of PCM molecules on chondrocytes against inflammation in osteoarthritis. Four zones (fibrous, proliferating, mature and hypertrophic) of condylar cartilage and three bands (anterior, intermediate and posterior) of disc were analysed by immunohistochemistry for the presence of PCM molecules in rat TMJs. Isolated chondrocytes were pre-treated with PCM molecules before being subjected to interleukin (IL)-1β treatment to stimulate inflammation. The responses of the chondrocytes were analysed using gene expression, nitric oxide release and matrix metalloproteinase (MMP)-13 production measures. Histomorphometric analyses revealed that the highest areal deposition of collagen VI (67.4%), collagen IV (45.7%) and laminin (52.4%) was in the proliferating zone of TMJ condylar cartilage. No significant difference in the distribution of PCM molecules was noted among the three bands of the TMJ disc. All three PCM molecules were expressed intracellularly by chondrocytes cultured in the monolayer. Among the PCM molecules, pre-treatment with collagen VI enhanced cellular proliferation, ameliorated IL-1β-induced MMP-3, MMP-9, MMP-13 and inducible nitric oxide synthase gene expression, and attenuated the downregulation of cartilage matrix genes, including collagen I, aggrecan and cartilage oligomeric matrix protein (COMP). Concurrently, collagen VI pretreatment inhibited nitric oxide and MMP-13 production. Our study demonstrates for the first time the distribution and role of PCM molecules, particularly collagen VI, in the protection of chondrocytes against inflammation. PMID:28282029

Autophagy and kidney inflammation

PubMed Central

Kimura, Tomonori; Isaka, Yoshitaka; Yoshimori, Tamotsu

2017-01-01

ABSTRACT Inflammation plays a pivotal role in pathophysiological processes of kidney diseases. Macroautophagy/autophagy plays multiple roles in inflammatory responses, and the regulation of inflammation by autophagy has great potential as a treatment for damaged kidneys. A growing body of evidence suggests autophagy protects kidney from versatile kidney inflammatory insults, including those that are acute, chronic, metabolic, and aging-related. It is noteworthy that, in kidney, mitophagy is active, and damaged lysosomes are removed by autophagy. In this mode, autophagy suppresses inflammation to protect the kidney. Systemic inflammation also affects the kidney via pro-inflammatory cytokines and infiltration of inflammatory cells, and autophagy also has a regulatory role in systemic inflammation. This review focuses on the roles of autophagy in kidney diseases and aging through inflammation, and discusses the potential usage of autophagy as an inflammatory modulator for the treatment of kidney diseases. PMID:28441075

Monocyte and macrophage-targeted NADPH oxidase mediates antifungal host defense and regulation of acute inflammation in mice

PubMed Central

Grimm, Melissa J.; Vethanayagam, R. Robert; Almyroudis, Nikolaos G.; Dennis, Carly G.; Khan, A. Nazmul H.; D’Auria, Anthony; Singel, Kelly L.; Davidson, Bruce A.; Knight, Paul R.; Blackwell, Timothy S.; Hohl, Tobias M.; Mansour, Michael K.; Vyas, Jatin M.; Röhm, Marc; Urban, Constantin F.; Kelkka, Tiina; Holmdahl, Rikard; Segal, Brahm H.

2013-01-01

Chronic granulomatous disease, an inherited disorder of the NADPH oxidase in which phagocytes are defective in the generation of superoxide anion and downstream reactive oxidant species, is characterized by severe bacterial and fungal infections and excessive inflammation. Although NADPH oxidase isoforms exist in several lineages, reactive oxidant generation is greatest in neutrophils, where NADPH oxidase has been deemed vital for pathogen killing. In contrast, the function and importance of NADPH oxidase in macrophages are less clear. Therefore, we evaluated susceptibility to pulmonary aspergillosis in globally NADPH oxidase-deficient mice versus transgenic mice with monocyte/macrophage-targeted NADPH oxidase activity. We found that the lethal inoculum was more than 100-fold greater in transgenic versus globally NADPH oxidase-deficient mice. Consistent with these in vivo results, NADPH oxidase in mouse alveolar macrophages limited germination of phagocytosed Aspergillus fumigatus spores. Finally, globally NADPH oxidase-deficient mice developed exuberant neutrophilic lung inflammation and pro-inflammatory cytokine responses to zymosan, a fungal cell wall-derived product composed principally of particulate beta-glucans, whereas inflammation in transgenic and wildtype mice was mild and transient. Together, our studies identify a central role for monocyte/macrophage NADPH oxidase in controlling fungal infection and in limiting acute lung inflammation. PMID:23509361

Horizontal and Vertical Stabilization of Acute Unstable Acromioclavicular Joint Injuries Arthroscopy-Assisted

PubMed Central

Cisneros, Luis Natera; Sarasquete Reiriz, Juan; Besalduch, Marina; Petrica, Alexandru; Escolà, Ana; Rodriguez, Joaquim; Fallone, Jan Carlo

2015-01-01

We describe the technical aspects of an arthroscopy-assisted procedure indicated for the management of acute unstable acromioclavicular joint injuries, consisting of a synthetic augmentation of both the coracoclavicular and acromioclavicular ligaments, that anatomically reproduces the coracoclavicular biomechanics and offers fixation that keeps the torn ends of the ligaments facing one another, thus allowing healing of the native structures without the need for a second surgical procedure for metal hardware removal. PMID:26870653

The effect of interleukins 27 and 35 and their role on mediating the action of insulin Like Growth Factor -1 on the inflammation and blood flow of chronically inflamed rat knee joint.

PubMed

Houshmandi, Nasrin; Najafipour, Hamid; Joukar, Siyavash; Dabiri, Shahriar; Abbasloo, Elham; Abdi, Elham; Safi, Zohreh

2016-05-01

Previous studies have shown that some cytokines mediate the effect of IGF-1 on inflammation and also association between IGF-1 and vascular endothelial dysfunction. Due to the discrepancies in the inflammatory and anti-inflammatory roles of IL-27 and IL-35, the effects of these cytokines and their IGF-1-mediating role were investigated regarding chronic joint inflammation and synovial blood flow. Male rats were divided into two main groups of histopathology (n=80) and blood flow (n=72). These were further divided into ten subgroups of control, vehicle, IGF-1, IL-27, IL-35, their antagonists, IGF-1+IL-27 antagonist, and IGF-1+IL-35 antagonist. Inflammation was induced by intra-articular injection of complete Freund adjuvant. Two weeks later (in order to induce chronic inflammation), vehicle or drugs were injected into the joint space every other day until day 28, on which inflammatory indices were assessed histopathologically. In the second subgroups, vehicle or drugs were administered by super-fusion on day 28 and their effects on the joint blood flow (JBF, laser Doppler perfusion method) and the systemic blood pressure were assessed. Endogenous IL-27 and IL-35 had inflammatory roles and IGF-1 had no effect. IL-27 and IL-35 antagonists had the highest anti-inflammatory and anti-angiogenesis effects and these effects were inhibited by IGF-1. Total inflammation score was 4.5 ± 0.42, 3.50 ± 0.5, 2.25 ± 0.45 and 1.50 ± 0.42 for vehicle, IGF-1 antagonist, IL-27 antagonist and IL-35 antagonist respectively. A significant increase was induced in JBF by IGF-1 antagonist and combination of IGF-1+IL-35 antagonist. IL-27 and IL-35 antagonists may be suitable goals for the treatment of chronic joint inflammation while their anti-inflammatory effects are not exerted via the changes in JBF. Copyright © 2016 Elsevier Ltd. All rights reserved.

Protocatechuic Aldehyde Attenuates Cisplatin-Induced Acute Kidney Injury by Suppressing Nox-Mediated Oxidative Stress and Renal Inflammation

PubMed Central

Gao, Li; Wu, Wei-Feng; Dong, Lei; Ren, Gui-Ling; Li, Hai-Di; Yang, Qin; Li, Xiao-Feng; Xu, Tao; Li, Zeng; Wu, Bao-Ming; Ma, Tao-Tao; Huang, Cheng; Huang, Yan; Zhang, Lei; Lv, Xiongwen; Li, Jun; Meng, Xiao-Ming

2016-01-01

Cisplatin is a classic chemotherapeutic agent widely used to treat different types of cancers including ovarian, head and neck, testicular and uterine cervical carcinomas. However, cisplatin induces acute kidney injury by directly triggering an excessive inflammatory response, oxidative stress, and programmed cell death of renal tubular epithelial cells, all of which lead to high mortality rates in patients. In this study, we examined the protective effect of protocatechuic aldehyde (PA) in vitro in cisplatin-treated tubular epithelial cells and in vivo in cisplatin nephropathy. PA is a monomer of Traditional Chinese Medicine isolated from the root of S. miltiorrhiza (Lamiaceae). Results show that PA prevented cisplatin-induced decline of renal function and histological damage, which was confirmed by attenuation of KIM1 in both mRNA and protein levels. Moreover, PA reduced renal inflammation by suppressing oxidative stress and programmed cell death in response to cisplatin, which was further evidenced by in vitro data. Of note, PA suppressed NAPDH oxidases, including Nox2 and Nox4, in a dosage-dependent manner. Moreover, silencing Nox4, but not Nox2, removed the inhibitory effect of PA on cisplatin-induced renal injury, indicating that Nox4 may play a pivotal role in mediating the protective effect of PA in cisplatin-induced acute kidney injury. Collectively, our data indicate that PA blocks cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation without compromising anti-tumor activity of cisplatin. These findings suggest that PA and its derivatives may serve as potential protective agents for cancer patients receiving cisplatin treatment. PMID:27999546

Oxidative stress, inflammation, and DNA damage in multiple organs of mice acutely exposed to amorphous silica nanoparticles.

PubMed

Nemmar, Abderrahim; Yuvaraju, Priya; Beegam, Sumaya; Yasin, Javed; Kazzam, Elsadig E; Ali, Badreldin H

2016-01-01

The use of amorphous silica (SiO2) in biopharmaceutical and industrial fields can lead to human exposure by injection, skin penetration, ingestion, or inhalation. However, the in vivo acute toxicity of amorphous SiO2 nanoparticles (SiNPs) on multiple organs and the mechanisms underlying these effects are not well understood. Presently, we investigated the acute (24 hours) effects of intraperitoneally administered 50 nm SiNPs (0.25 mg/kg) on systemic toxicity, oxidative stress, inflammation, and DNA damage in the lung, heart, liver, kidney, and brain of mice. Lipid peroxidation was significantly increased by SiNPs in the lung, liver, kidney, and brain, but was not changed in the heart. Similarly, superoxide dismutase and catalase activities were significantly affected by SiNPs in all organs studied. While the concentration of tumor necrosis factor α was insignificantly increased in the liver and brain, its increase was statistically significant in the lung, heart, and kidney. SiNPs induced a significant elevation in pulmonary and renal interleukin 6 and interleukin-1 beta in the lung, liver, and brain. Moreover, SiNPs caused a significant increase in DNA damage, assessed by comet assay, in all the organs studied. SiNPs caused leukocytosis and increased the plasma activities of lactate dehydrogenase, creatine kinase, alanine aminotranferase, and aspartate aminotransferase. These results indicate that acute systemic exposure to SiNPs causes oxidative stress, inflammation, and DNA damage in several major organs, and highlight the need for thorough evaluation of SiNPs before they can be safely used in human beings.

Plasmacytoid Dendritic Cells Die by the CD8 T Cell-Dependent Perforin Pathway during Acute Nonviral Inflammation.

PubMed

Mossu, Adrien; Daoui, Anna; Bonnefoy, Francis; Aubergeon, Lucie; Saas, Philippe; Perruche, Sylvain

2016-09-01

Regulation of the inflammatory response involves the control of dendritic cell survival. To our knowledge, nothing is known about the survival of plasmacytoid dendritic cells (pDC) in such situation. pDC are specialized in type I IFN (IFN-I) secretion to control viral infections, and IFN-I also negatively regulate pDC survival during the course of viral infections. In this study, we asked about pDC behavior in the setting of virus-free inflammation. We report that pDC survival was profoundly reduced during different nonviral inflammatory situations in the mouse, through a mechanism independent of IFN-I and TLR signaling. Indeed, we demonstrated that during inflammation, CD8(+) T cells induced pDC apoptosis through the perforin pathway. The data suggest, therefore, that pDC have to be turned down during ongoing acute inflammation to not initiate autoimmunity. Manipulating CD8(+) T cell response may therefore represent a new therapeutic opportunity for the treatment of pDC-associated autoimmune diseases, such as lupus or psoriasis. Copyright © 2016 by The American Association of Immunologists, Inc.

Anatomy of a Joint: Comparing Self-Reported and Actual Dose of Cannabis and Tobacco in a Joint, and How These Are Influenced by Controlled Acute Administration

PubMed Central

Hindocha, Chandni; Freeman, Tom P.; Curran, H. Valerie

2017-01-01

Abstract Introduction: Major gaps exist in the measurement of cannabis exposure. The accuracy of self-reported cannabis and tobacco dose per joint is poorly characterized and has never been investigated following acute cannabis/tobacco exposure. Using an innovative “Roll a Joint” paradigm, this study aims to (1) compare estimated and actual dose of cannabis and tobacco per joint at baseline and (2) examine the acute effects of cannabis and/or tobacco on estimated and actual dose. Materials and Methods: We investigated this by using a randomized, double-blind, placebo-controlled crossover 2 (active cannabis, placebo cannabis)×2 (active tobacco, placebo tobacco) design in a laboratory setting. Participants were 24 recreational cousers of cannabis and tobacco. At baseline, they were asked to measure out the amount of cannabis and tobacco they would put in an average joint for themselves (dose per joint). Then, on each of four drug administration sessions, participants were again asked to do this for a joint they would want to smoke “right now.” Self-reported and actual amount was recorded (g). Results: At baseline, the estimated amount of cannabis per joint (0.28±0.23 g) was double the actual amount (0.14±0.12 g) (p=0.003, d=0.723). No difference emerged between estimated (0.43±0.25 g) and actual (0.35±0.15 g) (p=0.125) amount of tobacco per joint. Compared to placebo, active cannabis reduced the actual dose of both cannabis (p=0.035) and tobacco (p<0.001) they put in a joint. Participants accurately estimated this reduction for tobacco (p=0.014), but not for cannabis (p=0.680). Conclusions: Self-reported dose per joint is accurate for tobacco but dramatically overestimates cannabis exposure and therefore should be viewed with caution. Cannabis administration reduced the amount of cannabis and tobacco added to joints, suggesting a reduction in dose during a smoking session. The “Roll A Joint” paradigm should be implemented for better accuracy

Evaluation of the novel avocado/soybean unsaponifiable Arthrocen to alter joint pain and inflammation in a rat model of osteoarthritis.

PubMed

Goudarzi, Ramin; Reid, Allison; McDougall, Jason J

2018-01-01

Avocado/soybean unsaponifiables such as Arthrocen have been reported to reduce cartilage catabolism and chondrocytic synthesis of inflammatory mediators associated with osteoarthritis (OA). While there is some clinical evidence that avocado/soybean unsaponifiables can reduce OA pain, no preclinical studies have corroborated this observation. The present study determined whether addition of an avocado/soybean unsaponifiable (Arthrocen) to the drinking water of OA rats reduced direct and referred joint pain. OA was induced in male Wistar rats by intra-articular injection of sodium monoiodoacetate (MIA: 0.3mg) and animals were allowed to recover for 14 days. Arthrocen was added to the drinking water which was available to animals ad libitum. On day 30, joint pain was assessed by dynamic incapacitance while referred pain was determined by von Frey hair algesiometry. The joint damage induced by MIA injection was severe and was consistent with end-stage OA. Arthrocen consumption (approximately 35 mg/day) attenuated the joint oedema associated with MIA injection. Hindlimb weight bearing also significantly improved in Arthrocen-treated rats (P<0.05); however, von Frey hair mechanosensitivity was unaffected by this treatment. These data indicate that Arthrocen has the potential to reduce joint inflammation and pain associated with end-stage OA.

Evaluation of the novel avocado/soybean unsaponifiable Arthrocen to alter joint pain and inflammation in a rat model of osteoarthritis

PubMed Central

Goudarzi, Ramin; Reid, Allison

2018-01-01

Background Avocado/soybean unsaponifiables such as Arthrocen have been reported to reduce cartilage catabolism and chondrocytic synthesis of inflammatory mediators associated with osteoarthritis (OA). While there is some clinical evidence that avocado/soybean unsaponifiables can reduce OA pain, no preclinical studies have corroborated this observation. The present study determined whether addition of an avocado/soybean unsaponifiable (Arthrocen) to the drinking water of OA rats reduced direct and referred joint pain. Methods OA was induced in male Wistar rats by intra-articular injection of sodium monoiodoacetate (MIA: 0.3mg) and animals were allowed to recover for 14 days. Arthrocen was added to the drinking water which was available to animals ad libitum. On day 30, joint pain was assessed by dynamic incapacitance while referred pain was determined by von Frey hair algesiometry. Results The joint damage induced by MIA injection was severe and was consistent with end-stage OA. Arthrocen consumption (approximately 35 mg/day) attenuated the joint oedema associated with MIA injection. Hindlimb weight bearing also significantly improved in Arthrocen-treated rats (P<0.05); however, von Frey hair mechanosensitivity was unaffected by this treatment. Conclusions These data indicate that Arthrocen has the potential to reduce joint inflammation and pain associated with end-stage OA. PMID:29489828

Acute Respiratory Inflammation in Children and Black Carbon in Ambient Air before and during the 2008 Beijing Olympics

PubMed Central

Lin, Weiwei; Huang, Wei; Hu, Min; Brunekreef, Bert; Zhang, Yuanhang; Liu, Xingang; Cheng, Hong; Gehring, Ulrike; Li, Chengcai; Tang, Xiaoyan

2011-01-01

Background: Epidemiologic evidence for a causative association between black carbon (BC) and health outcomes is limited. Objectives: We estimated associations and exposure–response relationships between acute respiratory inflammation in schoolchildren and concentrations of BC and particulate matter with an aerodynamic diameter of ≤ 2.5 μm (PM2.5) in ambient air before and during the air pollution intervention for the 2008 Beijing Olympics. Methods: We measured exhaled nitric oxide (eNO) as an acute respiratory inflammation biomarker and hourly mean air pollutant concentrations to estimate BC and PM2.5 exposure. We used 1,581 valid observations of 36 subjects over five visits in 2 years to estimate associations of eNO with BC and PM2.5 according to generalized estimating equations with polynomial distributed-lag models, controlling for body mass index, asthma, temperature, and relative humidity. We also assessed the relative importance of BC and PM2.5 with two-pollutant models. Results: Air pollution concentrations and eNO were clearly lower during the 2008 Olympics. BC and PM2.5 concentrations averaged over 0–24 hr were strongly associated with eNO, which increased by 16.6% [95% confidence interval (CI), 14.1–19.2%] and 18.7% (95% CI, 15.0–22.5%) per interquartile range (IQR) increase in BC (4.0 μg/m3) and PM2.5 (149 μg/m3), respectively. In the two-pollutant model, estimated effects of BC were robust, but associations between PM2.5 and eNO decreased with adjustment for BC. We found that eNO was associated with IQR increases in hourly BC concentrations up to 10 hr after exposure, consistent with effects primarily in the first hours after exposure. Conclusions: Recent exposure to BC was associated with acute respiratory inflammation in schoolchildren in Beijing. Lower air pollution levels during the 2008 Olympics also were associated with reduced eNO. PMID:21642045

Acute respiratory changes and pulmonary inflammation involving a pathway of TGF-β1 induction in a rat model of chlorine-induced lung injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wigenstam, Elisabeth; Elfsmark, Linda; Koch, Bo

We investigated acute and delayed respiratory changes after inhalation exposure to chlorine (Cl{sub 2}) with the aim to understand the pathogenesis of the long-term sequelae of Cl{sub 2}-induced lung-injury. In a rat model of nose-only exposure we analyzed changes in airway hyperresponsiveness (AHR), inflammatory responses in airways, expression of pro-inflammatory markers and development of lung fibrosis during a time-course from 5 h up to 90 days after a single inhalation of Cl{sub 2}. A single dose of dexamethasone (10 mg/kg) was administered 1 h following Cl{sub 2}-exposure. A 15-min inhalation of 200 ppm Cl{sub 2} was non-lethal in Sprague-Dawley rats.more » At 24 h post exposure, Cl{sub 2}-exposed rats displayed elevated numbers of leukocytes with an increase of neutrophils and eosinophils in bronchoalveolar lavage (BAL) and edema was shown both in lung tissue and the heart. At 24 h, the inflammasome-associated cytokines IL-1β and IL-18 were detected in BAL. Concomitant with the acute inflammation a significant AHR was detected. At the later time-points, a delayed inflammatory response was observed together with signs of lung fibrosis as indicated by increased pulmonary macrophages, elevated TGF-β expression in BAL and collagen deposition around airways. Dexamethasone reduced the numbers of neutrophils in BAL at 24 h but did not influence the AHR. Inhalation of Cl{sub 2} in rats leads to acute respiratory and cardiac changes as well as pulmonary inflammation involving induction of TGF-β1. The acute inflammatory response was followed by sustained macrophage response and lack of tissue repair. It was also found that pathways apart from the acute inflammatory response contribute to the Cl{sub 2}-induced respiratory dysfunction. - Highlights: • Inhalation of Cl{sub 2} leads to acute lung inflammation and airway hyperreactivity. • Cl{sub 2} activates an inflammasome pathway of TGF-β induction. • Cl{sub 2} leads to a fibrotic respiratory disease. �

Effect of tumour necrosis factor-α receptor 1 genetic deletion on carrageenan-induced acute inflammation: a comparison with etanercept

PubMed Central

Mazzon, E; Esposito, E; Di Paola, R; Muià, C; Crisafulli, C; Genovese, T; Caminiti, R; Meli, R; Bramanti, P; Cuzzocrea, S

2008-01-01

In the present study, we used tumour necrosis factor-α receptor 1 knock-out mice (TNF-αR1KO) to evaluate an in vivo role of TNF-αR1 on the pathogenesis of inflammatory diseases. We used a murine model of carrageenan-induced acute inflammation (pleurisy), a preclinical model of airway inflammation. The data proved that TNF-αR1KO were resistant to carrageenan-induced acute inflammation compared with TNF-α wild-type mice. TNF-αR1KO showed a significant reduction in accumulation of pleural exudate and in the number of inflammatory cells, in lung infiltration of polymorphonuclear leucocytes and lipid peroxidation and showed a decreased production of nitrite/nitrate in pleural exudates. Furthermore, the intensity and degree of the adhesion molecule intercellular adhesion molecule-1 and P-selectin, Fas ligand (FasL), inducible nitric oxide sythase and nitrotyrosine determined by immunohistochemical analysis were reduced markedly in lung tissues from TNF-αR1KO at 4 h and 24 h after carrageenan injection. Moreover, TNF-α and interleukin-1β concentrations were reduced in inflamed areas and in pleural exudates from TNF-αR1KO. To support the results generated using pleural inflammation, carrageenan-induced paw oedema models were also performed. In order to elucidate whether the observed anti-inflammatory effects were related to the inhibition of TNF-α, we also investigated the effect of etanercept, a TNF-α soluble receptor construct, on carrageenan-induced pleurisy. The treatment with etanercept (5 mg/kg subcutaneously 2 h before the carrageenan injection) reduces markedly both laboratory and histological signs of carrageenan-induced pleurisy. Our results showed that administration of etanercept resulted in the same outcome as that of deletion of the TNF-αR1 receptor, adding a new insight to TNF-α as an excellent target by therapeutic applications. PMID:18505433

Arthroscopic fixation of acute acromioclavicular joint disruption with TightRope™: Outcome and complications after minimum 2 (2-5) years follow-up.

PubMed

Zhang, Li-Feng; Yin, Bo; Hou, Su; Han, Bing; Huang, De-Fa

2017-01-01

To evaluate the midterm results of arthroscopic reconstruction of acute acromioclavicular (AC) joint disruption using TightRope™ system. We retrospectively assess the results of 24 patients of acute AC joint dislocation who were operated using TightRope system. Constant and University of California, Los Angeles (UCLA) scores and coracoclavicular distance were calculated pre- and postoperatively. Data was entered into MS excel and analyzed using the SPSS version 17. The mean follow-up was 39.45 months. Constant and UCLA scores were significantly increased postoperatively. Six patients had partial loss of reduction within 3-6 months and two patients had a failure of construct. Constant score was significantly lower in these patients. TightRope reconstruction of the AC joint is a reproducible and safe alternative to many other techniques of AC joint reconstruction. Early subluxation remains a concern and may reflect the need for technique modification.

Genetic sphingosine kinase 1 deficiency significantly decreases synovial inflammation and joint erosions in murine TNF-alpha-induced arthritis.

PubMed

Baker, DeAnna A; Barth, Jeremy; Chang, Raymond; Obeid, Lina M; Gilkeson, Gary S

2010-08-15

Sphingosine kinase 1 (SphK1) is an enzyme that converts sphingosine to bioactive sphingosine-1-phosphate. Recent in vitro data suggest a potential role of SphK1 in TNF-alpha-mediated inflammation. Our aims in this study were to determine the in vivo significance of SphK1 in TNF-alpha-mediated chronic inflammation and to define which pathogenic mechanisms induced by TNF-alpha are SphK1 dependent. To pursue these aims, we studied the effect of SphK1 deficiency in an in vivo model of TNF-alpha-induced chronic inflammatory arthritis. Transgenic hTNF-alpha mice, which develop spontaneous inflammatory erosive arthritis beginning at 14-16 wk, were crossed with SphK1 null mice (SphK1(-/-)), on the C57BL6 genetic background. Beginning at 4 mo of age, hTNF/SphK1(-/-) mice had significantly less severe clinically evident paw swelling and deformity, less synovial and periarticular inflammation, and markedly decreased bone erosions as measured quantitatively through micro-CT images. Mechanistically, the mice lacking SphK1 had less articular cyclooxygenase 2 protein and fewer synovial Th17 cells than did hTNF/SphK1(+/+) littermates. Microarray analysis and real-time RT-PCR of the ankle synovial tissue demonstrated that hTNF/SphK1(-/-) mice had increased transcript levels of suppressor of cytokine signaling 3 compared with hTNF/SphK1(+/+) mice, likely also contributing to the decreased inflammation in the SphK1-deficient mice. Finally, significantly fewer mature osteoclasts were detected in the ankle joints of hTNF/SphK1(-/-) mice compared with hTNF/SphK1(+/+) mice. These data indicate that SphK1 plays a key role in hTNF-alpha-induced inflammatory arthritis via impacting synovial inflammation and osteoclast number.

IL-1β mediating high mobility group box protein-1 expression in condylar chondrocyte during temporomandibular joint inflammation.

PubMed

Li, Cheng; Cai, Hengxing; Meng, Qinggong; Feng, Yaping; Guo, Huilin; Fang, Wei; Long, Xing

2016-08-01

Temporomandibular joint (TMJ) osteoarthritis(OA)characterized with cartilage degen-eration is associated with inflammation. High mobility group box chromosomal protein-1(HMGB-1)is a potent mediator of inflammation and the trigger of OA. The expression of HMGB-1 in TMJ OA was uncovered, but the role of HMGB-1 in TMJ cartilage degeneration is not fully understood. In this study, the regulation of HMGB-1 in TMJ condylar cartilage was revealed. A complete Freund's adjuvant (CFA)-induced TMJ inflammation animal model was employed and the expression of HMGB-1 was detected at 1st, 2nd, and 6th weeks by immunohistochemistry. TMJ condylar chondrocytes were incubated with IL-1β (10 and 40 ng/ml) at 24, 48, and 72 h, and the translocation and protein level of HMGB-1 were evaluated by immunofluorescence and Western blot. Nuclear HMGB-1 staining was predominantly located in chondrocytes of both the fibrosis and proliferative zones in healthy TMJ. 1st week and 2nd week after CFA injection, immunoreaction could be detected in the cytoplasms of HMGB-1-positive cells and cartilage matrix especially in hypertrophic zone. At 6th week after CFA injection, cartilage matrix expression was disappeared and the cytoplasm expression of HMGB-1 was very weak in hypertrophic zone. HMGB-1 was translocated from the nucleus to the cytoplasm at 48 h after incubated with IL-1β (10 ng/ml and 40 ng/ml). The protein level of HMGB-1 was increased after stimulation and had a peak at 48 h. HMGB-1 might be associated with TMJ inflammation and OA. Insight into the role of HMGB-1 in TMJ inflammation is helpful to add the new knowledge into the pathogenesis of TMJ OA. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cryoglobulin-induced inflammation.

PubMed

Denko, C W

1985-10-01

Inflammation of the rat footpad followed injection of cryoglobulin in crystalline form (Type I) and injection of cryoglobulin in solution (Type II). Rats deficient in essential fatty acids responded with diminished swelling which corrected to normal levels by addition of prostaglandin E1 suggesting that this reaction is prostaglandin mediated. Addition of bradykinin produced no effect. Aggregated cryoglobulin proved more inflammogenic than non-aggregated cryoglobulin. Pre-treatment with choline salicylate and colchicine reduced swelling while pre-treatment with dipyridamole increased edema following cryoglobulin inoculation. Cryoglobulin is considered to be an acute phase reactant in inflammation.

The pathology of acute appendicitis.

PubMed

Carr, N J

2000-02-01

Although acute appendicitis is frequent, it is subject to common misconceptions. Furthermore, there is little good evidence to support some of our beliefs. This report reviews the role of the anatomic pathologist in diagnosis when acute appendicitis is suspected clinically and discusses what is known of its pathology. The conclusions that can be legitimately drawn from the literature are emphasized. A classification is proposed that incorporates intraluminal inflammation, acute mucosal inflammation, acute mucosal and submucosal inflammation, suppurative (phlegmonous) appendicitis, gangrenous appendicitis, and periappendicitis, and the significance of each of these diagnoses is discussed. The etiology and pathogenesis of acute appendicitis is reviewed. Contrary to popular belief, the best evidence indicates that obstruction is unlikely to be the primary cause, at least in the majority of cases. Ancillary techniques in the diagnosis of appendicitis, including laparoscopy and peritoneal aspiration cytology, are discussed.

Clinical Effect of Acute Complete Acromioclavicular Joint Dislocation Treated with Micro-Movable and Anatomical Acromioclavicular Plate

PubMed Central

Liu, Qingjun; Miao, Jianyun; Lin, Bin; Guo, Zhimin

2012-01-01

Objectives: We evaluated the long-term clinical results of acute complete acromioclavicular dislocations treated with micro-movable and anatomical acromioclavicular plate. Methods: Open reduction and internal fixation was performed using the MAAP in 16 patients (10 males, 6 females; mean age 36 years; range16 to 63 years) with acute complete acromioclavicular joint dislocation. Radiographic evaluations were routinely conducted every 3 weeks until 3 months postoperatively. The MAAP were removed under local anesthesia after 3 months postoperatively. We evaluated the functional results by using the constant scoring system and radiological results in the last follow-up time. The mean follow up was 26 months (range 16 to 38 months). Results: The mean Constant score was 94 (range, 78 to 100). The results were excellent in 12 patients (75.0%), good in 3 patients (18.8%) and satisfactory in 1patient (6.2%). Three patients with scores of 80 to 90 had mild pain during activity, but have not affected the shoulder range of motion. One patient has both some pain and limited range of motion of shoulder joint. All patients but one have returned to their preoperative work without any limitations. Compared to the contralateral side, radiography showed anatomical reposition in the vertical plane in 14 cases, slight loss of reduction in 2 older patients. Conclusion: We recommend the MAAP fixation for surgical treatment of acute complete acromioclavicular joint dislocation as it could provide satisfactory shoulder functions and clinical results, with lower complication rate. However, it is necessary to continue to observe the clinical effects of this fixation technique. PMID:23091410

Pain related inflammation analysis using infrared images

NASA Astrophysics Data System (ADS)

Bhowmik, Mrinal Kanti; Bardhan, Shawli; Das, Kakali; Bhattacharjee, Debotosh; Nath, Satyabrata

2016-05-01

Medical Infrared Thermography (MIT) offers a potential non-invasive, non-contact and radiation free imaging modality for assessment of abnormal inflammation having pain in the human body. The assessment of inflammation mainly depends on the emission of heat from the skin surface. Arthritis is a disease of joint damage that generates inflammation in one or more anatomical joints of the body. Osteoarthritis (OA) is the most frequent appearing form of arthritis, and rheumatoid arthritis (RA) is the most threatening form of them. In this study, the inflammatory analysis has been performed on the infrared images of patients suffering from RA and OA. For the analysis, a dataset of 30 bilateral knee thermograms has been captured from the patient of RA and OA by following a thermogram acquisition standard. The thermograms are pre-processed, and areas of interest are extracted for further processing. The investigation of the spread of inflammation is performed along with the statistical analysis of the pre-processed thermograms. The objectives of the study include: i) Generation of a novel thermogram acquisition standard for inflammatory pain disease ii) Analysis of the spread of the inflammation related to RA and OA using K-means clustering. iii) First and second order statistical analysis of pre-processed thermograms. The conclusion reflects that, in most of the cases, RA oriented inflammation affects bilateral knees whereas inflammation related to OA present in the unilateral knee. Also due to the spread of inflammation in OA, contralateral asymmetries are detected through the statistical analysis.

Low level laser therapy reduces acute lung inflammation without impairing lung function.

PubMed

Cury, Vivian; de Lima, Thais Martins; Prado, Carla Maximo; Pinheiro, Nathalia; Ariga, Suely K K; Barbeiro, Denise F; Moretti, Ana I; Souza, Heraldo P

2016-12-01

Acute lung injury is a condition characterized by exacerbate inflammatory reaction in distal airways and lung dysfunction. Here we investigate the treatment of acute lung injury (ALI) by low level laser therapy (LLLT), an effective therapy used for the treatment of patients with inflammatory disorders or traumatic injuries, due to its ability to reduce inflammation and promote tissue regeneration. However, studies in internal viscera remains unclear. C57BL/6 mice were treated with intratracheal lipopolysaccharide (LPS) (5 mg/kg) or phosphate buffer saline (PBS). Six hours after instillation, two groups were irradiated with laser at 660 nm and radiant exposure of 10 J/cm 2 . Intratracheal LPS inoculation induced a marked increase in the number of inflammatory cells in perivascular and alveolar spaces. There was also an increase in the expression and secretion of cytokines (TNF-α, IL-1β, IL-6,) and chemokine (MCP-1). The LLLT application induced a significant decrease in both inflammatory cells influx and inflammatory mediators secretion. These effects did not affect lung mechanical properties, since no change was observed in tissue resistance or elastance. In conclusion LLLT is able to reduce inflammatory reaction in lungs exposed to LPS without affecting the pulmonary function and recovery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Scintigraphy of sacroliac joints in acute anterior uveitis. A study of thirty patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russell, A.S.; Lentle, B.C.; Percy, J.S.

1976-11-01

HLA-B27 is a transplantation antigen found in a high proportion of patients with ankylosing spondylitis. Recently, an association has been shown to exist between HLA-B27 and acute uveitis, even in the absence of ankylosing spondylitis. We have examined the HLA antigen profile of 45 patients with acute nongranulomatous anterior uveitis and have confirmed this relation. In addition, using 90m technetium stannous pyrophosphate we have been able to demonstrate abnormal bone scan in 19 of 30 patients studied. Such abnormalities are limited to the sacroiliac joints but are otherwise the same as those seen in overt ankylosing spondylitis. Seven of themore » 19 patients did not have HLA-B27. These factors suggest that acute anterior uveitis may often represent a manifestation of a spondylitic diathesis even in the complete absence of any suggestive symptomatic or radiologic change and, in some cases, even through the antigenic marker HLA-B27 may be absent.« less

Scintigraphy of sacroiliac joints in acute anterior uveitis. A study of thirty patients.

PubMed

Russell, A S; Lentle, B C; Percy, J S; Jackson, F I

1976-11-01

HLA-B27 is a transplantation antigen found in a high proportion of patients with ankylosing spondylitis. Recently, an association has been shown to exist between HLA-B27 and acute uveitis, even in the absence of ankylosing spondylitis. We have examined the HLA antigen profile of 45 patients with acute nongranulomatous anterior uveitis and have confirmed this relation. In addition, using 90mtechnetium stannous pyrophosphate we have been able to demonstrate abnormal bone scan in 19 of 30 patients studied. Such abnormalities are limited to the sacroiliac joints but are otherwise the same as those seen in overt ankylosing spondylitis. Seven of the 19 patients did not have HLA-B27. These factors suggest that acute anterior uveitis may often represent a manifestation of a spondylitic diathesis even in the complete absence of any suggestive symptomatic or radiologic change and, in some cases, even though the antigenic marker HLA-B27 may be absent.

Evolutionary medicine and bone loss in chronic inflammatory diseases--A theory of inflammation-related osteopenia.

PubMed

Straub, Rainer H; Cutolo, Maurizio; Pacifici, Roberto

2015-10-01

Bone loss is typical in chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, pemphigus vulgaris, and others. It is also typical in transplantation-related inflammation and during the process of aging. While we recognized that bone loss is tightly linked to immune system activation or inflamm-aging in the form of acute, chronic active, or chronic smoldering inflammation, bone loss is typically discussed to be an "accident of inflammation." Extensive literature search in PubMed central. Using elements of evolutionary medicine, energy regulation, and neuroendocrine regulation of homeostasis and immune function, we work out that bone waste is an adaptive, evolutionarily positively selected program that is absolutely necessary during acute inflammation. However, when acute inflammation enters a chronic state due to the inability to terminate inflammation (e.g., in autoimmunity or in continuous immunity against microbes), the acute program of bone loss is a misguided adaptive program. The article highlights the complexity of interwoven pathways of osteopenia. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Label-free monitoring of inflammatory tissue conditions using a carrageenan-induced acute inflammation rat model.

PubMed

Lee, Seung Ho; Lee, Sang Hwa; Shin, Jae-Ho; Choi, Samjin

2018-06-01

Although the confirmation of inflammatory changes within tissues at the onset of various diseases is critical for the early detection of disease and selection of appropriate treatment, most therapies are based on complex and time-consuming diagnostic procedures. Raman spectroscopy has the ability to provide non-invasive, real-time, chemical bonding analysis through the inelastic scattering of photons. In this study, we evaluate the feasibility of Raman spectroscopy as a new, easy, fast, and accurate diagnostic method to support diagnostic decisions. The molecular changes in carrageenan-induced acute inflammation rat tissues were assessed by Raman spectroscopy. Volumes of 0 (control), 100, 150, and 200 µL of 1% carrageenan were administered to rat hind paws to control the degree of inflammation. The prominent peaks at [1,062, 1,131] cm -1 and [2,847, 2,881] cm -1 were selected as characteristic measurements corresponding to the C-C stretching vibrational modes and the symmetric and asymmetric C-H (CH 2 ) stretching vibrational modes, respectively. Principal component analysis of the inflammatory Raman spectra enabled graphical representation of the degree of inflammation through principal component loading profiles of inflammatory tissues on a two-dimensional plot. Therefore, Raman spectroscopy with multivariate statistical analysis represents a promising method for detecting biomolecular responses based on different types of inflammatory tissues. © 2018 Wiley Periodicals, Inc.

Exposure to traffic pollution, acute inflammation and autonomic response in a panel of car commuters.

PubMed

Sarnat, Jeremy A; Golan, Rachel; Greenwald, Roby; Raysoni, Amit U; Kewada, Priya; Winquist, Andrea; Sarnat, Stefanie E; Dana Flanders, W; Mirabelli, Maria C; Zora, Jennifer E; Bergin, Michael H; Yip, Fuyuen

2014-08-01

Exposure to traffic pollution has been linked to numerous adverse health endpoints. Despite this, limited data examining traffic exposures during realistic commutes and acute response exists. We conducted the Atlanta Commuters Exposures (ACE-1) Study, an extensive panel-based exposure and health study, to measure chemically-resolved in-vehicle exposures and corresponding changes in acute oxidative stress, lipid peroxidation, pulmonary and systemic inflammation and autonomic response. We recruited 42 adults (21 with and 21 without asthma) to conduct two 2-h scripted highway commutes during morning rush hour in the metropolitan Atlanta area. A suite of in-vehicle particulate components were measured in the subjects' private vehicles. Biomarker measurements were conducted before, during, and immediately after the commutes and in 3 hourly intervals after commutes. At measurement time points within 3h after the commute, we observed mild to pronounced elevations relative to baseline in exhaled nitric oxide, C-reactive-protein, and exhaled malondialdehyde, indicative of pulmonary and systemic inflammation and oxidative stress initiation, as well as decreases relative to baseline levels in the time-domain heart-rate variability parameters, SDNN and rMSSD, indicative of autonomic dysfunction. We did not observe any detectable changes in lung function measurements (FEV1, FVC), the frequency-domain heart-rate variability parameter or other systemic biomarkers of vascular injury. Water soluble organic carbon was associated with changes in eNO at all post-commute time-points (p<0.0001). Our results point to measureable changes in pulmonary and autonomic biomarkers following a scripted 2-h highway commute. Copyright © 2014 Elsevier Inc. All rights reserved.

Exposure to traffic pollution, acute inflammation and autonomic response in a panel of car commuters

PubMed Central

Sarnat, Jeremy A.; Golan, Rachel; Greenwald, Roby; Raysoni, Amit U.; Kewada, Priya; Winquist, Andrea; Sarnat, Stefanie E.; Flanders, W. Dana; Mirabelli, Maria C.; Zora, Jennifer E.; Bergin, Michael H.; Yip, Fuyuen

2015-01-01

Background Exposure to traffic pollution has been linked to numerous adverse health endpoints. Despite this, limited data examining traffic exposures during realistic commutes and acute response exists. Objectives: We conducted the Atlanta Commuters Exposures (ACE-1) Study, an extensive panel-based exposure and health study, to measure chemically-resolved in-vehicle exposures and corresponding changes in acute oxidative stress, lipid peroxidation, pulmonary and systemic inflammation and autonomic response. Methods We recruited 42 adults (21 with and 21 without asthma) to conduct two 2-h scripted highway commutes during morning rush hour in the metropolitan Atlanta area. A suite of in-vehicle particulate components were measured in the subjects’ private vehicles. Biomarker measurements were conducted before, during, and immediately after the commutes and in 3 hourly intervals after commutes. Results At measurement time points within 3 h after the commute, we observed mild to pronounced elevations relative to baseline in exhaled nitric oxide, C-reactive-protein, and exhaled malondialdehyde, indicative of pulmonary and systemic inflammation and oxidative stress initiation, as well as decreases relative to baseline levels in the time-domain heart-rate variability parameters, SDNN and rMSSD, indicative of autonomic dysfunction. We did not observe any detectable changes in lung function measurements (FEV1, FVC), the frequency-domain heart-rate variability parameter or other systemic biomarkers of vascular injury. Water soluble organic carbon was associated with changes in eNO at all post-commute time-points (p < 0.0001). Conclusions Our results point to measureable changes in pulmonary and autonomic biomarkers following a scripted 2-h highway commute. PMID:24906070

Surgical treatment of acute type V acromioclavicular joint dislocations in professional athletes: an anatomic ligament reconstruction with synthetic implant augmentation.

PubMed

Triantafyllopoulos, Ioannis K; Lampropoulou-Adamidou, Kalliopi; Schizas, Nikitas P; Karadimas, Eleftherios V

2017-12-01

Most acromioclavicular (AC) joint injuries occur in men in their third decade of life during high-speed or high-impact body contact sports. The management of acute complete AC joint dislocation is surgical. Current surgical techniques include anatomic reconstruction of the main restraints of the AC joint and aim to improve functional outcomes and to reduce the complication rate. We present 10 cases of acute type V AC joint dislocation in professional athletes treated surgically with anatomic reconstruction of the coracoclavicular and AC ligaments and augmentation with the use of a synthetic polyester tape. The minimum follow-up of the patients was 2 years (mean, 48 months; range, 24-86 months). The postoperative functional outcome was assessed at 1 year and 2 years using the Constant-Murley, American Shoulder and Elbow Surgeons, and modified University of California-Los Angeles scoring systems. In all cases, the postoperative scores were significantly improved (P < .005 in all comparisons with the preoperative scores), and all patients returned to their preinjury high level of activity 6 months postoperatively. Radiographs at 1 month and 6 months revealed the maintenance of reduction. There were no complications. According to the results of our series of patients, demanding cases of acute AC joint dislocation Rockwood type V, in professional athletes, require anatomic fixation of both coracoclavicular and AC ligaments for return to sports as soon as possible and at the preinjury level of performance. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Evaluation of acute toxicity, genotoxicity and inhibitory effect on acute inflammation of an ethanol extract of Morus alba L. (Moraceae) in mice.

PubMed

Oliveira, Alisson Macário de; Nascimento, Matheus Ferreira do; Ferreira, Magda Rhayanny Assunção; Moura, Danielle Feijó de; Souza, Talita Giselly Dos Santos; Silva, Gabriela Cavalcante da; Ramos, Eduardo Henrique da Silva; Paiva, Patrícia Maria Guedes; Medeiros, Paloma Lys de; Silva, Teresinha Gonçalves da; Soares, Luiz Alberto Lira; Chagas, Cristiano Aparecido; Souza, Ivone Antônia de; Napoleão, Thiago Henrique

2016-12-24

Morus alba L. (white mulberry) is used in traditional medicine worldwide, including Brazil. The leaves of this plant are used to treat inflammatory disorders. Universal interest in this plant necessitates studies on the toxicological safety and scientific substantiation of the medicinal properties of M. alba. In previous work, we investigated the acute toxicity of orally administered M. alba ethanol extract in mice. This work was designed to investigate the ethanol extract obtained from M. alba leaves for acute toxicity when intraperitoneally administered, in vivo genotoxicity, and potential to reduce acute inflammation. In order to further investigate the constituents of the extract, we also obtained the high-performance liquid chromatography (HPLC) fingerprint of the extract. Phytochemical analysis by thin layer chromatography (TLC) was performed and the results were used to obtain the HPLC fingerprint. Acute toxicity of 300 and 2000mg/kg b.w. i.p. doses administered to mice for 14 days was evaluated. Genotoxicity was evaluated by counting the number of micronucleated polychromatic erythrocytes in the blood of mice that either received or did not receive the extract at 75, 150 and 300mg/kg b.w. per os. The anti-inflammatory effect of the same doses administered per os was investigated using the carrageenan air pouch model. The TLC analysis of the extract revealed the presence of a remarkable amount of flavonoids and cinnamic acids. The HPLC fingerprint showed the presence of one major peak corresponding to chlorogenic acid and two smaller peaks corresponding to flavonoids. In the toxicity assays, there were no deaths or deviations in behavior of treated mice as compared to the control at any dose. However, biochemical, hematological, and histological analyses showed that intraperitoneal injection caused several forms of damage to the mice, which were not observed in case of oral administration, studied in our previous work. Oral administration of the extract did

Near infrared lymphatic imaging demonstrates the dynamics of lymph flow and lymphangiogenesis during the acute vs. chronic phases of arthritis in mice

PubMed Central

Zhou, Quan; Wood, Ronald; Schwarz, Edward M.; Wang, Yong-Jun; Xing, Lianping

2010-01-01

Objective Development of an in vivo imaging method to assess lymphatic draining function in the K/B×N mouse model of inflammatory arthritis. Methods Indocyanine green (ICG), a near-infrared (NIR) fluorescent dye, was injected intradermally into the footpad of wild-type mice, the limb was illuminated with an 806 nm NIR laser, and the movement of ICG from the injection site to the draining popliteal lymph node (PLN) was recorded with a CCD camera. ICG-NIR images were analyzed to obtain 5 measures of lymphatic function across time. K/B×N arthritic mice and control non-arthritic littermates were imaged at one-month of age when acute joint inflammation commenced, and repeated at 3 months when joint inflammation became chronic. Lymphangiogenesis in PLNs was assessed by immunochemistry. Results ICG and its transport within lymphatic vessels were readily visualized and quantitative measures derived. During the acute phase of arthritis, the lymphatic vessels were dilated with increased ICG signal intensity and lymphatic pulses, and PLNs became fluorescent quickly. During the chronic phase, new lymphatic vessels were present near the foot. However, ICG appearance in lymphatic vessels was delayed. The size and area of PLN lymphatic sinuses progressively increased in the K/B×N mice. Conclusion ICG-NIR lymphatic imaging is a valuable method to assess the lymphatic draining function in mice with inflammatory arthritis. ICG-NIR imaging of K/B×N mice identified two distinct lymphatic phenotypes during the acute and chronic phase of inflammation. This technique can be used to assess new therapies for lymphatic disorders. PMID:20309866

Post-acute care disparities in total joint arthroplasty.

PubMed

Lan, Roy H; Kamath, Atul F

2017-09-01

Understanding the socioeconomic factors that influence hospitalization and post-discharge metrics after joint replacement is important for identifying key areas of improvement in the delivery of orthopaedic care. An institutional administrative data set of 2869 patients from an academic arthroplasty referral center was analyzed to quantify the relationship between socioeconomic factors and post-acute rehabilitation care received, length of stay, and cost of care. The study used International Classification of Disease, ninth edition coding in order to identify cohorts of patients who received joint arthroplasty of the knee and hip between January 2007 and May 2015. The study found that females (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.74-2.46), minorities (OR, 2.11; 95% CI, 1.78-2.51), and non-private insurance holders (OR, 1.56; 95% CI, 1.26-1.94) were more likely to be assigned to institutional care after discharge. The study also found that minorities (OR, 1.45; 95% CI, 1.24-1.70) and non-private insurance holders (OR, 1.43; 95% CI, 1.16-1.77) are more likely to exhibit longer length of stay. Mean charges were higher for males when compared to females ($80,010 vs $74,855; P < .001), as well as total costs ($19,910 vs $18,613; P  = .001). Socioeconomic factors such as gender, race, and insurance status should be further explored with respect to healthcare policies seeking to influence quality of care and health outcomes.

Early, asymptomatic stage of degenerative joint disease in canine hip joints.

PubMed

Lust, G; Summers, B A

1981-11-01

The early stages of degenerative joint disease were investigated in coxofemoral joints from dogs with a hereditary predisposition to hip dysplasia. Alterations observed included mild nonsuppurative synovitis, increased volume of both synovial fluid and the ligamentum teres, and focal degenerative articular cartilage lesions. On radiologic examination, subluxation of the femoral head was seen, but only in the most severely affected joints. Synovial inflammation with increased synovial fluid and ligament volumes were indicators of early degenerative joint disease in dogs. These changes seemed to coincide with, or perhaps to precede, microscopic evidence for articular cartilage degeneration and occurred before radiologic abnormalities were detected.

Low-grade chronic inflammation mediated by mast cells in fibromyalgia: role of IL-37.

PubMed

Mastrangelo, F; Frydas, I; Ronconi, G; Kritas, S K; Tettamanti, L; Caraffa, Al; D Ovidio, C; Younes, A; Gallenga, C E; Conti, P

2018-01-01

It has been observed that acute stress causes the activation of TH1 cells, while TH2 cells regulate and act on chronic inflammation. Fibromyalgia (FM) is a chronic, idiopathic disorder which affects about twelve million people in the United States. FM is characterized by chronic widespread pain, fatigue, aching, joint stiffness, depression, cognitive dysfunction and non-restorative sleep. The mechanism of induction of muscle pain and inflammation is not yet clear. In FM there is an increase in reactivity of central neurons with increased sensitivity localized mainly in the CNS. Mast cells are involved in FM by releasing proinflammatory cytokines, chemokines, chemical mediators, and PGD2. TNF is a cytokine generated by MCs and its level is higher in FM. The inhibition of pro-inflammatory IL-1 family members and TNF by IL-37 in FM could have a therapeutic effect. Here, we report for the first time the relationship between MCs, inflammatory cytokines and the new anti-inflammatory cytokine IL-37 in FM.

Laser therapy reduces gelatinolytic activity in the rat trigeminal ganglion during temporomandibular joint inflammation.

PubMed

Desiderá, A C; Nascimento, G C; Gerlach, R F; Leite-Panissi, C R A

2015-07-01

To investigate whether low-level laser therapy (LLLT) alters the expression and activity of MMP-2 and MMP-9 in the trigeminal ganglion (TG) during different stages of temporomandibular joint (TMJ) inflammation in rats. It also evaluated whether LLLT modifies mechanical allodynia and orofacial hyperalgesia. Wistar rats (±250 g) were divided into groups that received saline (SAL) or complete Freund's adjuvant (CFA, 50 μl) in the TMJ, and that later underwent LLLT (20 J cm(-2) ) at their TMJ or not (groups SAL, SAL + LLLT, CFA, and CFA + LLLT). LLLT was applied on days 3, 5, 7, and 9 after SAL or CFA. Mechanical allodynia was evaluated on days 1, 3, 5, 7, and 10; orofacial hyperalgesia was assessed on day 10. Gelatin zymography and in situ zymography aided quantification of MMPs in the TG. Low-level laser therapy abolished the reduction in the mechanical orofacial threshold and the increase in orofacial rubbing during the orofacial formalin test induced by CFA. LLLT also decreased the CFA-induced rise in the levels of MMP-9 and MMP-2 as well as the gelatinolytic activity in the TG. Low-level laser therapy could constitute an adjuvant therapy to treat temporomandibular disorders and prevent inflammation-induced alterations in the levels of MMP-2 and MMP-9 and in the gelatinolytic activity in TGs. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Activated fibrinolytic enzymes in the synovial fluid during acute arthritis induced by urate crystal injection in dogs.

PubMed

Morimoto, N; Sumi, H; Tsushima, H; Etou, Y; Yoshida, E; Mihara, H

1991-10-01

To identify the relationship of the severity of inflammation and fibrinolytic activity in arthritis, the fibrinolytic activity of synovial fluid was studied in acute experimental arthritis induced by injecting monosodium urate crystals into dogs' knee joints. The maximum activity in the synovial fluid was observed 6 h after crystal injection. It was inferred that the fibrinolytic activity was mainly due to plasminogen activator based on fibrin plate assays, substrate specificity, inhibitor effects and zymography. On the other hand, the activity of lysosomal enzymes (beta-glucuronidase and cathepsin G) reached a peak in the synovia after 12 h. Histological examination of the synovial membrane after 12 h also showed greater inflammation than at 6 h. The peak in fibrinolytic activity preceded the peak of lysosomal enzymes and histological changes. These results suggest that an increase in fibrinolytic activity by plasminogen activator may contribute to the development of an acute inflammatory response.

Suppression of NLRP3 inflammasome by oral treatment with sulforaphane alleviates acute gouty inflammation.

PubMed

Yang, Gabsik; Yeon, Sang Hyeon; Lee, Hye Eun; Kang, Han Chang; Cho, Yong Yeon; Lee, Hye Suk; Lee, Joo Young

2018-04-01

The aetiology of gout is closely linked to the deposition of monosodium uric acid (MSU) crystals and the consequent activation of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. In this study, we investigated whether oral administration of an NLRP3 inhibitor would be effective to attenuate the symptoms of gout. The effects of oral administration with sulforaphane (SFN) were examined in two mouse models of acute gout induced by injection of MSU crystals into footpads or air pouch. The production of caspase-1 (p10) and IL-1β was examined by immunoblotting and ELISA as hallmarks of NLRP3 inflammasome activation. Oral administration of SFN attenuated MSU crystal-induced swelling and neutrophil recruitment in a mouse foot acute gout model, correlating with the suppression of the NLRP3 inflammasome activation in foot tissues. Consistently, oral administration of SFN blocked MSU-crystal-induced activation of the NLRP3 inflammasome in a mouse air pouch gout model. SFN suppressed NLRP3 inflammasome activation induced by MSU crystals, adenosine triphosphate and nigericin but not by poly(dA:dT) in primary mouse macrophages, independent of the reactive oxygen species pathway. SFN inhibited ligand-independent activation of the NLRP3 inflammasome, suggesting that SFN may act directly on the NLRP3 inflammasome complex. Oral administration of SFN effectively alleviated acute gouty inflammation by suppression of the NLRP3 inflammasome. Our results provide a novel strategy in which oral treatment with SFN may be beneficial in preventing acute attacks of gout.

Inflammation in acute and chronic pancreatitis.

PubMed

Habtezion, Aida

2015-09-01

This report reviews recent animal model and human studies associated with inflammatory responses in acute and chronic pancreatitis. Animal model and limited human acute and chronic pancreatitis studies unravel the dynamic nature of the inflammatory processes and the ability of the immune cells to sense danger and environmental signals. In acute pancreatitis, such molecules include pathogen-associated molecular pattern recognition receptors such as toll-like receptors, and the more recently appreciated damage-associated molecular pattern molecules or 'alarmin' high mobility group box 1 and IL-33. In chronic pancreatitis, a recent understanding of a critical role for macrophage-pancreatic stellate cell interaction offers a potential targetable pathway that can alter fibrogenesis. Microbiome research in pancreatitis is a new field gaining interest but will require further investigation. Immune cell contribution to the pathogenesis of acute and chronic pancreatitis is gaining more appreciation and further understanding in immune signaling presents potential therapeutic targets that can alter disease progression.

SP600125 promotes resolution of allergic airway inflammation via TLR9 in an OVA-induced murine acute asthma model.

PubMed

Wu, Hui-Mei; Fang, Lei; Shen, Qi-Ying; Liu, Rong-Yu

2015-10-01

c-Jun N-terminal kinase (JNK) relays extracellular stimuli through phosphorylation cascades that lead to various cell responses. In the present study, we aimed to investigate the effect of the JNK inhibitor SP600125 on the resolution of airway inflammation, and the underlying mechanism using a murine acute asthma model. Female C57BL/6 mice were sensitized with saline or ovalbumin (OVA) on day 0, and challenged with OVA on day 14-20. Meanwhile, some of the mice were treated with SP600125 (30 mg/kg) intraperitoneally 2 h before each challenge. The airway inflammation was evaluated by counting the numbers of various types of inflammatory cells in bronchoalveolar lavage fluid (BALF), histopathology, cytokines production and mucus secretion in individual mouse. In addition, we analyzed the protein levels of phosphorylated JNK and TLR9 in the lung tissues. SP600125 markedly reduced the invasion of inflammatory cells into the peribronchial regions, and decreased the numbers of eosinophils, monocytes, neutrophils and lymphocytes in BALF. SP600125 also reduced the level of plasma OVA-specific IgE, lowered the production of pro-inflammatory cytokines in BALF and alleviated mucus secretion. Meanwhile, SP600125 inhibited OVA-induced, increased expression of p-JNK and TLR9 in the lung tissues. Collectively, our data demonstrated that SP600125 promoted resolution of allergic airway inflammation via TLR9 in an OVA-induced murine acute asthma model. The JNK-TLR9 pathway may be a new therapeutic target in the treatment for the allergic asthma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Punica granatum L. Leaf Extract Attenuates Lung Inflammation in Mice with Acute Lung Injury

PubMed Central

Pinheiro, Aruanã Joaquim Matheus Costa Rodrigues; Gonçalves, Jaciara Sá; Dourado, Ádylla Wilenna Alves; de Sousa, Eduardo Martins; Brito, Natilene Mesquita; Silva, Lanna Karinny; Batista, Marisa Cristina Aranha; de Sá, Joicy Cortez; Monteiro, Cinara Regina Aragão Vieira; Fernandes, Elizabeth Soares; Campbell, Lee Ann; Zago, Patrícia Maria Wiziack

2018-01-01

The hydroalcoholic extract of Punica granatum (pomegranate) leaves was previously demonstrated to be anti-inflammatory in a rat model of lipopolysaccharide- (LPS-) induced acute peritonitis. Here, we investigated the anti-inflammatory effects of the ethyl acetate fraction obtained from the pomegranate leaf hydroalcoholic extract (EAFPg) on the LPS-induced acute lung injury (ALI) mouse model. Male Swiss mice received either EAFPg at different doses or dexamethasone (per os) prior to LPS intranasal instillation. Vehicle-treated mice were used as controls. Animals were culled at 4 h after LPS challenge, and the bronchoalveolar lavage fluid (BALF) and lung samples were collected for analysis. EAFPg and kaempferol effects on NO and cytokine production by LPS-stimulated RAW 264.7 macrophages were also investigated. Pretreatment with EAFPg (100–300 mg/kg) markedly reduced cell accumulation (specially neutrophils) and collagen deposition in the lungs of ALI mice. The same animals presented with reduced lung and BALF TNF-α and IL-1β expression in comparison with vehicle controls (p < 0.05). Additionally, incubation with either EAFPg or kaempferol (100 μg/ml) reduced NO production and cytokine gene expression in cultured LPS-treated RAW 264.7 macrophages. Overall, these results demonstrate that the prophylactic treatment with EAFPg attenuates acute lung inflammation. We suggest this fraction may be useful in treating ALI. PMID:29675437

Inflammation is more distinct in temporomandibular joint osteoarthritis compared to the knee joint.

PubMed

Vos, Lukas M; Kuijer, Roel; Huddleston Slater, James J R; Bulstra, Sjoerd K; Stegenga, Boudewijn

2014-01-01

Most of the current understanding of articular cartilage maintenance and degradation is derived from large load-bearing synovial joints, in particular the knee joint. The aim of this study was to identify valuable degradation markers for cartilage degradation in the temporomandibular joint (TMJ) by comparing the relative concentrations of carboxyterminal telopeptides of collagen types I and II (CTX-I and CTX-II), cartilage oligomeric matrix protein (COMP), and prostaglandin E2 (PGE2) in synovial fluid (SF) of TMJ and knee joints with cartilage degradation. In this cross-sectional comparative study, participants were recruited from the University Medical Center Groningen, The Netherlands. Patients with TMJ osteoarthritis were compared with patients with knee osteoarthritis. The outcome variables were the relative SF concentrations of CTX-I, CTX-II, COMP, and PGE2. An independent samples Mann-Whitney U test was used to compare the relative concentrations. Thirty consecutive patients (9 male, 21 female; mean age, 40.1 yr; standard deviation, 15.3 yr) with TMJ osteoarthritis and 31 consecutive patients (20 male, 11 female; mean age, 37.4 yr; standard deviation, 13.7 yr) who were scheduled for arthroscopy of the knee joint participated in this study. Significant differences were found between relative concentrations of COMP (P = .000) and PGE2 (P = .005), and no significant differences were found between relative concentrations of CTX-I (P = .720) and CTX-II (P = .242). Relative SF concentrations of COMP and PGE2 showed significant differences between the TMJ and the knee joint, suggesting that there are differences in pathophysiology and that the inflammatory component may be more distinct in the TMJ. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Immunomodulatory effects of high-protein diet with resveratrol supplementation on radiation-induced acute-phase inflammation in rats.

PubMed

Kim, Kyoung-Ok; Park, HyunJin; Chun, Mison; Kim, Hyun-Sook

2014-09-01

We hypothesized that a high-protein diet and/or resveratrol supplementation will improve acute inflammatory responses in rats after receiving experimental abdominal radiation treatment (ART). Based on our previous study, the period of 10 days after ART was used as an acute inflammation model. Rats were exposed to a radiation dose of 17.5 Gy and were supplied with a control (C), 30% high-protein diet (HP), resveratrol supplementation (RES), or HP with RES diet ([HP+RES]). At day 10 after ART, we measured profiles of lipids, proteins, and immune cells in blood. The levels of clusters of differentiating 4(+) (CD4(+)) cells and regulatory T cells, serum proinflammatory cytokines, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine were also measured. ART caused significant disturbances of lipid profiles by increasing triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), and decreasing high-density lipoprotein cholesterol. The proinflammatroy cytokine levels were also increased by ART. All the experimental diets (HP, RES, and [HP+RES]) significantly decreased levels of TG, monocytes, proinflammatory cytokines, and 8-OHdG, whereas the platelet counts were increased. In addition, the HP and [HP+RES] diets decreased the concentrations of plasma LDL-C and total cholesterol. Also, the HP and RES diets decreased regulatory T cells compared with those of the control diet in ART group. Further, the HP diet led to a significant recovery of white blood cell counts, as well as increased percentages of lymphocyte and decreased percentages of neutrophils. In summary, RES appeared to be significantly effective in minimizing radiation-induced damage to lipid metabolism and immune responses. Our study also demonstrated the importance of dietary protein intake in recovering from acute inflammation by radiation.

Loss of cellular FLICE-inhibitory protein promotes acute cholestatic liver injury and inflammation from bile duct ligation.

PubMed

Gehrke, Nadine; Nagel, Michael; Straub, Beate K; Wörns, Marcus A; Schuchmann, Marcus; Galle, Peter R; Schattenberg, Jörn M

2018-03-01

Cholestatic liver injury results from impaired bile flow or metabolism and promotes hepatic inflammation and fibrogenesis. Toxic bile acids that accumulate in cholestasis induce apoptosis and contribute to early cholestatic liver injury, which is amplified by accompanying inflammation. The aim of the current study was to evaluate the role of the antiapoptotic caspase 8-homolog cellular FLICE-inhibitory (cFLIP) protein during acute cholestatic liver injury. Transgenic mice exhibiting hepatocyte-specific deletion of cFLIP (cFLIP -/- ) were used for in vivo and in vitro analysis of cholestatic liver injury using bile duct ligation (BDL) and the addition of bile acids ex vivo. Loss of cFLIP in hepatocytes promoted acute cholestatic liver injury early after BDL, which was characterized by a rapid release of proinflammatory and chemotactic cytokines (TNF, IL-6, IL-1β, CCL2, CXCL1, and CXCL2), an increased presence of CD68 + macrophages and an influx of neutrophils in the liver, and resulting apoptotic and necrotic hepatocyte cell death. Mechanistically, liver injury in cFLIP -/- mice was aggravated by reactive oxygen species, and sustained activation of the JNK signaling pathway. In parallel, cytoprotective NF-κB p65, A20, and the MAPK p38 were inhibited. Increased injury in cFLIP -/- mice was accompanied by activation of hepatic stellate cells and profibrogenic regulators. The antagonistic caspase 8-homolog cFLIP is a critical regulator of acute, cholestatic liver injury. NEW & NOTEWORTHY The current paper explores the role of a classical modulator of hepatocellular apoptosis in early, cholestatic liver injury. These include activation of NF-κB and MAPK signaling, production of inflammatory cytokines, and recruitment of neutrophils in response to cholestasis. Because these signaling pathways are currently exploited in clinical trials for the treatment of nonalcoholic steatohepatitis and cirrhosis, the current data will help in the development of novel pharmacological

Soluble Flt-1 improves the repair of ankle joint injury in rats

PubMed Central

Tian, Jing; Xie, Bing; Xiang, Liangbi; Zhao, Yong; Zhou, Dapeng

2016-01-01

The ankle injuries create great pain to a great number of patients worldwide. Past studies have focused on the development of practical treatments to relieve pain and improve recovery, but the molecular mechanisms underlying the ankle injuries, especially the local inflammation in the damaged ankle joint, have been rarely studied. Moreover, although reduction of production and secretion of pro-inflammatory cytokines may reduce the pain and promote the recovery, a practical approach is currently lacking. Here, we detected significantly higher levels of placental growth factor (PLGF) and pro-inflammatory cytokines in the joint fluid from the patients of acute ankle joint injury (AAJI). Interestingly, the levels of PLGF and pro-inflammatory cytokines in the joint fluid strongly correlated. In order to examine whether PLGF may regulate the production and secretion of pro-inflammatory cytokines in the injured joint, we used a rat carrageenan-induced ankle injury model for AAJI in humans. We injected soluble Flt-1 (sFlt-1) into the articular cavity of the injured ankle joint to block PLGF signaling and found that injection of sFlt-1 significantly improved the rat behavior in activity wheels test, which appeared to result from reduced secretion of the pro-inflammatory cytokines in the ankle joint. Thus, our study suggests that blocking PLGF signaling may be a novel therapeutic approach for treating AAJI in humans. PMID:27904694

Comparing diffusion weighted imaging with clinical and blood parameters, and with short tau inversion recovery sequence in detecting spinal and sacroiliac joint inflammation in axial spondyloarthritis.

PubMed

Chung, Ho Yin; Xu, Xiaopei; Lau, Vince Wing Hang; Ho, Grace; Lee, Ka Lai; Li, Philip Hei; Tsang, Helen Hoi Lun; Kwok, Suet Kei; Lau, Chak Sing; Wong, Chun Sing

2017-01-01

To investigate the usefulness of diffusion weighted imaging (DWI) by comparing with clinical features, blood parameters and traditional short tau inversion recovery (STIR) sequence in detecting spinal and sacroiliac (SI) joint inflammation in axial spondyloarthritis (axSpA) patients. One hundred and ten axSpA patients were recruited. Clinical, radiological and blood parameters were recorded. DWI and STIR MRI were performed simultaneously and results were scored according to the Spondyloarthritis Research Consortium of Canada (SPARCC) for comparison. Apparent diffusion coef cient (ADC) values were also calculated. DWI did not correlate with clinical parameters or blood parameters. It also had lowered sensitivity. When compared with STIR sequence, it correlated well with STIR sequence at the SI joint level (CC 0.76, p<0.001), but weakly at the spinal level (CC 0.23, p=0.02). At the SI joint level, the presence of inflammation on both STIR sequence and DWI was associated with an increase in maximum (B=0.24, p=0.02 in STIR; B=0.37, p<0.001 in DWI) and mean ADC values (B=0.17, p=0.003 in STIR; B=0.15, p=0.01 in DWI). Maximum (B=0.19, p=0.04) and mean spinal ADC values (B=0.18, p=0.01) were also positively associated with DWI detected spinal inflammation. Presence of Modic lesions showed positive correlation with STIR sequence (B=7.12, p=0.01) but not spinal ADC values. Despite DWI correlates with STIR sequence, it has lower sensitivity. However, ADC values appear to be independent of Modic lesions and may supplement STIR sequence to differentiate degeneration.

Analysis of the Effects of Normal Walking on Ankle Joint Contact Characteristics After Acute Inversion Ankle Sprain.

PubMed

Bae, Ji Yong; Park, Kyung Soon; Seon, Jong Keun; Jeon, Insu

2015-12-01

To show the causal relationship between normal walking after various lateral ankle ligament (LAL) injuries caused by acute inversion ankle sprains and alterations in ankle joint contact characteristics, finite element simulations of normal walking were carried out using an intact ankle joint model and LAL injury models. A walking experiment using a volunteer with a normal ankle joint was performed to obtain the boundary conditions for the simulations and to support the appropriateness of the simulation results. Contact pressure and strain on the talus articular cartilage and anteroposterior and mediolateral translations of the talus were calculated. Ankles with ruptured anterior talofibular ligaments (ATFLs) had a higher likelihood of experiencing increased ankle joint contact pressures, strains and translations than ATFL-deficient ankles. In particular, ankles with ruptured ATFL + calcaneofibular ligaments and all ruptured ankles had a similar likelihood as the ATFL-ruptured ankles. The push off stance phase was the most likely situation for increased ankle joint contact pressures, strains and translations in LAL-injured ankles.

Role of Quzhou Fructus Aurantii Extract in Preventing and Treating Acute Lung Injury and Inflammation.

PubMed

Li, Lili; Zhang, Sheng; Xin, Yanfei; Sun, Junying; Xie, Feng; Yang, Lin; Chen, Zhiqin; Chen, Hao; Liu, Fang; Xuan, Yaoxian; You, Zhenqiang

2018-01-26

Quzhou Fructus Aurantii (QFA) is an authentic herb of local varieties in Zhejiang, China, which is usually used to treat gastrointestinal illnesses, but its effects on respiratory inflammation have not been reported yet. In our study, the anti-inflammatory activity of QFA extract (QFAE) was evaluated on copper sulfate pentahydrate (CuSO 4 ·5H 2 O)-induced transgenic neutrophil fluorescent zebrafish model. QFAE showed a significant effect of anti-inflammation in CuSO 4 ·5H 2 O-induced zebrafish by reducing the neutrophil number in the inflammatory site. We investigated the anti-inflammatory activity of QFAE on lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice models and RAW 264.7 cells. QFAE had an anti-inflammatory effect on reducing total cells, neutrophils, and macrophages in BALF and attenuated alveolus collapse, neutrophils infiltration, lung W/D ratio, myeloperoxidase (MPO) protein expression and other pulmonary histological changes in lung tissues, as well as hematological changes. Levels of pro-inflammatory cytokines, including TNF, IL-6, IFN-γ, MCP-1, and IL-12p70, were decreased, whereas anti-inflammatory cytokine IL-10 was increased after treatment with QFAE both in vivo and in vitro. In summary, our results suggested that QFAE had apparent anti-inflammatory effects on CuSO 4 ·5H 2 O-induced zebrafish, LPS-induced ALI mice, and RAW 264.7 cells. Furthermore, QFAE may be a therapeutic drug to treat ALI/ARDS and other respiratory inflammations.

Reg3β is associated with cardiac inflammation and provides prognostic information in patients with acute coronary syndrome.

PubMed

Lörchner, Holger; Widera, Christian; Hou, Yunlong; Elsässer, Albrecht; Warnecke, Henning; Giannitsis, Evangelos; Hulot, Jean-Sebastien; Braun, Thomas; Wollert, Kai C; Pöling, Jochen

2018-05-01

Regenerating islet-derived protein 3 beta (Reg3β) is a cardiomyocyte-derived chemokine for macrophages that is upregulated after myocardial infarction (MI) in mice. Here, we hypothesized that monitoring Reg3β expression might provide specific information on the degree of cardiac inflammation, which is a key determinant in disease progression and prognosis of patients with acute coronary syndrome (ACS). The expression of Reg3β and other inflammatory markers including C-reactive protein (CRP) and myeloperoxidase (MPO) was measured by immunoblotting at serial time points in the hearts and serum of mice with acute MI. We identified a rapid increase of Reg3β, CRP and MPO expression in cardiac tissue and serum within the first 24 h after MI. The expression of Reg3β peaked at day 4 and thereby paralleled the kinetic profile of the early immune-inflammatory response at sites of cardiac injury, which has been characterized by multicolor flow cytometry. In a retrospective analysis including 322 ACS patients and 117 apparently healthy individuals, we detected increased Reg3β serum concentrations in ACS patients on admission by ELISA. Multiple regression analysis revealed significant relationships between Reg3β and hs-CRP, age, diabetes and NT-proBNP in ACS. Moreover, elevated Reg3β levels on admission were associated with an increased risk of death independent of cardiovascular risk factors and hs-CRP. Reg3β is a prognostic biomarker for ACS and is strongly associated with the intensity of cardiac inflammation. Accordingly, Reg3β may complement established strategies of acute risk assessment in the management of ACS. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of budesonide on the lung functions, inflammation and apoptosis in a saline-lavage model of acute lung injury.

PubMed

Mokra, D; Kosutova, P; Balentova, S; Adamkov, M; Mikolka, P; Mokry, J; Antosova, M; Calkovska, A

2016-12-01

Diffuse alveolar injury, edema, and inflammation are fundamental signs of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Whereas the systemic administration of corticosteroids previously led to controversial results, this study evaluated if corticosteroids given intratracheally may improve lung functions and reduce edema formation, migration of cells into the lung and their activation in experimentally-induced ALI. In oxygen-ventilated rabbits, ALI was induced by repetitive saline lung lavage, until PaO2 decreased to < 26.7 kPa in FiO 2 1.0. Then, one group of animals was treated with corticosteroid budesonide (Pulmicort susp inh, AstraZeneca; 0.25 mg/kg) given intratracheally by means of inpulsion regime of high-frequency jet ventilation, while another group was non-treated, and both groups were oxygen-ventilated for following 5 hours. Another group of animals served as healthy controls. After sacrifice of animals, left lung was saline-lavaged and protein content was measured and cells in the lavage fluid were determined microscopically. Right lung tissue was used for estimation of edema formation (expressed as wet/dry weight ratio), for histomorphological investigation, immunohistochemical determination of apoptosis of lung cells, and for determination of markers of inflammation and lung injury (IL-1β, IL-6, IL-8, TNF-α, IFNγ, esRAGE, caspase-3) by ELISA methods. Levels of several cytokines were estimated also in plasma. Repetitive lung lavage worsened gas exchange, induced lung injury, inflammation and lung edema and increased apoptosis of lung epithelial cells. Budesonide reduced lung edema, cell infiltration into the lung and apoptosis of epithelial cells and decreased concentrations of proinflammatory markers in the lung and blood. These changes resulted in improved ventilation. Concluding, curative intratracheal treatment with budesonide alleviated lung injury, inflammation, apoptosis of lung epithelial cells and lung edema and

Conditional Macrophage Depletion Increases Inflammation and Does Not Inhibit the Development of Osteoarthritis in Obese Macrophage Fas-Induced Apoptosis-Transgenic Mice.

PubMed

Wu, Chia-Lung; McNeill, Jenna; Goon, Kelsey; Little, Dianne; Kimmerling, Kelly; Huebner, Janet; Kraus, Virginia; Guilak, Farshid

2017-09-01

To investigate whether short-term, systemic depletion of macrophages can mitigate osteoarthritis (OA) following injury in the setting of obesity. CSF-1R-GFP+ macrophage Fas-induced apoptosis (MaFIA)-transgenic mice that allow conditional depletion of macrophages were placed on a high-fat diet and underwent surgery to induce knee OA. A small molecule (AP20187) was administrated to deplete macrophages in MaFIA mice. The effects of macrophage depletion on acute joint inflammation, OA severity, and arthritic bone changes were evaluated using histology and micro-computed tomography. Immunohistochemical analysis was performed to identify various immune cells. The levels of serum and synovial fluid cytokines were also measured. Macrophage-depleted mice had significantly fewer M1 and M2 macrophages in the surgically operated joints relative to controls and exhibited decreased osteophyte formation immediately following depletion. Surprisingly, macrophage depletion did not attenuate the severity of OA in obese mice; instead, it induced systemic inflammation and led to a massive infiltration of CD3+ T cells and particularly neutrophils, but not B cells, into the injured joints. Macrophage-depleted mice also demonstrated a markedly increased number of proinflammatory cytokines including granulocyte colony-stimulating factor, interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor in both serum and joint synovial fluid, although the mice showed a trend toward decreased levels of insulin and leptin in serum after macrophage depletion. Our findings indicate that macrophages are vital for modulating homeostasis of immune cells in the setting of obesity and suggest that more targeted approaches of depleting specific macrophage subtypes may be necessary to mitigate inflammation and OA in the setting of obesity. © 2017, American College of Rheumatology.

The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

PubMed Central

Dumnicka, Paulina; Maduzia, Dawid; Ceranowicz, Piotr; Olszanecki, Rafał; Drożdż, Ryszard; Kuśnierz-Cabala, Beata

2017-01-01

Acute pancreatitis (AP) is an inflammatory disease with varied severity, ranging from mild local inflammation to severe systemic involvement resulting in substantial mortality. Early pathologic events in AP, both local and systemic, are associated with vascular derangements, including endothelial activation and injury, dysregulation of vasomotor tone, increased vascular permeability, increased leukocyte migration to tissues, and activation of coagulation. The purpose of the review was to summarize current evidence regarding the interplay between inflammation, coagulation and endothelial dysfunction in the early phase of AP. Practical aspects were emphasized: (1) we summarized available data on diagnostic usefulness of the markers of endothelial dysfunction and activated coagulation in early prediction of severe AP; (2) we reviewed in detail the results of experimental studies and clinical trials targeting coagulation-inflammation interactions in severe AP. Among laboratory tests, d-dimer and angiopoietin-2 measurements seem the most useful in early prediction of severe AP. Although most clinical trials evaluating anticoagulants in treatment of severe AP did not show benefits, they also did not show significantly increased bleeding risk. Promising results of human trials were published for low molecular weight heparin treatment. Several anticoagulants that proved beneficial in animal experiments are thus worth testing in patients. PMID:28208708

Hesperetin derivative-14 alleviates inflammation by activating PPAR-γ in mice with CCl4-induced acute liver injury and LPS-treated RAW264.7 cells.

PubMed

Chen, Xin; Ding, Hai-Wen; Li, Hai-Di; Huang, Hui-Min; Li, Xiao-Feng; Yang, Yang; Zhang, Yi-Long; Pan, Xue-Yin; Huang, Cheng; Meng, Xiao-Ming; Li, Jun

2017-05-15

Hesperetin is a flavanone glycoside compound naturally occurring in the fruit peel of Citrusaurantium L. (Rutaceae). Previous studies revealed that hesperetin possesses various pharmacological effects, including anti-inflammation, anti-tumor, anti-oxidant and neuroprotective properties. Hesperetin derivative-14 (HD-14) is a derivative of hesperetin improved in water solubility and bioavailability. In this study, we indicated that HD-14 (2μM) significantly attenuated inflammation in LPS-treated RAW264.7 cells, besides, HD-14 (100mg/kg) exhibited hepato-protective effects and anti-inflammatory effects on C57BL/6J mice with CCl 4 -induced acute liver injury. In addition, it was demonstrated that HD-14 dramatically up-regulated the expression of PPAR-γ in vivo and in vitro. Interestingly, over-expression of PPAR-γ had anti-inflammatory effects on the expressions of TNF-α, IL-6, and IL-1β, whereas, knockdown of PPAR-γ with small interfering RNA had pro-inflammatory effects in LPS-treated RAW264.7 cells. Thus, our findings demonstrated that HD-14 alleviated inflammation by activating PPAR-γ expression at least in part. Further studies founded that HD-14 remarkably inhibited the expression of p-JAK1 and p-STAT1 through up-regulating PPAR-γ. Together, these results suggested that HD-14 served as an activator of PPAR-γ and the JAK1/STAT1 signaling pathway may be involved in the progress of inflammation. Collectively, HD-14 may be utilized as a potential anti-inflammation monomeric compound in the treatment of acute liver injury. Copyright © 2017 Elsevier B.V. All rights reserved.

Curcumin alone and in combination with augmentin protects against pulmonary inflammation and acute lung injury generated during Klebsiella pneumoniae B5055-induced lung infection in BALB/c mice.

PubMed

Bansal, Shruti; Chhibber, Sanjay

2010-04-01

Acute lung injuries due to acute lung infections remain a major cause of mortality. Thus a combination of an antibiotic and a compound with immunomodulatory and anti-inflammatory activities can help to overcome acute lung infection-induced injuries. Curcumin derived from the rhizome of turmeric has been used for decades and it exhibits anti-inflammatory, anti-carcinogenic, immunomodulatory properties by downregulation of various inflammatory mediators. Keeping these properties in mind, we investigated the anti-inflammatory properties of curcumin in a mouse model of acute inflammation by introducing Klebsiella pneumoniae B5055 into BALB/c mice via the intranasal route. Intranasal instillation of bacteria in this mouse model of acute pneumonia-induced inflammation resulted in a significant increase in neutrophil infiltration in the lungs along with increased production of various inflammatory mediators [i.e. malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO), tumour necrosis factor (TNF)-alpha] in the lung tissue. The animals that received curcumin alone orally or in combination with augmentin, 15 days prior to bacterial instillation into the lungs via the intranasal route, showed a significant (P <0.05) decrease in neutrophil influx into the lungs and a significant (P <0.05) decrease in the production of MDA, NO, MPO activity and TNF-alpha levels. Augmentin treatment alone did not decrease the MDA, MPO, NO and TNF-alpha levels significantly (P >0.05) as compared to the control group. We therefore conclude that curcumin ameliorates lung inflammation induced by K. pneumoniae B5055 without significantly (P <0.05) decreasing the bacterial load in the lung tissue whereas augmentin takes care of bacterial proliferation. Hence, curcumin can be used as an adjunct therapy along with antibiotics as an anti-inflammatory or an immunomodulatory agent in the case of acute lung infection.

Near-infrared lymphatic imaging demonstrates the dynamics of lymph flow and lymphangiogenesis during the acute versus chronic phases of arthritis in mice.

PubMed

Zhou, Quan; Wood, Ronald; Schwarz, Edward M; Wang, Yong-Jun; Xing, Lianping

2010-07-01

To develop an in vivo imaging method to assess lymphatic draining function in the K/BxN mouse model of inflammatory arthritis. Indocyanine green, a near-infrared fluorescent dye, was injected intradermally into the footpads of wild-type mice, mouse limbs were illuminated with an 806-nm near-infrared laser, and the movement of indocyanine green from the injection site to the draining popliteal lymph node (LN) was recorded with a CCD camera. Indocyanine green near-infrared images were analyzed to obtain 5 measures of lymphatic function across time. Images of K/BxN arthritic mice and control nonarthritic littermates were obtained at 1 month of age, when acute joint inflammation commenced, and again at 3 months of age, when joint inflammation became chronic. Lymphangiogenesis in popliteal LNs was assessed by immunochemistry. Indocyanine green and its transport within lymphatic vessels were readily visualized, and quantitative measures were derived. During the acute phase of arthritis, the lymphatic vessels were dilated, with increased indocyanine green signal intensity and lymphatic pulses, and popliteal LNs became fluorescent quickly. During the chronic phase, new lymphatic vessels were present near the foot. However, the appearance of indocyanine green in lymphatic vessels was delayed. The size and area of popliteal LN lymphatic sinuses progressively increased in the K/BxN mice. Our findings indicate that indocyanine green near-infrared lymphatic imaging is a valuable method for assessing the lymphatic draining function in mice with inflammatory arthritis. Indocyanine green-near-infrared imaging of K/BxN mice identified 2 distinct lymphatic phenotypes during the acute and chronic phase of inflammation. This technique can be used to assess new therapies for lymphatic disorders.

Epigenetic modifiers reduce inflammation and modulate macrophage phenotype during endotoxemia-induced acute lung injury

PubMed Central

Thangavel, Jayakumar; Samanta, Saheli; Rajasingh, Sheeja; Barani, Bahar; Xuan, Yu-Ting; Dawn, Buddhadeb; Rajasingh, Johnson

2015-01-01

ABSTRACT Acute lung injury (ALI) during sepsis is characterized by bilateral alveolar infiltrates, lung edema and respiratory failure. Here, we examined the efficacy the DNA methyl transferase (DNMT) inhibitor 5-Aza 2-deoxycytidine (Aza), the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA), as well as the combination therapy of Aza and TSA (Aza+TSA) provides in the protection of ALI. In LPS-induced mouse ALI, post-treatment with a single dose of Aza+TSA showed substantial attenuation of adverse lung histopathological changes and inflammation. Importantly, these protective effects were due to substantial macrophage phenotypic changes observed in LPS-stimulated macrophages treated with Aza+TSA as compared with untreated LPS-induced macrophages or LPS-stimulated macrophages treated with either drug alone. Further, we observed significantly lower levels of pro-inflammatory molecules and higher levels of anti-inflammatory molecules in LPS-induced macrophages treated with Aza+TSA than in LPS-induced macrophages treated with either drug alone. The protection was ascribed to dual effects by an inhibition of MAPK–HuR–TNF and activation of STAT3–Bcl2 pathways. Combinatorial treatment with Aza+TSA reduces inflammation and promotes an anti-inflammatory M2 macrophage phenotype in ALI, and has a therapeutic potential for patients with sepsis. PMID:26116574

Regulation of the trigeminal NR1 subunit expression induced by inflammation of the temporomandibular joint region in rats.

PubMed

Wang, Shuxing; Lim, Grewo; Mao, Ji; Sung, Backil; Mao, Jianren

2009-01-01

Expression of the N-methyl-d-aspartate (NMDA) receptor in trigeminal nuclei has been shown to play a role in the mechanisms of trigeminal pain. Here, we examined the hypothesis that the upregulation of the NR1 subunit of the NMDA receptor (NR1) in the trigeminal subnucleus caudalis (Sp5c) following inflammation of the temporomandibular joint (TMJ) region would be regulated by interleukin-6 (IL-6) and the nuclear factor-kappa B (NF-kappaB). Inflammation of a unilateral TMJ region was produced in rats by injecting 50mul of complete Freund's adjuvant (CFA) into a TMJ and adjacent tissues, which resulted in persistent pain behavior as assessed using algometer before (baseline) and on days 1, 3, and 7 after the CFA injection. The CFA injection also induced a significant upregulation of NR1 and NF-kappaB on days 3 and 7, and of IL-6 on days 1, 3, and 7, within the ipsilateral Sp5c, as compared with the sham TMJ injection group. Once daily intracisternal injection of an IL-6 antiserum or NF-kappaB inhibitor (PDTC) for 6 days, beginning on day 1 immediately after the CFA injection, prevented both the upregulation of NR1 in the ipsilateral Sp5C and pain behavior. Moreover, once daily intracisternal IL-6 administration for 6 days in naïve rats induced the NR1 upregulation and pain behavior similar to that after TMJ inflammation. These results indicate that the upregulation of IL-6 and NF-kappaB after inflammation of the unilateral TMJ region is a critical regulatory mechanism for the expression of NR1 in the ipsilateral Sp5c, which contributed to the development of TMJ pain behavior in rats.

Regulation of the Trigeminal NR1 Subunit Expression Induced by Inflammation of the Temporomandibular Joint Region in Rats

PubMed Central

Wang, Shuxing; Lim, Grewo; Mao, Ji; Sung, Backil; Mao, Jianren

2012-01-01

Expression of the N-methyl-D-aspartate receptor (NMDA) receptor in trigeminal nuclei has been shown to play a role in the mechanisms of trigeminal pain. Here, we examined the hypothesis that the upregulation of the NR1 subunit of the NMDA receptor (NR1) in the trigeminal subnucleus caudalis (Sp5c) following inflammation of the temporomandibular joint (TMJ) region would be regulated by interleukin-6 (IL-6) and the nuclear factor kappa B (NF-κB). Inflammation of a unilateral TMJ region was produced in rats by injecting 50 μl of complete Freund’s adjuvant (CFA) into a TMJ and adjacent tissues, which resulted in persistent pain behavior as assessed using algometer before (baseline) and on day 1, 3 and 7 after the CFA injection. The CFA injection also induced a significant upregulation of NR1 and NF-κB on day 3 and 7, and of IL-6 on day 1, 3, and 7, within the ipsilateral Sp5c, as compared with the sham TMJ injection group. Once daily intracisternal injection of an IL-6 antiserum or NF-κB inhibitor (PDTC) for six days, beginning on day 1 immediately after the CFA injection, prevented both the upregulation of NR1 in the ipsilateral Sp5C and pain behavior. Moreover, once daily intracisternal IL-6 administration for six days in naïve rats induced the NR1 upregulation and pain behavior similar to that after TMJ inflammation. These results indicate that the upregulation of IL-6 and NF-κB after inflammation of the unilateral TMJ region is a critical regulatory mechanism for the expression of NR1 in the ipsilateral Sp5c, which contributed to the development of TMJ pain behavior in rats. PMID:19058915

Acute and joint toxicity of three agrochemicals to Chinese tiger frog (Hoplobatrachus chinensis) tadpoles

PubMed Central

WEI, Li; SHAO, Wei-Wei; DING, Guo-Hua; FAN, Xiao-Li; YU, Miao-Ling; LIN, Zhi-Hua

2014-01-01

We studied acute and joint toxicity of three different agrochemicals (chlorantraniliprole, flubendiamide-abamectin and penoxsulam) to Chinese tiger frog (Hoplobatrachus chinensis) tadpoles with the method of stability water tests. Results showed that the three agrochemicals increased tadpole mortality. For acute toxicity, the LC50 values after 24, 48 and 72 h of chlorantraniliprole, flubendiamide-abamectin and penoxsulam exposure were 5.37, 4.90 and 4.68 mg/L; 0.035, 0.025 and 0.021 mg/L; 1.74, 1.45 and 1.29 mg/L, respectively. The safety concentrations (SC) of chlorantraniliprole, flubendiamide-abamectin and penoxsulam to the tadpoles were 1.23, 0.30 and 0.003 mg/L, respectively. Based on these findings, chlorantraniliprole and penoxsulam were moderately toxic, while flubendiamide-abamectin was highly toxic. All pairwise joint toxicity tests showed moderate toxicity. The LC50 values after 24, 48 and 72 h of exposure were 7.08, 6.61 and 6.03 mg/L for chlorantraniliprole+penoxsulam, with corresponding values of 2.455, 2.328 and 2.183 mg/L for chlorantraniliprole+flubendiamide-abamectin, and 1.132, 1.084 and 1.050 mg/L for penoxsulam+flubendiamide-abamectin, with safe concentrations of 1.73, 0.63 and 0.30 mg/L, respectively. For toxic evaluations of pairwise combinations of the three agrochemicals, only the joint toxicity of chlorantraniliprole and flubendiamide-abamectin after 24 h was found to be synergistic, whereas all other tests were antagonistic. Our findings provide valuable information on the toxic effects of agrochemicals on amphibians and how various types of agrochemicals can be reasonably used in agricultural areas. PMID:25017745

Acute and joint toxicity of three agrochemicals to Chinese tiger frog (Hoplobatrachus chinensis) tadpoles.

PubMed

Wei, Li; Shao, Wei-Wei; Ding, Guo-Hua; Fan, Xiao-Li; Yu, Miao-Ling; Lin, Zhi-Hua

2014-07-01

We studied acute and joint toxicity of three different agrochemicals (chlorantraniliprole, flubendiamide-abamectin and penoxsulam) to Chinese tiger frog (Hoplobatrachus chinensis) tadpoles with the method of stability water tests. Results showed that the three agrochemicals increased tadpole mortality. For acute toxicity, the LC50 values after 24, 48 and 72 h of chlorantraniliprole, flubendiamide-abamectin and penoxsulam exposure were 5.37, 4.90 and 4.68 mg/L; 0.035, 0.025 and 0.021 mg/L; 1.74, 1.45 and 1.29 mg/L, respectively. The safety concentrations (SC) of chlorantraniliprole, flubendiamide-abamectin and penoxsulam to the tadpoles were 1.23, 0.30 and 0.003 mg/L, respectively. Based on these findings, chlorantraniliprole and penoxsulam were moderately toxic, while flubendiamide-abamectin was highly toxic. All pairwise joint toxicity tests showed moderate toxicity. The LC50 values after 24, 48 and 72 h of exposure were 7.08, 6.61 and 6.03 mg/L for chlorantraniliprole+penoxsulam, with corresponding values of 2.455, 2.328 and 2.183 mg/L for chlorantraniliprole+flubendiamide-abamectin, and 1.132, 1.084 and 1.050 mg/L for penoxsulam+flubendiamide-abamectin, with safe concentrations of 1.73, 0.63 and 0.30 mg/L, respectively. For toxic evaluations of pairwise combinations of the three agrochemicals, only the joint toxicity of chlorantraniliprole and flubendiamide-abamectin after 24 h was found to be synergistic, whereas all other tests were antagonistic. Our findings provide valuable information on the toxic effects of agrochemicals on amphibians and how various types of agrochemicals can be reasonably used in agricultural areas.

A Critical Role for Monocytes/Macrophages During Intestinal Inflammation-associated Lymphangiogenesis

PubMed Central

Becker, Felix; Kurmaeva, Elvira; Gavins, Felicity N. E.; Stevenson, Emily V.; Navratil, Aaron R.; Jin, Long; Tsunoda, Ikuo; Orr, A. Wayne; Alexander, Jonathan S.; Ostanin, Dmitry V.

2016-01-01

Background Inflammation-associated lymphangiogenesis (IAL) is frequently observed in inflammatory bowel diseases. IAL is believed to limit inflammation by enhancing fluid and immune cell clearance. Although monocytes/macrophages (MΦ) are known to contribute to intestinal pathology in inflammatory bowel disease, their role in intestinal IAL has never been studied mechanistically. We investigated contributions of monocytes/MΦ to the development of intestinal inflammation and IAL. Methods Because inflammatory monocytes express CC chemokine receptor 2 (CCR2), we used CCR2 diphtheria toxin receptor transgenic (CCR2.DTR) mice, in which monocytes can be depleted by diphtheria toxin injection, and CCR2−/− mice, which have reduced circulating monocytes. Acute or chronic colitis was induced by dextran sodium sulfate or adoptive transfer of CD4+CD45RBhigh T cells, respectively. Intestinal inflammation was assessed by flow cytometry, immunofluorescence, disease activity, and histopathology, whereas IAL was assessed by lymphatic vessel morphology and density. Results We demonstrated that intestinal MΦ expressed vascular endothelial growth factor-C/D. In acute colitis, monocyte-depleted mice were protected from intestinal injury and showed reduced IAL, which was reversed after transfer of wild-type monocytes into CCR2−/− mice. In chronic colitis, CCR2 deficiency did not attenuate inflammation but reduced IAL. Conclusions We propose a dual role of MΦ in (1) promoting acute inflammation and (2) contributing to IAL. Our data suggest that intestinal inflammation and IAL could occur independently, because IAL was reduced in the absence of monocytes/MΦ, even when inflammation was present. Future inflammatory bowel disease therapies might exploit promotion of IAL and suppression of MΦ independently, to restore lymphatic clearance and reduce inflammation. PMID:26950310

Bioactive Egg Components and Inflammation

PubMed Central

Andersen, Catherine J.

2015-01-01

Inflammation is a normal acute response of the immune system to pathogens and tissue injury. However, chronic inflammation is known to play a significant role in the pathophysiology of numerous chronic diseases, such as cardiovascular disease, type 2 diabetes mellitus, and cancer. Thus, the impact of dietary factors on inflammation may provide key insight into mitigating chronic disease risk. Eggs are recognized as a functional food that contain a variety of bioactive compounds that can influence pro- and anti-inflammatory pathways. Interestingly, the effects of egg consumption on inflammation varies across different populations, including those that are classified as healthy, overweight, metabolic syndrome, and type 2 diabetic. The following review will discuss the pro- and anti-inflammatory properties of egg components, with a focus on egg phospholipids, cholesterol, the carotenoids lutein and zeaxanthin, and bioactive proteins. The effects of egg consumption of inflammation across human populations will additionally be presented. Together, these findings have implications for population-specific dietary recommendations and chronic disease risk. PMID:26389951

Identification of inflammation sites in arthritic joints using hyperspectral imaging

NASA Astrophysics Data System (ADS)

Paluchowski, Lukasz A.; Milanic, Matija; Bjorgan, Asgeir; Grandaunet, Berit; Dhainaut, Alvilde; Hoff, Mari; Randeberg, Lise L.

2014-03-01

Inflammatory arthritic diseases have prevalence between 2 and 3% and may lead to joint destruction and deformation resulting in a loss of function. Patient's quality of life is often severely affected as the disease attacks hands and finger joints. Pathology involved in arthritis includes angiogenesis, hyper-vascularization, hyper-metabolism and relative hypoxia. We have employed hyperspectral imaging to study the hemodynamics of affected- and non-affected joints and tissue. Two hyperspectral, push-broom cameras were used (VNIR-1600, SWIR-320i, Norsk Elektro Optikk AS, Norway). Optical spectra (400nm - 1700nm) of high spectral resolution were collected from 15 patients with visible symptoms of arthritic rheumatic diseases in at least one joint. The control group consisted of 10 healthy individuals. Concentrations of dominant chromophores were calculated based on analytical calculations of light transport in tissue. Image processing was used to analyze hyperspectral data and retrieve information, e.g. blood concentration and tissue oxygenation maps. The obtained results indicate that hyperspectral imaging can be used to quantify changes within affected joints and surrounding tissue. Further improvement of this method will have positive impact on diagnosis of arthritic joints at an early stage. Moreover it will enable development of fast, noninvasive and noncontact diagnostic tool of arthritic joints

Involvement of inflammation in acute coronary syndromes assessed by levels of high-sensitivity C-reactive protein, matrix metalloproteinase-9 and soluble vascular-cell adhesion molecule-1.

PubMed

Nomoto, Kazumiki; Oguchi, Sumito; Watanabe, Ikuyoshi; Kushiro, Toshio; Kanmatsuse, Katsuo

2003-11-01

Inflammation is important in the development of atherosclerosis. Matrix metalloproteinases (MMPs) and interferon-gamma which participate in collagen degradation are pathological factors in plaque vulnerability as an important mechanism underlying acute coronary syndrome. This study investigated whether inflammation is related to the onset of acute coronary syndrome. This study included 56 patients with acute coronary syndrome (ACS group), 104 patients with chronic coronary artery disease (S group), and 38 control subjects with no evidence of ischemic heart disease (C group). High-sensitivity C-reactive protein (hs-CRP), MMP-9, and interferon-gamma were measured in peripheral blood samples. Soluble adhesion molecules (VCAM-1, ICAM-1) were also measured as inflammatory markers. The hs-CRP level was significantly higher in the ACS group (44.5 mg/l) than in the S group (2.1 mg/l) and the C group (0.6 mg/l) (p < 0.0001). The MMP-9 level was also significantly higher in the ACS group (333.8 ng/ml) than in the S group (110.8 ng/ml) and the C group (72.0 ng/ml) (p < 0.0001). The VCAM-1 level was significantly higher in the ACS group (506.5 ng/ml) than in the C group (448.8 ng/ml) (p < 0.05). The ICAM-1 level and the interferon-gamma level did not differ between the groups. There was a significant positive correlation between the level of hs-CRP and the level of the collagen degradation product MMP-9 (r = 0.52) in all subjects. These results suggest that plaque destabilized by MMP-9 produced in response to inflammation participates in the mechanism of acute coronary syndrome.

Pathogenic and Obesogenic Factors Associated with Inflammation in Chinese Children, Adolescents and Adults

PubMed Central

Thompson, Amanda L.; Houck, Kelly M.; Adair, Linda; Gordon-Larsen, Penny; Du, Shufa; Zhang, Bing; Popkin, Barry

2014-01-01

Objectives Influenced by pathogen exposure and obesity, inflammation provides a critical biological pathway linking changing environments to the development of cardiometabolic disease. This study tests the relative contribution of obesogenic and pathogenic factors to moderate and acute CRP elevations in Chinese children, adolescents and adults. Methods Data come from 8795 participants in the China Health and Nutrition Study. Age-stratified multinomial logistic models were used to test the association between illness history, pathogenic exposures, adiposity, health behaviors and moderate (1-10 mg/L in children and 3-10 mg/L in adults) and acute (>10mg/L) CRP elevations, controlling for age, sex and clustering by household. Backward model selection was used to assess which pathogenic and obesogenic predictors remained independently associated with moderate and acute CRP levels when accounting for simultaneous exposures. Results Overweight was the only significant independent risk factor for moderate inflammation in children (RRR 2.10, 95%CI 1.13-3.89). History of infectious (RRR 1.28, 95%CI 1.08-1.52) and non-communicable (RRR 1.37, 95%CI 1.12-1.69) disease, overweight (RRR 1.66, 95%CI 1.45-1.89) and high waist circumference (RRR 1.63, 95%CI 1.42-1.87) were independently associated with a greater likelihood of moderate inflammation in adults while history of infectious disease (RRR 1.87, 95%CI 1.35-2.56) and overweight (RRR 1.40, 95%CI 1.04-1.88) were independently associated with acute inflammation. Environmental pathogenicity was associated with a reduced likelihood of moderate inflammation, but a greater likelihood of acute inflammation in adults. Conclusions These results highlight the importance of both obesogenic and pathogenic factors in shaping inflammation risk in societies undergoing nutritional and epidemiological transitions. PMID:24123588

Monoarticular Arthritis.

PubMed

Singh, Namrata; Vogelgesang, Scott A

2017-05-01

Monoarticular arthritis is inflammation characterized by joint pain, swelling, and sometimes periarticular erythema. Although chronic causes are seen, the onset is often acute. An infected joint can quickly lead to permanent damage, making it a medical emergency. However, acute gout presenting as monoarticular arthritis is often so uncomfortable it requires urgent attention. Monoarticular crystalline arthritis is common and a septic joint is a medical emergency so it is no surprise that these diagnoses come to mind with complaint of inflammation in 1 joint. However, there are many causes of monoarticular arthritis that clinicians must consider. Copyright © 2016 Elsevier Inc. All rights reserved.

Introduction of an agent-based multi-scale modular architecture for dynamic knowledge representation of acute inflammation.

PubMed

An, Gary

2008-05-27

One of the greatest challenges facing biomedical research is the integration and sharing of vast amounts of information, not only for individual researchers, but also for the community at large. Agent Based Modeling (ABM) can provide a means of addressing this challenge via a unifying translational architecture for dynamic knowledge representation. This paper presents a series of linked ABMs representing multiple levels of biological organization. They are intended to translate the knowledge derived from in vitro models of acute inflammation to clinically relevant phenomenon such as multiple organ failure. ABM development followed a sequence starting with relatively direct translation from in-vitro derived rules into a cell-as-agent level ABM, leading on to concatenated ABMs into multi-tissue models, eventually resulting in topologically linked aggregate multi-tissue ABMs modeling organ-organ crosstalk. As an underlying design principle organs were considered to be functionally composed of an epithelial surface, which determined organ integrity, and an endothelial/blood interface, representing the reaction surface for the initiation and propagation of inflammation. The development of the epithelial ABM derived from an in-vitro model of gut epithelial permeability is described. Next, the epithelial ABM was concatenated with the endothelial/inflammatory cell ABM to produce an organ model of the gut. This model was validated against in-vivo models of the inflammatory response of the gut to ischemia. Finally, the gut ABM was linked to a similarly constructed pulmonary ABM to simulate the gut-pulmonary axis in the pathogenesis of multiple organ failure. The behavior of this model was validated against in-vivo and clinical observations on the cross-talk between these two organ systems. A series of ABMs are presented extending from the level of intracellular mechanism to clinically observed behavior in the intensive care setting. The ABMs all utilize cell-level agents

Resolvin D3 Is Dysregulated in Arthritis and Reduces Arthritic Inflammation.

PubMed

Arnardottir, Hildur H; Dalli, Jesmond; Norling, Lucy V; Colas, Romain A; Perretti, Mauro; Serhan, Charles N

2016-09-15

Uncontrolled inflammation is a unifying component of many chronic inflammatory diseases, such as arthritis. Resolvins (Rvs) are a new family from the endogenous specialized proresolving mediators (SPMs) that actively stimulate resolution of inflammation. In this study, using lipid mediator metabololipidomics with murine joints we found a temporal regulation of endogenous SPMs during self-resolving inflammatory arthritis. The SPMs present in self-resolving arthritic joints include the D-series Rvs, for example, RvD1, RvD2, RvD3, and RvD4. Of note, RvD3 levels were reduced in inflamed joints from mice with delayed-resolving arthritis when compared with self-resolving inflammatory arthritis. RvD3 was also reduced in serum from rheumatoid arthritis patients compared with healthy controls. RvD3 administration reduced joint leukocytes as well as paw joint eicosanoids, clinical scores, and edema. Taken together, these findings provide evidence for dysregulated endogenous RvD3 levels in inflamed paw joints and its potent actions in reducing murine arthritis. Copyright © 2016 by The American Association of Immunologists, Inc.

Resolvin D3 is dysregulated in arthritis and reduces arthritic inflammation

PubMed Central

Arnardottir, Hildur H.; Dalli, Jesmond; Norling, Lucy V.; Colas, Romain A.; Perretti, Mauro; Serhan, Charles N.

2016-01-01

Uncontrolled inflammation is a unifying component of many chronic inflammatory diseases, such as arthritis. Resolvins (Rv) are a new family from the endogenous specialized pro-resolving lipid mediators (SPM) that actively stimulate resolution of inflammation. Herein, using lipid mediator (LM) metabololipidomics with murine joints we found a temporal regulation of endogenous SPM during self-resolving inflammatory arthritis. The SPMs present in self-resolving arthritic joints include the D-series resolvins, e.g. Resolvin (Rv) D1, RvD2, RvD3 and RvD4. Of note, RvD3 levels were reduced in inflamed joints from mice with delayed-resolving arthritis when compared to self-resolving inflammatory arthritis. RvD3 was also reduced in serum from rheumatoid arthritis (RA) patients compared to healthy controls. RvD3 administration reduced joint leukocytes as well as paw joint eicosanoids, clinical scores and edema. Together, these findings provide evidence for dysregulated endogenous RvD3 levels in inflamed paw joints and its potent actions in reducing murine arthritis. PMID:27534559

Irisin-mediated protective effect on LPS-induced acute lung injury via suppressing inflammation and apoptosis of alveolar epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shao, Lei; Jinan Central Hospital Affiliated to Shandong University, Jinan 250012; Meng, Di

It is considered that the essence of acute lung injury (ALI) is an excessive and uncontrolled inflammatory response in lung, of which mainly is attributed to the release of inflammatory mediators. Recent studies demonstrated that irisin, which is a metabolism associated factor after physical exercise could suppression of inflammation by regulating cellular signaling pathways, however, the underlying molecular mechanism remains to be determined. The present study aimed to reveal the potential mechanism responsible for the anti-inflammatory effects of irisin on LPS-induced acute lung injury in mice and in A549 cells. The results of histopathological changes showed that irisin ameliorated the lungmore » injury that was induced by LPS in time- and dose-dependent manner. QRT-PCR assays demonstrated that irisin suppressed the production of IL-1β, IL-6, MCP-1 and TNF-α, and western blot assays demonstrated that irisin suppressed apoptosis of ALI. The expression of caspase-3 and Bax were decreased and Bcl-2 was increased by irisin administration. Further study was conducted on nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) using pathways using western blots. The results showed that irisin inhibited reduced LPS-induced activation of MAPK and NF-κB signaling. All results indicated that irisin has protective effect on LPS-induced ALI in mice and in A549 cells. Thus, irisn related with physical exercise may be a potential therapy for the treatment of pulmonary inflammation. - Highlights: • Irisin inhibited the inflammation reactivity of cells and pathological changes of LPS-induced lung injury in mice. • Irisin inhibited mRNA expression of inflammatory cytokines induced by LPS in A549 cells. • Irisin inhibited apoptosis induced by LPS in the injured lung. • Irisin reduced LPS-induced activation of MAPK and NF-κB signaling pathways.« less

Use of Metal Oxide Nanoparticle Band Gap to Develop a Predictive Paradigm for Oxidative Stress and Acute Pulmonary Inflammation

PubMed Central

Zhang, Haiyuan; Ji, Zhaoxia; Xia, Tian; Meng, Huan; Low-Kam, Cecile; Liu, Rong; Pokhrel, Suman; Lin, Sijie; Wang, Xiang; Liao, Yu-Pei; Wang, Meiying; Li, Linjiang; Rallo, Robert; Damoiseaux, Robert; Telesca, Donatello; Mädler, Lutz; Cohen, Yoram; Zink, Jeffrey I.; Nel, Andre E.

2014-01-01

We demonstrate for 24 metal oxide (MOx) nanoparticles that it is possible to use conduction band energy levels to delineate their toxicological potential at cellular and whole animal levels. Among the materials, the overlap of conduction band energy (Ec) levels with the cellular redox potential (−4.12 to −4.84 eV) was strongly correlated to the ability of Co3O4, Cr2O3, Ni2O3, Mn2O3 and CoO nanoparticles to induce oxygen radicals, oxidative stress and inflammation. This outcome is premised on permissible electron transfers from the biological redox couples that maintain the cellular redox equilibrium to the conduction band of the semiconductor particles. Both single parameter cytotoxic as well as multi-parameter oxidative stress assays in cells showed excellent correlation to the generation of acute neutrophilic inflammation and cytokine responses in the lungs of CB57 Bl/6 mice. Co3O4, Ni2O3, Mn2O3 and CoO nanoparticles could also oxidize cytochrome c as a representative redox couple involved in redox homeostasis. While CuO and ZnO generated oxidative stress and acute pulmonary inflammation that is not predicted by Ec levels, the adverse biological effects of these materials could be explained by their solubility, as demonstrated by ICP-MS analysis. Taken together, these results demonstrate, for the first time, that it is possible to predict the toxicity of a large series of MOx nanoparticles in the lung premised on semiconductor properties and an integrated in vitro/in vivo hazard ranking model premised on oxidative stress. This establishes a robust platform for modeling of MOx structure-activity relationships based on band gap energy levels and particle dissolution. This predictive toxicological paradigm is also of considerable importance for regulatory decision-making about this important class of engineered nanomaterials. PMID:22502734

Use of metal oxide nanoparticle band gap to develop a predictive paradigm for oxidative stress and acute pulmonary inflammation.

PubMed

Zhang, Haiyuan; Ji, Zhaoxia; Xia, Tian; Meng, Huan; Low-Kam, Cecile; Liu, Rong; Pokhrel, Suman; Lin, Sijie; Wang, Xiang; Liao, Yu-Pei; Wang, Meiying; Li, Linjiang; Rallo, Robert; Damoiseaux, Robert; Telesca, Donatello; Mädler, Lutz; Cohen, Yoram; Zink, Jeffrey I; Nel, Andre E

2012-05-22

We demonstrate for 24 metal oxide (MOx) nanoparticles that it is possible to use conduction band energy levels to delineate their toxicological potential at cellular and whole animal levels. Among the materials, the overlap of conduction band energy (E(c)) levels with the cellular redox potential (-4.12 to -4.84 eV) was strongly correlated to the ability of Co(3)O(4), Cr(2)O(3), Ni(2)O(3), Mn(2)O(3), and CoO nanoparticles to induce oxygen radicals, oxidative stress, and inflammation. This outcome is premised on permissible electron transfers from the biological redox couples that maintain the cellular redox equilibrium to the conduction band of the semiconductor particles. Both single-parameter cytotoxic as well as multi-parameter oxidative stress assays in cells showed excellent correlation to the generation of acute neutrophilic inflammation and cytokine responses in the lungs of C57 BL/6 mice. Co(3)O(4), Ni(2)O(3), Mn(2)O(3), and CoO nanoparticles could also oxidize cytochrome c as a representative redox couple involved in redox homeostasis. While CuO and ZnO generated oxidative stress and acute pulmonary inflammation that is not predicted by E(c) levels, the adverse biological effects of these materials could be explained by their solubility, as demonstrated by ICP-MS analysis. These results demonstrate that it is possible to predict the toxicity of a large series of MOx nanoparticles in the lung premised on semiconductor properties and an integrated in vitro/in vivo hazard ranking model premised on oxidative stress. This establishes a robust platform for modeling of MOx structure-activity relationships based on band gap energy levels and particle dissolution. This predictive toxicological paradigm is also of considerable importance for regulatory decision-making about this important class of engineered nanomaterials.

[The way of self-defence of the organism: inflammation].

PubMed

Jakab, Lajos

2013-08-11

The acute and chronic constitutional reactions of the organism elicited by sterile causes and pathogenic structures threatening the soundness of the organism are surveyed by the author. It is emphasized that depending on causes which can be very different, there are various syndromes occurring in the clinical practice. On the basis of multitudiness of pathogenic factors and individual differences, the infammatory reactions are clinically, pathologically and pathobiochemically can be hugely variable. The acute inflammatory response may be sterile. It is often difficult to recognize in these processes whether the inflammation is harmful or beneficial for the organism as a whole. It is possible that the inflammatory response itself is the defending resource of the individual. The non-sterile acute inflammation is evoked by pathogenic microorganisms. The variety of clinical syndromes are explained by the high diversity of pathogenic microbes, the individualities of the defending organisms, and the natural and adaptive immunity of the organism which may be intact or possibly defective. In the latter case the inflammation itself is the disease, as a consequence of a pathological process conducted by the cortico-hypothalamo-adernal axis. The acute inflammation is a defending, preventing and repairing process, constituting an important part of the natural innate immune response. It is inseparable from the natural innate immune response, which is in close cooperation with the adaptive, specific immune response with mutual effects on each of the other. The conductor and the response reactions of the two immune responses are also the same. There are alterations in serum proteins/glycoproteins synthesized mostly by the hepatocytes. Because the concentration of almost all proteins/glycoproteins may change, the use of the discriminative term "acute phase reactant" is hardly relevant. For example, the HDL molecule is a negative "acute phase reactant". On the gound of clinical

Synergistic interaction between choline and aspirin against acute inflammation induced by carrageenan and lipopolysaccharide.

PubMed

Pan, Zhi-Yuan; Wang, Hai

2014-05-01

The simultaneous use of drugs with different mechanisms of anti-inflammatory action is a strategy for achieving effective control of inflammation while minimizing dose-related side effects. Choline was described to potentiate the antinociceptive action of aspirin at small doses in several inflammatory pain models. However, these findings are only limited to alleviating pain, more associated data are required to confirm the effectiveness of the combined choline and aspirin therapy against inflammatory disorders. Moreover, no report is available regarding the mechanism responsible for their synergism. Here, we first investigated the anti-inflammatory activity and pharmacological mechanisms of co-administration of choline and aspirin in 2 commonly studied inflammation models, carrageenan-induced paw edema and lipopolysaccharide (LPS)-induced sepsis in mice. Isobolographic analysis revealed that combined choline and aspirin administration exhibited a strong synergistic interaction in reducing carrageenan-mediated edema, and the estimated combination index values at 50%, 75%, and 90% effective dose (ED50, ED75, and ED90) were 0.25, 0.32, and 0.44. Drug co-administration also afforded synergistic protection against LPS-induced sepsis and mortality, since aspirin or choline alone was inadequate to improve survival. The effects of choline-aspirin co-administration were blocked by methyllycaconitine, suggesting that activation of alpha 7 nicotinic acetylcholine receptor participates in the interaction between choline and aspirin. Furthermore, co-administration of choline and aspirin was more likely to inhibit the production of pro-inflammatory mediators induced by LPS. Our results indicated that combined choline and aspirin therapy represented a significant synergistic interaction in attenuating acute inflammatory response. This preclinical relevant evidence provides a promising approach to treat inflammation-based diseases such as arthritis and sepsis. Copyright © 2014

Comparative Effects of Volutrauma and Atelectrauma on Lung Inflammation in Experimental Acute Respiratory Distress Syndrome

PubMed Central

Güldner, Andreas; Braune, Anja; Ball, Lorenzo; Silva, Pedro L.; Samary, Cynthia; Insorsi, Angelo; Huhle, Robert; Rentzsch, Ines; Becker, Claudia; Oehme, Liane; Andreeff, Michael; Vidal Melo, Marcos F.; Winkler, Tilo; Pelosi, Paolo; Rocco, Patricia R. M.; Kotzerke, Jörg; de Abreu, Marcelo Gama

2016-01-01

Objective Volutrauma and atelectrauma promote ventilator-induced lung injury, but their relative contribution to inflammation in ventilator-induced lung injury is not well established. The aim of this study was to determine the impact of volutrauma and atelectrauma on the distribution of lung inflammation in experimental acute respiratory distress syndrome. Design Laboratory investigation. Setting University-hospital research facility. Subjects Ten pigs (five per group; 34.7–49.9 kg) Interventions Animals were anesthetized and intubated, and saline lung lavage was performed. Lungs were separated with a double-lumen tube. Following lung recruitment and decremental positive end-expiratory pressure trial, animals were randomly assigned to 4 hours of ventilation of the left (ventilator-induced lung injury) lung with tidal volume of approximately 3 mL/kg and 1) high positive end-expiratory pressure set above the level where dynamic compliance increased more than 5% during positive end-expiratory pressure trial (volutrauma); or 2) low positive end-expiratory pressure to achieve driving pressure comparable with volutrauma (atelectrauma). The right (control) lung was kept on continuous positive airway pressure of 20 cm H2O, and Co2 was partially removed extracorporeally. Measurements and Main Results Regional lung aeration, specific [18F]fluorodeoxyglucose uptake rate, and perfusion were assessed using computed and positron emission tomography. Volutrauma yielded higher [18F]fluorodeoxyglucose uptake rate in the ventilated lung compared with atelectrauma (median [interquartile range], 0.017 [0.014–0.025] vs 0.013 min−1 [0.010–0.014min−1]; p < 0.01), mainly in central lung regions. Volutrauma yielded higher [18F]fluorodeoxyglucose uptake rate in ventilator-induced lung injury versus control lung (0.017 [0.014–0.025] vs 0.011 min−1 [0.010–0.016min−1]; p < 0.05), whereas atelectrauma did not. Volutrauma decreased blood fraction at similar perfusion and

Joint nociceptor nerve activity and pain in an animal model of acute gout and its modulation by intra-articular hyaluronan

PubMed Central

Marcotti, Aida; Miralles, Ana; Dominguez, Eduardo; Pascual, Eliseo; Gomis, Ana; Belmonte, Carlos; de la Peña, Elvira

2018-01-01

Abstract The mechanisms whereby deposition of monosodium urate (MSU) crystals in gout activates nociceptors to induce joint pain are incompletely understood. We tried to reproduce the signs of painful gouty arthritis, injecting into the knee joint of rats suspensions containing amorphous or triclinic, needle MSU crystals. The magnitude of MSU-induced inflammation and pain behavior signs were correlated with the changes in firing frequency of spontaneous and movement-evoked nerve impulse activity recorded in single knee joint nociceptor saphenous nerve fibers. Joint swelling, mechanical and cold allodynia, and hyperalgesia appeared 3 hours after joint injection of MSU crystals. In parallel, spontaneous and movement-evoked joint nociceptor impulse activity raised significantly. Solutions containing amorphous or needle-shaped MSU crystals had similar inflammatory and electrophysiological effects. Intra-articular injection of hyaluronan (HA, Synvisc), a high-MW glycosaminoglycan present in the synovial fluid with analgesic effects in osteoarthritis, significantly reduced MSU-induced behavioral signs of pain and decreased the enhanced joint nociceptor activity. Our results support the interpretation that pain and nociceptor activation are not triggered by direct mechanical stimulation of nociceptors by MSU crystals, but are primarily caused by the release of excitatory mediators by inflammatory cells activated by MSU crystals. Intra-articular HA decreased behavioral and electrophysiological signs of pain, possibly through its viscoelastic filtering effect on the mechanical forces acting over sensitized joint sensory endings and probably also by a direct interaction of HA molecules with the transducing channels expressed in joint nociceptor terminals. PMID:29319609

[A flow diagram for the diagnosis of acute, non-traumatic joint complaints during childhood, retrospectively applied to 115 children].

PubMed

ten Cate, R; Lankester, A C; van der Straaten, P J C; van Suijlekom-Smit, L W A; Wit, J M

2002-06-29

Acute, non-traumatic joint complaints during childhood can be caused by conditions which require a quick and adequate recognition and treatment as well as by conditions in which an expectant policy can be pursued. On the basis of certain data from the anamnesis, supplemented with findings from the physical examination it is often possible to arrive at a (probable) diagnosis. An algorithm was designed, the differential steps of which were: fever, C-reactive protein titre, involvement of the hip joint, the presence of extra-articular manifestations and the results of a full blood count, erythrocyte sedimentation rate and imaging techniques. When this algorithm was retrospectively applied to the disease data of 115 children with acute, non-traumatic joint complaints, for whom the diagnosis in the status was taken as the gold standard, the correct diagnosis was established for every single child: for 98 (85.2%) by the shortest route and for 17 (14.8%) indirectly. In the case of 4 children, use of this algorithm would have led to unnecessary laboratory investigations and/or treatment. None of the diseases requiring immediate treatment were missed.

Acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza infection, but does not exacerbate deficits in lung function

PubMed Central

Larcombe, Alexander N.; Foong, Rachel E.; Boylen, Catherine E.; Zosky, Graeme R.

2012-01-01

Please cite this paper as: Larcombe et al. (2012) Acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza infection, but does not exacerbate deficits in lung function. Influenza and Other Respiratory Viruses DOI:10.1111/irv.12012. Background  Exposure to diesel exhaust particles (DEP) is thought to exacerbate many pre‐existing respiratory diseases, including asthma, bronchitis and chronic obstructive pulmonary disease, however, there is a paucity of data on whether DEP exacerbates illness due to respiratory viral infection. Objectives  To assess the physiological consequences of an acute DEP exposure during the peak of influenza‐induced illness. Methods  We exposed adult female BALB/c mice to 100 μg DEP (or control) 3·75 days after infection with 104·5 plaque forming units of influenza A/Mem71 (or control). Six hours, 24 hours and 7 days after DEP exposure we measured thoracic gas volume and lung function at functional residual capacity. Bronchoalveolar lavage fluid was taken for analyses of cellular inflammation and cytokines, and whole lungs were taken for measurement of viral titre. Results  Influenza infection resulted in significantly increased inflammation, cytokine influx and impairment to lung function. DEP exposure alone resulted in less inflammation and cytokine influx, and no impairment to lung function. Mice infected with influenza and exposed to DEP had higher viral titres and neutrophilia compared with infected mice, yet they did not have more impaired lung mechanics than mice infected with influenza alone. Conclusions  A single dose of DEP is not sufficient to physiologically exacerbate pre‐existing respiratory disease caused by influenza infection in mice. PMID:22994877

Influence of Pneumococcal Conjugate Vaccine on Acute Otitis Media with Severe Middle Ear Inflammation: A Retrospective Multicenter Study.

PubMed

Sugino, Hirotoshi; Tsumura, Shigeru; Kunimoto, Masaru; Noda, Masuhiro; Chikuie, Daisuke; Noda, Chieko; Yamashita, Mariko; Watanabe, Hiroshi; Ishii, Hidemasa; Tashiro, Toru; Iwata, Kazuhiro; Kono, Takashi; Tsumura, Kaoru; Sumiya, Takahiro; Takeno, Sachio; Hirakawa, Katsuhiro

2015-01-01

The Japanese guidelines for acute otitis media in children recommend classifying acute otitis media by age, manifestations and local findings, and also recommend myringotomy for moderate-grade cases with severe local findings, severe-grade cases, and treatment-resistant cases. The heptavalent pneumococcal conjugate vaccine was released in Japan in February 2010. In Hiroshima City, public funding allowing free inoculation with this vaccine was initiated from January 2011, and the number of vaccinated individuals has since increased dramatically. This study investigated changes in the number of myringotomies performed to treat acute otitis media during the 5-year period from January 2008 to December 2012 at two hospitals and five clinics in the Asa Area of Hiroshima City, Japan. A total of 3,165 myringotomies for acute otitis media were performed. The rate of procedures per child-year performed in <5-year-old children decreased by 29.1% in 2011 and by 25.2% in 2012 compared to the mean rate performed in the 3 years prior to the introduction of public funding. A total of 895 myringotomies were performed for 1-year-old infants. The rate of myringotomies per child-year performed for acute otitis media in 1-year-old infants decreased significantly in the 2 years after the introduction of public funding for heptavalent pneumococcal conjugate vaccine compared to all years before introduction (p<0.000001). Our results suggest a benefit of heptavalent pneumococcal conjugate vaccine for acute otitis media in reducing the financial burden of myringotomy. In addition, this vaccine may help prevent acute otitis media with severe middle ear inflammation in 1-year-old infants.

Evolutionary medicine and bone loss in chronic inflammatory diseases – a theory of inflammation-related osteopenia

PubMed Central

Straub, Rainer H.; Cutolo, Maurizio; Pacifici, Roberto

2015-01-01

Objective Bone loss is typical in chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, pemphigus vulgaris, and others. It is also typical in transplantation-related inflammation and during the process of aging. While we recognized that bone loss is tightly linked to immune system activation or inflammaging in the form of acute, chronic active, or chronic smoldering inflammation, bone loss is typically discussed to be an “accident of inflammation”. Methods Extensive literature search in PubMed central. Results Using elements of evolutionary medicine, energy regulation, and neuroendocrine regulation of homeostasis and immune function, we work out that bone waste is an adaptive, evolutionarily positively selected program that is absolutely necessary during acute inflammation. However, when acute inflammation enters a chronic state due to the inability to terminate inflammation (e.g., in autoimmunity or in continuous immunity against microbes), the acute program of bone loss is a misguided adaptive program. Conclusions The article highlights the complexity of interwoven pathways of osteopenia. PMID:26044543

FABP4 inhibitors suppress inflammation and oxidative stress in murine and cell models of acute lung injury.

PubMed

Gong, Yuanqi; Yu, Zhihong; Gao, Yi; Deng, Linlin; Wang, Meng; Chen, Yu; Li, Jingying; Cheng, Bin

2018-02-19

Acute lung injury (ALI) is a severe disease with high morbidity and mortality, and is characterized by devastating inflammation of the lung and increased production of reactive oxygen species (ROS). Recent studies have indicated that fatty acid binding protein (FABP4) is important in the regulation of inflammation. However, the role of FABP4 in sepsis-related ALI, and the specific mechanism of action have not been examined. In vitro, the exposure of human alveolar epithelial A549 cells to lipopolysaccharide (LPS) and recombinant FABP4 (hrFABP4) resulted in the production of pro-inflammatory cytokines, inflammatory cytokines, and ROS, while these changes were ameliorated by pretreatment with the FABP4 inhibitor BMS309403 and FABP4 siRNA. Sequentially, treatment of A549 cells with N-acetylcysteine (NAC) significantly attenuated LPS and hrFABP4-induced the generation of ROS and the release of inflammatory cytokines. In vivo, a cecal ligation and puncture (CLP)-induced ALI murine model was successfully established. Then, the mice were treated with FABP4 inhibitor BMS309403. The results showed treatment with BMS309403 improved the survival rate of CLP-induced ALI mice, and prevented lung inflammation, histopathological changes, and increase of FABP4 induced by CLP. These data indicate that FABP4 plays an important role in lung inflammation of sepsis-induced ALI. Blockade of FABP4 signaling exhibits a protective effect in a CLP-induced ALI mouse model, and in A549 cell LPS specifically induces enhanced expression of FABP4, which then causes inflammatory cytokine production by elevating the ROS level. Copyright © 2018 Elsevier Inc. All rights reserved.

Curbing Inflammation in the Ischemic Heart Disease

PubMed Central

Evora, Paulo Roberto B.; Nather, Julio; Tubino, Paulo Victor; Albuquerque, Agnes Afrodite S.; Celotto, Andrea Carla; Rodrigues, Alfredo J.

2013-01-01

A modern concept considers acute coronary syndrome as an autoinflammatory disorder. From the onset to the healing stage, an endless inflammation has been presented with complex, multiple cross-talk mechanisms at the molecular, cellular, and organ levels. Inflammatory response following acute myocardial infarction has been well documented since the 1940s and 1950s, including increased erythrocyte sedimentation rate, the C-reactive protein analysis, and the determination of serum complement. It is surprising to note, based on a wide literature overview including the following 30 years (decades of 1960, 1970, and 1980), that the inflammatory acute myocardium infarction lost its focus, virtually disappearing from the literature reports. The reversal of this historical process occurs in the 1990s with the explosion of studies involving cytokines. Considering the importance of inflammation in the pathophysiology of ischemic heart disease, the aim of this paper is to present a conceptual overview in order to explore the possibility of curbing this inflammatory process. PMID:23819098

Statin Use, Serum Lipids, and Prostate Inflammation in Men with a Negative Prostate Biopsy: Results from the REDUCE Trial.

PubMed

Allott, Emma H; Howard, Lauren E; Vidal, Adriana C; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freedland, Stephen J

2017-06-01

Statin use is associated with lower advanced prostate cancer risk. In addition to cholesterol lowering, statins have systemic anti-inflammatory properties. However, their effect on histologic prostate inflammation is not well understood, particularly among men at increased prostate cancer risk but with a negative prostate biopsy. We examined associations between serum lipid levels, statin use, and histologic prostate inflammation using data from 6,655 men with a negative baseline prostate biopsy in the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial. Statin use and lipid levels [total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides] were assessed at baseline. Inflammation was assessed by central review. Logistic regression was used to examine the effects of lipids and statin use on presence and extent of chronic and acute prostate inflammation [none, moderate (<20%), severe (≥20% biopsy cores)]. Chronic and acute inflammation affected 77% and 15% of men, respectively. Men with high HDL (≥60 vs. <40 mg/dL) had reduced presence of acute inflammation [OR, 0.79; 95% confidence interval (CI), 0.63-0.99] and were less likely to have severe acute inflammation (OR, 0.66; 95% CI, 0.45-0.97), but there were no other associations between lipids and inflammation. Statin users had reduced presence of chronic inflammation (OR, 0.81; 95% CI, 0.69-0.95) and were less likely to have severe chronic (OR, 0.80; 95% CI, 0.68-0.95) and severe acute inflammation (OR, 0.73; 95% CI, 0.53-1.00), relative to non-users. Given the possible role for inflammation in prostate cancer, the inverse association between statins and prostate inflammation suggests a mechanism linking statins with lower advanced prostate cancer risk. Cancer Prev Res; 10(6); 319-26. ©2017 AACR . ©2017 American Association for Cancer Research.

Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis

PubMed Central

Robinson, William H.; Lepus, Christin M.; Wang, Qian; Raghu, Harini; Mao, Rong; Lindstrom, Tamsin M.; Sokolove, Jeremy

2017-01-01

Osteoarthritis (OA) has long been viewed as a degenerative disease of cartilage, but accumulating evidence indicates that inflammation has a critical role in its pathogenesis. Furthermore, we now appreciate that OA pathogenesis involves not only breakdown of cartilage, but also remodelling of the underlying bone, formation of ectopic bone, hypertrophy of the joint capsule, and inflammation of the synovial lining. That is, OA is a disorder of the joint as a whole, with inflammation driving many pathologic changes. The inflammation in OA is distinct from that in rheumatoid arthritis and other autoimmune diseases: it is chronic, comparatively low-grade, and mediated primarily by the innate immune system. Current treatments for OA only control the symptoms, and none has been FDA-approved for the prevention or slowing of disease progression. However, increasing insight into the inflammatory underpinnings of OA holds promise for the development of new, disease-modifying therapies. Indeed, several anti-inflammatory therapies have shown promise in animal models of OA. Further work is needed to identify effective inhibitors of the low-grade inflammation in OA, and to determine whether therapies that target this inflammation can prevent or slow the development and progression of the disease. PMID:27539668

Comparison of oral robenacoxib and ketoprofen for the treatment of acute pain and inflammation associated with musculoskeletal disorders in cats: a randomised clinical trial.

PubMed

Sano, Tadashi; King, Jonathan N; Seewald, Wolfgang; Sakakibara, Nobuhiro; Okumura, Masahiro

2012-08-01

The objective of the study was to evaluate the efficacy and tolerability of robenacoxib, a selective cyclooxygenase-2 inhibitor, for the treatment of acute pain and inflammation associated with musculoskeletal disorders in cats. The study was a prospective, multi-centre, randomised, blinded, non-inferiority design clinical trial comparing robenacoxib to ketoprofen. A total of 68 cats presenting with pain and inflammation associated with acute musculoskeletal disorders were recruited and allocated randomly to receive, orally once daily for 5-6 days, either 1.0-2.4 mg/kg robenacoxib (n=47) or 1mg/kg ketoprofen (n=21). The primary efficacy endpoint was the total clinician score, which was the sum of clinician numerical rating scale scores for pain, inflammation and mobility. Assessments were made at baseline, on day 2, and day 4 or 5. For the total clinician score, non-inferior efficacy of robenacoxib was demonstrated with a relative efficacy of 1.151 (95% confidence interval 0.872-1.494). Non-inferior efficacy of robenacoxib was also demonstrated for the secondary endpoint of the total owner score. Robenacoxib was superior (P<0.05) to ketoprofen for the owner's assessment of activity and human/animal relationship. The tolerability of both treatments was good as assessed by monitoring adverse events, clinical signs and haematology and serum biochemistry variables. Copyright © 2012. Published by Elsevier Ltd.

Resolution of inflammation: state of the art, definitions and terms

PubMed Central

Serhan, Charles N.; Brain, Sue D.; Buckley, Christopher D.; Gilroy, Derek W.; Haslett, Christopher; O’Neill, Luke A. J.; Perretti, Mauro; Rossi, Adriano G.; Wallace, John L.

2011-01-01

A recent focus meeting on Controlling Acute Inflammation was held in London, April 27-28, 2006, organized by D.W. Gilroy and S.D. Brain for the British Pharmacology Society. We concluded at the meeting that a consensus report was needed that addresses the rapid progress in this emerging field and details how the specific study of resolution of acute inflammation provides leads for novel anti-inflammatory therapeutics, as well as defines the terms and key components of interest in the resolution process within tissues as appreciated today. The inflammatory response protects the body against infection and injury but can itself become dysregulated with deleterious consequences to the host. It is now evident that endogenous biochemical pathways activated during defense reactions can counter-regulate inflammation and promote resolution. Hence, resolution is an active rather than a passive process, as once believed, which now promises novel approaches for the treatment of inflammation-associated diseases based on endogenous agonists of resolution. PMID:17267386

Current Risk Adjustment and Comorbidity Index Underperformance in Predicting Post-Acute Utilization and Hospital Readmissions After Joint Replacements: Implications for Comprehensive Care for Joint Replacement Model.

PubMed

Kumar, Amit; Karmarkar, Amol; Downer, Brian; Vashist, Amit; Adhikari, Deepak; Al Snih, Soham; Ottenbacher, Kenneth

2017-11-01

To compare the performances of 3 comorbidity indices, the Charlson Comorbidity Index, the Elixhauser Comorbidity Index, and the Centers for Medicare & Medicaid Services (CMS) risk adjustment model, Hierarchical Condition Category (HCC), in predicting post-acute discharge settings and hospital readmission for patients after joint replacement. A retrospective study of Medicare beneficiaries with total knee replacement (TKR) or total hip replacement (THR) discharged from hospitals in 2009-2011 (n = 607,349) was performed. Study outcomes were post-acute discharge setting and unplanned 30-, 60-, and 90-day hospital readmissions. Logistic regression models were built to compare the performance of the 3 comorbidity indices using C statistics. The base model included patient demographics and hospital use. Subsequent models included 1 of the 3 comorbidity indices. Additional multivariable logistic regression models were built to identify individual comorbid conditions associated with high risk of hospital readmissions. The 30-, 60-, and 90-day unplanned hospital readmission rates were 5.3%, 7.2%, and 8.5%, respectively. Patients were most frequently discharged to home health (46.3%), followed by skilled nursing facility (40.9%) and inpatient rehabilitation facility (12.7%). The C statistics for the base model in predicting post-acute discharge setting and 30-, 60-, and 90-day readmission in TKR and THR were between 0.63 and 0.67. Adding the Charlson Comorbidity Index, the Elixhauser Comorbidity Index, or HCC increased the C statistic minimally from the base model for predicting both discharge settings and hospital readmission. The health conditions most frequently associated with hospital readmission were diabetes mellitus, pulmonary disease, arrhythmias, and heart disease. The comorbidity indices and CMS-HCC demonstrated weak discriminatory ability to predict post-acute discharge settings and hospital readmission following joint replacement. © 2017, American College of

Taraxerol, a pentacyclic triterpene from Abroma augusta leaf, attenuates acute inflammation via inhibition of NF-κB signaling.

PubMed

Khanra, Ritu; Dewanjee, Saikat; Dua, Tarun K; Bhattacharjee, Niloy

2017-04-01

Abroma augusta L. (Malvaceae) leaf is traditionally used to treat inflammatory disorders. In our laboratory, we have scientifically validated the anti-inflammatory effect of A. augusta leaf extract. In this study, it has been aimed to evaluate in vivo anti-inflammatory effect of taraxerol isolated from the methanol extract of A. augusta leaf. It was further intended to find out the probable mechanism of anti-inflammatory effect of taraxerol. The anti-inflammatory effect of taraxerol (5 and 10mg/kg, i.p.) was measured employing carrageenan-induced paw edema model of acute inflammation. The carrageenan injection resulted significant edema formation in the right paw when compared with un-injected left paw. However, taraxerol (10mg/kg) treatment could significantly (p<0.05-0.01) attenuate carrageenan induced paw edema 2h onward. The effect of taraxerol at the dose of 5mg/kg was found to be significant (p<0.05) only after 4h of carrageenan treatment. Taraxerol (10mg/kg) treatment could significantly (p<0.01) attenuate carrageenan mediated up-regulation in the levels of IL 1β, IL 6, IL 12 and TNF α in the right paw tissues. In search of molecular mechanism, taraxerol (10mg/kg) could significantly (p<0.05-0.01) reinstate carrageenan provoked NF-κB signaling and thereby caused significant down-regulation in the expressions of COX-2 (p<0.01) and iNOS (p<0.05). In conclusion, taraxerol would attenuate acute inflammation via inhibition of NF-κB signaling. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

[Sacroiliac joint dysfunction presented with acute low back pain: three case reports].

PubMed

Hamauchi, Shuji; Morimoto, Daijiro; Isu, Toyohiko; Sugawara, Atsushi; Kim, Kyongsong; Shimoda, Yusuke; Motegi, Hiroaki; Matsumoto, Ryoji; Isobe, Masanori

2010-07-01

Sacroiliac joint (SIJ) can cause low back pain when its joint capsule and ligamentous tissue are damaged. We report our experience in treating three SIJ dysfunction patients presenting with acute low back pain (a 38 year-old male, a 24 year-old male, and a 32 year-old female). SIJ dysfunction was diagnosed using the one-finger test, the modified Newton test, and SIJ injection. In all three patients, lumbar MRI demonstrated slightly degenerated lumbar lesions (lumbar canal stenosis, lumbar disc hernia). Two patients had paresthesia or pain in the leg and all three patients showed iliac muscle tenderness in the groin, which was thought to be a referred symptom because of improvement after SIJ injection. The two male patients returned to work and the problems have not recurred. Although our female patient resumed daily life as a housewife, her condition recurred at intervals of 2-3 months and she required regular SIJ injections. The prevalence of SIJ dysfunction of low back pain is about 10%, so it should be considered as a differential diagnosis when treating low back pain and designing treatment for lumbar spinal disorders.

Phospholipase C-ε signaling mediates endothelial cell inflammation and barrier disruption in acute lung injury

PubMed Central

Bijli, Kaiser M.; Fazal, Fabeha; Slavin, Spencer A.; Leonard, Antony; Grose, Valerie; Alexander, William B.; Smrcka, Alan V.

2016-01-01

Phospholipase C-ε (PLC-ε) is a unique PLC isoform that can be regulated by multiple signaling inputs from both Ras family GTPases and heterotrimeric G proteins and has primary sites of expression in the heart and lung. Whereas the role of PLC-ε in cardiac function and pathology has been documented, its relevance in acute lung injury (ALI) is unclear. We used PLC-ε−/− mice to address the role of PLC-ε in regulating lung vascular inflammation and injury in an aerosolized bacterial LPS inhalation mouse model of ALI. PLC-ε−/− mice showed a marked decrease in LPS-induced proinflammatory mediators (ICAM-1, VCAM-1, TNF-α, IL-1β, IL-6, macrophage inflammatory protein 2, keratinocyte-derived cytokine, monocyte chemoattractant protein 1, and granulocyte-macrophage colony-stimulating factor), lung neutrophil infiltration and microvascular leakage, and loss of VE-cadherin compared with PLC-ε+/+ mice. These data identify PLC-ε as a critical determinant of proinflammatory and leaky phenotype of the lung. To test the possibility that PLC-ε activity in endothelial cells (EC) could contribute to ALI, we determined its role in EC inflammation and barrier disruption. RNAi knockdown of PLC-ε inhibited NF-κB activity in response to diverse proinflammatory stimuli, thrombin, LPS, TNF-α, and the nonreceptor agonist phorbol 13-myristate 12-acetate (phorbol esters) in EC. Depletion of PLC-ε also inhibited thrombin-induced expression of NF-κB target gene, VCAM-1. Importantly, PLC-ε knockdown also protected against thrombin-induced EC barrier disruption by inhibiting the loss of VE-cadherin at adherens junctions and formation of actin stress fibers. These data identify PLC-ε as a novel regulator of EC inflammation and permeability and show a hitherto unknown role of PLC-ε in the pathogenesis of ALI. PMID:27371732

Phospholipase C-ε signaling mediates endothelial cell inflammation and barrier disruption in acute lung injury.

PubMed

Bijli, Kaiser M; Fazal, Fabeha; Slavin, Spencer A; Leonard, Antony; Grose, Valerie; Alexander, William B; Smrcka, Alan V; Rahman, Arshad

2016-08-01

Phospholipase C-ε (PLC-ε) is a unique PLC isoform that can be regulated by multiple signaling inputs from both Ras family GTPases and heterotrimeric G proteins and has primary sites of expression in the heart and lung. Whereas the role of PLC-ε in cardiac function and pathology has been documented, its relevance in acute lung injury (ALI) is unclear. We used PLC-ε(-/-) mice to address the role of PLC-ε in regulating lung vascular inflammation and injury in an aerosolized bacterial LPS inhalation mouse model of ALI. PLC-ε(-/-) mice showed a marked decrease in LPS-induced proinflammatory mediators (ICAM-1, VCAM-1, TNF-α, IL-1β, IL-6, macrophage inflammatory protein 2, keratinocyte-derived cytokine, monocyte chemoattractant protein 1, and granulocyte-macrophage colony-stimulating factor), lung neutrophil infiltration and microvascular leakage, and loss of VE-cadherin compared with PLC-ε(+/+) mice. These data identify PLC-ε as a critical determinant of proinflammatory and leaky phenotype of the lung. To test the possibility that PLC-ε activity in endothelial cells (EC) could contribute to ALI, we determined its role in EC inflammation and barrier disruption. RNAi knockdown of PLC-ε inhibited NF-κB activity in response to diverse proinflammatory stimuli, thrombin, LPS, TNF-α, and the nonreceptor agonist phorbol 13-myristate 12-acetate (phorbol esters) in EC. Depletion of PLC-ε also inhibited thrombin-induced expression of NF-κB target gene, VCAM-1. Importantly, PLC-ε knockdown also protected against thrombin-induced EC barrier disruption by inhibiting the loss of VE-cadherin at adherens junctions and formation of actin stress fibers. These data identify PLC-ε as a novel regulator of EC inflammation and permeability and show a hitherto unknown role of PLC-ε in the pathogenesis of ALI. Copyright © 2016 the American Physiological Society.

Adenosine-dependent phrenic motor facilitation is inflammation resistant

PubMed Central

Agosto-Marlin, Ibis M.; Nichols, Nicole L.

2016-01-01

Phrenic motor facilitation (pMF), a form of respiratory plasticity, can be elicited by acute intermittent hypoxia (i.e., phrenic long-term facilitation, pLTF) or direct application of drugs to the cervical spinal cord. Moderate acute intermittent hypoxia (mAIH; 3 × 5-min episodes of 35–50 mmHg arterial Po2, 5-min normoxic intervals) induces pLTF by a serotonin-dependent mechanism; mAIH-induced pLTF is abolished by mild systemic inflammation induced by a low dose of lipopolysaccharide (LPS; 100 μg/kg ip). In contrast, severe acute intermittent hypoxia (sAIH; 3 × 5-min episodes of 25–30 mmHg arterial Po2, 5-min normoxic intervals) elicits pLTF by a distinct, adenosine-dependent mechanism. Since it is not known if systemic LPS blocks the mechanism giving rise to sAIH-induced pLTF, we tested the hypothesis that sAIH-induced pLTF and adenosine 2A (A2A) receptor-induced pMF are insensitive to mild systemic inflammation elicited by the same low dose of LPS. In agreement with our hypothesis, neither sAIH-induced pLTF nor cervical intrathecal A2A receptor agonist (CGS-21680; 200 μM, 10 μl × 3)-induced pMF were affected 24 h post-LPS. Pretreatment with intrathecal A2A receptor antagonist injections (MSX-3; 10 μM, 12 μl) blocked sAIH-induced pLTF 24 h post LPS, confirming that pLTF was adenosine dependent. Our results give insights concerning the differential impact of systemic inflammation and the functional significance of multiple cascades capable of giving rise to phrenic motor plasticity. The relative resistance of adenosine-dependent pMF to inflammation suggests that it provides a “backup” system in animals lacking serotonin-dependent pMF due to ongoing inflammation associated with systemic infections and/or neural injury. NEW & NOTEWORTHY This study gives novel insights concerning how a mild systemic inflammation impacts phrenic motor plasticity (pMF), particularly adenosine-dependent pMF. We suggest that since this adenosine-dependent pathway is

Possible Mediation by Methylation in Acute Inflammation Following Personal Exposure to Fine Particulate Air Pollution

PubMed Central

Wang, Cuicui; Chen, Renjie; Shi, Min; Cai, Jing; Shi, Jingjin; Yang, Changyuan; Li, Huichu; Lin, Zhijing; Meng, Xia; Liu, Cong; Niu, Yue; Xia, Yongjie; Zhao, Zhuohui; Kan, Haidong; Weinberg, Clarice R

2018-01-01

Abstract Air pollution may increase cardiovascular and respiratory risk through inflammatory pathways, but evidence for acute effects has been weak and indirect. Between December 2014 and July 2015, we enrolled 36 healthy, nonsmoking college students for a panel study in Shanghai, China, a city with highly variable levels of air pollution. We measured personal exposure to particulate matter with an aerodynamic diameter less than or equal to 2.5 μm (PM2.5) continuously for 72 hours preceding each of 4 clinical visits that included phlebotomy. We measured 4 inflammation proteins and DNA methylation at nearby regulatory cytosine-phosphate-guanine (CpG) loci. We applied linear mixed-effect models to examine associations over various lag times. When results suggested mediation, we evaluated methylation as mediator. Increased PM2.5 concentration was positively associated with all 4 inflammation proteins and negatively associated with DNA methylation at regulatory loci for tumor necrosis factor alpha (TNF-α) and soluble intercellular adhesion molecule-1. A 10-μg/m3 increase in average PM2.5 during the 24 hours preceding blood draw corresponded to a 4.4% increase in TNF-α and a statistically significant decrease in methylation at one of the two studied candidate CpG loci for TNF-α. Epigenetics may play an important role in mediating effects of PM2.5 on inflammatory pathways. PMID:29020142

Effects of Ghrelin miRNA on Inflammation and Calcium Pathway in Pancreatic Acinar Cells of Acute Pancreatitis.

PubMed

Tang, Xiping; Tang, Guodu; Liang, Zhihai; Qin, Mengbin; Fang, Chunyun; Zhang, Luyi

The study investigated the effects of endogenous targeted inhibition of ghrelin gene on inflammation and calcium pathway in an in vitro pancreatic acinar cell model of acute pancreatitis. Lentiviral expression vector against ghrelin gene was constructed and transfected into AR42J cells. The mRNA and protein expression of each gene were detected by reverse transcription polymerase chain reaction, Western blotting, or enzyme-linked immunosorbent assay. The concentration of intracellular calcium ([Ca]i) was determined by calcium fluorescence mark probe combined with laser scanning confocal microscopy. Compared with the control group, cerulein could upregulate mRNA and protein expression of inflammatory factors, calcium pathway, ghrelin, and [Ca]i. mRNA and protein expression of inflammatory factors increased significantly in cells transfected with ghrelin miRNA compared with the other groups. Intracellular calcium and expression of some calcium pathway proteins decreased significantly in cells transfected with ghrelin miRNA compared with the other groups. Targeted inhibition of ghrelin gene in pancreatic acinar cells of acute pancreatitis can upregulate the expression of the intracellular inflammatory factors and alleviate the intracellular calcium overload.

Regulatory T Cells Contribute to the Inhibition of Radiation-Induced Acute Lung Inflammation via Bee Venom Phospholipase A2 in Mice

PubMed Central

Shin, Dasom; Lee, Gihyun; Sohn, Sung-Hwa; Park, Soojin; Jung, Kyung-Hwa; Lee, Ji Min; Yang, Jieun; Cho, Jaeho; Bae, Hyunsu

2016-01-01

Bee venom has long been used to treat various inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis. Previously, we reported that bee venom phospholipase A2 (bvPLA2) has an anti-inflammatory effect through the induction of regulatory T cells. Radiotherapy is a common anti-cancer method, but often causes adverse effects, such as inflammation. This study was conducted to evaluate the protective effects of bvPLA2 in radiation-induced acute lung inflammation. Mice were focally irradiated with 75 Gy of X-rays in the lung and administered bvPLA2 six times after radiation. To evaluate the level of inflammation, the number of immune cells, mRNA level of inflammatory cytokine, and histological changes in the lung were measured. BvPLA2 treatment reduced the accumulation of immune cells, such as macrophages, neutrophils, lymphocytes, and eosinophils. In addition, bvPLA2 treatment decreased inflammasome-, chemokine-, cytokine- and fibrosis-related genes’ mRNA expression. The histological results also demonstrated the attenuating effect of bvPLA2 on radiation-induced lung inflammation. Furthermore, regulatory T cell depletion abolished the therapeutic effects of bvPLA2 in radiation-induced pneumonitis, implicating the anti-inflammatory effects of bvPLA2 are dependent upon regulatory T cells. These results support the therapeutic potential of bvPLA2 in radiation pneumonitis and fibrosis treatments. PMID:27144583

A Study of Acute and Chronic Tissue Changes in Surgical and Traumatically-Induced Experimental Models of Knee Joint Injury Using Magnetic Resonance Imaging and Micro-Computed Tomography

PubMed Central

Fischenich, Kristine M.; Pauly, Hannah M.; Button, Keith D.; Fajardo, Ryan S.; DeCamp, Charles E.; Haut, Roger C.; Haut Donahue, Tammy L.

2016-01-01

Objective The objective of this study was to monitor the progression of joint damage in two animal models of knee joint trauma using two non-invasive, clinically available imaging modalities. Methods A 3-T clinical magnet and micro-computed tomography (mCT) was used to document changes immediately following injury (acute) and post-injury (chronic) at time points of 4, 8, or 12 weeks. Joint damage was recorded at dissection and compared to the chronic magnetic resonance imaging (MRI) record. Fifteen Flemish Giant rabbits were subjected to a single tibiofemoral compressive impact (ACLF), and 18 underwent a combination of anterior cruciate ligament (ACL) and meniscal transection (mACLT). Results All ACLF animals experienced ACL rupture, and 13 also experienced acute meniscal damage. All ACLF and mACLT animals showed meniscal and articular cartilage damages at dissection. Meniscal damage was documented as early as 4 weeks and worsened in 87% of the ACLF animals and 71% of the mACLT animals. Acute cartilage damage also developed further and increased in occurrence with time in both models. A progressive decrease in bone quantity and quality was documented in both models. The MRI data closely aligned with dissection notes suggesting this clinical tool may be a non-invasive method for documenting joint damage in lapine models of knee joint trauma. Conclusions The study investigates the acute to chronic progression of meniscal and cartilage damage at various time points, and chronic changes to the underlying bone in two models of posttraumatic osteoarthritis (PTOA), and highlights the dependency of the model on the location, type, and progression of damage over time. PMID:27756698

Primary Severe Acute Respiratory Syndrome Coronavirus Infection Limits Replication but Not Lung Inflammation upon Homologous Rechallenge

PubMed Central

Clay, Candice; Donart, Nathan; Fomukong, Ndingsa; Knight, Jennifer B.; Lei, Wanli; Price, Lance; Hahn, Fletcher; Van Westrienen, Jesse

2012-01-01

Our knowledge regarding immune-protective and immunopathogenic events in severe acute respiratory syndrome coronavirus (SARS-CoV) infection is limited, and little is known about the dynamics of the immune response at the primary site of disease. Here, an African green monkey (AGM) model was used to elucidate immune mechanisms that facilitate viral clearance but may also contribute to persistent lung inflammation following SARS-CoV infection. During primary infection, SARS-CoV replicated in the AGM lung for up to 10 days. Interestingly, lung inflammation was more prevalent following viral clearance, as leukocyte numbers peaked at 14 days postinfection (dpi) and remained elevated at 28 dpi compared to those of mock-infected controls. Lung macrophages but not dendritic cells were rapidly activated, and both cell types had high activation marker expression at late infection time points. Lung proinflammatory cytokines were induced at 1 to 14 dpi, but most returned to baseline by 28 dpi except interleukin 12 (IL-12) and gamma interferon. In SARS-CoV homologous rechallenge studies, 11 of the 12 animals were free of replicating virus at day 5 after rechallenge. However, incidence and severity of lung inflammation was not reduced despite the limited viral replication upon rechallenge. Evaluating the role of antibodies in immune protection or potentiation revealed a progressive increase in anti-SARS-CoV antibodies in lung and serum that did not correlate temporally or spatially with enhanced viral replication. This study represents one of the first comprehensive analyses of lung immunity, including changes in leukocyte populations, lung-specific cytokines, and antibody responses following SARS-CoV rechallenge in AGMs. PMID:22345460

Systemic inflammatory response following acute myocardial infarction

PubMed Central

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

2015-01-01

Acute cardiomyocyte necrosis in the infarcted heart generates damage-associated molecular patterns, activating complement and toll-like receptor/interleukin-1 signaling, and triggering an intense inflammatory response. Inflammasomes also recognize danger signals and mediate sterile inflammatory response following acute myocardial infarction (AMI). Inflammatory response serves to repair the heart, but excessive inflammation leads to adverse left ventricular remodeling and heart failure. In addition to local inflammation, profound systemic inflammation response has been documented in patients with AMI, which includes elevation of circulating inflammatory cytokines, chemokines and cell adhesion molecules, and activation of peripheral leukocytes and platelets. The excessive inflammatory response could be caused by a deregulated immune system. AMI is also associated with bone marrow activation and spleen monocytopoiesis, which sustains a continuous supply of monocytes at the site of inflammation. Accumulating evidence has shown that systemic inflammation aggravates atherosclerosis and markers for systemic inflammation are predictors of adverse clinical outcomes (such as death, recurrent myocardial infarction, and heart failure) in patients with AMI. PMID:26089856

Ion channels in inflammation.

PubMed

Eisenhut, Michael; Wallace, Helen

2011-04-01

Most physical illness in vertebrates involves inflammation. Inflammation causes disease by fluid shifts across cell membranes and cell layers, changes in muscle function and generation of pain. These disease processes can be explained by changes in numbers or function of ion channels. Changes in ion channels have been detected in diarrhoeal illnesses, pyelonephritis, allergy, acute lung injury and systemic inflammatory response syndromes involving septic shock. The key role played by changes in ion transport is directly evident in inflammation-induced pain. Expression or function of all major categories of ion channels like sodium, chloride, calcium, potassium, transient receptor potential, purinergic receptor and acid-sensing ion channels can be influenced by cyto- and chemokines, prostaglandins, leukotrienes, histamine, ATP, reactive oxygen species and protons released in inflammation. Key pathways in this interaction are cyclic nucleotide, phosphoinositide and mitogen-activated protein kinase-mediated signalling, direct modification by reactive oxygen species like nitric oxide, ATP or protons and disruption of the cytoskeleton. Therapeutic interventions to modulate the adverse and overlapping effects of the numerous different inflammatory mediators on each ion transport system need to target adversely affected ion transport systems directly and locally.

Inflammation in Acute and Chronic Pancreatitis

PubMed Central

Habtezion, Aida

2015-01-01

Summary Immune cell contribution to the pathogenesis of acute and chronic pancreatitis is gaining more appreciation and further understanding in immune signaling presents potential therapeutic targets that can alter disease progression. PMID:26107390

The etiology of 'smoker's paradox' in acute myocardial infarction with special emphasis on the association with inflammation.

PubMed

Katayama, Toshiro; Iwasaki, Yoshihiro; Sakoda, Naoya; Yoshioka, Masato

2008-01-01

Despite increased risk for coronary artery disease and acute myocardial infarction (AMI), prior studies have found that smokers with AMI have lower mortality rates than nonsmokers, a phenomenon often termed 'smoker's paradox'. The present study was designed to examine the etiology of 'smoker's paradox', especially with respect to the association with inflammation. The subjects included 528 consecutive AMI patients who were admitted within 24 hours of onset and underwent successful coronary intervention. Of the 528 subjects, 232 (44%) were smokers. The cardiac mortality rates over a 6 month period was significantly lower in the smoking group than the nonsmoking group (3% versus 9%, P = 0.01). There were significantly more male patients in the smoking group, and the smoking group was significantly younger than the nonsmoking group (P < 0.0001). The value of high sensitivity C-reactive protein (hs-CRP) on admission and 24 hours after onset, and serum amyloid A protein (SAA) were significantly higher, and acute phase BNP was significantly lower (hs-CRP on admission 1.36 +/- 1.03 mg/dL versus 0.75 +/- 0.82 mg/dL, P = 0.02, hs-CRP at 24 hours 3.86 +/- 4.32 mg/dL versus 2.90 +/- 3.46 mg/dL, P = 0.008, SAA; 288 +/- 392 microg/dL versus 176 +/- 206 microg/dL, P < 0.05, BNP; 248 +/- 342 pg/mL versus 444 +/- 496 pg/mL, P = 0.0002) in the smoking group than in the nonsmoking group. The early ST-segment resolution rate was higher in the smoking group compared with the nonsmoking group (80% versus 66%, P = 0.003). The reason why smokers with AMI have lower mortality rates than nonsmokers, the so-called 'smoker's paradox', is believed to be because smoking induces inflammation and smokers may have less damage to microvascular function after primary percutaneous coronary intervention.

New insights into the impact of neuro-inflammation in rheumatoid arthritis

PubMed Central

Fuggle, Nicholas R.; Howe, Franklyn A.; Allen, Rachel L.; Sofat, Nidhi

2014-01-01

Rheumatoid arthritis (RA) is considered to be, in many respects, an archetypal autoimmune disease that causes activation of pro-inflammatory pathways resulting in joint and systemic inflammation. RA remains a major clinical problem with the development of several new therapies targeted at cytokine inhibition in recent years. In RA, biologic therapies targeted at inhibition of tumor necrosis factor alpha (TNFα) have been shown to reduce joint inflammation, limit erosive change, reduce disability and improve quality of life. The cytokine TNFα has a central role in systemic RA inflammation and has also been shown to have pro-inflammatory effects in the brain. Emerging data suggests there is an important bidirectional communication between the brain and immune system in inflammatory conditions like RA. Recent work has shown how TNF inhibitor therapy in people with RA is protective for Alzheimer's disease. Functional MRI studies to measure brain activation in people with RA to stimulus by finger joint compression, have also shown that those who responded to TNF inhibition showed a significantly greater activation volume in thalamic, limbic, and associative areas of the brain than non-responders. Infections are the main risk of therapies with biologic drugs and infections have been shown to be related to disease flares in RA. Recent basic science data has also emerged suggesting that bacterial components including lipopolysaccharide induce pain by directly activating sensory neurons that modulate inflammation, a previously unsuspected role for the nervous system in host-pathogen interactions. In this review, we discuss the current evidence for neuro-inflammation as an important factor that impacts on disease persistence and pain in RA. PMID:25414636

Inhibition of carrageenan-induced acute inflammation in mice by oral administration of anthocyanin mixture from wild mulberry and cyanidin-3-glucoside.

PubMed

Hassimotto, Neuza Mariko Aymoto; Moreira, Vanessa; do Nascimento, Neide Galvão; Souto, Pollyana Cristina Maggio de Castro; Teixeira, Catarina; Lajolo, Franco Maria

2013-01-01

Anthocyanins are flavonoids which demonstrated biological activities in in vivo and in vitro models. Here in the anti-inflammatory properties of an anthocyanin-enriched fraction (AF) extracted from wild mulberry and the cyanidin-3-glucoside (C3G), the most abundant anthocyanin in diet, were studied in two acute inflammation experimental models, in the peritonitis and in the paw oedema assays, both of which were induced by carrageenan (cg) in mice. In each trial, AF and C3G (4 mg/100 g/animal) were orally administered in two distinct protocols: 30 min before and 1 h after cg stimulus. The administration of both AF and C3G suppresses the paw oedema in both administration times (P < 0.05). In the peritonitis, AF and C3G reduced the polymorphonuclear leukocytes (PMN) influx in the peritoneal exudates when administered 1 h after cg injection. AF was more efficient reducing the PMN when administered 30 min before cg. Both AF and C3G were found to suppress mRNA as well as protein levels of COX-2 upregulated by cg in both protocols, but the inhibitory effect on PGE2 production in the peritoneal exudates was observed when administered 30 min before cg (P < 0.05). Our findings suggest that AF and C3G minimize acute inflammation and they present positive contributions as dietary supplements.

Magnetic resonance imaging changes of sacroiliac joints in patients with recent-onset inflammatory back pain: inter-reader reliability and prevalence of abnormalities.

PubMed

Heuft-Dorenbosch, Liesbeth; Weijers, René; Landewé, Robert; van der Linden, Sjef; van der Heijde, Désirée

2006-01-01

To study the inter-reader reliability of detecting abnormalities of sacroiliac (SI) joints in patients with recent-onset inflammatory back pain by magnetic resonance imaging (MRI), and to study the prevalence of inflammation and structural changes at various sites of the SI joints. Sixty-eight patients with inflammatory back pain (at least four of the five following criteria: symptom onset before age 40, insidious onset, morning stiffness, duration >3 months, improvement with exercise--or three out of five of these plus night pain) were included (38% male; mean age, 34.9 years [standard deviation 10.3]; 46% HLA-B27-positive; mean symptom duration, 18 months), with symptom duration <2 years. A MRI scan of the SI joints was made in the coronal plane with the following sequences: T1-weighted spin echo, short-tau inversion recovery, T2-weighted fast-spin echo with fat saturation, and T1-spin echo with fat saturation after the administration of gadolinium. Both SI joints were scored for inflammation (separately for subchondral bone and bone marrow, joint space, joint capsule, ligaments) as well as for structural changes (erosions, sclerosis, ankylosis), by two observers independently. Agreement between the two readers was analysed by concordance and discordance rates and by kappa statistics. Inflammation was present in 32 SI joints of 22 patients, most frequently located in bone marrow and/or subchondral bone (29 joints in 21 patients). Readers agreed on the presence of inflammation in 85% of the cases in the right SI joint and in 78% of the cases in the left SI joint. Structural changes on MRI were present in 11 patients. Ten of these 11 patients also showed signs of inflammation. Agreement on the presence or absence of inflammation and structural changes of SI joints by MRI was acceptable, and was sufficiently high to be useful in ascertaining inflammatory and structural changes due to sacroiliitis. About one-third of patients with recent-onset inflammatory back pain

Kinematic Analysis of Gait Following Intra-articular Corticosteroid Injection into the Knee Joint with an Acute Exacerbation of Arthritis

PubMed Central

Mehta, Saurabh; Szturm, Tony; El-Gabalawy, Hani S.

2011-01-01

ABSTRACT Purpose: The objective of this study was to examine the effects of intra-articular corticosteroid injection (ICI) on ipsilateral knee flexion/extension, ankle dorsiflexion/plantarflexion (DF/PF), and hip abduction/adduction (abd/add) during stance phase in people with an acute exacerbation of rheumatoid arthritis (RA) of the knee joint. The study also assessed the effects of ICI on spatiotemporal parameters of gait and functional status in this group. Methods: Nine people with an exacerbation of RA of the knee were recruited. Kinematic and spatiotemporal gait parameters were obtained for each participant. Knee-related functional status was assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS). Spatiotemporal gait parameters and joint angles (knee flexion, ankle DF/PF, hip abd/add) of the affected side were compared pre- and post-ICI. Results: Data for eight people were available for analysis. Median values for knee flexion and ankle PF increased significantly following ICI. Gait parameters of cadence, velocity, bilateral stride length, bilateral step length, step width, double-support percentage, and step time on the affected side also showed improvement. Pain and knee-related functional status as measured by the KOOS showed improvement. Conclusions: This study demonstrated a beneficial short-term effect of ICI on knee-joint movements, gait parameters, and knee-related functional status in people with acute exacerbation of RA of the knee. PMID:22942516

Amino acid supplementation is anabolic during the acute phase of endotoxin-induced inflammation: A human randomized crossover trial.

PubMed

Rittig, N; Bach, E; Thomsen, H H; Johannsen, M; Jørgensen, J O; Richelsen, B; Jessen, N; Møller, N

2016-04-01

Inflammation is catabolic and causes muscle loss. It is unknown if amino acid supplementation reverses these effects during the acute phase of inflammation. The aim was to test whether amino acid supplementation counteracts endotoxin-induced catabolism. Eight young, healthy, lean males were investigated three times in randomized order: (i) normal conditions (Placebo), (ii) endotoxemia (LPS), and (iii) endotoxemia with amino acid supplementation (LPS + A). Protein kinetics were determined using phenylalanine, tyrosine, and urea tracers. Each study day consisted of a four-hour non-insulin stimulated period and a two-hour hyperinsulinemic euglycemic clamp period. Muscle biopsies were collected once each period. Endotoxin administration created a significant inflammatory response (cytokines, hormones, and vital parameters) without significant differences between LPS and LPS + A. Whole body protein breakdown was elevated during LPS compared with Placebo and LPS + A (p < 0.05). Whole body protein synthesis was higher during LPS + A than both Placebo and LPS (p < 0.003). Furthermore, protein synthesis was higher during LPS than during Placebo (p < 0.02). Net muscle phenylalanine release was markedly decreased during LPS + A (p < 0.004), even though muscle protein synthesis and breakdown rates did not differ significantly between interventions. LPS + A increased mammalian target of rapamycin (mTOR) phosphorylation (p < 0.05) and eukaryotic translation factor 4E-binding protein 1 (4EBP1) phosphorylation (p = 0.007) without activating AMPK or affecting insulin signaling through Akt. During insulin stimulation net muscle phenylalanine release and protein degradation were further reduced. Amino acid supplementation in the acute phase of inflammation reduces whole body and muscle protein loss, and this effect is associated with activation of mTOR and downstream signaling to protein synthesis through mTORC1, suggesting a therapeutic role for intravenous

Specialized pro-resolving mediators: endogenous regulators of infection and inflammation

PubMed Central

Basil, Maria C.; Levy, Bruce D.

2017-01-01

Specialized pro-resolving mediators (SPMs) are enzymatically derived from essential fatty acids and have important roles in orchestrating the resolution of tissue inflammation — that is, catabasis. Host responses to tissue infection elicit acute inflammation in an attempt to control invading pathogens. SPMs are lipid mediators that are part of a larger family of pro-resolving molecules, which includes proteins and gases, that together restrain inflammation and resolve the infection. These immunoresolvents are distinct from immunosuppressive molecules as they not only dampen inflammation but also promote host defence. Here, we focus primarily on SPMs and their roles in lung infection and inflammation to illustrate the potent actions these mediators play in restoring tissue homeostasis after an infection. PMID:26688348

Blockade of Dickkopf (DKK)-1 induces fusion of sacroiliac joints.

PubMed

Uderhardt, S; Diarra, D; Katzenbeisser, J; David, J-P; Zwerina, J; Richards, W; Kronke, G; Schett, G

2010-03-01

To study whether Dickkopf (DKK)-1, an inhibitor of wingless (Wnt) signalling, is involved in the fusion of sacroiliac joints. Mice transgenic for tumour necrosis factor (TNFtg mice), which develop bilateral sacroiliitis, were treated with vehicle, anti-TNF antibody or anti-DKK1 antibody. Sacroiliac joints were analysed for histological signs of inflammation, bone erosion, osteoclast formation and ankylosis. Moreover, expression of collagen type X, beta-catenin and DKK-1 was assessed by immunohistochemistry. There were no signs of spontaneous ankylosis of the sacroiliac joints in TNFtg mice. TNF blockade effectively reduced inflammation, bone erosion and osteoclast numbers in the sacroiliac joints, but did not lead to ankylosis. Blockade of DKK1 had no effect on inflammatory signs of sacroiliitis, but significantly reduced bone erosions and osteoclast counts. Moreover, DKK1 blockade promoted expression of collagen type X, the formation of hypertrophic chondrocytes and ankylosis of sacroiliac joints. DKK1 influences inflammatory remodelling of sacroiliac joints by prevention of joint ankylosis. This may indicate an important role of the Wnt signalling pathway in the structural bone changes of axial joint disease. Although this model does not reflect the entire spectrum of ankylosing spondylitis in humans, it helps to explain the pathophysiological processes of sacroiliac joint ankylosis, which is a hallmark of the spondyloarthritides.

Multispectral diffuse optical tomography of finger joints

NASA Astrophysics Data System (ADS)

Lighter, Daniel; Filer, Andrew; Dehghani, Hamid

2017-07-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation. The current treatment paradigm for earlier, more aggressive therapy places importance on development of functional imaging modalities, capable of quantifying joint changes at the earliest stages. Diffuse optical tomography (DOT) has shown great promise in this regard, due to its cheap, non-invasive, non-ionizing and high contrast nature. Underlying pathological activity in afflicted joints leads to altered optical properties of the synovial region, with absorption and scattering increasing. Previous studies have used these optical changes as features for classifying diseased joints from healthy. Non-tomographic, single wavelength, continuous wave (CW) measurements of trans-illuminated joints have previously reported achieving this with specificity and sensitivity in the range 80 - 90% [1]. A single wavelength, frequency domain DOT system, combined with machine learning techniques, has been shown to achieve sensitivity and specificity in the range of 93.8 - 100% [2]. A CW system is presented here which collects data at 5 wavelengths, enabling reconstruction of pathophysiological parameters such as oxygenation and total hemoglobin, with the aim of identifying localized hypoxia and angiogenesis associated with inflammation in RA joints. These initial studies focus on establishing levels of variation in recovered parameters from images of healthy controls.

Chondroprotective activity of N-acetyl phenylalanine glucosamine derivative on knee joint structure and inflammation in a murine model of osteoarthritis.

PubMed

Veronesi, F; Giavaresi, G; Maglio, M; Scotto d'Abusco, A; Politi, L; Scandurra, R; Olivotto, E; Grigolo, B; Borzì, R M; Fini, M

2017-04-01

Osteoarthritis (OA), the most common chronic degenerative joint disease, is characterized by joint structure changes and inflammation, both mediated by the IκB kinase (IKK) signalosome complex. The ability of N-acetyl phenylalanine derivative (NAPA) to increase cartilage matrix components and to reduce inflammatory cytokines, inhibiting IKKα kinase activity, has been observed in vitro. The present study aims to further clarify the effect of NAPA in counteracting OA progression, in an in vivo mouse model after destabilization of the medial meniscus (DMM). 26 mice were divided into three groups: (1) DMM surgery without treatment; (2) DMM surgery treated after 2 weeks with one intra-articular injection of NAPA (2.5 mM) and (3) no DMM surgery. At the end of experimental times, both knee joints of the animals were analyzed through histology, histomorphometry, immunohistochemistry and microhardness of subchondral bone (SB) tests. The injection of NAPA significantly improved cartilage thickness (CT) and reduced Chambers and Mankin modified scores and fibrillation index (FI), with weaker MMP13, ADAMTS5, MMP10 and IKKα staining. The microhardness measurements did not shown statistically significant differences between the different groups. NAPA markedly improved the physical structure of articular cartilage while reducing catabolic enzymes, extracellular matrix (ECM) remodeling and IKKα expression, showing to be able to exert a chondroprotective activity in vivo. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Human bone marrow-derived clonal mesenchymal stem cells inhibit inflammation and reduce acute pancreatitis in rats.

PubMed

Jung, Kyung Hee; Song, Sun U; Yi, Tacghee; Jeon, Myung-Shin; Hong, Sang-Won; Zheng, Hong-Mei; Lee, Hee-Seung; Choi, Myung-Joo; Lee, Don-Haeng; Hong, Soon-Sun

2011-03-01

Acute pancreatitis (AP) has a high mortality rate; repetitive AP induces chronic AP and pancreatic adenocarcinoma. Mesenchymal stem cells (MSCs) have immunoregulatory effects and reduce inflammation. We developed a protocol to isolate human bone marrow-derived clonal MSCs (hcMSCs) from bone marrow aspirate and investigated the effects of these cells in rat models of mild and severe AP. Mild AP was induced in Sprague-Dawley rats by 3 intraperitoneal injections of cerulein (100 μg/kg), given at 2-hour intervals; severe AP was induced by intraparenchymal injection of 3% sodium taurocholate solution. hcMSCs were labeled with CM-1,1'-dioctadecyl-3,3,3'-tetramethylindo-carbocyanine perchloride and administered to rats through the tail vein. hcMSCs underwent self-renewal and had multipotent differentiation capacities and immunoregulatory functions. Greater numbers of infused hcMSCs were detected in pancreas of rats with mild and severe AP than of control rats. Infused hcMSCs reduced acinar-cell degeneration, pancreatic edema, and inflammatory cell infiltration in each model of pancreatitis. The hcMSCs reduced expression of inflammation mediators and cytokines in rats with mild and severe AP. hcMSCs suppressed the mixed lymphocyte reaction and increased expression of Foxp3(+) (a marker of regulatory T cells) in cultured rat lymph node cells. Rats with mild or severe AP that were given infusions of hcMSCs had reduced numbers of CD3(+) T cells and increased expression of Foxp3(+) in pancreas tissues. hcMSCs reduced inflammation and damage to pancreatic tissue in a rat model of AP; they reduced levels of cytokines and induced numbers of Foxp3(+) regulatory T cells. hcMSCs might be developed as a cell therapy for pancreatitis. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Acute Bronchitis

MedlinePlus

... bronchitis? Acute bronchitis is inflammation of your bronchial tree. The bronchial tree consists of tubes that carry air into your ... weeks or months. This happens because the bronchial tree takes a while to heal. A lasting cough ...

Endoplasmic reticulum stress-regulated CXCR3 pathway mediates inflammation and neuronal injury in acute glaucoma

PubMed Central

Ha, Y; Liu, H; Xu, Z; Yokota, H; Narayanan, S P; Lemtalsi, T; Smith, S B; Caldwell, R W; Caldwell, R B; Zhang, W

2015-01-01

Acute glaucoma is a leading cause of irreversible blindness in East Asia. The mechanisms underlying retinal neuronal injury induced by a sudden rise in intraocular pressure (IOP) remain obscure. Here we demonstrate that the activation of CXCL10/CXCR3 axis, which mediates the recruitment and activation of inflammatory cells, has a critical role in a mouse model of acute glaucoma. The mRNA and protein expression levels of CXCL10 and CXCR3 were significantly increased after IOP-induced retinal ischemia. Blockade of the CXCR3 pathway by deleting CXCR3 gene significantly attenuated ischemic injury-induced upregulation of inflammatory molecules (interleukin-1β and E-selectin), inhibited the recruitment of microglia/monocyte to the superficial retina, reduced peroxynitrite formation, and prevented the loss of neurons within the ganglion cell layer. In contrast, intravitreal delivery of CXCL10 increased leukocyte recruitment and retinal cell apoptosis. Inhibition of endoplasmic reticulum (ER) stress with chemical chaperones partially blocked ischemic injury-induced CXCL10 upregulation, whereas induction of ER stress with tunicamycin enhanced CXCL10 expression in retina and primary retinal ganglion cells. Interestingly, deleting CXCR3 attenuated ER stress-induced retinal cell death. In conclusion, these results indicate that ER stress-medicated activation of CXCL10/CXCR3 pathway has an important role in retinal inflammation and neuronal injury after high IOP-induced ischemia. PMID:26448323

The joint in psoriatic arthritis.

PubMed

Mortezavi, Mahta; Thiele, Ralph; Ritchlin, Christopher

2015-01-01

Psoriatic arthritis (PsA), a chronic inflammatory joint disease associated with psoriasis, is notable for diversity in disease presentation, course and response to treatment. Equally varied are the types of musculoskeletal involvement which include peripheral and axial joint disease, dactylitis and enthesitis. In this review, we focus on the psoriatic joint and discuss pathways that underlie synovial, cartilage and bone inflammation and highlight key histopathologic features. The pivotal inflammatory mechanisms and pathobiology of PsA parallel findings in other forms of spondyloarthritis but are distinct from disease pathways described in rheumatoid synovitis and bone disease. The diagnosis of PsA from both a clinical and imaging perspective is also discussed.

Temporomandibular joint dislocation

PubMed Central

Sharma, Naresh Kumar; Singh, Akhilesh Kumar; Pandey, Arun; Verma, Vishal; Singh, Shreya

2015-01-01

Temporomandibular joint (TMJ) dislocation is an uncommon but debilitating condition of the facial skeleton. The condition may be acute or chronic. Acute TMJ dislocation is common in clinical practice and can be managed easily with manual reduction. Chronic recurrent TMJ dislocation is a challenging situation to manage. In this article, we discuss the comprehensive review of the different treatment modalities in managing TMJ dislocation. PMID:26668447

Involvement of the cytokine-IDO1-AhR loop in zinc oxide nanoparticle-induced acute pulmonary inflammation.

PubMed

Ho, Chia-Chi; Lee, Hui-Ling; Chen, Chao-Yu; Luo, Yueh-Hsia; Tsai, Ming-Hsien; Tsai, Hui-Ti; Lin, Pinpin

2017-04-01

Zinc oxide nanoparticles (ZnONPs) are widely used in our daily life, such as in sunscreens and electronic nanodevices. However, pulmonary exposure to ZnONPs causes acute pulmonary inflammation, which is considered as an initial event for various respiratory diseases. Thus, elucidation of the underlying cellular mechanisms of ZnONPs can help us in predicting their potential effects in respiratory diseases. In this study, we observed that ZnONPs increased proinflammatory cytokines, accompanied with an increased expression of aryl hydrocarbon receptor (AhR) and its downstream target cytochrome P450 1A1 (CYP1A1) in macrophages in vitro and in mouse lung epithelia in vivo. Moreover, zinc nitrate, but not silica or titanium dioxide nanoparticles (NPs), had similar effects on macrophages, indicating that the zinc element or ion released from ZnONPs is likely responsible for the activation of the AhR pathway. Cotreatment with an AhR antagonist or AhR knockout reduced ZnONPs-induced cytokine secretion in macrophages or mice, respectively. Furthermore, kynurenine (KYN), an endogenous AhR agonist and a tryptophan metabolite catalyzed by indoleamine 2,3-dioxygenase (IDO), was increased in the serums of mice that aspirated ZnONPs. Consistently, ZnONPs increased IDO1 expression in lung cells in vitro and in vivo. Finally, AhR knockout reduced ZnONPs-induced pulmonary inflammation, cytokine secretion and KYN production in mice, suggesting that AhR activation is involved in ZnONPs-induced cytokine secretion and pulmonary inflammation. In summary, we demonstrated that the pulmonary exposure of ZnONPs stimulated the cytokine-IDO1-AhR loop in the lungs, which has been implied to play roles in immune dysfunctions.

Hyperenhancement of the Pericardium on Cardiac Magnetic Resonance Imaging: A Marker of Acute Inflammation and Neovascularization or a Chronic Fibrotic State.

PubMed

Mullen, Liam; Chew, Pei Gee; Frost, Frederick; Ahmed, Ayesha; Khand, Aleem

2016-01-01

In cardiac magnetic resonance imaging, hyperenhancement of the pericardium post gadolinium administration in acute chest pain often signifies pericarditis with an acute inflammatory response and neovascularization. In the context of constrictive pericarditis, case series have indicated that the intensity of hyperenhancement and the thickness of the pericardium imply reversibility of the physiology of the constrictive pericarditis. We present a case of intense hyperenhancement and marked thickening of the pericardium in a patient with constrictive pericarditis with antecedent chest pain. Surgical resection of the pericardium and microscopy revealed a chronic fibrotic state with no evidence of inflammation or neovascularization, thus clarifying the failure of initial medical/anti-inflammatory treatment. Our case highlights the fact that hyperenhancement of the pericardium post gadolinium is non-specific for histology and does not necessarily imply the reversibility of pericardial constriction. © 2016 S. Karger AG, Basel.

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

PubMed

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

2016-12-01

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

Blockage of glycolysis by targeting PFKFB3 alleviates sepsis-related acute lung injury via suppressing inflammation and apoptosis of alveolar epithelial cells.

PubMed

Gong, Yuanqi; Lan, Haibing; Yu, Zhihong; Wang, Meng; Wang, Shu; Chen, Yu; Rao, Haiwei; Li, Jingying; Sheng, Zhiyong; Shao, Jianghua

2017-09-16

Sepsis-related acute lung injury (ALI) is characterized by excessive lung inflammation and apoptosis of alveolar epithelial cells resulting in acute hypoxemic respiratory failure. Recent studies indicated that anaerobic glycolysis play an important role in sepsis. However, whether inhibition of aerobic glycolysis exhibits beneficial effect on sepsis-induced ALI is not known. In vivo, a cecal ligation and puncture (CLP)-induced ALI mouse model was set up and mice treated with glycolytic inhibitor 3PO after CLP. The mice treated with the 3PO ameliorated the survival rate, histopathological changes, lung inflammation, lactate increased and lung apoptosis of mice with CLP-induced sepsis. In vitro, the exposure of human alveolar epithelial A549 cells to lipopolysaccharide (LPS) resulted in cell apoptosis, inflammatory cytokine production, enhanced glycolytic flux and reactive oxygen species (ROS) increased. While these changes were attenuated by 3PO treatment. Sequentially, treatment of A549 cells with lactate caused cell apoptosis and enhancement of ROS. Pretreatment with N-acetylcysteine (NAC) significantly lowered LPS and lactate-induced the generation of ROS and cell apoptosis in A549 cells. Therefore, these results indicate that anaerobic glycolysis may be an important contributor in cell apoptosis of sepsis-related ALI. Moreover, LPS specifically induces apoptotic insults to A549 cell through lactate-mediated enhancement of ROS. Copyright © 2017 Elsevier Inc. All rights reserved.

Inflammation and epigenetic regulation in osteoarthritis

PubMed Central

Shen, Jie; Abu-Amer, Yousef; O'Keefe, Regis J.; McAlinden, Audrey

2017-01-01

Osteoarthritis (OA) was once defined as a non-inflammatory arthropathy, but it is now well-recognized that there is a major inflammatory component to this disease. In addition to synovial cells, articular chondrocytes and other cells of diarthrodial joints are also known to express inflammatory mediators. It has been proposed that targeting inflammation pathways could be a promising strategy to treat OA. There have been many reports of cross-talk between inflammation and epigenetic factors in cartilage. Specifically, inflammatory mediators have been shown to regulate levels of enzymes that catalyze changes in DNA methylation and histone structure, as well as alter levels of non-coding RNAs. In addition, expression levels of a number of these epigenetic factors have been shown to be altered in OA, thereby suggesting potential interplay between inflammation and epigenetics in this disease. This review provides information on inflammatory pathways in arthritis and summarizes published research on how epigenetic regulators are affected by inflammation in chondrocytes. Furthermore, we discuss data showing how altered expression of some of these epigenetic factors can induce either catabolic or anti-catabolic effects in response to inflammatory signals. A better understanding of how inflammation affects epigenetic factors in OA may provide us with novel therapeutic strategies to treat this condition. PMID:27389927

Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis.

PubMed

Camps, Montserrat; Rückle, Thomas; Ji, Hong; Ardissone, Vittoria; Rintelen, Felix; Shaw, Jeffrey; Ferrandi, Chiara; Chabert, Christian; Gillieron, Corine; Françon, Bernard; Martin, Thierry; Gretener, Denise; Perrin, Dominique; Leroy, Didier; Vitte, Pierre-Alain; Hirsch, Emilio; Wymann, Matthias P; Cirillo, Rocco; Schwarz, Matthias K; Rommel, Christian

2005-09-01

Phosphoinositide 3-kinases (PI3K) have long been considered promising drug targets for the treatment of inflammatory and autoimmune disorders as well as cancer and cardiovascular diseases. But the lack of specificity, isoform selectivity and poor biopharmaceutical profile of PI3K inhibitors have so far hampered rigorous disease-relevant target validation. Here we describe the identification and development of specific, selective and orally active small-molecule inhibitors of PI3Kgamma (encoded by Pik3cg). We show that Pik3cg(-/-) mice are largely protected in mouse models of rheumatoid arthritis; this protection correlates with defective neutrophil migration, further validating PI3Kgamma as a therapeutic target. We also describe that oral treatment with a PI3Kgamma inhibitor suppresses the progression of joint inflammation and damage in two distinct mouse models of rheumatoid arthritis, reproducing the protective effects shown by Pik3cg(-/-) mice. Our results identify selective PI3Kgamma inhibitors as potential therapeutic molecules for the treatment of chronic inflammatory disorders such as rheumatoid arthritis.

Low level laser therapy reduces acute lung inflammation in a model of pulmonary and extrapulmonary LPS-induced ARDS.

PubMed

Oliveira, Manoel Carneiro; Greiffo, Flávia Regina; Rigonato-Oliveira, Nicole Cristine; Custódio, Ricardo Wesley Alberca; Silva, Vanessa Roza; Damaceno-Rodrigues, Nilsa Regina; Almeida, Francine Maria; Albertini, Regiane; Lopes-Martins, Rodrigo Álvaro B; de Oliveira, Luis Vicente Franco; de Carvalho, Paulo de Tarso Camillo; Ligeiro de Oliveira, Ana Paula; Leal, Ernesto César P; Vieira, Rodolfo P

2014-05-05

The present study aimed to investigate the effects low level laser therapy (LLLT) in a LPS-induced pulmonary and extrapulmonary acute respiratory distress syndrome (ARDS) in BALB/c mice. Laser (830nm laser, 9J/cm(2), 35mW, 80s per point, 3 points per application) was applied in direct contact with skin, 1h after LPS administration. Mice were distributed in control (n=6; PBS), ARDS IT (n=7; LPS orotracheally 10μg/mouse), ARDS IP (n=7; LPS intra-peritoneally 100μg/mouse), ARDS IT+Laser (n=9; LPS intra-tracheally 10μg/mouse), ARDS IP+Laser (n=9; LPS intra-peritoneally 100μg/mouse). Twenty-four hours after last LPS administration, mice were studied for pulmonary inflammation by total and differential cell count in bronchoalveolar lavage (BAL), cytokines (IL-1beta, IL-6, KC and TNF-alpha) levels in BAL fluid and also by quantitative analysis of neutrophils number in the lung parenchyma. LLLT significantly reduced pulmonary and extrapulmonary inflammation in LPS-induced ARDS, as demonstrated by reduced number of total cells (p<0.001) and neutrophils (p<0.001) in BAL, reduced levels of IL-1beta, IL-6, KC and TNF-alpha in BAL fluid and in serum (p<0.001), as well as the number of neutrophils in lung parenchyma (p<0.001). LLLT is effective to reduce pulmonary inflammation in both pulmonary and extrapulmonary model of LPS-induced ARDS. Copyright © 2014 Elsevier B.V. All rights reserved.

Photoacoustic imaging of inflammatory arthritis in human joints

NASA Astrophysics Data System (ADS)

Jo, Janggun; Xu, Guan; Marquardt, April; Francis, Sheeja; Yuan, Jie; Girish, Dhanuj; Girish, Gandikota; Wang, Xueding

2016-02-01

The ducal imaging with photoacoustic imaging (PAI) that is an emerging technology and clinical ultrasound imaging that is an established modality is developed for the imaging of early inflammatory arthritis. PAI is sensitive to blood volume, not limited by flow like ultrasound, holding great promise for the earliest detection of increase in blood volume and angiogenesis - a key early finding inflammation PAI has the capability of assessing inflammation in superficial human soft tissues, offering potential benefits in diagnosis, treatment and monitoring of inflammatory arthritis. PAI combined with ultrasonography (US), is a real time dual-modality system developed and tested to identify active synovitis in metacarpophalangeal (MCP) joints of 10 arthritis patients and 10 normal volunteers. Photoacoustic images of the joints were acquired at 580-nm laser wavelength, which provided the desired balance between the optical contrast of hemoglobin over bone cortex and the imaging depth. Confirmed by US Doppler imaging, the results from ten patients and ten normal volunteers demonstrated satisfactory sensitivity of PAI in assessing enhanced blood flow due to active synovitis. This preliminary study suggests that photoacoustic imaging, by identifying early increase in blood volume, related to increased vascularity, a hallmark of joint inflammation, could be a valuable supplement to musculoskeletal US.

Inhibition of Carrageenan-Induced Acute Inflammation in Mice by Oral Administration of Anthocyanin Mixture from Wild Mulberry and Cyanidin-3-Glucoside

PubMed Central

Hassimotto, Neuza Mariko Aymoto; Moreira, Vanessa; do Nascimento, Neide Galvão; Souto, Pollyana Cristina Maggio de Castro; Teixeira, Catarina; Lajolo, Franco Maria

2013-01-01

Anthocyanins are flavonoids which demonstrated biological activities in in vivo and in vitro models. Here in the anti-inflammatory properties of an anthocyanin-enriched fraction (AF) extracted from wild mulberry and the cyanidin-3-glucoside (C3G), the most abundant anthocyanin in diet, were studied in two acute inflammation experimental models, in the peritonitis and in the paw oedema assays, both of which were induced by carrageenan (cg) in mice. In each trial, AF and C3G (4 mg/100 g/animal) were orally administered in two distinct protocols: 30 min before and 1 h after cg stimulus. The administration of both AF and C3G suppresses the paw oedema in both administration times (P < 0.05). In the peritonitis, AF and C3G reduced the polymorphonuclear leukocytes (PMN) influx in the peritoneal exudates when administered 1 h after cg injection. AF was more efficient reducing the PMN when administered 30 min before cg. Both AF and C3G were found to suppress mRNA as well as protein levels of COX-2 upregulated by cg in both protocols, but the inhibitory effect on PGE2 production in the peritoneal exudates was observed when administered 30 min before cg (P < 0.05). Our findings suggest that AF and C3G minimize acute inflammation and they present positive contributions as dietary supplements. PMID:23484081

Protective effects of tiotropium alone or combined with budesonide against cadmium inhalation induced acute neutrophilic pulmonary inflammation in rats

PubMed Central

Zhi, Jianming; Gustin, Pascal

2018-01-01

As a potent bronchodilator, the anti-inflammatory effects of tiotropium and its interaction with budesonide against cadmium-induced acute pulmonary inflammation were investigated. Compared to values obtained in rats exposed to cadmium, cytological analysis indicated a significant decrease of total cell and neutrophil counts and protein concentration in bronchoalveolar lavage fluid (BALF) in rats pretreated with tiotropium (70μg/15ml or 350μg/15ml). Zymographic tests showed a decrease of MMP-2 activity in BALF in rats pretreated only with high concentration of tiotropium. Histological examination revealed a significant decrease of the severity and extent of inflammatory lung injuries in rats pretreated with both tested concentrations of tiotropium. Though tiotropium (70μg/15ml) or budesonide (250μg/15ml) could not reduce cadmium-induced bronchial hyper-responsiveness, their combination significantly decreased bronchial contractile response to methacholine. These two drugs separately decreased the neutrophil number and protein concentration in BALF but no significant interaction was observed when both drugs were combined. Although no inhibitory effects on MMP-2 and MMP-9 was observed in rats pretreated with budesonide alone, the combination with the ineffective dose of tiotropium induced a significant reduction on these parameters. The inhibitory effect of tiotropium on lung injuries was not influenced by budesonide which alone induced a limited action on the severity and extent of inflammatory sites. Our findings show that tiotropium exerts anti-inflammatory effects on cadmium-induced acute neutrophilic pulmonary inflammation. The combination of tiotropium with budesonide inhibits cadmium-induced inflammatory injuries with a synergistic interaction on MMP-2 and MMP-9 activity and airway hyper-responsiveness. PMID:29489916

Protective effects of tiotropium alone or combined with budesonide against cadmium inhalation induced acute neutrophilic pulmonary inflammation in rats.

PubMed

Zhao, Shiwei; Yang, Qi; Yu, Zhixi; Lv, You; Zhi, Jianming; Gustin, Pascal; Zhang, Wenhui

2018-01-01

As a potent bronchodilator, the anti-inflammatory effects of tiotropium and its interaction with budesonide against cadmium-induced acute pulmonary inflammation were investigated. Compared to values obtained in rats exposed to cadmium, cytological analysis indicated a significant decrease of total cell and neutrophil counts and protein concentration in bronchoalveolar lavage fluid (BALF) in rats pretreated with tiotropium (70μg/15ml or 350μg/15ml). Zymographic tests showed a decrease of MMP-2 activity in BALF in rats pretreated only with high concentration of tiotropium. Histological examination revealed a significant decrease of the severity and extent of inflammatory lung injuries in rats pretreated with both tested concentrations of tiotropium. Though tiotropium (70μg/15ml) or budesonide (250μg/15ml) could not reduce cadmium-induced bronchial hyper-responsiveness, their combination significantly decreased bronchial contractile response to methacholine. These two drugs separately decreased the neutrophil number and protein concentration in BALF but no significant interaction was observed when both drugs were combined. Although no inhibitory effects on MMP-2 and MMP-9 was observed in rats pretreated with budesonide alone, the combination with the ineffective dose of tiotropium induced a significant reduction on these parameters. The inhibitory effect of tiotropium on lung injuries was not influenced by budesonide which alone induced a limited action on the severity and extent of inflammatory sites. Our findings show that tiotropium exerts anti-inflammatory effects on cadmium-induced acute neutrophilic pulmonary inflammation. The combination of tiotropium with budesonide inhibits cadmium-induced inflammatory injuries with a synergistic interaction on MMP-2 and MMP-9 activity and airway hyper-responsiveness.

Role of Antioxidants and Natural Products in Inflammation

PubMed Central

Fard, Masoumeh Tangestani; Tan, Woan Sean; Gothai, Sivapragasam; Kumar, S. Suresh

2016-01-01

Inflammation is a comprehensive array of physiological response to a foreign organism, including human pathogens, dust particles, and viruses. Inflammations are mainly divided into acute and chronic inflammation depending on various inflammatory processes and cellular mechanisms. Recent investigations have clarified that inflammation is a major factor for the progression of various chronic diseases/disorders, including diabetes, cancer, cardiovascular diseases, eye disorders, arthritis, obesity, autoimmune diseases, and inflammatory bowel disease. Free radical productions from different biological and environmental sources are due to an imbalance of natural antioxidants which further leads to various inflammatory associated diseases. In this review article, we have outlined the inflammatory process and its cellular mechanisms involved in the progression of various chronic modern human diseases. In addition, we have discussed the role of free radicals-induced tissue damage, antioxidant defence, and molecular mechanisms in chronic inflammatory diseases/disorders. The systematic knowledge regarding the role of inflammation and its associated adverse effects can provide a clear understanding in the development of innovative therapeutic targets from natural sources that are intended for suppression of various chronic inflammations associated diseases. PMID:27803762

Inflammatory process induced by carrageenan in adjacent tissue triggers the acute inflammation in deep digital flexor tendon of rats.

PubMed

Vieira, Cristiano Pedrozo; De Aro, Andrea Aparecida; Da Ré Guerra, Flávia; De Oliveira, Letícia Prado; De Almeida, Marcos Dos Santos; Pimentel, Edson Rosa

2013-08-01

Tendinopathy is a pathology found mainly in the rotator cuff, patellar, Achilles and flexor tendons. Tendinopathy is a significant impediment to performance in athletes and in workers in the labor market. Some studies have indicated that inflammation in adjacent tissues may affect the rotator cuff and Achilles tendon. In this study alterations were verified in the extracellular matrix (ECM) of the deep digital flexor tendon after two periods (12 and 24 hr) of induction inflammation in rat paw. Wistar rats were divided into three groups: those that received injection of 1% carrageenan; those that received 0.9% NaCl; and those that received no application. The tendon was divided into distal (d), proximal (p), and intermediate (i) regions. Biochemical analyses were performed and included non-collagenous proteins (NCP), glycosaminoglycans (GAGs), hydroxyproline (HoPro) and metalloproteinases 2 and 9. Tissue sections were stained with toluidine blue, hematoxylin-eosin, and Ponceau SS and observed under polarization microscopy. Remarkable results were detected that included the presence of MMP-9, degradation of NCP and GAG and the presence of cellular infiltrate closer to digits in d region. The different concentrations of HoPro, as well as alterations in the organization of the collagen fibers showed the collagenous matrix undergoing some alterations. The results indicated that the induced inflammation in rat paw exhibited characteristics similar to the typical acute inflammatory process observed in tendons. Copyright © 2013 Wiley Periodicals, Inc.

Inflammation and Alzheimer’s disease

PubMed Central

Akiyama, Haruhiko; Barger, Steven; Barnum, Scott; Bradt, Bonnie; Bauer, Joachim; Cole, Greg M.; Cooper, Neil R.; Eikelenboom, Piet; Emmerling, Mark; Fiebich, Berndt L.; Finch, Caleb E.; Frautschy, Sally; Griffin, W.S.T.; Hampel, Harald; Hull, Michael; Landreth, Gary; Lue, Lih–Fen; Mrak, Robert; Mackenzie, Ian R.; McGeer, Patrick L.; O’Banion, M. Kerry; Pachter, Joel; Pasinetti, Guilio; Plata–Salaman, Carlos; Rogers, Joseph; Rydel, Russell; Shen, Yong; Streit, Wolfgang; Strohmeyer, Ronald; Tooyoma, Ikuo; Van Muiswinkel, Freek L.; Veerhuis, Robert; Walker, Douglas; Webster, Scott; Wegrzyniak, Beatrice; Wenk, Gary; Wyss–Coray, Tony

2013-01-01

Inflammation clearly occurs in pathologically vulnerable regions of the Alzheimer’s disease (AD) brain, and it does so with the full complexity of local peripheral inflammatory responses. In the periphery, degenerating tissue and the deposition of highly insoluble abnormal materials are classical stimulants of inflammation. Likewise, in the AD brain damaged neurons and neurites and highly insoluble amyloid β peptide deposits and neurofibrillary tangles provide obvious stimuli for inflammation. Because these stimuli are discrete, microlocalized, and present from early preclinical to terminal stages of AD, local upregulation of complement, cytokines, acute phase reactants, and other inflammatory mediators is also discrete, microlocalized, and chronic. Cumulated over many years, direct and bystander damage from AD inflammatory mechanisms is likely to significantly exacerbate the very pathogenic processes that gave rise to it. Thus, animal models and clinical studies, although still in their infancy, strongly suggest that AD inflammation significantly contributes to AD pathogenesis. By better understanding AD inflammatory and immunoregulatory processes, it should be possible to develop anti-inflammatory approaches that may not cure AD but will likely help slow the progression or delay the onset of this devastating disorder. PMID:10858586

Regulation of the macrophage oxytocin receptor in response to inflammation

PubMed Central

Szeto, Angela; Sun-Suslow, Ni; Mendez, Armando J.; Hernandez, Rosa I.; Wagner, Klaus V.

2017-01-01

It has been demonstrated that the neuropeptide oxytocin (OT) attenuates oxidative stress and inflammation in macrophages. In the current study, we examined the role of inflammation on the expression of the oxytocin receptor (OXTR). We hypothesized that OXTR expression is increased during the inflammation through a nuclear factor-κB (NF-κB)-mediated pathway, thus responding as an acute-phase protein. Inflammation was induced by treating macrophages (human primary, THP-1, and murine) with lipopolysaccharide (LPS) and monitored by expression of IL-6. Expression of OXTR and vasopressin receptors was assessed by qPCR, and OXTR expression was confirmed by immunoblotting. Inflammation upregulated OXTR transcription 10- to 250-fold relative to control in THP-1 and human primary macrophages and increased OXTR protein expression. In contrast, vasopressin receptor-2 mRNA expression was reduced following LPS treatment. Blocking NF-κB activation prevented the increase in OXTR transcription. OT treatment of control cells and LPS-treated cells increased ERK1/2 phosphorylation, demonstrating activation of the OXTR/Gαq/11 signaling pathway. OT activation of OXTR reduced secretion of IL-6 in LPS-activated macrophages. Collectively, these findings suggest that OXTR is an acute-phase protein and that its increased expression is regulated by NF-κB and functions to attenuate cellular inflammatory responses in macrophages. PMID:28049625

Associations between preoperative physical therapy and post-acute care utilization patterns and cost in total joint replacement.

PubMed

Snow, Richard; Granata, Jaymes; Ruhil, Anirudh V S; Vogel, Karen; McShane, Michael; Wasielewski, Ray

2014-10-01

Health-care costs following acute hospital care have been identified as a major contributor to regional variation in Medicare spending. This study investigated the associations of preoperative physical therapy and post-acute care resource use and its effect on the total cost of care during primary hip or knee arthroplasty. Historical claims data were analyzed using the Centers for Medicare & Medicaid Services Limited Data Set files for Diagnosis Related Group 470. Analysis included descriptive statistics of patient demographic characteristics, comorbidities, procedures, and post-acute care utilization patterns, which included skilled nursing facility, home health agency, or inpatient rehabilitation facility, during the ninety-day period after a surgical hospitalization. To evaluate the associations, we used bivariate and multivariate techniques focused on post-acute care use and total episode-of-care costs. The Limited Data Set provided 4733 index hip or knee replacement cases for analysis within the thirty-nine-county Medicare hospital referral cluster. Post-acute care utilization was a significant variable in the total cost of care for the ninety-day episode. Overall, 77.0% of patients used post-acute care services after surgery. Post-acute care utilization decreased if preoperative physical therapy was used, with only 54.2% of the preoperative physical therapy cohort using post-acute care services. However, 79.7% of the non-preoperative physical therapy cohort used post-acute care services. After adjusting for demographic characteristics and comorbidities, the use of preoperative physical therapy was associated with a significant 29% reduction in post-acute care use, including an $871 reduction of episode payment driven largely by a reduction in payments for skilled nursing facility ($1093), home health agency ($527), and inpatient rehabilitation ($172). The use of preoperative physical therapy was associated with a 29% decrease in the use of any post-acute care

Inflammation in sickle cell disease.

PubMed

Conran, Nicola; Belcher, John D

2018-01-01

The primary β-globin gene mutation that causes sickle cell disease (SCD) has significant pathophysiological consequences that result in hemolytic events and the induction of the inflammatory processes that ultimately lead to vaso-occlusion. In addition to their role in the initiation of the acute painful vaso-occlusive episodes that are characteristic of SCD, inflammatory processes are also key components of many of the complications of the disease including autosplenectomy, acute chest syndrome, pulmonary hypertension, leg ulcers, nephropathy and stroke. We, herein, discuss the events that trigger inflammation in the disease, as well as the mechanisms, inflammatory molecules and cells that propagate these inflammatory processes. Given the central role that inflammation plays in SCD pathophysiology, many of the therapeutic approaches currently under pre-clinical and clinical development for the treatment of SCD endeavor to counter aspects or specific molecules of these inflammatory processes and it is possible that, in the future, we will see anti-inflammatory drugs being used either together with, or in place of, hydroxyurea in those SCD patients for whom hematopoietic stem cell transplants and evolving gene therapies are not a viable option.

P-Selectin Targeted Dexamethasone-Loaded Lipid Nanoemulsions: A Novel Therapy to Reduce Vascular Inflammation

PubMed Central

Simion, Viorel; Constantinescu, Cristina Ana; Stan, Daniela; Deleanu, Mariana; Tucureanu, Monica Madalina; Butoi, Elena; Manduteanu, Ileana; Simionescu, Maya

2016-01-01

Inflammation is a common process associated with numerous vascular pathologies. We hypothesized that targeting the inflamed endothelium by coupling a peptide with high affinity for P-selectin to the surface of dexamethasone-loaded lipid nanoemulsions will highly increase their specific binding to activated endothelial cells (EC) and reduce the cell activation. We developed and characterized dexamethasone-loaded lipid nanoemulsions directed towards P-selectin (PLN-Dex) and monitored their anti-inflammatory effects in vitro using cultured EC (EA.hy926 cells) and in vivo using a mouse model of acute inflammation [lipopolysaccharides (LPS) intravenously administered in C57BL/6 mice]. We found that PLN-Dex bound specifically to the surface of activated EC are efficiently internalized by EC and reduced the expression of proinflammatory genes, thus preventing the monocyte adhesion and transmigration to/through activated EC. Given intravenously in mice with acute inflammation, PLN-Dex accumulated at a significant high level in the lungs (compared to nontargeted nanoemulsions) and significantly reduced mRNA expression level of key proinflammatory cytokines such as IL-1β, IL-6, and MCP-1. In conclusion, the newly developed nanoformulation, PLN-Dex, is functional in vitro and in vivo, reducing selectively the endothelium activation and the consequent monocyte infiltration and diminishing significantly the lungs' inflammation, in a mouse model of acute inflammation. PMID:27703301

Hippocampal structure and function are maintained despite severe innate peripheral inflammation.

PubMed

Süß, Patrick; Kalinichenko, Liubov; Baum, Wolfgang; Reichel, Martin; Kornhuber, Johannes; Loskarn, Sandra; Ettle, Benjamin; Distler, Jörg H W; Schett, Georg; Winkler, Jürgen; Müller, Christian P; Schlachetzki, Johannes C M

2015-10-01

Chronic peripheral inflammation mediated by cytokines such as TNFα, IL-1β, and IL-6 is associated with psychiatric disorders like depression and anxiety. However, it remains elusive which distinct type of peripheral inflammation triggers neuroinflammation and affects hippocampal plasticity resulting in depressive-like behavior. We hypothesized that chronic peripheral inflammation in the human TNF-α transgenic (TNFtg) mouse model of rheumatoid arthritis spreads into the central nervous system and induces depressive state manifested in specific behavioral pattern and impaired adult hippocampal neurogenesis. TNFtg mice showed severe erosive arthritis with increased IL-1β and IL-6 expression in tarsal joints with highly elevated human TNF-α levels in the serum. Intriguingly, IL-1β and IL-6 mRNA levels were not altered in the hippocampus of TNFtg mice. In contrast to the pronounced monocytosis in joints and spleen of TNFtg mice, signs of hippocampal microgliosis or astrocytosis were lacking. Furthermore, locomotion was impaired, but there was no locomotion-independent depressive behavior in TNFtg mice. Proliferation and maturation of hippocampal neural precursor cells as well as survival of newly generated neurons were preserved in the dentate gyrus of TNFtg mice despite reduced motor activity and peripheral inflammatory signature. We conclude that peripheral inflammation in TNFtg mice is mediated by chronic activation of the innate immune system. However, severe peripheral inflammation, though impairing locomotor activity, does not elicit depressive-like behavior. These structural and functional findings indicate the maintenance of hippocampal immunity, cellular plasticity, and behavior despite peripheral innate inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

Combined arthroscopically assisted coraco- and acromioclavicular stabilization of acute high-grade acromioclavicular joint separations.

PubMed

Hann, Carmen; Kraus, Natascha; Minkus, Marvin; Maziak, Nina; Scheibel, Markus

2018-01-01

Due to high rate of persisting dynamic posterior translation (DPT) following isolated coracoclavicular double-button technique for reconstruction of the acromioclavicular (AC) joint reported in the literature, an additional acromioclavicular cerclage was added to the procedure. The aim of this study was to evaluate the clinical and radiological results of patients with high-grade AC-joint instability treated with a double TightRope technique with an additional percutaneous acromioclavicular cerclage. Fifty-nine patients (6 f/53 m; median age 38.3 (range 21.5-63.4 years) who sustained an acute high-grade AC-joint dislocation (Rockwood type V) were treated using the above-mentioned technique. At the final follow-up, the constant score (CS), the subjective shoulder value (SSV), the Taft score (TF) and the acromioclavicular joint instability score (ACJI) as well as bilateral anteroposterior stress views with 10 kg of axial load and bilateral modified Alexander views were obtained. At a median follow-up of 26.4 (range 20.3-61.0) months, 34 patients scored a median of 90 (33-100) points in the CS, 90 (25-100) % in the SSV, 11 (4-12) points in the TF and 87 (43-100) points in the ACJI. The coracoclavicular (CC) distance was 12.1 (6.5-19.8) mm and the CC difference 2.0 (0.0-11.0) mm. Two patients (5.8%) showed a complete DPT of the AC joint, and fourteen patients (41.1%) displayed a partial DPT. The overall revision rate was 11.7%. Two patients presented implant irritation, one patient a recurrent instability, and one patient suffered from a local infection. The arthroscopically assisted and image-intensifier-controlled double TightRope technique with an additional percutaneous acromioclavicular cerclage leads to good and excellent clinical results after a follow-up of 2 years. The incidence of persisting dynamic horizontal translation is lower compared to isolated coracoclavicular stabilization. Thus, we recommend using the double TightRope implant with an additional

Ovalbumin-induced allergic inflammation lead to structural alterations in mouse model and protective effects of intranasal curcumin: A comparative study.

PubMed

Subhashini; Chauhan, P S; Singh, R

2016-01-01

Antigen exposure and persistent inflammation leads to structural changes in the asthmatic airways which are collectively termed as "airway remodelling". Presently available asthma medications ameliorate inflammations but are unable to prevent or reverse the airway remodelling process as most of the treatment strategies are only focused on inflammation instead of remodelling. Curcumin, a phytochemical present in the rhizome of Curcuma longa is well known for its anti-inflammatory activity; however, the main drawback is its poor bioavailability which limits its therapeutic approval. So, the effect of nasal curcumin on acute and chronic asthma has been studied where short exposure to ovalbumin (4 days) represents acute phase whereas repeated exposures for longer (twice per week till 5 weeks) represents chronic asthma. Disodium cromoglycate (DSCG, 50mg/kg, i.p.) and dexamethasone (1mg/kg, i.p.) were used as standard drugs in acute and chronic model of asthma respectively. OVA-induced airway inflammation initiated in acute stage led to remodelling due to persistent inflammation, epithelial and sub epithelial thickening (smooth muscle thickening), extracellular matrix (ECM) deposition, goblet cell hyperplasia and mucus plug formation. Intranasal curcumin is effective in inhibiting airway inflammation and remodelling both by maintaining the structural integrity of lungs in terms of inflammation, airway wall thickening and mucus production. Our findings suggest that curcumin administered through nasal route might prove therapeutically efficient in inhibiting allergic airway inflammations and maintaining structural integrity in the mouse model of allergic asthma. This may lead to the development of curcumin aerosol in near future. Copyright © 2016 SEICAP. Published by Elsevier Espana. All rights reserved.

Interleukin-22-deficiency and microbiota contribute to the exacerbation of Toxoplasma gondii-induced intestinal inflammation.

PubMed

Couturier-Maillard, A; Froux, N; Piotet-Morin, J; Michaudel, C; Brault, L; Le Bérichel, J; Sénéchal, A; Robinet, P; Chenuet, P; Jejou, S; Dumoutier, L; Renauld, J C; Iovanna, J; Huber, S; Quesniaux, Vfj; Sokol, H; Ryffel, B

2018-05-04

Upon oral infection with Toxoplasma gondii cysts (76 K strain) tachyzoites are released into the intestinal lumen and cross the epithelial barrier causing damage and acute intestinal inflammation in C57BL/6 (B6) mice. Here we investigated the role of microbiota and IL-22 in T.gondii-induced small intestinal inflammation. Oral T.gondii infection in B6 mice causes inflammation with IFNγ and IL-22 production. In IL-22-deficient mice, T.gondii infection augments the Th1 driven inflammation. Deficiency in either IL-22bp, the soluble IL-22 receptor or Reg3γ, an IL-22-dependent antimicrobial lectin/peptide, did not reduce inflammation. Under germ-free conditions, T.gondii-induced inflammation was reduced in correlation with parasite load. But intestinal inflammation is still present in germ-free mice, at low level, in the lamina propria, independently of IL-22 expression. Exacerbated intestinal inflammation driven by absence of IL-22 appears to be independent of IL-22 deficiency associated-dysbiosis as similar inflammation was observed after fecal transplantation of IL-22 -/- or WT microbiota to germ-free-WT mice. Our results suggest cooperation between parasite and intestinal microbiota in small intestine inflammation development and endogenous IL-22 seems to exert a protective role independently of its effect on the microbiota. In conclusion, IL-22 participates in T.gondii induced acute small intestinal inflammation independently of microbiota and Reg3γ.

Effect of Acute Ozone Induced Airway Inflammation on Human Sympathetic Nerve Traffic: A Randomized, Placebo Controlled, Crossover Study

PubMed Central

Tank, Jens; Biller, Heike; Heusser, Karsten; Holz, Olaf; Diedrich, André; Framke, Theodor; Koch, Armin; Grosshennig, Anika; Koch, Wolfgang; Krug, Norbert; Jordan, Jens; Hohlfeld, Jens M.

2011-01-01

Background Ozone concentrations in ambient air are related to cardiopulmonary perturbations in the aging population. Increased central sympathetic nerve activity induced by local airway inflammation may be one possible mechanism. Methodology/Principal Findings To elucidate this issue further, we performed a randomized, double-blind, cross-over study, including 14 healthy subjects (3 females, age 22–47 years), who underwent a 3 h exposure with intermittent exercise to either ozone (250 ppb) or clean air. Induced sputum was collected 3 h after exposure. Nineteen to 22 hours after exposure, we recorded ECG, finger blood pressure, brachial blood pressure, respiration, cardiac output, and muscle sympathetic nerve activity (MSNA) at rest, during deep breathing, maximum-inspiratory breath hold, and a Valsalva maneuver. While the ozone exposure induced the expected airway inflammation, as indicated by a significant increase in sputum neutrophils, we did not detect a significant estimated treatment effect adjusted for period on cardiovascular measurements. Resting heart rate (clean air: 59±2, ozone 60±2 bpm), blood pressure (clean air: 121±3/71±2 mmHg; ozone: 121±2/71±2 mmHg), cardiac output (clean air: 7.42±0.29 mmHg; ozone: 7.98±0.60 l/min), and plasma norepinephrine levels (clean air: 213±21 pg/ml; ozone: 202±16 pg/ml), were similar on both study days. No difference of resting MSNA was observed between ozone and air exposure (air: 23±2, ozone: 23±2 bursts/min). Maximum MSNA obtained at the end of apnea (air: 44±4, ozone: 48±4 bursts/min) and during the phase II of the Valsalva maneuver (air: 64±5, ozone: 57±6 bursts/min) was similar. Conclusions/Significance Our study suggests that acute ozone-induced airway inflammation does not increase resting sympathetic nerve traffic in healthy subjects, an observation that is relevant for environmental health. However, we can not exclude that chronic airway inflammation may contribute to sympathetic activation

Effects of acute ingestion of different fats on oxidative stress and inflammation in overweight and obese adults.

PubMed

Peairs, Abigail D; Rankin, Janet W; Lee, Yong Woo

2011-11-07

Studies show that obese individuals have prolonged elevations in postprandial lipemia and an exacerbated inflammatory response to high fat meals, which can increase risk for cardiovascular diseases. As epidemiological studies indicate an association between type of fat and circulating inflammatory markers, the purpose of this study was to investigate the acute effect of different fat sources on inflammation and oxidative stress in overweight and obese individuals. Eleven overweight and obese subjects consumed three high fat milkshakes rich in monounsaturated fat (MFA), saturated fat (SFA), or long-chain omega 3 polyunsaturated fat (O3FA) in random order. Blood samples collected at baseline, 1, 2, 4, and 6 hours postprandial were analyzed for markers of inflammation (soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor- α (TNF-α), and C-reactive protein (CRP)), oxidative stress (8-epi-prostaglandin-F2α (8-epi) and nuclear factor-κB (NF-κB)), and metabolic factors (glucose, insulin, non-esterified free fatty acids, and triglycerides (TG)). O3FA enhanced NF-kB activation compared to SFA, but did not increase any inflammatory factors measured. Conversely, SFA led to higher ICAM-1 levels than MFA (p = 0.051), while MFA increased TG more than SFA (p < 0.05). CRP increased while TNF-α and 8-epi decreased with no difference between treatments. While most of the inflammatory factors measured had modest or no change following the meal, ICAM-1 and NF-κB responded differently by meal type. These results are provocative and suggest that type of fat in meals may differentially influence postprandial inflammation and endothelial activation. © 2011 Peairs et al; licensee BioMed Central Ltd.

Simulation of Healing Threshold in Strain-Induced Inflammation Through a Discrete Informatics Model.

PubMed

Ibrahim, Israr Bin M; Sarma O V, Sanjay; Pidaparti, Ramana M

2018-05-01

Respiratory diseases such as asthma and acute respiratory distress syndrome as well as acute lung injury involve inflammation at the cellular level. The inflammation process is very complex and is characterized by the emergence of cytokines along with other changes in cellular processes. Due to the complexity of the various constituents that makes up the inflammation dynamics, it is necessary to develop models that can complement experiments to fully understand inflammatory diseases. In this study, we developed a discrete informatics model based on cellular automata (CA) approach to investigate the influence of elastic field (stretch/strain) on the dynamics of inflammation and account for probabilistic adaptation based on statistical interpretation of existing experimental data. Our simulation model investigated the effects of low, medium, and high strain conditions on inflammation dynamics. Results suggest that the model is able to indicate the threshold of innate healing of tissue as a response to strain experienced by the tissue. When strain is under the threshold, the tissue is still capable of adapting its structure to heal the damaged part. However, there exists a strain threshold where healing capability breaks down. The results obtained demonstrate that the developed discrete informatics based CA model is capable of modeling and giving insights into inflammation dynamics parameters under various mechanical strain/stretch environments.

Inflammation: maladies, models, mechanisms and molecules.

PubMed

Stewart, A G; Beart, P M

2016-02-01

The continued focus of attention on the diversity of mechanisms underpinning inflammation has improved our understanding of the potential to target specific pathways in the inflammatory network to achieve meaningful therapeutic gains. In this themed issue of the British Journal of Pharmacology our scope was deliberately broad, ranging across both acute and chronic disease in various organs. Pro- and anti-inflammatory mechanisms receive attention as does the phenotype of macrophages. Whilst the manifestations of neuro-inflammation are less obvious than those in peripheral tissues, central innate and adaptive immunity in brain and the M1/M2 phenotypes of microglia are topics of special interest. The contributions to the inflammatory milieu of cytokines, chemokines and associated signalling cascades are considered. Overall, the coverage herein advances the basic science underpinning our understanding of inflammation and emphasizes its importance in different pathologies. © 2016 The British Pharmacological Society.

LTβR expression on hematopoietic cells regulates acute inflammation and influences maturation of myeloid subpopulations.

PubMed

Wege, Anja K; Huber, Barbara; Wimmer, Nadin; Männel, Daniela N; Hehlgans, Thomas

2014-07-01

Lymphotoxin beta-receptor (LTβR) is involved in the formation and maintenance of secondary lymphoid structures, as well as in the regulation of inflammatory responses. Because LTβR lymphoid structure formation continues to develop in infants, we compared two different chimera models: one using adult mice and the other using a transplantation model of neonatal mice. To elucidate the function of LTβR on lymphoid and non-lymphoid cells, we generated bone marrow chimeras on the wild type C57Bl/6 and the LTβR-deficient (LTβR(-/-)) background, and reconstituted the mice with bone marrow cells reciprocally. These chimeric mice were analyzed in the experimental model of acute dextran sulfate sodium-induced colitis. Interestingly, both models revealed not only equal reconstitution levels but also similar immunological responses: LTβR expression on stromal cells is essential for lymph node formation, whereas LTBR on hematopoietic cells is crucial for a decrease in inflammation. In addition, mice lacking LTβR on hematopoietic cells revealed (a) an increase of immature granulocytic cells in the spleen and (b) a reduced proportion of myeloid cells in peripheral blood and spleen expressing CD11b(+)Ly6C(+)Ly6G(-) (myeloid-derived suppressor cells expression profile). In conclusion, LTβR expression on hematopoietic cells seems to be involved in the down-regulation of acute inflammatory reactions paralleled by the appearance of immature myeloid cells. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

A retrospective comparative study of arthroscopic fixation in acute Rockwood type IV acromioclavicular joint dislocation: single versus double paired Endobutton technique.

PubMed

Xu, Jian; Liu, Haifeng; Lu, Wei; Li, Dingfu; Zhu, Weimin; Ouyang, Kan; Wu, Bing; Peng, Liangquan; Wang, Daping

2018-05-24

Rockwood type IV acromioclavicular joint (ACJ) dislocation is a trauma usually needs surgical treatment. Paired EndoButton technique (PET) is used in treating such condition. However, the effect of using different types of PET (single versus double PET) for fixation remains controversial. This study aims to evaluate and compare the efficacy of single and double PET and to provide a suitable option for the surgeons. We retrospectively reviewed the charts of patients with acute Rockwood type IV ACJ dislocation who had undergone arthroscopic fixation using single or double PET fixation between March 2009 and March 2015. Seventy-eight consecutive patients identified from chart review were picked and were divided into the single and double PET group with 39 cases in each group. The indexes of visual analog scale score (VAS) for pain, the radiographs of the affected shoulder at different time points of the follow-up, the time of return to activities and sports, the constant functional score, and the Karlsson acromioclavicular joint (ACJ) score, were assessed in a minimum of 2 years postoperation. The average coracoclavicular (CC) and acromioclavicular (AC) distances of the affected joints in the double PET group were significantly smaller than those of the single PET group 2 years postoperation (P < 0.05). The average AC and CC distances in the healthy shoulder joints were significantly smaller than those of the affected joints in the single PET group (P < 0.05); however, these values were not significantly different from those of the affected joints in the double PET group (P > 0.05). The mean VAS pain score was not significantly different, while significant difference was found for the number and times of cases return to activities and sports, constant functional score, and Karlsson ACJ score (P < 0.05) between the two groups. Therefore, the double PET group has better outcome than the single PET group. Complications including redislocation, button

Peripheral hyperpolarization-activated cyclic nucleotide-gated channels contribute to inflammation-induced hypersensitivity of the rat temporomandibular joint.

PubMed

Hatch, R J; Jennings, E A; Ivanusic, J J

2013-08-01

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels conduct an inward cation current (Ih ) that contributes to the maintenance of neuronal membrane potential and have been implicated in a number of animal models of neuropathic and inflammatory pain. In the current study, we investigated HCN channel involvement in inflammatory pain of the temporomandibular joint (TMJ). The contribution of HCN channels to inflammation (complete Freund's adjuvant; CFA)-induced mechanical hypersensitivity of the rat TMJ was tested with injections of the HCN channel blocker ZD7288. Retrograde labelling and immunohistochemistry was used to explore HCN channel expression in sensory neurons that innervate the TMJ. Injection of CFA into the TMJ (n = 7) resulted in a significantly increased mechanical sensitivity relative to vehicle injection (n = 7) (p < 0.05). The mechanical hypersensitivity generated by CFA injection was blocked by co-injection of ZD7288 with the CFA (n = 7). Retrograde labelling and immunohistochemistry experiments revealed expression predominantly of HCN1 and HCN2 channel subunits in trigeminal ganglion neurons that innervate the TMJ (n = 3). No change in the proportion or intensity of HCN channel expression was found in inflamed (n = 6) versus control (n = 5) animals at the time point tested. Our findings suggest a role for peripheral HCN channels in inflammation-induced pain of the TMJ. Peripheral application of a HCN channel blocker could provide therapeutic benefit for inflammatory TMJ pain and avoid side effects associated with activation of HCN channels in the central nervous system. © 2012 European Federation of International Association for the Study of Pain Chapters.

Systemic Inflammation after Third Molar Removal: A Case-Control Study.

PubMed

Graziani, F; D'Aiuto, F; Gennai, S; Petrini, M; Nisi, M; Cirigliano, N; Landini, L; Bruno, R M; Taddei, S; Ghiadoni, L

2017-12-01

Third molar extraction is one of the most frequent interventions in dentistry. Nevertheless, there is scarce evidence on the host response of individuals with impacted or semi-impacted third molars and the possible effects of surgical removal. A case-control study of 40 patients was designed to evaluate 1) the differences in biomarkers of systemic inflammation, vascular function, and metabolism (high-sensitive C-reactive protein, lipids, fibrinogen, oxidative stress, and endothelial function analysis) and 2) the acute and short-term effects of surgical removal in patients with bilateral impacted or semi-impacted third molars compared to controls with no third molars. Patients undergoing third molar extraction exhibited greater levels of systemic inflammation, oxidative stress, and triglycerides than controls. Raised white blood cell counts as well as peaks of serum levels of C-reactive protein and fibrinogen were noticed in the first postoperative week. Three months after the extraction, all markers returned to baseline values. Malondialdehyde, an indicator of oxidative stress indicator, was significantly reduced after third molar removal. Semi-impacted or impacted third molars are associated with higher systemic inflammation, and their removal may represent a useful human model to study acute inflammation and determine beneficial systemic effects ( ClinicalTrials.gov NCT03048175).

A combination of lactic acid bacteria regulates Escherichia coli infection and inflammation of the bovine endometrium.

PubMed

Genís, Sandra; Sánchez-Chardi, Alejandro; Bach, Àlex; Fàbregas, Francesc; Arís, Anna

2017-01-01

Uterine function in cattle is compromised by bacterial contamination and inflammation after calving. The objective of this study was to select a combination of lactic acid bacteria (LAB) to decrease endometrium inflammation and Escherichia coli infection. Primary endometrial epithelial cells were cultured in vitro to select the most favorable LAB combination modulating basal tissue inflammation and E. coli infection. Supernatants were obtained to determine expression of pro-inflammatory cytokines, and E. coli infection was evaluated after harvesting the tissue and plate counting. The selected LAB combination was tested in uterus explants to assess its capacity to modulate basal and acute inflammation (associated with E. coli infection). The combination of Lactobacillus rhamnosus, Pediococcus acidilactici, and Lactobacillus reuteri at a ratio of 25:25:2, respectively, reduced E. coli infection in vitro with (89.77%) or without basal tissue inflammation (95.10%) compared with single LAB strains. Lactic acid bacteria treatment reduced CXCL8 and IL1B expression 4.7- and 2.2-fold, respectively, under acute inflammation. Ex vivo, the tested LAB combination reduced acute inflammation under E. coli infection, decreasing IL-8, IL-1β, and IL-6 up to 2.2-, 2.5-, and 2.2-fold, respectively. In the total inflammation model, the LAB combination decreased IL-8 1.6-fold and IL-6 1.2-fold. Ultrastructural evaluation of the tissue suggested no direct interaction between the LAB and E. coli, although pathological effects of E. coli in endometrial cells were greatly diminished or even reversed by the LAB combination. This study shows the promising potential of LAB probiotics for therapeutic use against endometrial inflammation and infection. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Whole-body MRI assessment of disease activity and structural damage in rheumatoid arthritis: first step towards an MRI joint count.

PubMed

Axelsen, Mette Bjørndal; Eshed, Iris; Duer-Jensen, Anne; Møller, Jakob M; Pedersen, Susanne Juhl; Østergaard, Mikkel

2014-05-01

The aim of this study was to investigate the ability of whole-body MRI (WBMRI) to visualize inflammation [synovitis, bone marrow oedema (BME) and enthesitis] and structural damage in patients with RA. The 3T WBMR images were acquired in a head-to-toe scan in 20 patients with RA and at least one swollen or tender joint. Short Tau Inversion Recovery and pre- and post-contrast T1-weighted images were evaluated for readability and the presence/absence of inflammation (synovitis, BME and enthesitis) and structural damage (erosions and fat infiltrations) in 76 peripheral joints, 30 entheseal sites and in the spine. The readability was >70% for all individual joints, except for the most peripheral joints of the hands and feet. Synovitis was most frequent in the wrist, first tarsometatarsal, first CMC joints and glenohumeral joints (67-61%); BME in the wrist, CMC, acromioclavicular and glenohumeral joints (45-35%) and erosions in the wrist, MTP and CMC joints (19-16%). Enthesitis at ≥ 1 site was registered in 16 patients. BME was frequently seen in the cervical (20%) but not the thoracic and lumbar spine, while fat infiltrations and erosions were rare. The intrareader agreement was high (85-100%) for all pathologies. The agreement between WBMRI and clinical findings was low. Peripheral and axial inflammation and structural damage at joints and entheses was frequently identified by WBMRI, and more frequently than by clinical examination. WBMRI is a promising tool for evaluation of the total inflammatory load of inflammation (an MRI joint count) and structural damage in RA patients.

An inflammation-responsive transcription factor in the pathophysiology of osteoarthritis.

PubMed

Ray, Alpana; Ray, Bimal K

2008-01-01

A number of risk factors including biomechanical stress on the articular cartilage imposed by joint overloading due to obesity, repetitive damage of the joint tissues by injury of the menisci and ligaments, and abnormal joint alignment play a significant role in the onset of osteoarthritis (OA). Genetic predisposition can also lead to the formation of defective cartilage matrix because of abnormal gene expression in the cartilage-specific cells. Another important biochemical event in OA is the consequence of inflammation. It has been shown that synovial inflammation triggers the synthesis of biological stimuli such as cytokines and growth factors which subsequently reach the chondrocyte cells of the articular cartilage activating inflammatory events in the chondrocytes leading to cartilage destruction. In addition to cartilage degradation, hypertrophy of the subchondral bone and osteophyte formation at the joint margins also takes place in OA. Both processes involve abnormal expression of a number of genes including matrix metalloproteinases (MMPs) for cartilage degradation and those associated with bone formation during osteophyte development. To address how diverse groups of genes are activated in OA chondrocyte, we have studied their induction mechanism. We present evidence for abundant expression of an inflammation-responsive transcription factor, SAF-1, in moderate to severely damaged OA cartilage tissues. In contrast, cells in normal cartilage matrix contain very low level of SAF-1 protein. SAF-1 is identified as a major regulator of increased synthesis of MMP-1 and -9 and pro-angiogenic factor, vascular endothelial growth factor (VEGF). While VEGF by stimulating angiogenesis plays a key role in new bone formation in osteophyte, increase of MMP-1 and -9 is instrumental for cartilage erosion in the pathogenesis of OA. Increased expression in degenerated cartilage matrix and in the osteophytes indicate for a key regulatory role of SAF-1 in directing catabolic

Dorsoradial capsulodesis for trapeziometacarpal joint instability.

PubMed

Rayan, Ghazi; Do, Viet

2013-02-01

We describe an alternative method for treating chronic trapeziometacarpal (TM) joint instability after acute injury or chronic repetitive use of the thumb by performing a dorsoradial capsulodesis procedure. The procedure is done by imbricating the redundant TM joint dorsoradial ligament and capsule after reducing the joint by pronating the thumb. The dorsoradial capsulodesis is a reasonable reconstructive option for chronic TM joint instability and subluxation. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Antioxidant Effect of Spirulina (Arthrospira) maxima on Chronic Inflammation Induced by Freund's Complete Adjuvant in Rats

PubMed Central

Gutiérrez-Rebolledo, Gabriel Alfonso; Galar-Martínez, Marcela; García-Rodríguez, Rosa Virginia; Chamorro-Cevallos, Germán A.; Hernández-Reyes, Ana Gabriela

2015-01-01

Abstract One of the major mechanisms in the pathogenesis of chronic inflammation is the excessive production of reactive oxygen and reactive nitrogen species, and therefore, oxidative stress. Spirulina (Arthrospira) maxima has marked antioxidant activity in vivo and in vitro, as well as anti-inflammatory activity in certain experimental models, the latter activity being mediated probably by the antioxidant activity of this cyanobacterium. In the present study, chronic inflammation was induced through injection of Freund's complete adjuvant (CFA) in rats treated daily with Spirulina (Arthrospira) maxima for 2 weeks beginning on day 14. Joint diameter, body temperature, and motor capacity were assessed each week. On days 0 and 28, total and differential leukocyte counts and serum oxidative damage were determined, the latter by assessing lipid peroxidation and protein carbonyl content. At the end of the study, oxidative damage to joints was likewise evaluated. Results show that S. maxima favors increased mobility, as well as body temperature regulation, and a number of circulating leukocytes, lymphocytes, and monocytes in specimens with CFA-induced chronic inflammation and also protects against oxidative damage in joint tissue as well as serum. In conclusion, the protection afforded by S. maxima against development of chronic inflammation is due to its antioxidant activity. PMID:25599112

Antioxidant Effect of Spirulina (Arthrospira) maxima on Chronic Inflammation Induced by Freund's Complete Adjuvant in Rats.

PubMed

Gutiérrez-Rebolledo, Gabriel Alfonso; Galar-Martínez, Marcela; García-Rodríguez, Rosa Virginia; Chamorro-Cevallos, Germán A; Hernández-Reyes, Ana Gabriela; Martínez-Galero, Elizdath

2015-08-01

One of the major mechanisms in the pathogenesis of chronic inflammation is the excessive production of reactive oxygen and reactive nitrogen species, and therefore, oxidative stress. Spirulina (Arthrospira) maxima has marked antioxidant activity in vivo and in vitro, as well as anti-inflammatory activity in certain experimental models, the latter activity being mediated probably by the antioxidant activity of this cyanobacterium. In the present study, chronic inflammation was induced through injection of Freund's complete adjuvant (CFA) in rats treated daily with Spirulina (Arthrospira) maxima for 2 weeks beginning on day 14. Joint diameter, body temperature, and motor capacity were assessed each week. On days 0 and 28, total and differential leukocyte counts and serum oxidative damage were determined, the latter by assessing lipid peroxidation and protein carbonyl content. At the end of the study, oxidative damage to joints was likewise evaluated. Results show that S. maxima favors increased mobility, as well as body temperature regulation, and a number of circulating leukocytes, lymphocytes, and monocytes in specimens with CFA-induced chronic inflammation and also protects against oxidative damage in joint tissue as well as serum. In conclusion, the protection afforded by S. maxima against development of chronic inflammation is due to its antioxidant activity.

Chronic baseline prostate inflammation is associated with lower tumor volume in men with prostate cancer on repeat biopsy: Results from the REDUCE study.

PubMed

Moreira, Daniel M; Nickel, J Curtis; Andriole, Gerald L; Castro-Santamaria, Ramiro; Freedland, Stephen J

2015-09-01

To evaluate whether baseline acute and chronic prostate inflammation among men with initial negative biopsy for prostate cancer (PC) is associated with PC volume at the 2-year repeat prostate biopsy in a clinical trial with systematic biopsies. Retrospective analysis of 886 men with negative baseline prostate biopsy and positive 2-year repeat biopsy in the Reduction by Dutasteride of PC Events (REDUCE) study. Acute and chronic inflammation and tumor volume were determined by central pathology. The association of baseline inflammation with 2-year repeat biopsy cancer volume was evaluated with linear and Poisson regressions controlling for demographics and laboratory variables. Chronic, acute inflammation, and both were detected in 531 (60%), 12 (1%), and 84 (9%) baseline biopsies, respectively. Acute and chronic inflammation were significantly associated with each other (P < 0.001). Chronic inflammation was associated with larger prostate (P < 0.001) and lower pre-repeat biopsy PSA (P = 0.01). At 2-year biopsy, baseline chronic inflammation was associated with lower mean tumor volume (2.07 µl vs. 3.15 µl; P = 0.001), number of biopsy cores involved (1.78 vs. 2.19; P < 0.001), percent of cores involved (17.8% vs. 22.8%; P < 0.001), core involvement (0.21 µl vs. 0.31 µl; P < 0.001), and overall percent tumor involvement (1.40% vs. 2.01%; P < 0.001). Results were unchanged in multivariable analysis. Baseline acute inflammation was not associated with any tumor volume measurement. In a cohort of men with 2-year repeat prostate biopsy positive for PC after a negative baseline biopsy, baseline chronic inflammation was associated with lower PC volume. © 2015 Wiley Periodicals, Inc.

The Interplay between inflammation and fibrosis in kidney transplantation.

PubMed

Torres, Irina B; Moreso, Francesc; Sarró, Eduard; Meseguer, Anna; Serón, Daniel

2014-01-01

Serial surveillance renal allograft biopsies have shown that early subclinical inflammation constitutes a risk factor for the development of interstitial fibrosis. More recently, it has been observed that persistent inflammation is also associated with fibrosis progression and chronic humoral rejection, two histological conditions associated with poor allograft survival. Treatment of subclinical inflammation with steroid boluses prevents progression of fibrosis and preserves renal function in patients treated with a cyclosporine-based regimen. Subclinical inflammation has been reduced after the introduction of tacrolimus based regimens, and it has been shown that immunosuppressive schedules that are effective in preventing acute rejection and subclinical inflammation may prevent the progression of fibrosis and chronic humoral rejection. On the other hand, minimization protocols are associated with progression of fibrosis, and noncompliance with the immunosuppressive regime constitutes a major risk factor for chronic humoral rejection. Thus, adequate immunosuppressive treatment, avoiding minimization strategies and reinforcing educational actions to prevent noncompliance, is at present an effective approach to combat the progression of fibrosis.

The Interplay between Inflammation and Fibrosis in Kidney Transplantation

PubMed Central

Torres, Irina B.; Moreso, Francesc; Sarró, Eduard; Serón, Daniel

2014-01-01

Serial surveillance renal allograft biopsies have shown that early subclinical inflammation constitutes a risk factor for the development of interstitial fibrosis. More recently, it has been observed that persistent inflammation is also associated with fibrosis progression and chronic humoral rejection, two histological conditions associated with poor allograft survival. Treatment of subclinical inflammation with steroid boluses prevents progression of fibrosis and preserves renal function in patients treated with a cyclosporine-based regimen. Subclinical inflammation has been reduced after the introduction of tacrolimus based regimens, and it has been shown that immunosuppressive schedules that are effective in preventing acute rejection and subclinical inflammation may prevent the progression of fibrosis and chronic humoral rejection. On the other hand, minimization protocols are associated with progression of fibrosis, and noncompliance with the immunosuppressive regime constitutes a major risk factor for chronic humoral rejection. Thus, adequate immunosuppressive treatment, avoiding minimization strategies and reinforcing educational actions to prevent noncompliance, is at present an effective approach to combat the progression of fibrosis. PMID:24991565

Hydrocortisone concentration influences time to clinically significant healing of acute inflammation of the ocular surface and adnexa - results from a double-blind randomized controlled trial.

PubMed

Sergiyenko, Nikolay; Sukhina, Ludmila; Bezdetko, Pavel; Kovalenko, Yuriy; Nikitin, Nikolai; Merzbacher, Matthias; Gross, Dorothea; Kohnen, Ralf

2014-05-10

The efficacy of topical ophthalmic corticosteroids depends upon small modifications in preparations, such as drug concentration.The aim of this study was to confirm that hydrocortisone acetate (HC-ac) ophthalmic ointments of 2.5% and 1% are more effective than a 0.5% eye ointment. In this randomized, double-blind, placebo-controlled, parallel-group clinical study, the change of signs and symptoms of acute inflammation of the ocular surface and adnexa was evaluated in 411 subjects. Median time to clinically relevant response as estimated by 50% reduction in clinical signs and symptoms (CSS) total score over the entire trial was similar for subjects treated with HC-ac 2.5% (73.5 h) and for subjects treated with HC-ac 1.0% (67.7 h) and was considerably and significantly longer for subjects treated with HC-ac 0.5% (111.8 h) [p < 0.001 for both dosages]. All trial medications were safe and well tolerated. Hydrocortisone acetate 2.5% and Hydrocortisone acetate 1% eye ointments are efficacious and safe treatments for acute inflammations of the ocular surface or adnexa, and showed significantly better efficacy than a control group treated with Hydrocortisone acetate 0.5% therapy. Current Controlled Trials ISRCTN15464650.

A newly synthesized macakurzin C-derivative attenuates acute and chronic skin inflammation: The Nrf2/heme oxygenase signaling as a potential target

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akram, Muhammad

Impaired immune responses in skin play a pivotal role in the development and progression of chemical-associated inflammatory skin disorders. In this study, we synthesized new flavonoid derivatives from macakurzin C, and identified in vitro and in vivo efficacy of a potent anti-inflammatory flavonoid, Compound 14 (CPD 14), with its underlying mechanisms. In lipopolysaccharide (LPS)-stimulated murine macrophages and IFN-γ/TNF-α-stimulated human keratinocytes, CPD 14 significantly inhibited the release of inflammatory mediators including nitric oxide (NO), prostaglandins, and cytokines (IC{sub 50} for NO inhibition in macrophages: 4.61 μM). Attenuated NF-κB signaling and activated Nrf2/HO-1 pathway were responsible for the anti-inflammatory effects of CPDmore » 14. The in vivo relevance was examined in phorbol 12-myristate 13-acetate (TPA)-induced acute skin inflammation and oxazolone-induced atopic dermatitis models. Topically applied CPD 14 significantly protected both irritation- and sensitization-associated skin inflammation by suppressing the expression of inflammatory mediators. In summary, we demonstrated that a newly synthesized flavonoid, CPD 14, has potent inhibitory effects on skin inflammation, suggesting it is a potential therapeutic candidate to treat skin disorders associated with excessive inflammation. - Highlights: • An anti-inflammatory flavonoid CPD 14 was newly synthesized from macakurzin C. • CPD 14 potently inhibited inflammatory reaction in keratinocytes and macrophages. • Dermal toxicity by irritation or sensitization in rats was protected by CPD 14. • Attenuated NF-κB and activated Nrf2/HO-1 were main mechanisms of CPD 14 action.« less

Canakinumab relieves symptoms of acute flares and improves health-related quality of life in patients with difficult-to-treat Gouty Arthritis by suppressing inflammation: results of a randomized, dose-ranging study

PubMed Central

2011-01-01

Introduction We report the impact of canakinumab, a fully human anti-interleukin-1β monoclonal antibody, on inflammation and health-related quality of life (HRQoL) in patients with difficult-to-treat Gouty Arthritis. Methods In this eight-week, single-blind, double-dummy, dose-ranging study, patients with acute Gouty Arthritis flares who were unresponsive or intolerant to - or had contraindications for - non-steroidal anti-inflammatory drugs and/or colchicine were randomized to receive a single subcutaneous dose of canakinumab (10, 25, 50, 90, or 150 mg) (N = 143) or an intramuscular dose of triamcinolone acetonide 40 mg (N = 57). Patients assessed pain using a Likert scale, physicians assessed clinical signs of joint inflammation, and HRQoL was measured using the 36-item Short-Form Health Survey (SF-36) (acute version). Results At baseline, 98% of patients were suffering from moderate-to-extreme pain. The percentage of patients with no or mild pain was numerically greater in most canakinumab groups compared with triamcinolone acetonide from 24 to 72 hours post-dose; the difference was statistically significant for canakinumab 150 mg at these time points (P < 0.05). Treatment with canakinumab 150 mg was associated with statistically significant lower Likert scores for tenderness (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.27 to 7.89; P = 0.014) and swelling (OR, 2.7; 95% CI, 1.09 to 6.50, P = 0.032) at 72 hours compared with triamcinolone acetonide. Median C-reactive protein and serum amyloid A levels were normalized by seven days post-dose in most canakinumab groups, but remained elevated in the triamcinolone acetonide group. Improvements in physical health were observed at seven days post-dose in all treatment groups; increases in scores were highest for canakinumab 150 mg. In this group, the mean SF-36 physical component summary score increased by 12.0 points from baseline to 48.3 at seven days post-dose. SF-36 scores for physical functioning and

Potentiated Interaction between Ineffective Doses of Budesonide and Formoterol to Control the Inhaled Cadmium-Induced Up-Regulation of Metalloproteinases and Acute Pulmonary Inflammation in Rats

PubMed Central

Zhang, Wenhui; Zhi, Jianming; Cui, Yongyao; Zhang, Fan; Habyarimana, Adélite; Cambier, Carole; Gustin, Pascal

2014-01-01

The anti-inflammatory properties of glucocorticoids are well known but their protective effects exerted with a low potency against heavy metals-induced pulmonary inflammation remain unclear. In this study, a model of acute pulmonary inflammation induced by a single inhalation of cadmium in male Sprague-Dawley rats was used to investigate whether formoterol can improve the anti-inflammatory effects of budesonide. The cadmium-related inflammatory responses, including matrix metalloproteinase-9 (MMP-9) activity, were evaluated. Compared to the values obtained in rats exposed to cadmium, pretreatment of inhaled budesonide (0.5 mg/15 ml) elicited a significant decrease in total cell and neutrophil counts in bronchoalveolar lavage fluid (BALF) associated with a significant reduction of MMP-9 activity which was highly correlated with the number of inflammatory cells in BALF. Additionally, cadmium-induced lung injuries characterized by inflammatory cell infiltration within alveoli and the interstitium were attenuated by the pre-treatment of budesonide. Though the low concentration of budesonide (0.25 mg/15 ml) exerted a very limited inhibitory effects in the present rat model, its combination with an inefficient concentration of formoterol (0.5 mg/30 ml) showed an enhanced inhibitory effect on neutrophil and total cell counts as well as on the histological lung injuries associated with a potentiation of inhibition on the MMP-9 activity. In conclusion, high concentration of budesonide alone could partially protect the lungs against cadmium exposure induced-acute neutrophilic pulmonary inflammation via the inhibition of MMP-9 activity. The combination with formoterol could enhance the protective effects of both drugs, suggesting a new therapeutic strategy for the treatment of heavy metals-induced lung diseases. PMID:25313925

Are ultrasound features at the first metatarsophalangeal joint associated with clinically-assessed pain and function? A study of people with gout, asymptomatic hyperuricaemia and normouricaemia.

PubMed

Stewart, Sarah; Dalbeth, Nicola; Vandal, Alain C; Allen, Bruce; Miranda, Rhian; Rome, Keith

2017-01-01

The first metatatarsophalangeal joint (1st MTP joint) is a common location for sonographic evidence of urate deposition in people with gout and asymptomatic hyperuricaemia. However, it is unclear whether these are related to clinically-assessed pain and function. This study aimed to determine the association between ultrasound features and clinical characteristics of the 1st MTP joint in people with gout, asymptomatic hyperuricaemia and age- and sex-matched normouricaemic individuals. Twenty-three people with gout, 29 with asymptomatic hyperuricaemia and 34 with normouricaemia participated in a cross-sectional study. No participant had clinical evidence of acute inflammatory arthritis at the time of assessment. Four sonographic features at the 1st MTP joint were analysed: double contour sign, tophus, bone erosion and synovitis. Clinical characteristics included in the analysis were 1st MTP joint pain, overall foot pain and disability, 1st MTP joint temperature, 1st MTP joint range of motion and gait velocity. Statistical analyses adjusted for the diagnostic group of the participant. After accounting for the diagnostic group, double contour sign was associated with higher foot pain and disability scores ( P  < 0.001). Ultrasound tophus was associated with higher foot pain and disability scores ( P  < 0.001), increased temperature ( P  = 0.005), and reduced walking velocity ( P  = 0.001). No associations were observed between ultrasound synovitis or erosion and the clinical characteristics. Ultrasound features of urate crystal deposition, rather than soft tissue inflammation or bone erosion, are associated with clinical measures of foot-related functional impairment and disability even in the absence of clinical evidence of current acute inflammatory arthritis. This association persisted regardless of the diagnosis of the participant as having gout or asymptomatic hyperuricaemia.

The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation.

PubMed

Grabiec, Aleksander M; Hussell, Tracy

2016-07-01

Acute and chronic inflammatory responses in the lung are associated with the accumulation of large quantities of immune and structural cells undergoing apoptosis, which need to be engulfed by phagocytes in a process called 'efferocytosis'. Apoptotic cell recognition and removal from the lung is mediated predominantly by airway macrophages, though immature dendritic cells and non-professional phagocytes, such as epithelial cells and mesenchymal cells, can also display this function. Efficient clearance of apoptotic cells from the airways is essential for successful resolution of inflammation and the return to lung homeostasis. Disruption of this process leads to secondary necrosis of accumulating apoptotic cells, release of necrotic cell debris and subsequent uncontrolled inflammatory activation of the innate immune system by the released 'damage associated molecular patterns' (DAMPS). To control the duration of the immune response and prevent autoimmune reactions, anti-inflammatory signalling cascades are initiated in the phagocyte upon apoptotic cell uptake, mediated by a range of receptors that recognise specific phospholipids or proteins externalised on, or secreted by, the apoptotic cell. However, prolonged activation of apoptotic cell recognition receptors, such as the family of receptor tyrosine kinases Tyro3, Axl and MerTK (TAM), may delay or prevent inflammatory responses to subsequent infections. In this review, we will discuss recent advances in our understanding of the mechanism controlling apoptotic cell recognition and removal from the lung in homeostasis and during inflammation, the contribution of defective efferocytosis to chronic inflammatory lung diseases, such as chronic obstructive pulmonary disease, asthma and cystic fibrosis, and implications of the signals triggered by apoptotic cells in the susceptibility to pulmonary microbial infections.

Metabolic Cost of the Activation of Immune Response in the Fish-Eating Myotis (Myotis vivesi): The Effects of Inflammation and the Acute Phase Response

PubMed Central

Otálora-Ardila, Aída; Herrera M., L. Gerardo; Flores-Martínez, José Juan; Welch, Kenneth C.

2016-01-01

Inflammation and activation of the acute phase response (APR) are energetically demanding processes that protect against pathogens. Phytohaemagglutinin (PHA) and lipopolysaccharide (LPS) are antigens commonly used to stimulate inflammation and the APR, respectively. We tested the hypothesis that the APR after an LPS challenge was energetically more costly than the inflammatory response after a PHA challenge in the fish-eating Myotis bat (Myotis vivesi). We measured resting metabolic rate (RMR) after bats were administered PHA and LPS. We also measured skin temperature (Tskin) after the LPS challenge and skin swelling after the PHA challenge. Injection of PHA elicited swelling that lasted for several days but changes in RMR and body mass were not significant. LPS injection produced a significant increase in Tskin and in RMR, and significant body mass loss. RMR after LPS injection increased by 140–185% and the total cost of the response was 6.50 kJ. Inflammation was an energetically low-cost process but the APR entailed a significant energetic investment. Examination of APR in other bats suggests that the way in which bats deal with infections might not be uniform. PMID:27792729

Metabolic Cost of the Activation of Immune Response in the Fish-Eating Myotis (Myotis vivesi): The Effects of Inflammation and the Acute Phase Response.

PubMed

Otálora-Ardila, Aída; Herrera M, L Gerardo; Flores-Martínez, José Juan; Welch, Kenneth C

2016-01-01

Inflammation and activation of the acute phase response (APR) are energetically demanding processes that protect against pathogens. Phytohaemagglutinin (PHA) and lipopolysaccharide (LPS) are antigens commonly used to stimulate inflammation and the APR, respectively. We tested the hypothesis that the APR after an LPS challenge was energetically more costly than the inflammatory response after a PHA challenge in the fish-eating Myotis bat (Myotis vivesi). We measured resting metabolic rate (RMR) after bats were administered PHA and LPS. We also measured skin temperature (Tskin) after the LPS challenge and skin swelling after the PHA challenge. Injection of PHA elicited swelling that lasted for several days but changes in RMR and body mass were not significant. LPS injection produced a significant increase in Tskin and in RMR, and significant body mass loss. RMR after LPS injection increased by 140-185% and the total cost of the response was 6.50 kJ. Inflammation was an energetically low-cost process but the APR entailed a significant energetic investment. Examination of APR in other bats suggests that the way in which bats deal with infections might not be uniform.

Arthroscopically assisted reduction of acute acromioclavicular joint dislocation using a single double-button device: Medium-term clinical and radiological outcomes.

PubMed

Issa, S-P; Payan, C; Le Hanneur, M; Loriaut, P; Boyer, P

2018-02-01

Double-button devices for endoscopic management of acute acromioclavicular joint dislocation (ACJD) provide satisfactory short-term functional and radiological results. However, little exists in the literature regarding the long- and medium-term results of these implants, especially regarding the evolution of the acromioclavicular joint (ACJ). Satisfactory and steady long- and medium-term outcomes can be achieved in patients with acute ACJD undergoing endoscopically assisted ACJ repair using a single double-button device. A retrospective single-center study was conducted in patients with acute Rockwood III and IV ACJD treated endoscopically with a single double-button device from October 2008 to October 2010, allowing a minimum 5-year follow-up. Functional evaluation used Constant and Quick-DASH scores. Clinical evidence of dislocation recurrence was combined with bilateral Zanca views to assess coracoclavicular distance. Acromioclavicular osteoarthritis was evaluated on the Paxinos test and Zanca views. Nineteen of the 25 operated patients were seen at a mean 76.9±8.5 months' follow-up. Mean age was 34.4±8.3 years. Mean Constant and Quick-DASH scores were 96.2±5.1 and 0.9±1.6 points, respectively. Four patients had a recurrence of their initial dislocation, 3 of whom had positive Paxinos test, whereas the 15 patients without recurrence had a negative test (p=0.004). Five patients had radiological evidence of ACJ osteoarthritis: all 4 patients with recurrence and 1 without (p=0.001). Long- and medium-term radioclinical outcome of endoscopically assisted management of acute ACJD using a single double-button device seems to be satisfactory and steady over time. Recurrence of the initial dislocation appears to be related to onset of degenerative ACJ arthropathy. Therapeutic type IV-Retrospective case series. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Microbiota alterations in acute and chronic gastrointestinal inflammation of cats and dogs

PubMed Central

Honneffer, Julia B; Minamoto, Yasushi; Suchodolski, Jan S

2014-01-01

The intestinal microbiota is the collection of the living microorganisms (bacteria, fungi, protozoa, and viruses) inhabiting the gastrointestinal tract. Novel bacterial identification approaches have revealed that the gastrointestinal microbiota of dogs and cats is, similarly to humans, a highly complex ecosystem. Studies in dogs and cats have demonstrated that acute and chronic gastrointestinal diseases, including inflammatory bowel disease (IBD), are associated with alterations in the small intestinal and fecal microbial communities. Of interest is that these alterations are generally similar to the dysbiosis observed in humans with IBD or animal models of intestinal inflammation, suggesting that microbial responses to inflammatory conditions of the gut are conserved across mammalian host types. Studies have also revealed possible underlying susceptibilities in the innate immune system of dogs and cats with IBD, which further demonstrate the intricate relationship between gut microbiota and host health. Commonly identified microbiome changes in IBD are decreases in bacterial groups within the phyla Firmicutes and Bacteroidetes, and increases within Proteobacteia. Furthermore, a reduction in the diversity of Clostridium clusters XIVa and IV (i.e., Lachnospiraceae and Clostridium coccoides subgroups) are associated with IBD, suggesting that these bacterial groups may play an important role in maintenance of gastrointestinal health. Future studies are warranted to evaluate the functional changes associated with intestinal dysbiosis in dogs and cats. PMID:25469017

Joint Distraction Treatments of Intra-Articular Fracture-Induced Posttraumatic Osteoarthritis in a Large Animal Model

DTIC Science & Technology

2016-10-01

acute joint distraction treatment suffered some complications and did not appear to improve cartilage health when applied at this acute phase. We have...immature animals from their herd as a result of PRRS (porcine respiratory and reproduction syndrome ). This forced purchase of animals from alternative more...joint distraction applied acutely after IAF are the focus of Aim 1, and the effects of joint distraction applied shortly after the bone has healed are

Cannabinoids, inflammation, and fibrosis.

PubMed

Zurier, Robert B; Burstein, Sumner H

2016-11-01

Cannabinoids apparently act on inflammation through mechanisms different from those of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs). As a class, the cannabinoids are generally free from the adverse effects associated with NSAIDs. Their clinical development thus provides a new approach to treatment of diseases characterized by acute and chronic inflammation and fibrosis. A concise survey of the anti-inflammatory actions of the phytocannabinoids Δ 9 -tetrahydrocannabinol (THC), cannabidiol, cannabichromene, and cannabinol is presented. Mention is also made of the noncannabinoid plant components and pyrolysis products, followed by a discussion of 3 synthetic preparations-Cesamet (nabilone; Meda Pharmaceuticals, Somerset, NJ, USA), Marinol (dronabinol; THC; AbbVie, Inc., North Chicago, IL, USA), and Sativex (Cannabis extract; GW Pharmaceuticals, Cambridge United Kingdom)-that have anti-inflammatory effects. A fourth synthetic cannabinoid, ajulemic acid (AJA; CT-3; Resunab; Corbus Pharmaceuticals, Norwood, MA, USA), is discussed in greater detail because it represents the most recent advance in this area and is currently undergoing 3 phase 2 clinical trials by Corbus Pharmaceuticals. The endogenous cannabinoids, including the closely related lipoamino acids, are then discussed. The review concludes with a presentation of a possible mechanism for the anti-inflammatory and antifibrotic actions of these substances. Thus, several cannabinoids may be considered candidates for development as anti-inflammatory and antifibrotic agents. Of special interest is their possible use for treatment of chronic inflammation, a major unmet medical need.-Zurier, R. B., Burstein, S. H. Cannabinoids, inflammation, and fibrosis. © FASEB.

Acute influence of restricted ankle dorsiflexion angle on knee joint mechanics during gait.

PubMed

Ota, S; Ueda, M; Aimoto, K; Suzuki, Y; Sigward, S M

2014-06-01

Restrictions in range of ankle dorsiflexion (DF) motion can persist following ankle injuries. Ankle DF is necessary during terminal stance of gait, and its restricted range may affect knee joint kinematics and kinetics. The purpose of this study was to investigate the acute influence of varied levels of restricted ankle DF on knee joint sagittal and frontal plane kinematics and kinetics during gait. Thirty healthy volunteers walked with a custom-designed ankle brace that restricted ankle DF. Kinematics and kinetics were collected using a 7-camera motion analysis system and two force plates. Ankle dorsiflexion was restricted in 10-degree increments, allowing for four conditions: Free, light (LR), moderate (MR) and severe restriction (SR). Knee angles and moments were measured during terminal stance. Real peak ankle DF for Free, LR, MR, and SR were 13.7±4.8°, 11.6±5.0°, 7.5±5.3°, and 4.2±7.2°, respectively. Peak knee extension angles under the same conditions were -6.7±6.7°, -5.4±6.4°, -2.5±7.5°, and 0.6±7.8°, respectively, and the peak knee varus moment was 0.48±0.17 Nm/kg, 0.47±0.17 Nm/kg, 0.53±0.20 Nm/kg, and 0.57±0.20 Nm/kg. The knee varus moment was significantly increased from MR condition with an 8-degree restriction in ankle DF. Knee joint kinematics and kinetics in the sagittal and frontal planes were affected by reduced ankle DF during terminal stance of gait. Differences were observed with restriction in ankle DF range of approximately 8°. level III. Copyright © 2014 Elsevier B.V. All rights reserved.

Additive Contributions of Childhood Adversity and Recent Stressors to Inflammation at Midlife: Findings from the MIDUS Study

ERIC Educational Resources Information Center

Hostinar, Camelia E.; Lachman, Margie E.; Mroczek, Daniel K.; Seeman, Teresa E.; Miller, Gregory E.

2015-01-01

We examined the joint contributions of self-reported adverse childhood experiences (ACEs) and recent life events (RLEs) to inflammation at midlife, by testing 3 competing theoretical models: stress generation, stress accumulation, and early life stress sensitization. We aimed to identify potential mediators between adversity and inflammation.…

Joint prognostic effect of obesity and chronic systemic inflammation in patients with metastatic colorectal cancer.

PubMed

Shah, Manasi S; Fogelman, David R; Raghav, Kanwal Pratap Singh; Heymach, John V; Tran, Hai T; Jiang, Zhi-Qin; Kopetz, Scott; Daniel, Carrie R

2015-09-01

Obesity is strongly linked with chronic systemic inflammation, and each has been linked with disease progression and survival in patients with colorectal cancer (CRC). The authors investigated the joint prognostic effects of obesity and circulating cytokines in patients with metastatic CRC (mCRC), an understudied patient group. In 242 chemotherapy-naive patients with mCRC, the authors measured a multiplex cytokine panel and abstracted clinicopathological features, height, and weight from medical records. Overall survival (OS) was calculated from the date of mCRC diagnosis until the date of death from any cause and evaluated by Kaplan-Meier analysis and multivariable Cox proportional hazards regression models. Cut points for cytokines were determined by restricted cubic spline regression. In multivariable models, elevated interleukin (IL)-8, IL-2 receptor alpha, and lactate dehydrogenase (LDH) emerged as significant predictors of poor OS (hazard ratio [HR] and 95% confidence interval [95% CI] for above vs below the (referent) knot point: 2.5 [95% CI, 1.7-3.7], 1.9 [95% CI, 1.3-2.7], and 2.2 [95% CI, 1.6-3.1], respectively; all P<.001). Obesity (body mass index ≥30 kg/m(2) ) was not found to be associated with OS, but appeared to modify the relationships observed with IL-8 and LDH, which were associated with a significant 4-fold and 5-fold risk of death, respectively, in obese patients compared with a 2-fold risk of death in nonobese patients (P for interaction of .06 and .04, respectively). Similar results emerged from joint effects analysis, in which obese patients with high IL-8 (or LDH) experienced the highest risk of death. Although obesity itself was not found to be independently associated with survival in patients with mCRC, the adverse prognostic significance of LDH and IL-8 was found to be enhanced in obese patients. © 2015 American Cancer Society.

Early treatment of chlorine-induced airway hyperresponsiveness and inflammation with corticosteroids.

PubMed

Jonasson, Sofia; Wigenstam, Elisabeth; Koch, Bo; Bucht, Anders

2013-09-01

Chlorine (Cl2) is an industrial gas that is highly toxic and irritating when inhaled causing tissue damage and an acute inflammatory response in the airways followed by a long-term airway dysfunction. The aim of this study was to evaluate whether early anti-inflammatory treatment can protect against the delayed symptoms in Cl2-exposed mice. BALB/c mice were exposed by nose-only inhalation using 200ppm Cl2 during 15min. Assessment of airway hyperresponsiveness (AHR), inflammatory cell counts in bronchoalveolar lavage, occurrence of lung edema and lung fibrosis were analyzed 24h or 14days post-exposure. A single dose of the corticosteroid dexamethasone (10 or 100mg/kg) was administered intraperitoneally 1, 3, 6, or 12h following Cl2 exposure. High-dose of dexamethasone reduced the acute inflammation if administered within 6h after exposure but treated animals still displayed a significant lung injury. The effect of dexamethasone administered within 1h was dose-dependent; high-dose significantly reduced acute airway inflammation (100mg/kg) but not treatment with the relatively low-dose (10mg/kg). Both doses reduced AHR 14days later, while lung fibrosis measured as collagen deposition was not significantly reduced. The results point out that the acute inflammation in the lungs due to Cl2 exposure only partly is associated with the long-term AHR. We hypothesize that additional pathogenic mechanisms apart from the inflammatory reactions contribute to the development of long-term airway dysfunction. By using this mouse model, we have validated early administration of corticosteroids in terms of efficacy to prevent acute lung injury and delayed symptoms induced by Cl2 exposure. Copyright © 2013 Elsevier Inc. All rights reserved.

Whiplash injuries of the temporomandibular joint in motor vehicle accidents: speculations and facts.

PubMed

McKay, D C; Christensen, L V

1998-10-01

Referring to the temporomandibular joint (TMJ) of the human mandibular locomotor system, it has been asserted that displacement of the TMJ disc and inflammation of TMJ tissues are the results of acute and indirect trauma to the TMJ; on occasion this is allegedly experienced in motor vehicle accidents and commonly known as a TMJ whiplash injury. It is postulated that the TMJ whiplash injury is released in the occupant or occupants of a target vehicle when its rear end is impacted by the front end of a bullet vehicle. On the basis of detailed analyses of TMJ trauma/pain histories and TMJ magnetic resonance images, presented as circumstantial evidence in favour of the postulated TMJ whiplash injury, and detailed analyses of the mathematical biophysics of the mandibular locomotor system as well as direct experimental evidence, it is concluded that the postulated TMJ whiplash injury does not exist as a single and independent disease entity caused by motor vehicle accidents. If TMJ disc displacement and inflammation are present, they are expressions of an insidious and progressive pre-existing (pre-accident) disease entity that is comprised of TMJ synovitis/osteoarthritis (phase of inflammation with presence of immune system cells), TMJ internal derangement (phase of disc displacement and deformation with presence of proteinases), and TMJ osteoarthrosis (phase of degeneration with absence of immune system cells). For the asserted TMJ whiplash manoeuvre and ensuing injury to occur as postulated, the laws of physics and biology would have to be suspended.

Monocyte dysregulation and systemic inflammation during pediatric falciparum malaria

PubMed Central

Dobbs, Katherine R.; Embury, Paula; Odada, Peter S.; Rosa, Bruce A.; Mitreva, Makedonka; Kazura, James W.; Dent, Arlene E.

2017-01-01

BACKGROUND. Inflammation and monocytes are thought to be important to human malaria pathogenesis. However, the relationship of inflammation and various monocyte functions to acute malaria, recovery from acute malaria, and asymptomatic parasitemia in endemic populations is poorly understood. METHODS. We evaluated plasma cytokine levels, monocyte subsets, monocyte functional responses, and monocyte inflammatory transcriptional profiles of 1- to 10-year-old Kenyan children at the time of presentation with acute uncomplicated malaria and at recovery 6 weeks later; these results were compared with analogous data from asymptomatic children and adults in the same community. RESULTS. Acute malaria was marked by elevated levels of proinflammatory and regulatory cytokines and expansion of the inflammatory “intermediate” monocyte subset that returned to levels of healthy asymptomatic children 6 weeks later. Monocytes displayed activated phenotypes during acute malaria, with changes in surface expression of markers important to innate and adaptive immunity. Functionally, acute malaria monocytes and monocytes from asymptomatic infected children had impaired phagocytosis of P. falciparum–infected erythrocytes relative to asymptomatic children with no blood-stage infection. Monocytes from both acute malaria and recovery time points displayed strong and equivalent cytokine responsiveness to innate immune agonists that were independent of infection status. Monocyte transcriptional profiles revealed regulated and balanced proinflammatory and antiinflammatory and altered phagocytosis gene expression patterns distinct from malaria-naive monocytes. CONCLUSION. These observations provide insights into monocyte functions and the innate immune response during uncomplicated malaria and suggest that asymptomatic parasitemia in children is not clinically benign. FUNDING. Support for this work was provided by NIH/National Institute of Allergy and Infectious Diseases (R01AI095192

Changes in serum interleukin-33 levels in patients with acute cerebral infarction.

PubMed

Liu, Jingyao; Xing, Yingqi; Gao, Ying; Zhou, Chunkui

2014-02-01

Inflammation is widely considered to be involved in the pathogenesis of cerebral ischemic injury. The balance between inflammatory and anti-inflammatory factors significantly affects the prognosis of patients with cerebral infarction. Interleukin-33 (IL-33), a newly identified member of the interkeukin-1 superfamily, has been found to play very important roles in the inflammation of several human diseases including asthma, inflammatory bowel disease, and central nervous system inflammation. To our knowledge its role in the pathology of acute cerebral infarction has not yet been reported. In this study, we demonstrated that serum IL-33 levels were significantly increased in patients with acute cerebral infarction compared to control patients without acute cerebral infarction. Furthermore, serum IL-33 levels increased with the infarction volume. Our study suggests that IL-33 may be involved in the pathogenesis and/or progression of acute cerebral infarction. Copyright © 2013 Elsevier Ltd. All rights reserved.

Late stage erythroid precursor production is impaired in mice with chronic inflammation.

PubMed

Prince, Olivier D; Langdon, Jacqueline M; Layman, Andrew J; Prince, Ian C; Sabogal, Miguel; Mak, Howard H; Berger, Alan E; Cheadle, Chris; Chrest, Francis J; Yu, Qilu; Andrews, Nancy C; Xue, Qian-Li; Civin, Curt I; Walston, Jeremy D; Roy, Cindy N

2012-11-01

We and others have shown previously that over-expression of hepcidin antimicrobial peptide, independently of inflammation, induces several features of anemia of inflammation and chronic disease, including hypoferremia, sequestration of iron stores and iron-restricted erythropoiesis. Because the iron-restricted erythropoiesis evident in hepcidin transgenic mice differs from the normocytic, normochromic anemia most often observed in anemia of inflammation, we tested the hypothesis that chronic inflammation may contribute additional features to anemia of inflammation which continue to impair erythropoiesis following the acute phase of inflammation in which hepcidin is active. We compared erythropoiesis and iron handling in mice with turpentine-induced sterile abscesses with erythropoiesis and iron handling in hepcidin transgenic mice. We compared erythrocyte indices, expression of genes in the hepcidin regulatory pathway, tissue iron distribution, expression of heme and iron transport genes in splenic macrophages, the phenotype of erythroid maturation and chloromethyl dichlorodihydrofluorescein diacetate, acetyl ester fluorescence. Mice with sterile abscesses exhibited an intense, acute inflammatory phase followed by a mild to moderate chronic inflammatory phase. We found that erythrocytes in mice with sterile abscesses were normocytic and normochromic in contrast to those in hepcidin transgenic mice. We also observed that although hypoferremia resolved in the late phases of inflammation, erythropoiesis remained suppressed, with evidence of inefficient maturation of erythroid precursors in the bone marrow of mice with sterile abscesses. Finally, we observed increased oxidative stress in erythroid progenitors and circulating erythrocytes of mice with sterile abscesses which was not evident in hepcidin transgenic mice. Our results suggest that chronic inflammation inhibits late stages of erythroid production in the turpentine-induced sterile abscess model and induces

Late stage erythroid precursor production is impaired in mice with chronic inflammation

PubMed Central

Prince, Olivier D.; Langdon, Jacqueline M.; Layman, Andrew J.; Prince, Ian C.; Sabogal, Miguel; Mak, Howard H.; Berger, Alan E.; Cheadle, Chris; Chrest, Francis J.; Yu, Qilu; Andrews, Nancy C.; Xue, Qian-Li; Civin, Curt I.; Walston, Jeremy D.; Roy, Cindy N.

2012-01-01

Background We and others have shown previously that over-expression of hepcidin antimicrobial peptide, independently of inflammation, induces several features of anemia of inflammation and chronic disease, including hypoferremia, sequestration of iron stores and iron-restricted erythropoiesis. Because the iron-restricted erythropoiesis evident in hepcidin transgenic mice differs from the normocytic, normochromic anemia most often observed in anemia of inflammation, we tested the hypothesis that chronic inflammation may contribute additional features to anemia of inflammation which continue to impair erythropoiesis following the acute phase of inflammation in which hepcidin is active. Design and Methods We compared erythropoiesis and iron handling in mice with turpentine-induced sterile abscesses with erythropoiesis and iron handling in hepcidin transgenic mice. We compared erythrocyte indices, expression of genes in the hepcidin regulatory pathway, tissue iron distribution, expression of heme and iron transport genes in splenic macrophages, the phenotype of erythroid maturation and chloromethyl dichlorodihydrofluorescein diacetate, acetyl ester fluorescence. Results Mice with sterile abscesses exhibited an intense, acute inflammatory phase followed by a mild to moderate chronic inflammatory phase. We found that erythrocytes in mice with sterile abscesses were normocytic and normochromic in contrast to those in hepcidin transgenic mice. We also observed that although hypoferremia resolved in the late phases of inflammation, erythropoiesis remained suppressed, with evidence of inefficient maturation of erythroid precursors in the bone marrow of mice with sterile abscesses. Finally, we observed increased oxidative stress in erythroid progenitors and circulating erythrocytes of mice with sterile abscesses which was not evident in hepcidin transgenic mice. Conclusions Our results suggest that chronic inflammation inhibits late stages of erythroid production in the

Drug fever and acute inflammation from hypercytokinemia triggered by dipeptidyl peptidase-4 inhibitor vildagliptin.

PubMed

Anno, Takatoshi; Kaneto, Hideaki; Kawasaki, Fumiko; Shigemoto, Ryo; Aoyama, Yumi; Kaku, Kohei; Okimoto, Niro

2018-04-01

A 69-year-old man started taking the dipeptidyl peptidase-4 inhibitor, vildagliptin. One week later, C-reactive protein and plasma immunoglobulin E levels were markedly elevated, and the vildagliptin was stopped. After the patient's laboratory findings were normalized, we decided to restart vildagliptin with the patient's agreement. The next day, he had a high fever, and C-reactive protein and procalcitonin levels were elevated. Although we failed to find a focus of infection, we started antibiotics therapy. Two days later, the high fever had improved, and the C-reactive protein level had decreased. A drug lymphocyte stimulation test showed a positive result for vildagliptin. We examined various kinds of cytokine and infection markers just before and after the treatment with vildagliptin. Finally, we diagnosed the patient with vildagliptin-induced drug fever, probably based on the increase of various inflammatory cytokine levels and the response to this. Taken together, we should be aware of the possibility of vildagliptin inducing drug fever and/or acute inflammation. © 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Mortality in children with complicated severe acute malnutrition is related to intestinal and systemic inflammation: an observational cohort study12

PubMed Central

van Vliet, Sara J; Di Giovanni, Valeria; Zhang, Ling; Richardson, Susan; van Rheenen, Patrick F

2016-01-01

Background: Diarrhea affects a large proportion of children with severe acute malnutrition (SAM). However, its etiology and clinical consequences remain unclear. Objective: We investigated diarrhea, enteropathogens, and systemic and intestinal inflammation for their interrelation and their associations with mortality in children with SAM. Design: Intestinal pathogens (n = 15), cytokines (n = 29), fecal calprotectin, and the short-chain fatty acids (SCFAs) butyrate and propionate were determined in children aged 6–59 mo (n = 79) hospitalized in Malawi for complicated SAM. The relation between variables, diarrhea, and death was assessed with partial least squares (PLS) path modeling. Results: Fatal subjects (n = 14; 18%) were younger (mean ± SD age: 17 ± 11 compared with 25 ± 11 mo; P = 0.01) with higher prevalence of diarrhea (46% compared with 18%, P = 0.03). Intestinal pathogens Shigella (36%), Giardia (33%), and Campylobacter (30%) predominated, but their presence was not associated with death or diarrhea. Calprotectin was significantly higher in children who died [median (IQR): 1360 mg/kg feces (2443–535 mg/kg feces) compared with 698 mg/kg feces (1438–244 mg/kg feces), P = 0.03]. Butyrate [median (IQR): 31 ng/mL (112–22 ng/mL) compared with 2036 ng/mL (5800–149 ng/mL), P = 0.02] and propionate [median (IQR): 167 ng/mL (831–131 ng/mL) compared with 3174 ng/mL (5819–357 ng/mL), P = 0.04] were lower in those who died. Mortality was directly related to high systemic inflammation (path coefficient = 0.49), whereas diarrhea, high calprotectin, and low SCFA production related to death indirectly via their more direct association with systemic inflammation. Conclusions: Diarrhea, high intestinal inflammation, low concentrations of fecal SCFAs, and high systemic inflammation are significantly related to mortality in SAM. However, these relations were not mediated by the presence of intestinal pathogens. These findings offer an important understanding of

A comparative study of matrix metalloproteinase and aggrecanase mediated release of latent cytokines at arthritic joints.

PubMed

Mullen, Lisa; Adams, Gill; Foster, Julie; Vessillier, Sandrine; Köster, Mario; Hauser, Hansjörg; Layward, Lorna; Gould, David; Chernajovsky, Yuti

2014-09-01

Latent cytokines are engineered by fusing the latency associated peptide (LAP) derived from transforming growth factor-β (TGF-β) with the therapeutic cytokine, in this case interferon-β (IFN-β), via an inflammation-specific matrix metalloproteinase (MMP) cleavage site. To demonstrate latency and specific delivery in vivo and to compare therapeutic efficacy of aggrecanase-mediated release of latent IFN-β in arthritic joints to the original MMP-specific release. Recombinant fusion proteins with MMP, aggrecanase or devoid of cleavage site were expressed in CHO cells, purified and characterised in vitro by Western blotting and anti-viral protection assays. Therapeutic efficacy and half-life were assessed in vivo using the mouse collagen-induced arthritis model (CIA) of rheumatoid arthritis and a model of acute paw inflammation, respectively. Transgenic mice with an IFN-regulated luciferase gene were used to assess latency in vivo and targeted delivery to sites of disease. Efficient localised delivery of IFN-β to inflamed paws, with low levels of systemic delivery, was demonstrated in transgenic mice using latent IFN-β. Engineering of latent IFN-β with an aggrecanase-sensitive cleavage site resulted in efficient cleavage by ADAMTS-4, ADAMTS-5 and synovial fluid from arthritic patients, with an extended half-life similar to the MMP-specific molecule and greater therapeutic efficacy in the CIA model. Latent cytokines require cleavage in vivo for therapeutic efficacy, and they are delivered in a dose dependent fashion only to arthritic joints. The aggrecanase-specific cleavage site is a viable alternative to the MMP cleavage site for the targeting of latent cytokines to arthritic joints. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Azithromycin reduces inflammation in a rat model of acute conjunctivitis

PubMed Central

Fernandez-Robredo, Patricia; Recalde, Sergio; Moreno-Orduña, Maite; García-García, Laura; Zarranz-Ventura, Javier; García-Layana, Alfredo

2013-01-01

Purpose Macrolide antibiotics are known to have various anti-inflammatory effects in addition to their antimicrobial activity, but the mechanisms are still unclear. The effect of azithromycin on inflammatory molecules in the lipopolysaccharide-induced rat conjunctivitis model was investigated. Methods Twenty-four Wistar rats were divided into two groups receiving topical ocular azithromycin (15 mg/g) or vehicle. In total, six doses (25 µl) were administered as one dose twice a day for three days before subconjunctival lipopolysaccharide injection (3 mg/ml). Before the rats were euthanized, mucus secretion, conjunctival and palpebral edema and redness were evaluated. Real-time polymerase chain reaction was used to determine gene expression for interleukin-6, cyclooxygenase-2, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, and MMP-9. Interleukin-6 was determined with enzyme-linked immunosorbent assay, nuclear factor-kappa B with western blot, and MMP-2 activity with gelatin zymogram. Four eyes per group were processed for histology and subsequent periodic acid-Schiff staining and CD68 for immunofluorescence. The Student t test or the Wilcoxon test for independent samples was applied (SPSS v.15.0). Results Azithromycin-treated animals showed a significant reduction in all clinical signs (p<0.05) compared to controls. Interleukin-6 (p<0.05), nuclear factor-kappa B protein expression (p<0.01), and MMP-2 activity (p<0.05) in conjunctival homogenates were significantly reduced compared with the control animals. MMP-2 gene expression showed a tendency to decrease in the azithromycin group (p=0.063). Mucus secretion by goblet cells and the macrophage count in conjunctival tissue were also decreased in the azithromycin group (p<0.05). Conclusions These results suggest that azithromycin administration ameliorates induced inflammation effects in a rat model of acute conjunctivitis. PMID:23378729

21 CFR 522.960c - Flumethasone solution.

Code of Federal Regulations, 2014 CFR

2014-04-01

... conditions due to inflammation, where permanent structural changes do not exist, e.g., bursitis, carpitis... use in the treatment of musculoskeletal conditions due to inflammation of muscles or joints and... administered); certain acute and chronic dermatoses of varying etiology to help control associated pruritus...

Age-related differences in biomarkers of acute inflammation during hospitalization for sepsis.

PubMed

Ginde, Adit A; Blatchford, Patrick J; Trzeciak, Stephen; Hollander, Judd E; Birkhahn, Robert; Otero, Ronny; Osborn, Tiffany M; Moretti, Eugene; Nguyen, H Bryant; Gunnerson, Kyle J; Milzman, David; Gaieski, David F; Goyal, Munish; Cairns, Charles B; Rivers, Emanuel P; Shapiro, Nathan I

2014-08-01

The authors aimed to evaluate age-related differences in inflammation biomarkers during the first 72 h of hospitalization for sepsis. This was a secondary analysis of a prospective observational cohort of adult patients (n = 855) from 10 urban academic emergency departments with confirmed infection and two or more systemic inflammatory response syndrome criteria. Six inflammation-related biomarkers were analyzed-chemokine (CC-motif) ligand-23, C-reactive protein, interleukin-1 receptor antagonist, neutrophil gelatinase-associated lipocalin (NGAL), peptidoglycan recognition protein, and tumor necrosis factor receptor-1a (TNFR-1a)-measured at presentation and 3, 6, 12, 24, 48, or 72 h later. The median age was 56 (interquartile range, 43 - 72) years, and sepsis severity was 38% sepsis, 16% severe sepsis without shock, and 46% septic shock; the overall 30-day mortality was 12%. Older age was associated with higher sepsis severity: 41% of subjects aged 18 to 34 years had severe sepsis or septic shock compared with 71% for those aged 65 years or older (P < 0.001). In longitudinal models adjusting for demographics, comorbidities, and infection source, older age was associated with higher baseline values for chemokine (CC-motif) ligand-23, interleukin-1 receptor antagonist, NGAL, and TNFR-1a (all P < 0.05). However, older adults had higher mean values during the entire 72-h period only for NGAL and TNFR-1a and higher final 72-h values only for TNFR-1a. Adjustment or stratification by sepsis severity did not change the age-inflammation associations. Although older adults had higher levels of inflammation at presentation and an increased incidence of severe sepsis and septic shock, these age-related differences in inflammation largely resolved during the first 72 h of hospitalization.

[Bronchial inflammation during chronic bronchitis, importance of fenspiride].

PubMed

Melloni, B

2002-09-01

PATHOPHYSIOLOGY OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD): Chronic inflammation of the upper airways, pulmonary parenchyma and pulmonary vasculature is the characteristic feature of COPD. Two mechanisms besides inflammation are also involved: oxidative stress and imbalance between proteinases and antiproteinases. Cellular infiltration of the upper airways involved neutrophils, macrophages, T lymphocytes and eosinophils. Inflammatory mediators appear to play a crucial role in the interaction between inflammation and obstruction. PROPERTIES OF FENSPIRIDE: A nonsteroidal drug, fenspiride, exhibits interesting properties documented in vitro: anti-bronchoconstriction activity, anti-secretory activity, and anti-inflammatory activity (reduction in the activity of phospholipase A2 and release of proinflammatory leukotriens). Two french clinical trials have studied the efficacy of fenspiride in patients with acute excerbation or stable COPD and have demonstrated an improvement in the group treated with fenspiride compared with the placebo group.

Positive correlation between inflammation on sacroiliac joint MRI and serum C-terminal telopeptide of type-I collagen in ankylosing spondylitis but not in non-radiographic axial spondyloarthritis.

PubMed

Kang, Kwi Young; Jung, Joon-Yong; Hong, Yeon Sik; Ju, Ji Hyeon; Park, Sung-Hwan

2017-01-01

To identify the clinical disease activity scores and laboratory markers that best reflect magnetic resonance imaging (MRI)-determined sacroiliac joint (SIJ) inflammation in ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). This cross-sectional study included all consecutive patients who presented with axial spondyloarthritis in 2013-2015. All underwent SIJ MRI. The bone marrow oedema in the inflammatory lesions on MRI was scored using the SPondyloArthritis Research Consortium of Canada (SPARCC) method. Bone-specific alkaline phosphatase (BALP), serum C-terminal telopeptide of type-I collagen (sCTX-I), and inflammatory markers were measured. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) were assessed. The correlations between the MRI-determined SIJ inflammation scores and disease activity scores and laboratory variables were evaluated. Of the 81 patients with axSpA, 45 had AS and 36 had nr-axSpA. The AS and nr-axSpA groups did not differ in terms of disease activity scores, physical functional index, or MRI-determined SIJ inflammation. Erythrocyte sedimentation rate, C-reactive protein, and ASDAS correlated with MRI inflammatory scores in nr-axSpA but not in AS. sCTX-I correlated with MRI-determined SIJ inflammatory scores in AS only. BASDAI and BALP levels did not associate with MRI inflammatory scores in either group. Multivariate analysis showed that sCTX-I associated independently with MRI inflammatory score in AS (β=17.047, p=0.038). Inflammatory markers and ASDAS correlated with active sacroiliitis on MRI in nr-axSpA only. In AS, only sCTX-I correlated with active inflammation on SIJ MRI. sCTX-I may be useful as a marker of objective inflammation in AS.

A stress MRI of the shoulder for evaluation of ligamentous stabilizers in acute and chronic acromioclavicular joint instabilities.

PubMed

Izadpanah, Kaywan; Winterer, Jan; Vicari, Marco; Jaeger, Martin; Maier, Dirk; Eisebraun, Leonie; Ute Will, Jutta; Kotter, Elmar; Langer, Mathias; Südkamp, Norbert P; Hennig, Jürgen; Weigel, Mathias

2013-06-01

To show the feasibility of a stress magnetic resonance imaging (MRI) as a new method for simultaneous evaluation of the morphology and the functional integrity of the acromioclavicular joint (ACJ) ligamentous stabilizers. MRI of four volunteers, 10 patients with acute, and six with chronic ACJ injuries was performed using a 0.25 T open MRI scanner. A 2D-proton-density and a 3D-gradient-echo sequence at rest and under 6.5 kg shoulder traction were performed. Comparative measurements of the coracoclavicular and the acromioclavicular distance were performed. Additionally, the conoid and trapezoid ligament lengths were measured with multiplanar reconstructions. MRI at rest correctly identified tears of the coracoclavicular and the acromioclavicular ligaments in eight patients suffering acute ACJ injuries. Stress application helped to distinguish between partial and complete coracoclavicular ligament tears in two cases. Insufficiency of the ACJ ligaments was present in all acute and chronic ACJ injuries. Stress application in chronic ACJ ligaments revealed isolated insufficiency of the conoid ligament in three cases and of the trapezoid ligament in one case. Combined insufficiency was present in two cases. Stress MRI facilitates simultaneous acquisition of morphologic and functional information of the ACJ stabilizers. In acute ACJ injuries it helps to distinguish between partial and complete ligament tears. In chronic ACJ injuries it provides functional information of the ligament regrinds. Copyright © 2012 Wiley Periodicals, Inc.

Joint BAP NAPICU evidence-based consensus guidelines for the clinical management of acute disturbance: De-escalation and rapid tranquillisation.

PubMed

Patel, Maxine X; Sethi, Faisil N; Barnes, Thomas Re; Dix, Roland; Dratcu, Luiz; Fox, Bernard; Garriga, Marina; Haste, Julie C; Kahl, Kai G; Lingford-Hughes, Anne; McAllister-Williams, Hamish; O'Brien, Aileen; Parker, Caroline; Paterson, Brodie; Paton, Carol; Posporelis, Sotiris; Taylor, David M; Vieta, Eduard; Völlm, Birgit; Wilson-Jones, Charlotte; Woods, Laura

2018-06-01

The British Association for Psychopharmacology and the National Association of Psychiatric Intensive Care and Low Secure Units developed this joint evidence-based consensus guideline for the clinical management of acute disturbance. It includes recommendations for clinical practice and an algorithm to guide treatment by healthcare professionals with various options outlined according to their route of administration and category of evidence. Fundamental overarching principles are included and highlight the importance of treating the underlying disorder. There is a focus on three key interventions: de-escalation, pharmacological interventions pre-rapid tranquillisation and rapid tranquillisation (intramuscular and intravenous). Most of the evidence reviewed relates to emergency psychiatric care or acute psychiatric adult inpatient care, although we also sought evidence relevant to other common clinical settings including the general acute hospital and forensic psychiatry. We conclude that the variety of options available for the management of acute disturbance goes beyond the standard choices of lorazepam, haloperidol and promethazine and includes oral-inhaled loxapine, buccal midazolam, as well as a number of oral antipsychotics in addition to parenteral options of intramuscular aripiprazole, intramuscular droperidol and intramuscular olanzapine. Intravenous options, for settings where resuscitation equipment and trained staff are available to manage medical emergencies, are also included.

Interleukin-17B Antagonizes Interleukin-25-Mediated Mucosal Inflammation.

PubMed

Reynolds, Joseph M; Lee, Young-Hee; Shi, Yun; Wang, Xiaohu; Angkasekwinai, Pornpimon; Nallaparaju, Kalyan C; Flaherty, Stephanie; Chang, Seon Hee; Watarai, Hiroshi; Dong, Chen

2015-04-21

The interleukin-17 (IL-17) family of cytokines has emerged as a critical player in inflammatory diseases. Among them, IL-25 has been shown to be important in allergic inflammation and protection against parasitic infection. Here we have demonstrated that IL-17B, a poorly understood cytokine, functions to inhibit IL-25-driven inflammation. IL-17B and IL-25, both binding to the interleukin-17 receptor B (IL-17RB), were upregulated in their expression after acute colonic inflammation. Individual inhibition of these cytokines revealed opposing functions in colon inflammation: IL-25 was pathogenic but IL-17B was protective. Similarly opposing phenotypes were observed in Citrobacter rodentium infection and allergic asthma. Moreover, IL-25 was found to promote IL-6 production from colon epithelial cells, which was inhibited by IL-17B. Therefore, our data demonstrate that IL-17B is an anti-inflammatory cytokine in the IL-17 family. Copyright © 2015 Elsevier Inc. All rights reserved.

MRI evidence of structural changes in the sacroiliac joints of patients with non-radiographic axial spondyloarthritis even in the absence of MRI inflammation.

PubMed

Maksymowych, Walter P; Wichuk, Stephanie; Dougados, Maxime; Jones, Heather; Szumski, Annette; Bukowski, Jack F; Marshall, Lisa; Lambert, Robert G

2017-06-06

Studies have shown that structural lesions may be present in patients with non-radiographic axial spondyloarthritis (nr-axSpA). However, the relevance of structural lesions in these patients is unclear, particularly without signs of inflammation on magnetic resonance imaging (MRI). We assessed the presence of structural lesions at baseline on MRI in the sacroiliac joints (SIJ) of patients with nr-axSpA with and without SIJ inflammation on MRI. Bone marrow edema (BME) was assessed on short tau inversion recovery (STIR) scans from 185 patients with nr-axSpA, by two independent readers at baseline using the Spondyloarthritis Research Consortium of Canada (SPARCC) score. Structural lesions were evaluated on T1 weighted spin echo scans, with readers blinded to STIR scans, using the SPARCC MRI SIJ structural score. Disease characteristics and structural lesions were compared in patients with SIJ BME (score ≥2) and without SIJ BME (score <2). Both SIJ BME and structural lesions scores were available for 183 patients; 128/183 (69.9%) patients had SIJ BME scores ≥2 and 55/183 (30.1%) had scores <2. Frequencies of MRI structural lesions in patients with vs without SIJ BME were: erosions (45.3% vs 10.9%, P < 0.001), backfill (20.3% vs 0%, P < 0.001), fat metaplasia (10.9% vs 1.8%, P = 0.04), and ankylosis (2.3% vs 1.8%, P = ns). Significantly more patients with both SIJ BME and structural lesions were male and/or HLA-B27 positive than patients with only SIJ BME. Mean (SD) spinal scores (23 discovertebral units) were significantly higher in patients with SIJ structural lesions than without: 6.5 (11.5) vs 3.3 (5.1), respectively, P = 0.01. In patients with nr-axSpA, SIJ structural lesions, particularly erosions, may be present on MRI when radiographs are normal or inconclusive, even in patients negative for MRI SIJ inflammation. They may reflect more severe disease with greater spinal inflammation. ClinicalTrials.gov, NCT01258738 . Registered on 9

Review of Prosthetic Joint Infection from Listeria monocytogenes.

PubMed

Bader, Gilbert; Al-Tarawneh, Mohammed; Myers, James

2016-12-01

Prosthetic joint infection from Listeria monocytogenes is rare. We decided to shed light on this illness and review the reported cases to better understand its characteristics. We conducted a comprehensive review of the English literature using PubMed. We also included one case that we had managed. We found 25 cases of prosthetic joint infection from L. monocytogenes reported individually and a retrospective study of 43 cases of joint and bone listerial infection, including 34 with prosthetic joint infection, conducted in France. We have described their clinical and para-clinical features and tried to elaborate on the pathophysiology, treatment, and prevention. Prosthetic joint infection from L. monocytogenes is mainly late. Systemic inflammation may be absent. Although rare, it must be suspected in patients at high risk for both prosthetic joint and listerial infections. In addition, those patients must be instructed on appropriate preventive measures.

Apigenin Attenuates Inflammation in Experimentally Induced Acute Pancreatitis-Associated Lung Injury.

PubMed

Basios, Neofitos; Lampropoulos, Pavlos; Papalois, Apostolos; Lambropoulou, Maria; Pitiakoudis, Michael K; Kotini, Athanasia; Simopoulos, Constantinos; Tsaroucha, Alexandra K

2016-06-01

Acute pancreatitis is associated with acute lung injury. The aim of the present study is to evaluate alterations of lungs in an experimental model of acute pancreatitis (AP) following both bilio-pancreatic duct obstruction close to the duodenum. Acute pancreatitis is a common disease with significant mortality. This situation makes the need of finding protective factors for the lung parenchyma, imperative. In the present study there is an effort to clarify the role of apigenin, a substance which is well known for its antioxidant and anti-inflammatory effects, on lung injury, following acute pancreatitis in rats. In the present study, 126 male Wistar-type rats 3-4 months old and 220-350 g weight were used. At time 0 we randomly assigned the following groups: Group Sham: Rats were subjected to virtual surgery. Group Control: Rats were subjected to surgery for induction of acute pancreatitis. Group Apigenin: Rats were subjected to surgery for induction of acute pancreatitis and enteral feeding with apigenin. Immunochemistry for TNF-α and IL-6 as well as MPO activity were measured at predetermined time intervals 6, 12, 24, 48, and 72 h, in order to evaluate architectural disturbances of the lung tissue. From the pathological reports we realized that comparing the control group with the apigenin group, there is an improvement of lung tissue damage following apigenin administration, with statistical significance. Apigenin reduces most histopathological alterations of the pulmonary tissue, reduces MPO and TNF-α activity at 48 hours and, furthermore, reduces IL-6 activity at 72 hours post-administration. Oral Apigenin administration in rats, following experimental induced acute pancreatitis, seems to be protective on the lung tissue. Apigenin administration to humans could potentially ameliorate acute lung injuries. However, special caution is required for humans' use, as more detailed studies are needed.

Role of systemic inflammation in cirrhosis: From pathogenesis to prognosis

PubMed Central

Dirchwolf, Melisa; Ruf, Andrés Eduardo

2015-01-01

The natural history of cirrhosis can be divided into an initial stage, known as compensated cirrhosis, and an advanced stage which encompasses both decompensated cirrhosis and acute-on-chronic liver failure (ACLF). The latter syndrome has been recently described as an acute deterioration of liver function in patients with cirrhosis, which is usually triggered by a precipitating event and results in the failure of one or more organs and high short-term mortality rates. Each stage is characterized by distinctive clinical manifestations and prognoses. One of the key elements involved in cirrhosis physiopathology is systemic inflammation, recently described as one of the components in the cirrhosis-associated immune dysfunction syndrome. This syndrome refers to the combination of immune deficiency and exacerbated inflammation that coexist during the course of cirrhosis and relates to the appearance of clinical complications. Since systemic inflammation is often difficult to assess in cirrhosis patients, new objective, reproducible and readily-available markers are needed in order to optimize prognosis and lengthen survival. Thus, surrogate serum markers and clinical parameters of systemic inflammation have been sought to improve disease follow-up and management, especially in decompensated cirrhosis and ACLF. Leukocyte counts (evaluated as total leukocytes, total eosinophils or neutrophil:lymphocyte ratio) and plasma levels of procalcitonin or C-reactive protein have been proposed as prognostic markers, each with advantages and shortcomings. Research and prospective randomized studies that validate these and other markers are clearly warranted. PMID:26261687

Evaluation of scattered light distributions of cw-transillumination for functional diagnostic of rheumatic disorders in interphalangeal joints

NASA Astrophysics Data System (ADS)

Prapavat, Viravuth; Schuetz, Rijk; Runge, Wolfram; Beuthan, Juergen; Mueller, Gerhard J.

1995-12-01

This paper presents in-vitro-studies using the scattered intensity distribution obtained by cw- transillumination to examine the condition of rheumatic disorders of interphalangeal joints. Inflammation of joints, due to rheumatic diseases, leads to changes in the synovial membrane, synovia composition and content, and anatomic geometrical variations. Measurements have shown that these rheumatic induced inflammation processes result in a variation in optical properties of joint systems. With a scanning system the interphalangeal joint is transilluminated with diode lasers (670 nm, 905 nm) perpendicular to the joint cavity. The detection of the entire distribution of the transmitted radiation intensity was performed with a CCD camera. As a function of the structure and optical properties of the transilluminated volume we achieved distributions of scattered radiation which show characteristic variations in intensity and shape. Using signal and image processing procedures we evaluated the measured scattered distributions regarding their information weight, shape and scale features. Mathematical methods were used to find classification criteria to determine variations of the joint condition.

Inadequate Processing of Decellularized Dermal Matrix Reduces Cell Viability In Vitro and Increases Apoptosis and Acute Inflammation In Vivo

PubMed Central

Morris, Aaron H.; Chang, Julie; Kyriakides, Themis R.

2016-01-01

Abstract Decellularized tissue scaffolds are commonly used in the clinic because they can be used as substitutes for more traditional biomaterials, while imparting additional physiological effects. Nevertheless, reports of complications associated with their use are widespread and poorly understood. This study probes possible causes of these complications by examining cell viability and apoptosis in response to eluents from decellularized dermis. Using multiple sources of decellularized dermis, this study shows that typical decellularized scaffolds (prepared with commonly used laboratory techniques, as well as purchased from commercial sources) contain soluble components that are cytotoxic and that these components can be removed by extensive washes in cell culture media. In addition, this study demonstrates that these observed in vitro phenotypes correlate with increased apoptosis and acute inflammation when implanted subcutaneously in mice. PMID:27500014

The anti-inflammatory effects of Yunnan Baiyao are involved in regulation of the phospholipase A2/arachidonic acid metabolites pathways in acute inflammation rat model.

PubMed

Ren, Xiaobin; Zhang, Mingzhu; Chen, Lingxiang; Zhang, Wanli; Huang, Yu; Luo, Huazhen; Li, Ling; He, Hongbing

2017-10-01

The traditional Chinese medicine Yunnan Baiyao (YNB) has been reported to possess anti‑inflammatory properties, however its mechanism of action remains unclear. It was previously reported that YNB ameliorated depression of arachidonic acid (AA) levels in a rat model of collagen-induced arthritis. In the current study, the capacity of YNB to ameliorate inflammation was compared in carrageenan‑induced and AA‑induced acute inflammation of the rat paw with celecoxib and mizolastine, respectively (n=24 per group). The capacity of YNB to affect the phospholipase A2 (PLA2)/AA pathway (using reverse transcription‑quantitative polymerase chain reaction) and release of inflammatory lipid mediators (by ELISA) were investigated. Celecoxib ameliorated carrageenan‑induced paw edema, and mizolastine ameliorated AA‑induced rat paw edema. YNB alleviated paw edema and inhibited inflammatory cell infiltration in the two models. YNB inhibited production of 5‑LOX AA metabolite leukotriene B4 (LTB4), and suppressed expression of 5‑LOX, cytosolic PLA2 (cPLA2), 5‑LOX‑activating protein, and LTB4 receptor mRNA in the AA‑induced inflammation model (P<0.05). YNB Inhibited the production of the COX‑2 AA metabolite prostaglandin E2 (PGE2) and suppressed expression of COX‑2, cPLA2, PGE2 mRNA in the carrageenan‑induced inflammation mode (P<0.05). Taken together, the data suggest that modulation of COX and LOX pathways in AA metabolism represent a novel anti-inflammatory mechanism of YNB.

Oleic acid induces acute pulmonary injury and inflammation in vivo

EPA Science Inventory

Oleic acid (OA) is frequently used as a representative fatty acid, and is found in meat-cooking fumes and biodiesel exhaust. Vascular damage and acute lung injury has been observed with OA vascular infusion in models of acute respiratory distress, but it is not yet established ...

6-Shogaol inhibits monosodium urate crystal-induced inflammation--an in vivo and in vitro study.

PubMed

Sabina, Evan Prince; Rasool, Mahaboobkhan; Mathew, Lazar; Ezilrani, Panneerselvam; Indu, Haridas

2010-01-01

Gout is a rheumatic disease that is manifestated by an intense inflammation secondary to monosodium urate crystal deposition in joints. In the present study, we assessed the effect of 6-shogaol (isolated active principle from ginger) on monosodium urate crystal-induced inflammation in mice; an experimental model for gouty arthritis and compared it with that of the non-steroidal anti-inflammatory drug, indomethacin. Paw volume and levels/activities of lysosomal enzymes, lipid peroxidation, anti-oxidant status and inflammatory mediator TNF-alpha were determined in control and monosodium urate crystal-induced mice. The levels of beta-glucuronidase and lactate dehydrogenase were also measured in monosodium urate crystal-incubated polymorphonuclear leucocytes (PMNL) in vitro. The levels of lysosomal enzymes, lipid peroxidation, and inflammatory mediator tumour necrosis factor-alpha and paw volume were increased significantly and the activities of anti-oxidant status were in turn decreased in monosodium urate crystal-induced mice, whereas these changes were reverted to near normal levels upon 6-shogaol administration. In vitro, 6-shogaol reduced the level of beta-glucuronidase and lactate dehydrogenase in monosodium urate crystal-incubated polymorphonuclear leucocytes in concentration dependent manner when compared to control cells. The present results clearly indicated that 6-shogaol exerted a strong anti-inflammatory effect and can be regarded as useful tool for the treatment of acute gouty arthritis. Copyright 2009 Elsevier Ltd. All rights reserved.

A human monoclonal anti-TNF alpha antibody (adalimumab) reduces airway inflammation and ameliorates lung histology in a murine model of acute asthma.

PubMed

Catal, F; Mete, E; Tayman, C; Topal, E; Albayrak, A; Sert, H

2015-01-01

A few experimental studies related to asthma have unveiled the beneficial effects of TNF alpha blocking agents on the airway histology, cytokine levels in bronchoalveolar lavage and bronchial hyper-responsiveness. In the current study, we aimed to assess the effect of adalimumab on the inflammation and histology of asthma in a murine model. Twelve-week-old BALB/c (H-2d/d) female rats (n=18) were allocated into three groups, including (group I) control (phosphate-buffered saline was implemented), (group II) asthma induced with OVA (n=6), and (group III) asthma induced with OVA+treated with adalimumab (n=6). Rats were executed on the 28th day of the study. The lung samples were fixed in 10% neutral buffered formalin. Lung parenchyma, alveolus, peribronchial and perivascular inflammation were assessed. Lung pathological scoring was performed. Severity of lung damage was found to be reduced significantly in the asthma induced with OVA+treated with adalimumab group. When compared with the untreated group, adalimumab significantly reduced the inflammatory cells around the bronchi and bronchioles, and reduced inflammation of the alveolar wall and alveolar wall thickness as well (median score=1, p=0.52). Peribronchial smooth muscle hypertrophy and oedema were significantly reduced after adalimumab administration. Adalimumab (a human monoclonal anti-TNF alpha antibody) therapy significantly reduced the severity of lung damage by decreasing cellular infiltration and improvement on the lung histology in a murine model of acute asthma. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

Lipid emulsions differentially affect LPS-induced acute monocytes inflammation: in vitro effects on membrane remodeling and cell viability.

PubMed

Boisramé-Helms, Julie; Delabranche, Xavier; Klymchenko, Andrey; Drai, Jocelyne; Blond, Emilie; Zobairi, Fatiha; Mely, Yves; Hasselmann, Michel; Toti, Florence; Meziani, Ferhat

2014-11-01

The aim of this study was to assess how lipid emulsions for parenteral nutrition affect lipopolysaccharide (LPS)-induced acute monocyte inflammation in vitro. An 18 h long LPS induced human monocyte leukemia cell stimulation was performed and the cell-growth medium was supplemented with three different industrial lipid emulsions: Intralipid(®), containing long-chain triglycerides (LCT--soybean oil); Medialipid(®), containing LCT (soybean oil) and medium-chain triglycerides (MCT--coconut oil); and SMOFlipid(®), containing LCT, MCT, omega-9 and -3 (soybean, coconut, olive and fish oils). Cell viability and apoptosis were assessed by Trypan blue exclusion and flow cytometry respectively. Monocyte composition and membrane remodeling were studied using gas chromatography and NR12S staining. Microparticles released in supernatant were measured by prothrombinase assay. After LPS challenge, both cellular necrosis and apoptosis were increased (threefold and twofold respectively) and microparticle release was enhanced (sevenfold) after supplementation with Medialipid(®) compared to Intralipid(®), SMOFlipid(®) and monocytes in the standard medium. The monocytes differentially incorporated fatty acids after lipid emulsion challenge. Finally, lipid-treated cells displayed microparticles characterized by disrupted membrane lipid order, reflecting lipid remodeling of the parental cell plasma membrane. Our data suggest that lipid emulsions differentially alter cell viability, monocyte composition and thereby microparticle release. While MCT have deleterious effects, we have shown that parenteral nutrition emulsion containing LCT or LCT and MCT associated to n-3 and n-9 fatty acids have no effect on endotoxin-induced cell death and inflammation.

A Review of Experimental Evidence Linking Neurotoxic Organophosphorus Compounds and Inflammation

PubMed Central

Banks, Christopher N.; Lein, Pamela J.

2012-01-01

Organophosphorus (OP) nerve agents and pesticides inhibit acetylcholinesterase (AChE), and this is thought to be a primary mechanism mediating the neurotoxicity of these compounds. However, a number of observations suggest that mechanisms other than or in addition to AChE inhibition contribute to OP neurotoxicity. There is significant experimental evidence that acute OP intoxication elicits a robust inflammatory response, and emerging evidence suggests that chronic repeated low-level OP exposure also upregulates inflammatory mediators. A critical question that is just beginning to be addressed experimentally is the pathophysiologic relevance of inflammation in either acute or chronic OP intoxication. The goal of this article is to provide a brief review of the current status of our knowledge linking inflammation to OP intoxication, and to discuss the implications of these findings in the context of therapeutic and diagnostic approaches to OP neurotoxicity. PMID:22342984

Inflammation on Prostate Needle Biopsy is Associated with Lower Prostate Cancer Risk: A Meta-Analysis.

PubMed

Vasavada, Shaleen R; Dobbs, Ryan W; Kajdacsy-Balla, André A; Abern, Michael R; Moreira, Daniel M

2018-05-01

We performed a comprehensive literature review and meta-analysis to evaluate the association of inflammation on prostate needle biopsies and prostate cancer risk. We searched Embase®, PubMed® and Web of Science™ from January 1, 1990 to October 1, 2016 for abstracts containing the key words prostate cancer, inflammation and biopsy. Study inclusion criteria were original research, adult human subjects, cohort or case-control study design, histological inflammation on prostate needle biopsy and prostate cancer on histology. Two independent teams reviewed abstracts and extracted data from the selected manuscripts. Combined ORs and 95% CIs of any, acute and chronic inflammation were calculated using the random effects method. Of the 1,030 retrieved abstracts 46 underwent full text review and 25 were included in the final analysis, comprising a total of 20,585 subjects and 6,641 patients with prostate cancer. There was significant heterogeneity among studies (I 2 = 84.4%, p <0.001). The presence of any inflammation was significantly associated with a lower prostate cancer risk in 25 studies (OR 0.455, 95% CI 0.337-0.573). There was no evidence of publication bias (p >0.05). When subanalyzed by inflammation type, acute inflammation in 4 studies and chronic inflammation in 15 were each associated with a lower prostate cancer risk (OR 0.681, 95% CI 0.450-0.913 and OR 0.499, 95% CI 0.334-0.665, respectively). In a meta-analysis of 25 studies inflammation on prostate needle biopsy was associated with a lower prostate cancer risk. Clinically the presence of inflammation on prostate needle biopsy may lower the risk of a subsequent prostate cancer diagnosis. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Obesity, Inflammation and Acute Myocardial Infarction - Expression of leptin, IL-6 and high sensitivity-CRP in Chennai based population.

PubMed

Rajendran, Karthick; Devarajan, Nalini; Ganesan, Manohar; Ragunathan, Malathi

2012-08-14

Obesity, characterised by increased fat mass and is currently regarded as a pro-inflammatory state and often associated with increased risk of cardiovascular diseases (CVD) including Myocardial infarction. There is an upregulation of inflammatory markers such as interleukin-6, interleukin-6 receptor and acute phase protein CRP in Acute Myocardial Infarction (AMI) patients but the exact mechanism linking obesity and inflammation is not known. It is of our interest to investigate if serum leptin (ob gene product) is associated with AMI and correlated with inflammatory proteins namely Interleukin-6 (IL-6) and high sensitivity - C reactive protein (hs-CRP). Serum leptin levels were significantly higher in AMI patients when compared to Non-CVD controls. IL-6 and hs-CRP were also elevated in the AMI group and leptin correlated positively with IL-6 and hs-CRP. Incidentally this is the first report from Chennai based population, India. The strong correlation between serum levels of leptin and IL-6 implicates an involvement of leptin in the upregulation of inflammatory cytokines during AMI. We hypothesise that the increase in values of IL-6, hs-CRP and their correlation to leptin in AMI patients could be due to participation of leptin in the signaling cascade after myocardial ischemia.

Targeting inflammatory mediators with ferulic acid, a dietary polyphenol, for the suppression of monosodium urate crystal-induced inflammation in rats.

PubMed

Doss, Hari Madhuri; Dey, Chandrima; Sudandiradoss, C; Rasool, Mahaboob Khan

2016-03-01

The aim of this study was to investigate the anti-inflammatory effect of ferulic acid, a dietary phenol, on monosodium urate (MSU) crystal-induced inflammation in rats, an experimental model for acute gouty arthritis. For the purpose of comparison, colchicine was used as a reference drug. Paw edema, levels/activities of elastase, lysosomal enzymes (acid phosphatase and β-galactosidase), nitric oxide, lipid peroxidation, antioxidant status and pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β), and histology of ankle joints were evaluated in rats with MSU crystal-induced inflammation. The messenger RNA (mRNA) expression of pro-inflammatory cytokines (TNF-α and IL-1β), NLRP3 (nucleotide oligomerization domain (NOD)-like receptor family, pyrin domain containing 3) inflammasomes, caspase-1, and the transcription factor nuclear factor kappa B p65 (NF-κB p65) was determined by real-time polymerase chain reaction (PCR) analysis. The protein expression of NF-κB p65 and TNF-α was detected by immunohistochemical analysis. Further, a molecular docking analysis was conducted to determine the ligand efficiency of ferulic acid towards NF-κB, apoptosis-associated speck-like protein containing a CARD (PYCARD/ASC), NLRP3, and pro-caspase-1. In the joint homogenate of rats with MSU crystal-induced inflammation, treatment with ferulic acid (30mg/kg body weight (b.wt)) decreased paw edema; the level/activity of elastase, lysosomal enzymes, nitric oxide, lipid peroxidation, and pro-inflammatory cytokines (TNF-α and IL-1β); and the mRNA expression of NLRP3 inflammasomes, caspase-1, pro-inflammatory cytokines, and NF-κB p65. In addition, the protein expression of NF-κB p65 and TNF-α was also found to be significantly decreased. However, the antioxidant status (superoxide dismutase (SOD) and catalase (CAT)) were found to be increased. The molecular docking analysis showed that ferulic acid exhibited significant ligand efficiency towards

Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis

PubMed Central

Hammell, D.C.; Zhang, L.P.; Ma, F.; Abshire, S.M.; McIlwrath, S.L.; Stinchcomb, A.L.; Westlund, K.N.

2015-01-01

Background Current arthritis treatments often have side-effects attributable to active compounds as well as route of administration. Cannabidiol (CBD) attenuates inflammation and pain without side-effects, but CBD is hydrophobic and has poor oral bioavailability. Topical drug application avoids gastrointestinal administration, first pass metabolism, providing more constant plasma levels. Methods This study examined efficacy of transdermal CBD for reduction in inflammation and pain, assessing any adverse effects in a rat complete Freund’s adjuvant-induced monoarthritic knee joint model. CBD gels (0.6, 3.1, 6.2 or 62.3 mg/day) were applied for 4 consecutive days after arthritis induction. Joint circumference and immune cell invasion in histological sections were measured to indicate level of inflammation. Paw withdrawal latency (PWL) in response to noxious heat stimulation determined nociceptive sensitization, and exploratory behaviour ascertained animal’s activity level. Results Measurement of plasma CBD concentration provided by transdermal absorption revealed linearity with 0.6–6.2 mg/day doses. Transdermal CBD gel significantly reduced joint swelling, limb posture scores as a rating of spontaneous pain, immune cell infiltration and thickening of the synovial membrane in a dose-dependent manner. PWL recovered to near baseline level. Immunohistochemical analysis of spinal cord (CGRP, OX42) and dorsal root ganglia (TNFα) revealed dose-dependent reductions of pro-inflammatory biomarkers. Results showed 6.2 and 62 mg/day were effective doses. Exploratory behaviour was not altered by CBD indicating limited effect on higher brain function. Conclusions These data indicate that topical CBD application has therapeutic potential for relief of arthritis pain-related behaviours and inflammation without evident side-effects. PMID:26517407

Infrared (810-nm) low-level laser therapy on rat experimental knee inflammation.

PubMed

Pallotta, Rodney Capp; Bjordal, Jan Magnus; Frigo, Lúcio; Leal Junior, Ernesto Cesar Pinto; Teixeira, Simone; Marcos, Rodrigo Labat; Ramos, Luciano; Messias, Felipe de Moura; Lopes-Martins, Rodrigo Alvaro Brandão

2012-01-01

Arthritis of the knee is the most common type of joint inflammatory disorder and it is associated with pain and inflammation of the joint capsule. Few studies address the effects of the 810-nm laser in such conditions. Here we investigated the effects of low-level laser therapy (LLLT; infrared, 810-nm) in experimentally induced rat knee inflammation. Thirty male Wistar rats (230-250 g) were anesthetized and injected with carrageenan by an intra-articular route. After 6 and 12 h, all animals were killed by CO(2) inhalation and the articular cavity was washed for cellular and biochemical analysis. Articular tissue was carefully removed for real-time PCR analysis in order to evaluate COX-1 and COX-2 expression. LLLT was able to significantly inhibit the total number of leukocytes, as well as the myeloperoxidase activity with 1, 3, and 6 J (Joules) of energy. This result was corroborated by cell counting showing the reduction of polymorphonuclear cells at the inflammatory site. Vascular extravasation was significantly inhibited at the higher dose of energy of 10 J. Both COX-1 and 2 gene expression were significantly enhanced by laser irradiation while PGE(2) production was inhibited. Low-level laser therapy operating at 810 nm markedly reduced inflammatory signs of inflammation but increased COX-1 and 2 gene expression. Further studies are necessary to investigate the possible production of antiinflammatory mediators by COX enzymes induced by laser irradiation in knee inflammation.

Effects of Erdosteine on Experimental Acute Pancreatitis Model.

PubMed

Karapolat, Banu; Karapolat, Sami; Gurleyik, Emin; Yasar, Mehmet

2017-10-01

To create acute pancreatitis condition experimentally in rats using cerulein, and to reveal histopathological effects in pancreatic tissue with erdosteine. An experimental study. Department of General Surgery, Duzce University, Turkey, from June to October 2014. Thirty male Wistar albino rats were divided into three groups. No procedures were applied to Group 1. The rats in Group 2 and Group 3 were injected cerulein, to establish an experimental pancreatitis model and the blood amylase and lipase values were examined. The rats in Group 3 were given 10 mg/kg erdosteine. This treatment was continued for another 2 days and the rats were sacrificed. The pancreatic tissues were examined histopathologically for edema, inflammation, acinar necrosis, fat necrosis, and vacuolization. The lipase and amylase values and the histopathological examination of pancreatic tissues evidenced that the experimental acute pancreatitis model was established and edema, inflammation, acinar necrosis, fat necrosis, and vacuolization were observed in the pancreatic tissues. The statistical results suggest that erdosteine can decrease the edema, inflammation, acinar necrosis, fat necrosis and vacuolization scores in the tissues. The severity of acute pancreatitis, induced by cerulein in rats, is reduced with the use of erdosteine.

Early treatment of chlorine-induced airway hyperresponsiveness and inflammation with corticosteroids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jonasson, Sofia, E-mail: sofia.jonasson@foi.se; Wigenstam, Elisabeth; Department of Public Health and Clinical Medicine, Unit of Respiratory Medicine, Umeå University, Umeå

Chlorine (Cl{sub 2}) is an industrial gas that is highly toxic and irritating when inhaled causing tissue damage and an acute inflammatory response in the airways followed by a long-term airway dysfunction. The aim of this study was to evaluate whether early anti-inflammatory treatment can protect against the delayed symptoms in Cl{sub 2}-exposed mice. BALB/c mice were exposed by nose-only inhalation using 200 ppm Cl{sub 2} during 15 min. Assessment of airway hyperresponsiveness (AHR), inflammatory cell counts in bronchoalveolar lavage, occurrence of lung edema and lung fibrosis were analyzed 24 h or 14 days post-exposure. A single dose of themore » corticosteroid dexamethasone (10 or 100 mg/kg) was administered intraperitoneally 1, 3, 6, or 12 h following Cl{sub 2} exposure. High-dose of dexamethasone reduced the acute inflammation if administered within 6 h after exposure but treated animals still displayed a significant lung injury. The effect of dexamethasone administered within 1 h was dose-dependent; high-dose significantly reduced acute airway inflammation (100 mg/kg) but not treatment with the relatively low-dose (10 mg/kg). Both doses reduced AHR 14 days later, while lung fibrosis measured as collagen deposition was not significantly reduced. The results point out that the acute inflammation in the lungs due to Cl{sub 2} exposure only partly is associated with the long-term AHR. We hypothesize that additional pathogenic mechanisms apart from the inflammatory reactions contribute to the development of long-term airway dysfunction. By using this mouse model, we have validated early administration of corticosteroids in terms of efficacy to prevent acute lung injury and delayed symptoms induced by Cl{sub 2} exposure. - Highlights: • Inhalation of Cl{sub 2} may lead to a long-standing airway hyperresponsiveness. • The symptoms in Cl{sub 2}-exposed mice are similar to those described for RADS in humans. • Corticosteroids prevent delayed symptoms such as

Joint Inflammation and Early Degeneration Induced by High-Force Reaching Are Attenuated by Ibuprofen in an Animal Model of Work-Related Musculoskeletal Disorder

PubMed Central

Driban, Jeffrey B.; Barr, Ann E.; Amin, Mamta; Sitler, Michael R.; Barbe, Mary F.

2011-01-01

We used our voluntary rat model of reaching and grasping to study the effect of performing a high-repetition and high-force (HRHF) task for 12 weeks on wrist joints. We also studied the effectiveness of ibuprofen, administered in the last 8 weeks, in attenuating HRHF-induced changes in these joints. With HRHF task performance, ED1+ and COX2+ cells were present in subchondral radius, carpal bones and synovium; IL-1alpha and TNF-alpha increased in distal radius/ulna/carpal bones; chondrocytes stained with Terminal deoxynucleotidyl Transferase- (TDT-) mediated dUTP-biotin nick end-labeling (TUNEL) increased in wrist articular cartilages; superficial structural changes (e.g., pannus) and reduced proteoglycan staining were observed in wrist articular cartilages. These changes were not present in normal controls or ibuprofen treated rats, although IL-1alpha was increased in reach limbs of trained controls. HRHF-induced increases in serum C1,2C (a biomarker of collagen I and II degradation), and the ratio of collagen degradation to synthesis (C1,2C/CPII; the latter a biomarker of collage type II synthesis) were also attenuated by ibuprofen. Thus, ibuprofen treatment was effective in attenuating HRHF-induced inflammation and early articular cartilage degeneration. PMID:21403884

Young adult survivors of childhood acute lymphoblastic leukemia show evidence of chronic inflammation and cellular aging.

PubMed

Ariffin, Hany; Azanan, Mohamad Shafiq; Abd Ghafar, Sayyidatul Syahirah; Oh, Lixian; Lau, Kee Hie; Thirunavakarasu, Tharshanadhevasheri; Sedan, Atiqah; Ibrahim, Kamariah; Chan, Adelyne; Chin, Tong Foh; Liew, Fong Fong; Jeyamogan, Shareni; Rosli, Erda Syerena; Baharudin, Rashidah; Yap, Tsiao Yi; Skinner, Roderick; Lum, Su Han; Hainaut, Pierre

2017-11-01

Large epidemiologic studies have reported the premature onset of age-related conditions, such as ischemic heart disease and diabetes mellitus, in childhood cancer survivors, decades earlier than in their peers. The authors investigated whether young adult survivors of childhood acute lymphoblastic leukemia (ALL) have a biologic phenotype of cellular ageing and chronic inflammation. Plasma inflammatory cytokines were measured using a cytometric bead array in 87 asymptomatic young adult survivors of childhood ALL (median age, 25 years; age range, 18-35 years) who attended annual follow-up clinic and compared with healthy, age-matched and sex-matched controls. Leukocyte telomere length (LTL) was measured using Southern blot analysis. Survivors had significant elevation of plasma interleukin-2 (IL-2), IL-10, IL-17a, and high-sensitivity C-reactive protein levels (all P < .05). A raised high-sensitivity C-reactive protein level (>0.8 mg/dL) was related to increased odds of having metabolic syndrome (odds ratio, 7.256; 95% confidence interval, 1.501-35.074). Survivors also had significantly shorter LTL compared with controls (median, 9866 vs 10,392 base pairs; P = .021). Compared with published data, LTL in survivors was similar to that in healthy individuals aged 20 years older. Survivors who received cranial irradiation had shorter LTL compared with those who had not (P = .013). Asymptomatic young adult survivors of childhood ALL demonstrate a biologic profile of chronic inflammation and telomere attrition, consistent with an early onset of cellular processes that drive accelerated aging. These processes may explain the premature development of age-related chronic conditions in childhood cancer survivors. Understanding their molecular basis may facilitate targeted interventions to disrupt the accelerated aging process and its long-term impact on overall health. Cancer 2017;123:4207-4214. © 2017 American Cancer Society. © 2017 American Cancer Society.

The effect of cardioprotective diet rich with natural antioxidants on chronic inflammation and oxidized LDL during cardiac rehabilitation in patients after acute myocardial infarction.

PubMed

Mlakar, Polona; Salobir, Barbara; Čobo, Nusret; Strašek, Janja; Prezelj, Marija; Debevc, Ana; Jug, Borut; Terčelj, Marjeta; Šabovič, Mišo

2015-06-01

Chronic inflammation, the fundamental pathogenetic process of atherosclerosis, can be modified by pharmacological and non-pharmacological measures as a part of secondary prevention after acute myocardial infarction (AMI). The aim of our study was to determine the effect of diet, rich with natural antioxidants, added to physical activity (as a part of cardiac rehabilitation (CR) program) on inflammatory markers and ox-LDL, a marker of oxidative stress, closely involved in the process of chronic inflammation. 41 male patients after AMI undergoing CR were divided into a diet group (supervised cardioprotective diet throughout the CR), and control group (CR without diet). We measured hsCRP, leucocytes, neutrophils, IL-6, oxLDL, exercise capacity and classic risk factors before and after CR program. Patients from the diet group presented with a significant decline in classic risk factors (BMI, waist circumference, waist to hip ratio, systolic blood pressure, heart rate, blood glucose, total cholesterol, LDL, TAG) and inflammatory markers (hsCRP, leucocytes, neutrophils) compared to control group. Furthermore, when studying nonsmokers, we observed significant decline of oxLDL in the diet group. The addition of cardioprotective diet, rich with natural antioxidants, to physical activity as a part of a CR program, positively modifies not just classic risk factors and exercise capacity, but also diminishes chronic inflammation markers. These effects, and oxLDL decline were most prominent in nonsmoking patients.

Comparison of active constituents, acute toxicity, anti-nociceptive and anti-inflammatory activities of Porana sinensis Hemsl., Erycibe obtusifolia Benth. and Erycibe schmidtii Craib.

PubMed

Chen, Zhiyong; Liao, Liping; Zhang, Zijia; Wu, Lihong; Wang, Zhengtao

2013-11-25

Erycibe obtusifolia and Erycibe schmidtii, which belong to the same genus as Erycibe, are widely used in traditional medicine for the treatment of joint pain and rheumatoid arthritis (RA). Porana sinensis has become a widely used substitute for Erycibe obtusifolia and Erycibe schmidtii as they have declined in the wild. In the present work, the content of the main active components, the acute toxicity, the anti-nociceptive and anti-inflammatory activities of Porana sinensis, Erycibe obtusifolia and Erycibe schmidtii were compared, and the mechanisms of anti-nociceptive and anti-inflammatory activities were discussed. A quantitative HPLC (high performance liquid chromatography) method was first developed to compare the content of the main active components (scopoletin, scopolin and chlorogenic acid). The anti-inflammatory and anti-nociceptive activities of 40% ethanolic extracts of the three plants were compared using the models of xylene-induced ear edema, formalin-induced inflammation, carrageenan-induced air pouch inflammation, acetic acid-induced writhing and formalin-induced nociception. The acute toxicity of the 40% ethanolic extracts of the three plants was studied. The assay suggested a large content of scopoletin, scopolin and chlorogenic acid in the three plants. The 40% ethanolic extracts of the three plants were almost non-toxic at the dose of 5g/kg and all of them showed significant anti-inflammatory effects in the tests of xylene-induced ear edema and formalin-induced inflammation. In the carrageenan-induced air pouch inflammation test, the synthesis of PGE2 was significantly inhibited by all the extracts. They significantly inhibited the number of contortions induced by acetic acid and the second phase of the formalin-induced licking response. Naloxone was not able to reverse the analgesic effect of these extracts. The study identifies the similarity of the three plants in their main active components as well as acute toxicity, anti-nociceptive and

The role of IL-23 receptor signaling in inflammation-mediated erosive autoimmune arthritis and bone remodeling.

PubMed

Razawy, Wida; van Driel, Marjolein; Lubberts, Erik

2018-02-01

The IL-23/Th17 axis has been implicated in the development of autoimmune diseases, such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA). RA and PsA are heterogeneous diseases with substantial burden on patients. Increasing evidence suggests that the IL-23 signaling pathway may be involved in the development of autoimmunity and erosive joint damage. IL-23 can act either directly or indirectly on bone forming osteoblasts as well as on bone resorbing osteoclasts. As IL-23 regulates the activity of cells of the bone, it is conceivable that in addition to inflammation-mediated joint erosion, IL-23 may play a role in physiological bone remodeling. In this review, we focus on the role of IL-23 in autoimmune arthritis in patients and murine models, and provide an overview of IL-23 producing and responding cells in autoimmune arthritic joints. In addition, we discuss the role of IL-23 on bone forming osteoblasts and bone resorbing osteoclasts regarding inflammation-mediated joint damage and bone remodeling. At last, we briefly discuss the clinical implications of targeting this pathway for joint damage and systemic bone loss in autoimmune arthritis. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Population pharmacokinetic analysis of blood and joint synovial fluid concentrations of robenacoxib from healthy dogs and dogs with osteoarthritis.

PubMed

Silber, Hanna E; Burgener, Claudia; Letellier, Ingrid M; Peyrou, Mathieu; Jung, Martin; King, Jonathan N; Gruet, Philippe; Giraudel, Jerome M

2010-12-01

The purpose of this population analysis was to characterize the pharmacokinetic properties of robenacoxib in blood and stifle joint synovial fluid of dogs. Data were obtained from two studies: 1) 8 healthy Beagle dogs in which an acute inflammation was induced by injection of urate crystals into one joint; 2) 95 dogs from various breeds diagnosed with osteoarthritis (OA). Robenacoxib concentrations in blood and synovial fluid were measured using a validated HPLC-UV and LC-MS method. Non-linear mixed effects modeling was performed using NONMEM6. A two-compartment pharmacokinetic model with linear elimination was developed to describe blood concentrations of robenacoxib. Blood clearance in healthy animals was found to be 75% higher than in OA dogs. Synovial fluid concentrations were modeled using an effect-compartment-type model predicting longer residence times in OA dogs compared to healthy Beagles (e.g. concentrations above the IC(50) for COX-2, respectively, 16 h vs. 10 h at 1.5 mg/kg). Robenacoxib was found to reside longer at the effect site (inflamed joint) compared to blood in both healthy and OA dogs. These results may explain the good efficacy observed with once-daily dosing in clinical trials and the high safety index of robenacoxib in dogs.

Dietary phytosterols modulate T-helper immune response but do not induce apparent anti-inflammatory effects in a mouse model of acute, aseptic inflammation.

PubMed

Calpe-Berdiel, Laura; Escolà-Gil, Joan Carles; Benítez, Sonia; Bancells, Cristina; González-Sastre, Francesc; Palomer, Xavier; Blanco-Vaca, Francisco

2007-05-01

Although most studies have focused on the cholesterol-lowering activity of phytosterols, other biological actions have been ascribed to these plant sterol compounds, one of which is a potential immune modulatory effect. To gain insight into this issue, we used a mouse model of acute, aseptic inflammation induced by a single subcutaneous turpentine injection. Hypercholesterolemic apolipoprotein E-deficient (apoE(-/-)) mice, fed with or without a 2% phytosterol supplement, were treated with turpentine or saline and euthanized 48 h later. No differences were observed in spleen lymphocyte subsets between phytosterol- and control-fed apoE(-/-) mice. However, cultured spleen lymphocytes of apoE(-/-) mice fed with phytosterols and treated with turpentine showed increased IL-2 and IFN-gamma secretion (T-helper type1, Th1 lymphocyte cytokines) compared with turpentine-treated, control-fed animals. In contrast, there was no change in Th2 cytokines IL-4 and IL-10. Phytosterols also inhibit intestinal cholesterol absorption in wild-type C57BL/6J mice but, in this case, without decreasing plasma cholesterol. Spleen lymphocytes of turpentine-treated C57BL/6J mice fed with phytosterols also showed increased IL-2 production, but IFN-gamma, IL-4 and IL-10 production was unchanged. The Th1/Th2 ratio was significantly increased both in phytosterol-fed apoE(-/-) and C57BL/6J mice. We conclude that phytosterols modulate the T-helper immune response in vivo, in part independently of their hypocholesterolemic effect in a setting of acute, aseptic inflammation. Further study of phytosterol effects on immune-based diseases characterized by an exacerbated Th2 response is thus of interest.

Assessment of Biomarkers Associated with Joint Injury and Subsequent Post-Traumatic Arthritis

DTIC Science & Technology

2015-10-01

osteoarthritis, articular fracture, joint injury, trauma, biomarker, inflammation, MRI , knee, mouse model, translational research. 3. OVERALL PROJECT...intervention. MRI imaging of the injured knee will be obtained to assess the articular cartilage. Degenerative changes in the cartilage and joint space...successfully enrolled patients, collected and stored biosamples, obtained all post-operative MRI scans and are continuing to obtain 18- month MRI scans for

The Changes of Energy Interactions between Nucleus Function and Mitochondria Functions Causing Transmutation of Chronic Inflammation into Cancer Metabolism.

PubMed

Ponizovskiy, Michail R

2016-01-01

Interactions between nucleus and mitochondria functions induce the mechanism of maintenance stability of cellular internal energy according to the first law of thermodynamics in able-bodied cells and changes the mechanisms of maintenance stability of cellular internal energy creating a transition stationary state of ablebodied cells into quasi-stationary pathologic states of acute inflammation transiting then into chronic inflammation and then transmuting into cancer metabolism. The mechanisms' influences of intruding etiologic pathologic agents (microbe, virus, etc.) lead to these changes of energy interactions between nucleus and mitochondria functions causing general acute inflammation, then passing into local chronic inflammation, and reversing into cancer metabolism transmutation. Interactions between biochemical processes and biophysical processes of cellular capacitors' operations create a supplementary mechanism of maintenance stability of cellular internal energy in the norm and in pathology. Discussion of some scientific works eliminates doubts of the authors of these works.

Age-related cognitive impairment is associated with long-term neuroinflammation and oxidative stress in a mouse model of episodic systemic inflammation.

PubMed

d'Avila, Joana Costa; Siqueira, Luciana Domett; Mazeraud, Aurélien; Azevedo, Estefania Pereira; Foguel, Debora; Castro-Faria-Neto, Hugo Caire; Sharshar, Tarek; Chrétien, Fabrice; Bozza, Fernando Augusto

2018-01-30

Microglia function is essential to maintain the brain homeostasis. Evidence shows that aged microglia are primed and show exaggerated response to acute inflammatory challenge. Systemic inflammation signals to the brain inducing changes that impact cognitive function. However, the mechanisms involved in age-related cognitive decline associated to episodic systemic inflammation are not completely understood. The aim of this study was to identify neuropathological features associated to age-related cognitive decline in a mouse model of episodic systemic inflammation. Young and aged Swiss mice were injected with low doses of LPS once a week for 6 weeks to induce episodic systemic inflammation. Sickness behavior, inflammatory markers, and neuroinflammation were assessed in different phases of systemic inflammation in young and aged mice. Behavior was evaluated long term after episodic systemic inflammation by open field, forced swimming, object recognition, and water maze tests. Episodic systemic inflammation induced systemic inflammation and sickness behavior mainly in aged mice. Systemic inflammation induced depressive-like behavior in both young and aged mice. Memory and learning were significantly affected in aged mice that presented lower exploratory activity and deficits in episodic and spatial memories, compared to aged controls and to young after episodic systemic inflammation. Systemic inflammation induced acute microglia activation in young mice that returned to base levels long term after episodic systemic inflammation. Aged mice presented dystrophic microglia in the hippocampus and entorhinal cortex at basal level and did not change morphology in the acute response to SI. Regardless of their dystrophic microglia, aged mice produced higher levels of pro-inflammatory (IL-1β and IL-6) as well as pro-resolution (IL-10 and IL-4) cytokines in the brain. Also, higher levels of Nox2 expression, oxidized proteins and lower antioxidant defenses were found in the

Knee joint mobilization reduces secondary mechanical hyperalgesia induced by capsaicin injection into the ankle joint.

PubMed

Sluka, K A; Wright, A

2001-01-01

Joint mobilization is a treatment approach commonly used by physical therapists for the management of a variety of painful conditions. However, the clinical effectiveness when compared to placebo and the neurophysiological mechanism of action are not known. The purpose of this study was to establish that application of a manual therapy technique will produce antihyperalgesia in an animal model of joint inflammation and that the antihyperalgesia produced by joint mobilization depends on the time of treatment application. Capsaicin (0.2%, 50 microl) was injected into the lateral aspect of the left ankle joint and mechanical withdrawal threshold assessed before and after capsaicin injection in Sprague-Dawley rats. Joint mobilization of the ipsilateral knee joint was performed 2 h after capsaicin injection for a total of 3 min, 9 min or 15 min under halothane anaesthesia. Control groups included animals that received halothane for the same time as the group that received joint mobilization and those whose limbs were held for the same duration as the mobilization (no halothane). Capsaicin resulted in a decreased mechanical withdrawal threshold by 2 h after injection that was maintained through 4 h. Both 9 and 15 min of mobilization, but not 3 min of mobilization, increased the withdrawal threshold to mechanical stimuli to baseline values when compared with control groups. The antihyperalgesic effect of joint mobilization lasted 30 min. Thus, joint mobilization (9 or 15 min duration) produces a significant reversal of secondary mechanical hyperalgesia induced by intra-articular injection of capsaicin. Copyright 2001 European Federation of Chapters of the International Association for the Study of Pain.

Acute cellular rejection with isolated v-lesions is not associated with more favorable outcomes than vascular rejection with more tubulointerstitial inflammations.

PubMed

Wu, K Y; Budde, K; Schmidt, D; Neumayer, H H; Rudolph, B

2014-04-01

The impact of isolated v-lesions on clinical outcome in biopsies with acute cellular rejection (ACR) is unclear. Two hundred and sixty-five biopsies showing the highest ACR severity for each patient were recruited and classified into four groups: (i) acute interstitial rejection (AIR) I with minimal tubulointerstitial inflammation (TI), (ii) AIR II with intensive TI, (iii) acute vascular rejection (AVR) I with minimal TI, and (iv) AVR II with intensive TI. The complete reversal rates of AIR I and AIR II groups were marginally higher than AVR I and AVR II groups (p = 0.16). At eight yr of transplantation, the death-censored graft survival (DCGS) rate of AIR I group (93.3%) was significantly higher compared with the AVR I (72.7%) or AVR II (72.9%) group. AVR I group had a similar DCGS rate with AVR II group (72.7% vs. 74.1%), whereas AVR with v1-lesion showed significantly higher graft survival (GS) rate than those with v2-lesion (70.2% vs. 45.5%). The t-lesion of AIR and v-lesion of AVR group were associated with graft loss. The extent of TI is non-specifically associated with graft loss in biopsies with AVR; the higher grade v-lesion predicts the lower complete reversal rate and poorer long-term graft survival. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Non-Invasive Detection of Lung Inflammation by Near-Infrared Fluorescence Imaging Using Bimodal Liposomes.

PubMed

Desu, Hari R; Wood, George C; Thoma, Laura A

2016-01-01

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome results in respiratory obstruction and severe lung inflammation. Critical characteristics of ALI are alveolar edema, infiltration of leukocytes (neutrophils and monocytes), release of pro-inflammatory cytokines and chemokines into broncho-alveolar lavage fluid, and activation of integrin receptors. The purpose of the study was to demonstrate non-invasive detection of lung inflammation using integrin receptor targeted fluorescence liposomes. An inflammation similar to that observed in ALI was elicited in rodents by intra-tracheal instillation of interleukin-1beta (IL-1beta). Cyclic arginine glycine-(D)-aspartic acid-peptide (cRGD-peptide) grafted fluorescence liposomes were administered to ALI induced male Sprague-Dawley rats for targeting lung integrin receptors. Near-infrared fluorescence imaging (NIRFI) was applied for visualization and quantitation of lung inflammation. NIRFI signals were correlated with inflammatory cellular and biochemical markers of lungs. A positive correlation was observed between NIRF signals and lung inflammation markers. Compared to control group, an intense NIRF signal was observed in ALI induced rats in the window 6-24 h post-IL-1beta instillation. Interaction of integrin receptors with targeted liposomes was assumed to contribute to intense NIRF signal. RT-PCR studies showed an elevated lung expression of alphavbeta5 integrin receptors, 12 h post-IL-1beta instillation. In vitro studies demonstrated integrin receptor specificity of targeted liposomes. These targeted liposomes showed binding to alphavbeta5 integrin receptors expressed on alveolar cells. Non-invasive detection of lung inflammation was demonstrated using a combination of integrin receptor targeting and NIRFI.

The management of acute and chronic pancreatitis.

PubMed

Banks, Peter A; Conwell, Darwin L; Toskes, Phillip P

2010-02-01

Pancreatitis, which is most generally described as any inflammation of the pancreas, is a serious condition that manifests in either acute or chronic forms. Chronic pancreatitis results from irreversible scarring of the pancreas, resulting from prolonged inflammation. Six major etiologies for chronic pancreatitis have been identified: toxic/ metabolic, idiopathic, genetic, autoimmune, recurrent and severe acute pancreatitis, and obstruction. The most common symptom associated with chronic pancreatitis is pain localized to the upper-to-middle abdomen, along with food malabsorption, and eventual development of diabetes. Treatment strategies for acute pancreatitis include fasting and short-term intravenous feeding, fluid therapy, and pain management with narcotics for severe pain or nonsteroidal anti-inflammatories for milder cases. Patients with chronic disease and symptoms require further care to address digestive issues and the possible development of diabetes. Dietary restrictions are recommended, along with enzyme replacement and vitamin supplementation. More definitive outcomes may be achieved with surgical or endoscopic methods, depending on the role of the pancreatic ducts in the manifestation of disease.

Inflammation-Induced Cell Proliferation Potentiates DNA Damage-Induced Mutations In Vivo

PubMed Central

Kiraly, Orsolya; Gong, Guanyu; Olipitz, Werner; Muthupalani, Sureshkumar; Engelward, Bevin P.

2015-01-01

Mutations are a critical driver of cancer initiation. While extensive studies have focused on exposure-induced mutations, few studies have explored the importance of tissue physiology as a modulator of mutation susceptibility in vivo. Of particular interest is inflammation, a known cancer risk factor relevant to chronic inflammatory diseases and pathogen-induced inflammation. Here, we used the fluorescent yellow direct repeat (FYDR) mice that harbor a reporter to detect misalignments during homologous recombination (HR), an important class of mutations. FYDR mice were exposed to cerulein, a potent inducer of pancreatic inflammation. We show that inflammation induces DSBs (γH2AX foci) and that several days later there is an increase in cell proliferation. While isolated bouts of inflammation did not induce HR, overlap between inflammation-induced DNA damage and inflammation-induced cell proliferation induced HR significantly. To study exogenously-induced DNA damage, animals were exposed to methylnitrosourea, a model alkylating agent that creates DNA lesions relevant to both environmental exposures and cancer chemotherapy. We found that exposure to alkylation damage induces HR, and importantly, that inflammation-induced cell proliferation and alkylation induce HR in a synergistic fashion. Taken together, these results show that, during an acute bout of inflammation, there is a kinetic barrier separating DNA damage from cell proliferation that protects against mutations, and that inflammation-induced cell proliferation greatly potentiates exposure-induced mutations. These studies demonstrate a fundamental mechanism by which inflammation can act synergistically with DNA damage to induce mutations that drive cancer and cancer recurrence. PMID:25647331

Original single-incision laparoscopic cholecystectomy for acute inflammation of the gallbladder

PubMed Central

Sasaki, Kazunari; Watanabe, Goro; Matsuda, Masamichi; Hashimoto, Masaji

2012-01-01

AIM: To investigate the safety and feasibility of our original single-incision laparoscopic cholecystectomy (SILC) for acute inflamed gallbladder (AIG). METHODS: One hundred and ten consecutive patients underwent original SILC for gallbladder disease without any selection criteria and 15 and 11 of these were diagnosed with acute cholecystitis and acute gallstone cholangitis, respectively. A retrospective review was performed not only between SILC for AIG and non-AIG, but also between SILC for AIG and traditional laparoscopic cholecystectomy (TLC) for AIG in the same period. RESULTS: Comparison between SILC for AIG and non-AIG revealed that the operative time was longer in SILC for AIG (97.5 min vs 85.0 min, P = 0.03). The open conversion rate (2/26 vs 2/84, P = 0.24) and complication rate (1/26 vs 3/84, P = 1.00) showed no differences, but a need for additional trocars was more frequent in SILC for AIG (5/24 vs 3/82, P = 0.01). Comparison between SILC for AIG and TLC for AIG revealed no differences based on statistical analysis. CONCLUSION: Our original SILC technique was adequately safe and feasible for the treatment of acute cholecystitis and acute gallstone cholangitis. PMID:22408354

Acute Septic Arthritis

PubMed Central

Shirtliff, Mark E.; Mader, Jon T.

2002-01-01

Acute septic arthritis may develop as a result of hematogenous seeding, direct introduction, or extension from a contiguous focus of infection. The pathogenesis of acute septic arthritis is multifactorial and depends on the interaction of the host immune response and the adherence factors, toxins, and immunoavoidance strategies of the invading pathogen. Neisseria gonorrhoeae and Staphylococcus aureus are used in discussing the host-pathogen interaction in the pathogenesis of acute septic arthritis. While diagnosis rests on isolation of the bacterial species from synovial fluid samples, patient history, clinical presentation, laboratory findings, and imaging studies are also important. Acute nongonococcal septic arthritis is a medical emergency that can lead to significant morbidity and mortality. Therefore, prompt recognition, rapid and aggressive antimicrobial therapy, and surgical treatment are critical to ensuring a good prognosis. Even with prompt diagnosis and treatment, high mortality and morbidity rates still occur. In contrast, gonococcal arthritis is often successfully treated with antimicrobial therapy alone and demonstrates a very low rate of complications and an excellent prognosis for full return of normal joint function. In the case of prosthetic joint infections, the hardware must be eventually removed by a two-stage revision in order to cure the infection. PMID:12364368

Impact of physical activity, cardiorespiratory fitness, and exercise training on markers of inflammation.

PubMed

Lavie, Carl J; Church, Timothy S; Milani, Richard V; Earnest, Conrad P

2011-01-01

Physical activity and exercise training (ET) enhance overall cardiorespiratory fitness (ie, fitness), thus producing many benefits in the primary and secondary prevention of cardiovascular diseases. Substantial evidence also indicates that acute and chronic inflammation is involved in the development and progression of atherosclerosis and major cardiovascular events. The most commonly utilized marker of inflammation is C-reactive protein (CRP). In this review, we discuss the importance of inflammation, especially CRP, as a cardiovascular risk marker by reviewing an abundant cross-sectional and clinical intervention literature providing evidence that physical activity, enhanced fitness, and ET are inversely associated with CRP and that being overweight or obese is directly related with inflammation/CRP. Although we discuss the controversy regarding whether or not ET reduces CRP independent of weight loss, clearly physical activity, improved fitness, and ET are associated with reductions in inflammation and overall cardiovascular risk in both primary and secondary prevention.

AMPA/kainate glutamate receptors contribute to inflammation, degeneration and pain related behaviour in inflammatory stages of arthritis

PubMed Central

Bonnet, Cleo S; Williams, Anwen S; Gilbert, Sophie J; Harvey, Ann K; Evans, Bronwen A; Mason, Deborah J

2015-01-01

Objectives Synovial fluid glutamate concentrations increase in arthritis. Activation of kainate (KA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors (GluRs) increase interleukin-6 (IL-6) release and cause arthritic pain, respectively. We hypothesised that AMPA and KA GluRs are expressed in human arthritis, and that intra-articular NBQX (AMPA/KA GluR antagonist) prevents pain and pathology in antigen-induced arthritis (AIA). Methods GluR immunohistochemistry was related to synovial inflammation and degradation in osteoarthritis (OA) and rheumatoid arthritis (RA). A single intra-articular NBQX injection was given at induction, and knee swelling and gait of AIA and AIA+NBQX rats compared over 21 days, before imaging, RT-qPCR, histology and immunohistochemistry of joints. Effects of NBQX on human primary osteoblast (HOB) activity were determined. Results AMPAR2 and KA1 immunolocalised to remodelling bone, cartilage and synovial cells in human OA and RA, and rat AIA. All arthritic tissues showed degradation and synovial inflammation. NBQX reduced GluR abundance, knee swelling (p<0.001, days 1–21), gait abnormalities (days 1–2), end-stage joint destruction (p<0.001), synovial inflammation (p<0.001), and messenger RNA expression of meniscal IL-6 (p<0.05) and whole joint cathepsin K (p<0.01). X-ray and MRI revealed fewer cartilage and bone erosions, and less inflammation after NBQX treatment. NBQX reduced HOB number and prevented mineralisation. Conclusions AMPA/KA GluRs are expressed in human OA and RA, and in AIA, where a single intra-articular injection of NBQX reduced swelling by 33%, and inflammation and degeneration scores by 34% and 27%, respectively, exceeding the efficacy of approved drugs in the same model. AMPA/KA GluR antagonists represent a potential treatment for arthritis. PMID:24130267

Chronic inflammation and impaired development of the preterm brain.

PubMed

Bennet, Laura; Dhillon, Simerdeep; Lear, Chris A; van den Heuij, Lotte; King, Victoria; Dean, Justin M; Wassink, Guido; Davidson, Joanne O; Gunn, Alistair Jan

2018-02-01

The preterm newborn is at significant risk of neural injury and impaired neurodevelopment. Infants with mild or no evidence of injury may also be at risk of altered brain development, with evidence impaired cell maturation. The underlying causes are multifactorial and include exposure of both the fetus and newborn to hypoxia-ischemia, inflammation (chorioamnionitis) and infection, adverse maternal lifestyle choices (smoking, drug and alcohol use, diet) and obesity, as well as the significant demand that adaptation to post-natal life places on immature organs. Further, many fetuses and infants may have combinations of these events, and repeated (multi-hit) events that may induce tolerance to injury or sensitize to greater injury. Currently there are no treatments to prevent preterm injury or impaired neurodevelopment. However, inflammation is a common pathway for many of these insults, and clinical and experimental evidence demonstrates that acute and chronic inflammation is associated with impaired brain development. This review examines our current knowledge about the relationship between inflammation and preterm brain development, and the potential for stem cell therapy to provide neuroprotection and neurorepair through reducing inflammation and release of trophic factors, which promote cell maturation and repair. Copyright © 2017 Elsevier B.V. All rights reserved.

Coronal plane radiographic evaluation of the single TightRope technique in the treatment of acute acromioclavicular joint injury.

PubMed

Yi, Young; Kim, Jeong Woo

2015-10-01

This study aimed to demonstrate the technical aspects of the single TightRope (Arthrex, Naples, FL, USA) procedure for acute acromioclavicular-coracoclavicular joint dislocation, identify the predictive factors influencing its outcome, and assess and validate the significance of specific radiologic parameters. We reviewed true anteroposterior shoulder radiographs of 62 consecutive patients who had undergone surgical reconstruction using TightRope for an acute acromioclavicular-coracoclavicular injury. All patients were followed up for at least 12 months between October 2009 and March 2012 and were divided into dissociated or nondissociated groups according to their surgical outcome. We measured the clavicle tunnel anteroposterior angle, distal clavicular tunnel placement, and tunnel-to-medial coracoid ratio, and compared the parameters in each group after a satisfactory intraclass correlation coefficient reliability test result. The angles of patients in the dissociated group were more acute compared with the angles of those in the nondissociated group, which were perpendicular, as verified statistically using the paired t test. The difference in the distal clavicular tunnel placement and tunnel-to-medial coracoid ratio between the groups was not significant. Therefore, tunnel placement is not influenced by coracoclavicular dissociation. The clavicle tunnel anteroposterior angle can be used as a predictor of surgical outcome in coracoclavicular augmentation surgery. The surgeon should strive to place a perpendicular hole from the clavicle to the coracoid process for the TightRope fixation to enable a successful reconstruction of the acute acromioclavicular-coracoclavicular injury. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Resolution of inflammation by interleukin-9-producing type 2 innate lymphoid cells

PubMed Central

Rauber, Simon; Luber, Markus; Weber, Stefanie; Maul, Lisa; Soare, Alina; Wohlfahrt, Thomas; Lin, Neng-Yu; Dietel, Katharina; Bozec, Aline; Herrmann, Martin; Kaplan, Mark H.; Weigmann, Benno; Zaiss, Mario M.; Fearon, Ursula; Veale, Douglas J.; Canete, Juan D.; Distler, Oliver; Rivellese, Felice; Pitzalis, Costantino; Neurath, Markus F.; McKenzie, Andrew N.J.; Wirtz, Stefan; Schett, Georg; Distler, Jörg H.W.; Ramming, Andreas

2017-01-01

Inflammatory diseases such as arthritis are chronic conditions that fail to resolve spontaneously. While the cytokine and cellular pathways triggering arthritis are well defined, those responsible for the resolution of inflammation are incompletely characterized. Here we identified IL-9-producing type 2 innate lymphoid cells (ILC2s) as a molecular and cellular pathway that orchestrates the resolution of chronic inflammation. In mice, the absence of IL-9 impaired ILC2 proliferation, activation of regulatory T cells (Treg) and resulted in chronic arthritis with excessive cartilage destruction and bone loss. In contrast, treatment with IL-9 promoted ILC2-dependent Treg activation and effectively induced resolution of inflammation and protection of bone. Rheumatoid arthritis patients in remission demonstrated high numbers of IL-9+ ILC2s in the joints and in the circulation. Hence, fostering IL-9-mediated ILC2 activation may offer a novel therapeutic approach inducing resolution of inflammation rather than suppression of inflammatory responses. PMID:28714991

Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice

PubMed Central

Suidan, Georgette L.; Demers, Melanie; Herr, Nadine; Carbo, Carla; Brill, Alexander; Cifuni, Stephen M.; Mauler, Maximilian; Cicko, Sanja; Bader, Michael; Idzko, Marco; Bode, Christoph

2013-01-01

The majority of peripheral serotonin is stored in platelets, which secrete it on activation. Serotonin releases Weibel-Palade bodies (WPBs) and we asked whether absence of platelet serotonin affects neutrophil recruitment in inflammatory responses. Tryptophan hydroxylase (Tph)1–deficient mice, lacking non-neuronal serotonin, showed mild leukocytosis compared with wild-type (WT), primarily driven by an elevated neutrophil count. Despite this, 50% fewer leukocytes rolled on unstimulated mesenteric venous endothelium of Tph1−/− mice. The velocity of rolling leukocytes was higher in Tph1−/− mice, indicating fewer selectin-mediated interactions with endothelium. Stimulation of endothelium with histamine, a secretagogue of WPBs, or injection of serotonin normalized the rolling in Tph1−/− mice. Diminished rolling in Tph1−/− mice resulted in reduced firm adhesion of leukocytes after lipopolysaccharide treatment. Blocking platelet serotonin uptake with fluoxetine in WT mice reduced serum serotonin by > 80% and similarly reduced leukocyte rolling and adhesion. Four hours after inflammatory stimulation, neutrophil extravasation into lung, peritoneum, and skin wounds was reduced in Tph1−/− mice, whereas in vitro neutrophil chemotaxis was independent of serotonin. Survival of lipopolysaccharide-induced endotoxic shock was improved in Tph1−/− mice. In conclusion, platelet serotonin promotes the recruitment of neutrophils in acute inflammation, supporting an important role for platelet serotonin in innate immunity. PMID:23243271

The effect of cooling on coagulation and haemostasis: should "Ice" be part of treatment of acute haemarthrosis in haemophilia?

PubMed

Forsyth, A L; Zourikian, N; Valentino, L A; Rivard, G E

2012-11-01

Repeated haemarthroses and the consequences of blood in the joint contribute to blood induced joint disease (BIJD) in people with haemophilia (PWH). Prevention of bleeding, through medical management, is the standard of care in developed countries, but is not universally available due to financial and other barriers. Ice application, as part of R.I.C.E. (Rest, Ice, Compression, Elevation) or alone, is commonly recommended as an adjunct treatment to decrease bleeding, pain, tissue metabolism, oedema, and inflammation. This article will review evidence regarding local cooling by commonly used ice application methods, to decrease the temperature of the skin and intra-articular (IA) joint space and the resultant effects on haemostasis and coagulation. The general literature was reviewed for articles in English describing temperatures achievable in the skin and IA space using clinically relevant ice protocols, and the effect of cooling on haemostasis and coagulation. The literature demonstrates that typical methods of ice application can cool both the skin and IA space. Published, general literature studies have also consistently demonstrated that experimental cooling of blood and/or tissue, both in vitro and in vivo in humans and in animal models, can significantly impair coagulation and prolong bleeding. In PWH with acute haemarthrosis, ice application has potential to increase haemorrhage morbidity by further impairing coagulation and haemostasis. Ice has not been shown to improve overall outcome, stop bleeding nor swelling from haemarthrosis. Although ice can help manage acute, haemarthrosis-related pain, there are other available interventions that will not impair coagulation and haemostasis. © 2012 Blackwell Publishing Ltd.

Memory and multitasking performance during acute allergic inflammation in seasonal allergic rhinitis.

PubMed

Trikojat, K; Buske-Kirschbaum, A; Plessow, F; Schmitt, J; Fischer, R

2017-04-01

In previous research, patients with seasonal allergic rhinitis (SAR) showed poorer school and work performance during periods of acute allergic inflammation, supporting the idea of an impact of SAR on cognitive functions. However, the specific cognitive domains particularly vulnerable to inflammatory processes are unclear. In this study, the influence of SAR on memory and multitasking performance, as two potentially vulnerable cognitive domains essential in everyday life functioning, was investigated in patients with SAR. Non-medicated patients with SAR (n = 41) and healthy non-allergic controls (n = 42) performed a dual-task paradigm and a verbal learning and memory test during and out of symptomatic allergy periods (pollen vs. non-pollen season). Disease-related factors (e.g. symptom severity, duration of symptoms, duration of disease) and allergy-related quality of life were evaluated as potential influences of cognitive performance. During the symptomatic allergy period, patients showed (1) poorer performance in word list-based learning (P = 0.028) and (2) a general slowing in processing speed (P < 0.001) and a shift in processing strategy (P < 0.001) in multitasking. Yet, typical parameters indicating specific multitasking costs were not affected. A significant negative association was found between learning performance and duration of disease (r = -0.451, P = 0.004), whereas symptom severity (r = 0.326; P = 0.037) and quality of life (r = 0.379; P = 0.015) were positively associated with multitasking strategy. Our findings suggest that SAR has a differentiated and complex impact on cognitive functions, which should be considered in the management of SAR symptoms. They also call attention to the importance of selecting sensitive measures and carefully interpreting cognitive outcomes. © 2017 John Wiley & Sons Ltd.

The Role of Neurogenic Inflammation in Blood-Brain Barrier Disruption and Development of Cerebral Oedema Following Acute Central Nervous System (CNS) Injury

PubMed Central

Sorby-Adams, Annabel J.; Marcoionni, Amanda M.; Dempsey, Eden R.; Woenig, Joshua A.; Turner, Renée J.

2017-01-01

Acute central nervous system (CNS) injury, encompassing traumatic brain injury (TBI) and stroke, accounts for a significant burden of morbidity and mortality worldwide, largely attributable to the development of cerebral oedema and elevated intracranial pressure (ICP). Despite this, clinical treatments are limited and new therapies are urgently required to improve patient outcomes and survival. Originally characterised in peripheral tissues, such as the skin and lungs as a neurally-elicited inflammatory process that contributes to increased microvascular permeability and tissue swelling, neurogenic inflammation has now been described in acute injury to the brain where it may play a key role in the secondary injury cascades that evolve following both TBI and stroke. In particular, release of the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) appear to be critically involved. In particular, increased SP expression is observed in perivascular tissue following acute CNS injury, with the magnitude of SP release being related to both the frequency and degree of the insult. SP release is associated with profound blood-brain barrier disruption and the subsequent development of vasogenic oedema, as well as neuronal injury and poor functional outcomes. Inhibition of SP through use of a neurokinin 1 (NK1) antagonist is highly beneficial following both TBI and ischaemic stroke in pre-clinical models. The role of CGRP is more unclear, especially with respect to TBI, with both elevations and reductions in CGRP levels reported following trauma. However, a beneficial role has been delineated in stroke, given its potent vasodilatory effects. Thus, modulating neuropeptides represents a novel therapeutic target in the treatment of cerebral oedema following acute CNS injury. PMID:28817088

Inhibition of lymphangiogenesis and lymphatic drainage via VEGFR-3 blockade increases the severity of inflammation in chronic inflammatory arthritis

PubMed Central

Guo, Ruolin; Zhou, Quan; Proulx, Steven T.; Wood, Ronald; Ji, Rui-Cheng; Ritchlin, Christopher T.; Pytowski, Bronislaw; Zhu, Zhenping; Wang, Yong-Jun; Schwarz, Edward M.; Xing, Lianping

2009-01-01

Object Investigation of the effect of lymphatic inhibition on joint and draining lymph node pathology during the course of arthritis progression in mice. Method TNF transgenic (TNF-Tg) mice were used as a model of chronic inflammatory arthritis. Mice received contrast enhanced MRI to obtain ankle and knee joint synovial volumes and draining popliteal lymph node (PLN) volumes before and 8 weeks after treatment with VEGFR-3 or VEGFR-2 neutralizing antibodies, or isotype IgG. The animals were subjected to near-infrared lymphatic imaging to determine the effect of VEGFR-3 neutralization on lymph transport from paws to draining PLNs prior to sacrifice. Lymphatic vessel formation and morphology of joints and PLNs were examined by histology, immunohistochemistry, and RT-PCR. Results Compared to IgG treatment, VEGFR-3 neutralizing antibody treatment significantly decreased the size of PLNs, the number of lymphatic vessels in joints and PLNs, the lymphatic drainage from paws to PLNs, and the number of VEGF-C expressing CD11b+ myeloid cells in PLNs. However, it increased the synovial volumes and inflammatory area in ankle and knee joints. VEGFR-2 neutralizing antibody, in contrast, inhibited both lymphangiogenesis and joint inflammation. Conclusion Lymphangiogenesis and lymphatic drainage are reciprocally related to the severity of joint lesions during the development of chronic arthritis. Lymphatic drainage plays a beneficial role in controlling the progression of chronic inflammation. PMID:19714652

miR‐34b‐5p inhibition attenuates lung inflammation and apoptosis in an LPS‐induced acute lung injury mouse model by targeting progranulin

PubMed Central

Xie, Wang; Lu, Qingchun; Wang, Kailing; Lu, Jingjing; Gu, Xia; Zhu, Dongyi; Liu, Fanglei

2018-01-01

Inflammation and apoptosis play important roles in the initiation and progression of acute lung injury (ALI). Our previous study has shown that progranulin (PGRN) exerts lung protective effects during LPS‐induced ALI. Here, we have investigated the potential roles of PGRN‐targeting microRNAs (miRNAs) in regulating inflammation and apoptosis in ALI and have highlighted the important role of PGRN. LPS‐induced lung injury and the protective roles of PGRN in ALI were first confirmed. The function of miR‐34b‐5p in ALI was determined by transfection of a miR‐34b‐5p mimic or inhibitor in intro and in vivo. The PGRN level gradually increased and subsequently significantly decreased, reaching its lowest value by 24 hr; PGRN was still elevated compared to the control. The change was accompanied by a release of inflammatory mediators and accumulation of inflammatory cells in the lungs. Using bioinformatics analysis and RT‐PCR, we demonstrated that, among 12 putative miRNAs, the kinetics of the miR‐34b‐5p levels were closely associated with PGRN expression in the lung homogenates. The gain‐ and loss‐of‐function analysis, dual‐luciferase reporter assays, and rescue experiments confirmed that PGRN was the functional target of miR‐34b‐5p. Intravenous injection of miR‐34b‐5p antagomir in vivo significantly inhibited miR‐34b‐5p up‐regulation, reduced inflammatory cytokine release, decreased alveolar epithelial cell apoptosis, attenuated lung inflammation, and improved survival by targeting PGRN during ALI. miR‐34b‐5p knockdown attenuates lung inflammation and apoptosis in an LPS‐induced ALI mouse model by targeting PGRN. This study shows that miR‐34b‐5p and PGRN may be potential targets for ALI treatments. PMID:29150939

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

FDP-E induces adipocyte inflammation and suppresses insulin-stimulated glucose disposal: effect of inflammation and obesity on fibrinogen Bβ mRNA.