Time Course Of Inflammation Research Articles

Humanization of the Reaction Specificity of Mouse Alox15b Inversely Modified the Susceptibility of Corresponding Knock-In Mice in Two Different Animal Inflammation Models.

Mammalian arachidonic acid lipoxygenases (ALOXs) have been implicated in the pathogenesis of inflammatory diseases, and its pro- and anti-inflammatory effects have been reported for different ALOX-isoforms. Human ALOX15B oxygenates arachidonic acid to its 15-hydroperoxy derivative, whereas the corresponding 8-hydroperoxide is formed by mouse Alox15b (Alox8). This functional difference impacts the biosynthetic capacity of the two enzymes for creating pro- and anti-inflammatory eicosanoids. To explore the functional consequences of the humanization of the reaction specificity of mouse Alox15b in vivo, we tested Alox15b knock-in mice that express the arachidonic acid 15-lipoxygenating Tyr603Asp and His604Val double mutant of Alox15b, instead of the arachidonic acid 8-lipoxygenating wildtype enzyme, in two different animal inflammation models. In the dextran sodium sulfate-induced colitis model, female Alox15b-KI mice lost significantly more bodyweight during the acute phase of inflammation and recovered less rapidly during the resolution phase. Although we observed significant differences in the colonic levels of selected pro- and anti-inflammatory eicosanoids during the time-course of inflammation, there were no differences between the two genotypes at any time-point of the disease. In Freund's complete adjuvant-induced paw edema model, Alox15b-KI mice were less susceptible than outbred wildtype controls, though we did not observe significant differences in pain perception (Hargreaves-test, von Frey-test) when the two genotypes were compared. our data indicate that humanization of the reaction specificity of mouse Alox15b (Alox8) sensitizes mice for dextran sodium sulfate-induced experimental colitis, but partly protects the animals in the complete Freund's adjuvant-induced paw edema model.

Is pulmonary inflammation a valid predictor of particle induced lung pathology? The case of amorphous and crystalline silicas

Although inflammation is a normal and beneficial response, it is also a key event in the pathology of many chronic diseases, including pulmonary and systemic particle-induced disease. In addition, inflammation is now considered as the key response in standard settings for inhaled particles and a critical endpoint in OECD-based sub-acute/ chronic animal inhalation testing protocols. In this paper, we discuss that whilst the role of inflammation in lung disease is undeniable, it is when inflammation deviates from normal parameters that adversity occurs. We introduce the importance of the time course and in particular, the reversibility of inflammation in the progression towards tissue remodelling and neoplastic changes as commonly seen in rat inhalation studies. For this purpose, we used sub-chronic/ chronic studies studies with synthetic amorphous silicas (SAS) and reactive crystalline silica (RCS) as a source of data to describe the time-course of inflammation towards and beyond adversity. Whilst amorphous silicas induce an acute but reversible inflammatory response, only RCS induces a persistent, progressive response after cessation of exposure, resulting in fibrosis and carcinogenicity in rodents and humans. This suggests that the use of inflammation as a fixed endpoint at the cessation of exposure may not be a reliable predictor of particle-induced lung pathology. We therefore suggest extending the current OECD testing guidelines with a recovery period, that allows inflammation to resolve or progress into altered structure and function, such as fibrosis.

Follow the time course of inflammation caused by intraperitoneal administration of multi-wall carbon nanotubes in mice.

Understand the progress of inflammation over time caused by multi-walled carbon nanotubes (MWCNT). Two types of MWCNTs were administered to C57BL/6N mice via intraperitoneal administration at low and high doses (0.05 and 1.0mg/mouse, respectively). Inflammation was evaluated until 6months after administration based on cytokine levels and pathological observations. The abdominal cavity lavage fluid was collected and analyzed 1 week, 1, 3, and 6month(s) after administration. IL-6 expression markedly increased 3 months after the administration of high-dose MWCNT-7. Notable inflammation was observed in the groups administered with one of the MWCNT, MWCNT-7. On the other hand, inflammation in another MWCNT-treated group was milder than that in the MWCNT-7-treated group. MWCNT-7 induced pronounced inflammation but did not induce tumor formation during the experimental period. Inflammation reaction is one of the most important biological responses to MWCNT. Three months post-exposure becomes a turning point for the harmful effects of the intraperitoneally administered MWCNT-7.

INFLAMMATION-RELATED MORPHOLOGICAL ALTERATIONS IN THE MICROVASCULATURE

Microvasculature is a complex structural and functional system that regulates blood supply of body organs, provides transcapillary exchange of fluid and supports the tissue homeostasis. The human microvasculature is represented by the system of small vessels: arterioles, capillaries, venules and arteriolovenular anastomoses. The vessels of this complex become flexible in the altered blood flow; they can deposit the blood corpuscles, get affected by spasms and pass plasma only, change their permeability for tissue fluid. Microvasculature is extremely sensitive to the insults of various factors. Microvascular dysfunction coexists or precedes the macrovascular diseases probably due to joint mechanisms of damage to vessels such as oxidative stress and inflammation. Disorders of microcirculation are one of the main components of inflammation. This article is aimed at the analysis of the scientific publications on the study of morphological alterations in the microvasculature in response to inflammation. The bibliosemantic method was used. The findings of current publications on the morphological alterations that occur in the microcirculation in response to inflammation have been investigated. The analysis has shown significant morphological alterations in the microvessels in response to the proinflammatory factors. Inflammatory processes are accompanied by the events of microvascular dysfunction, associated with hyperpermeability of capillaries, destruction of microvascular endothelial barrier, loss of antiadhesive function of endothelium, etc. In response to inflammation, the marked morphofunctional alterations in the microvasculature of the various organs are observed that are dependent on the time course of inflammation. Early onset is manifested mainly by the spasm of the vascular resistance and dilatation of the capacitance vessels. Disorders of blood rheological properties are manifested by stasis, sludge, microthrombosis.

Time Course of Inflammation in Dorsal Root Ganglia Correlates with Differential Reversibility of Mechanical Allodynia

Some individuals recover from the pain of nerve trauma within 12 months or less whereas others experience life-long intractable pain. This transition between reversible pain and the establishment of chronic neuropathic pain is poorly understood. We examined the role of persistent inflammation in the dorsal root ganglia (DRG) in the long-term maintenance of mechanical allodynia; an index of neuropathic pain. Male Sprague-Dawley rats underwent chronic constriction injury (CCI), spared nerve injury (SNI) or sham surgery. Both CCI and SNI animals displayed robust mechanical allodynia in the ipsilateral paw at 7 d post-surgery; however, only SNI animals maintained mechanical allodynia at 42 d post-surgery. DRGs were extracted at 7 d or 42 d post-surgery to assess inflammation via rt-qPCR or immunohistochemistry to measure colony stimulating factor 1 (CSF1) expression, satellite glial cell (SGC) activation, presence of Iba1 positive macrophages and interleukin1 β (IL-1β) mRNA levels. Whereas DRGs from SNI animals continued to display inflammatory markers at 42 d, those from CCI animals did not. Moreover, the level of allodynia displayed by each individual animal correlated with the extent of DRG inflammation. These data support the hypothesis that the amount of CSF1 immunoreactivity and the persistence of inflammation in ipsilateral DRGs contribute to the difference between transient and persistent mechanical allodynia observed in the CCI and SNI models. We also suggest that feedback loops involving cytokines and neurotransmitters may contribute to increased DRG activity in chronic neuropathic pain. Consequently, targeting persistent CSF1 production and peripheral neuroinflammation may be an effective approach to the management of chronic neuropathic pain.

Label-free Imaging of Tissue Architecture during Axolotl Peripheral Nerve Regeneration in Comparison to Functional Recovery

Human peripheral nerves hold the potential to regenerate after injuries; however, whether a successful axonal regrowth was achieved can be elucidated only months after injury by assessing function. The axolotl salamander is a regenerative model where nerves always regenerate quickly and fully after all types of injury. Here, de- and regeneration of the axolotl sciatic nerve were investigated in a single and double injury model by label-free multiphoton imaging in comparison to functional recovery. We used coherent anti-Stokes Raman scattering to visualize myelin fragmentation and axonal regeneration. The presence of axons at the lesion site corresponded to onset of functional recovery in both lesion models. In addition, we detected axonal regrowth later in the double injury model in agreement with a higher severity of injury. Moreover, endogenous two-photon excited fluorescence visualized macrophages and revealed a similar timecourse of inflammation in both injury models, which did not correlate with functional recovery. Finally, using the same techniques, axonal structure and status of myelin were visualized in vivo after sciatic nerve injury. Label-free imaging is a new experimental approach that provides mechanistic insights in animal models, with the potential to be used in the future for investigation of regeneration after nerve injuries in humans.

Highly Dynamic Transcriptional Signature of Distinct Macrophage Subsets during Sterile Inflammation, Resolution, and Tissue Repair.

Macrophage gene expression determines phagocyte responses and effector functions. Macrophage plasticity has been mainly addressed in in vitro models that do not account for the environmental complexity observed in vivo. In this study, we show that microarray gene expression profiling revealed a highly dynamic landscape of transcriptomic changes of Ly6C(pos)CX3CR1(lo) and Ly6C(neg)CX3CR1(hi) macrophage populations during skeletal muscle regeneration after a sterile damage. Systematic gene expression analysis revealed that the time elapsed, much more than Ly6C status, was correlated with the largest differential gene expression, indicating that the time course of inflammation was the predominant driving force of macrophage gene expression. Moreover, Ly6C(pos)/Ly6C(neg) subsets could not have been aligned to canonical M1/M2 profiles. Instead, a combination of analyses suggested the existence of four main features of muscle-derived macrophages specifying important steps of regeneration: 1) infiltrating Ly6C(pos) macrophages expressed acute-phase proteins and exhibited an inflammatory profile independent of IFN-γ, making them damage-associated macrophages; 2) metabolic changes of macrophages, characterized by a decreased glycolysis and an increased tricarboxylic acid cycle/oxidative pathway, preceded the switch to and sustained their anti-inflammatory profile; 3) Ly6C(neg) macrophages, originating from skewed Ly6C(pos) cells, actively proliferated; and 4) later on, restorative Ly6C(neg) macrophages were characterized by a novel profile, indicative of secretion of molecules involved in intercellular communications, notably matrix-related molecules. These results show the highly dynamic nature of the macrophage response at the molecular level after an acute tissue injury and subsequent repair, and associate a specific signature of macrophages to predictive specialized functions of macrophages at each step of tissue injury/repair.

Identification of polarized macrophage subsets in zebrafish

While the mammalian macrophage phenotypes have been intensively studied in vitro, the dynamic of their phenotypic polarization has never been investigated in live vertebrates. We used the zebrafish as a live model to identify and trail macrophage subtypes. We generated a transgenic line whose macrophages expressing tumour necrosis factor alpha (tnfa), a key feature of classically activated (M1) macrophages, express fluorescent proteins Tg(mpeg1:mCherryF/tnfa:eGFP-F). Using 4D-confocal microscopy, we showed that both aseptic wounding and Escherichia coli inoculation triggered macrophage recruitment, some of which started to express tnfa. RT-qPCR on Fluorescence Activated Cell Sorting (FACS)-sorted tnfa(+) and tnfa(-) macrophages showed that they, respectively, expressed M1 and alternatively activated (M2) mammalian markers. Fate tracing of tnfa(+) macrophages during the time-course of inflammation demonstrated that pro-inflammatory macrophages converted into M2-like phenotype during the resolution step. Our results reveal the diversity and plasticity of zebrafish macrophage subsets and underline the similarities with mammalian macrophages proposing a new system to study macrophage functional dynamic.

In vivo fluorescence reflectance imaging of protease activity in a mouse model of post-traumatic osteoarthritis

Joint injuries initiate a surge of inflammatory cytokines and proteases that contribute to cartilage and subchondral bone degeneration. Detecting these early processes in animal models of post-traumatic osteoarthritis (PTOA) typically involves ex vivo analysis of blood serum or synovial fluid biomarkers, or histological analysis of the joint. In this study, we used in vivo fluorescence reflectance imaging (FRI) to quantify protease, matrix metalloproteinase (MMP), and Cathepsin K activity in mice following anterior cruciate ligament (ACL) rupture. We hypothesized that these processes would be elevated at early time points following joint injury, but would return to control levels at later time points. Mice were injured via tibial compression overload, and FRI was performed at time points from 1 to 56 days after injury using commercially available activatable fluorescent tracers to quantify protease, MMP, and cathepsin K activity in injured vs uninjured knees. PTOA was assessed at 56 days post-injury using micro-computed tomography and whole-joint histology. Protease activity, MMP activity, and cathepsin K activity were all significantly increased in injured knees relative to uninjured knees at all time points, peaking at 1-7 days post-injury, then decreasing at later time points while still remaining elevated relative to controls. This study establishes FRI as a reliable method for in vivo quantification of early biological processes in a translatable mouse model of PTOA, and provides crucial information about the time course of inflammation and biological activity following joint injury. These data may inform future studies aimed at targeting these early processes to inhibit PTOA development.

Preferential Macrophage Recruitment and Polarization in LPS-Induced Animal Model for COPD: Noninvasive Tracking Using MRI

Noninvasive imaging of macrophages activity has raised increasing interest for diagnosis of chronic obstructive respiratory diseases (COPD), which make them attractive vehicles to deliver contrast agents for diagnostic or drugs for therapeutic purposes. This study was designed to monitor and evaluate the migration of differently polarized M1 and M2 iron labeled macrophage subsets to the lung of a LPS-induced COPD animal model and to assess their polarization state once they have reached the inflammatory sites in the lung after intravenous injection. Ex vivo polarized bone marrow derived M1 or M2 macrophages were first efficiently and safely labeled with amine-modified PEGylated dextran-coated SPIO nanoparticles and without altering their polarization profile. Their biodistribution in abdominal organs and their homing to the site of inflammation in the lung was tracked for the first time using a free-breathing non-invasive MR imaging protocol on a 4.7T magnet after their intravenous administration. This imaging protocol was optimized to allow both detection of iron labeled macrophages and visualization of inflammation in the lung. M1 and M2 macrophages were successfully detected in the lung starting from 2 hours post injection with no variation in their migration profile. Quantification of cytokines release, analysis of surface membrane expression using flow cytometry and immunohistochemistry investigations confirmed the successful recruitment of injected iron labeled macrophages in the lung of COPD mice and revealed that even with a continuum switch in the polarization profile of M1 and M2 macrophages during the time course of inflammation a balanced number of macrophage subsets predominate.

Pain and inflammatory response following off-pump coronary artery bypass grafting

Inflammation and pain are two common clinical issues following cardiac surgery, which are important to patient outcomes. This article reviews the literature regarding inflammation and pain following cardiac surgery with special emphasis on off-pump cardiac surgery. Off-pump surgery is associated with decreased intraoperative inflammatory response compared with procedures using cardiopulmonary bypass; however, the postoperative pattern of inflammatory response is similar to on-pump procedures. Multimodal analgesic regimens and protocol-based approaches to pain management improve analgesia compared to conventional approaches. Off-pump cardiac surgeries although known to decrease the inflammatory burden do not appear to impact the overall patient outcomes. Recent evidence indicates the prothrombotic tendency following off-pump procedures, which could be related to the time course of inflammation following off-pump cardiac surgery. There might be some benefit of off-pump procedures regarding neurological and renal function that needs further studies. Pain management following off-pump procedures is similar to that of patients undergoing on-pump cardiac surgery. Better caregiver and patient education is crucial for improving pain control following cardiac surgery. Analgesic regimens need to consider adjuvants and regional analgesic techniques and patient-controlled modalities while providing care.

Contusion Injury with Chronic In vivo Polyphenol Supplementation

In vivo, daily proanthocyanidolic oligomer (PCO) supplementation before and after experimental skeletal muscle contusion injury has been shown to result in a blunted neutrophil response in tissue, quicker macrophage infiltration into muscle, and faster recovery due to a left shift in time course of inflammation. The current study investigated effects of PCO on circulatory neutrophils and macrophage subpopulations as well as in vitro neutrophil migration. Primary cultured neutrophils obtained from control animals were incubated in media with 20% conditioned plasma. To obtain conditioned media, male Wistar rats were supplemented with PCO (20 mg·kg(-1)d(-1)) or placebo (PLA) for 2 wk before a mass-drop contusion injury. Conditioned plasma was prepared from blood collected at different time points after injury (12 h, 1 d, 3 d, and 5 d). Macrophage subpopulation distribution, inflammatory cytokine, and myeloperoxidase levels were assessed for all time points. On day 1 postinjury, circulating neutrophil numbers were significantly lower in PLA than PCO, suggesting that extravasation from the blood was reduced by PCO. Concurrently, neutrophil migration in vitro was blunted in the presence of conditioned plasma from PCO supplemented rats compared with PLA supplemented rats. Plasma M1 and M2c macrophage numbers differed over time and between groups. M1 macrophage numbers peaked on day 3 with PCO supplementation, followed by a rise in M2c macrophages on day 5, when M1 macrophages numbers were still high in PLA. We conclude that PCO supplementation limits neutrophil migration capacity in vitro despite a chemotactic gradient. Furthermore, the earlier appearance of type M2 macrophages suggests a switch to an anti-inflammatory phenotype after injury even in circulation.

Time Course of Inflammation, Myocardial Injury, and Prothrombotic Response After Radiofrequency Catheter Ablation for Atrial Fibrillation

Inflammation has been linked to the genesis of stroke in atrial fibrillation (AF) and is implicated in early recurrent arrhythmia after AF ablation. We aimed to define the time course of inflammation, myocardial injury, and prothrombotic markers after radiofrequency ablation for AF and its relation to AF recurrence. Ninety consecutive AF patients (53% paroxysmal) undergoing radiofrequency ablation were recruited. High-sensitivity C-reactive protein (hs-CRP), Troponin-T, creatine kinase-MB, fibrinogen, and D-Dimer concentrations were measured at baseline, at 1, 2, 3, 7 days, and at 1 month after ablation. AF recurrence was documented at 3 days and at 1, 3, and 6 months follow-up. Troponin-T and creatine kinase-MB peaked at day 1 after procedure (both P<0.05). Hs-CRP peaked at day 3 after procedure (P<0.05). Fibrinogen (P<0.05) and D-Dimer (P<0.05) concentrations were significantly elevated at 1 week after procedure. Ln hs-CRP elevation correlated with Ln Troponin-T and fibrinogen elevation. The extent of Ln hs-CRP, Ln Troponin-T, and fibrinogen elevation predicted early AF recurrence within 3 days after procedure (P<0.05, respectively), but not at 3 and 6 months. Patients undergoing radiofrequency ablation for AF exhibit an inflammatory response within 3 days. The extent of inflammatory response predicts early AF recurrence but not late recurrence. Prothrombotic markers are elevated at 1 week after ablation and may contribute to increased risk of early thrombotic events after AF ablation.

Time course of inflammation, oxidative stress and tissue damage induced by hyperoxia in mouse lungs

In this study our aim was to investigate the time courses of inflammation, oxidative stress and tissue damage after hyperoxia in the mouse lung. Groups of BALB/c mice were exposed to 100% oxygen in a chamber for 12, 24 or 48 h. The controls were subjected to normoxia. The results showed that IL-6 increased progressively after 12 (P < 0.001) and 24 h (P < 0.001) of hyperoxia with a reduction at 48 h (P < 0.01), whereas TNF-α increased after 24 (P < 0.001) and 48 h (P < 0.001). The number of macrophages increased after 24 h (P < 0.001), whereas the number of neutrophils increased after 24 h (P < 0.01) and 48 h (P < 0.001). Superoxide dismutase activity decreased in all groups exposed to hyperoxia (P < 0.01). Catalase activity increased only at 48 h (P < 0.001). The reduced glutathione/oxidized glutathione ratio decreased after 12 h (P < 0.01) and 24 h (P < 0.05). Histological evidence of lung injury was observed at 24 and 48 h. This study shows that hyperoxia initially causes an inflammatory response at 12 h, resulting in inflammation associated with the oxidative response at 24 h and culminating in histological damage at 48 h. Knowledge of the time course of inflammation and oxidative stress prior to histological evidence of acute lung injury can improve the safety of oxygen therapy in patients.

An Investigation of Enzymatic Detergents as a Potential Cause of Toxic Anterior Segment Syndrome

To investigate whether enzymatic detergents used in cleaning ophthalmic surgical instruments can cause toxic anterior segment syndrome (TASS)-like responses in a rabbit model. Randomized, investigator-masked, controlled experimental animal study. Thirty-five New Zealand white rabbits. The rabbit eyes were randomized into 7 treatment groups to receive intracameral injection of 1 of 3 different doses of Medline Dual Detergent or Enzol Detergent, or sterile limulus amoebocyte lysate reagent water as a control. The eyes were evaluated for anterior segment inflammation at baseline and at 1, 3, 6, 24, 48, and 72 hours after treatment by slit-lamp biomicroscopy. Anterior chamber (AC) inflammation, including cells, flare, fibrin, and iris injection; time course of inflammation; and residual detergent levels in luminated instruments. Moderate to marked injection of the iris vessels was seen as early as 1 hour after treatment with the enzymatic detergents in 41 of 60 eyes, with the response being more severe in the Enzol Detergent-exposed eyes. Severe iris hemorrhages were accompanied by blood in the AC in 13 eyes, which usually persisted through 72 hours, with an associated increase in AC cell and flare. Corneal haze was present in 52 of 56 eyes 1 hour after treatment, but was mild and resolved within 24 hours in all but the Enzol 4.5%-exposed eyes. Median AC cell and flare peaked at 6 hours and resolved by 48 hours. Enzymatic detergents caused a severe but unusual response from the iris when injected intracamerally into rabbit eyes. This response has not been reported in humans with TASS. The time course of inflammation was faster (peak at 6 hours) and resolved more quickly (within 48 hours) than TASS. Simulated cleaning and extraction studies indicate that the level of residual detergent to which a patient could be exposed is significantly less than the lowest dose used in this study. Because that low dose caused no significant observations other than injection of the iris vessels, these results do not support residual enzymatic detergents on surgical instruments as a cause for TASS.

Differential Inflammatory Response to Inhaled Lipopolysaccharide Targeted Either to the Airways or the Alveoli in Man

Endotoxin (Lipopolysaccharide, LPS) is a potent inducer of inflammation and there is various LPS contamination in the environment, being a trigger of lung diseases and exacerbation. The objective of this study was to assess the time course of inflammation and the sensitivities of the airways and alveoli to targeted LPS inhalation in order to understand the role of LPS challenge in airway disease.In healthy volunteers without any bronchial hyperresponsiveness we targeted sequentially 1, 5 and 20 µg LPS to the airways and 5 µg LPS to the alveoli using controlled aerosol bolus inhalation. Inflammatory parameters were assessed during a 72 h time period. LPS deposited in the airways induced dose dependent systemic responses with increases of blood neutrophils (peaking at 6 h), Interleukin-6 (peaking at 6 h), body temperature (peaking at 12 h), and CRP (peaking at 24 h). 5 µg LPS targeted to the alveoli caused significantly stronger effects compared to 5 µg airway LPS deposition. Local responses were studied by measuring lung function (FEV1) and reactive oxygen production, assessed by hydrogen peroxide (H2O2) in fractionated exhaled breath condensate (EBC). FEV1 showed a dose dependent decline, with lowest values at 12 h post LPS challenge. There was a significant 2-fold H2O2 induction in airway-EBC at 2 h post LPS inhalation. Alveolar LPS targeting resulted in the induction of very low levels of EBC-H2O2.Targeting LPS to the alveoli leads to stronger systemic responses compared to airway LPS targeting. Targeted LPS inhalation may provide a novel model of airway inflammation for studying the role of LPS contamination of air pollution in lung diseases, exacerbation and anti-inflammatory drugs.

Dietary Cod Protein Improves Skeletal Muscle Regeneration Partly Through Its High Levels of Arginine, Lysine, Glycine and Taurine

Feeding cod protein may beneficially influence the time course of inflammation during recovery following skeletal muscle injury. The objective of this study was to identify amino acids in cod protein having a beneficial impact on muscle repair. Male Wistar rats were fed isoenergetic diets containing either casein (C), cod protein (CP), or casein supplemented with arginine (1.9%), glycine (1.9%), taurine (0.7%) and lysine (1.7%) (C+). After 21 d of ad libitum feeding, one tibialis anterior muscle (TA) was injured by injecting 200μl of bupivacaine while the contra‐lateral TA was injected with saline and served as sham. Rats fed CP exhibited higher muscle weight at days 5, 14, and 28 post‐injury and higher myofiber cross‐sectional area at days 5 and 28 post‐injury compared with C. CP and C+ similarly modulated the inflammation as they decreased ED1+ macrophages and COX‐2 level at day 2 post injury compared with casein (p=0.01), and increased ED2+ macrophages compared with C. The C+ diet upregulated (p=0.02) whereas the CP diet tended to upregulate myogenin expression at day 5 post‐injury compared with C (p=0.06). These data support the hypothesis that the beneficial impact of cod protein on skeletal muscle recovery is partly attributed to the anti‐inflammatory and myogenic action of its high arginine, lysine, glycine and taurine levels.Supported by The Natural Sciences and Engineering Research Council of Canada.

Impaired resolution of inflammatory response in the lungs of JF1/Msf mice following carbon nanoparticle instillation

BackgroundDeclined lung function is a risk factor for particulate matter associated respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD). Carbon nanoparticles (CNP) are a prominent component of outdoor air pollution that causes pulmonary toxicity mainly through inflammation. Recently we demonstrated that mice (C3H/HeJ) with higher than normal pulmonary function resolved the elicited pulmonary inflammation following CNP exposure through activation of defense and homeostasis maintenance pathways. To test whether CNP-induced inflammation is affected by declined lung function, we exposed JF1/Msf (JF1) mice with lower than normal pulmonary function to CNP and studied the pulmonary inflammation and its resolution.Methods5 μg, 20 μg and 50 μg CNP (Printex 90) were intratracheally instilled in JF1 mice to determine the dose response and the time course of inflammation over 7 days (20 μg dosage). Inflammation was assessed using histology, bronchoalveolar lavage (BAL) analysis and by a panel of 62 protein markers.Results24 h after instillation, 20 μg and 50 μg CNP caused a 25 fold and 19 fold increased polymorphonuclear leucocytes (PMN) respectively while the 5 μg represented the 'no observable adverse effect level' as reflected by PMN influx (9.7 × 10E3 vs 8.9 × 10E3), and BAL/lung concentrations of pro-inflammatory cytokines. Time course assessment of the inflammatory response revealed that compared to day1 the elevated BAL PMN counts (246.4 × 10E3) were significantly decreased at day 3 (72.9 × 10E3) and day 7 (48.5 × 10E3) but did not reach baseline levels indicating slow PMN resolution kinetics. Strikingly on day 7 the number of macrophages doubled (455.0 × 10E3 vs 204.7 × 10E3) and lymphocytes were 7-fold induced (80.6 × 10E3 vs 11.2 × 10E3) compared to day1. At day 7 elevated levels of IL1B, TNF, IL4, MDC/CCL22, FVII, and vWF were detected in JF1 lungs which can be associated to macrophage and lymphocyte activation.ConclusionThis explorative study indicates that JF1 mice with impaired pulmonary function also exhibits delayed resolution of particle mediated lung inflammation as evident from elevated PMN and accumulation of macrophages and lymphocytes on day7. It is plausible that elevated levels of IL1B, IL4, TNF, CCL22/MDC, FVII and vWF counteract defense and homeostatic pathways thereby driving this phenomenon.

Minocycline Attenuates Photoreceptor Degeneration in a Mouse Model of Subretinal Hemorrhage: Microglial Inhibition as a Potential Therapeutic Strategy

Minocycline Attenuates Photoreceptor Degeneration in a Mouse Model of Subretinal Hemorrhage: Microglial Inhibition as a Potential Therapeutic Strategy

Effect of Subcutaneous Glucose Sensor Implantation on Skin mRNA Expression in Pigs

Tight glycemic control has the potential to reduce long- and short-term effects of diabetes mellitus. New and improved glucose sensors for short-term implantation in the subcutis offer an alternative to the classical self-monitored blood glucose concentration in the management of diabetes. The use of glucose sensors has an advantage over the latter due to its capacity to obtain continuous glucose measurements. However, instability of in vivo glucose sensor measurements has been reported, and this bioinstability is likely to be influenced by the inflammatory reaction to the implanted sensor. Gene expression analysis is now performed in an existing porcine model of subcutaneous glucose sensor implantation to investigate the time course of inflammation from a new perspective. Tissue surrounding glucose sensors was sampled to different time points (2 h, 24 h, 3 days, and 7 days) after implantation in the subcutis of pigs. From the tissue RNA was extracted, cDNA was synthesized, and real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed for the quantification of immunoregulatory genes. Genes coding for adhesion molecules, chemokines, cytokines, CD markers, and antigen presentation molecules were differentially expressed over time. Most of the investigated genes were significantly up-regulated 24 h and 7 days after implantation. The present study demonstrated that the technology for targeted multiple-gene expression by real-time RT-PCR is useful in the evaluation of the immune response to subcutaneously implanted glucose sensors and that the expression levels also seemed to correspond to the histomorphological observations over time.