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PubMed1998

Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators.

BACKGROUND: We studied whether inflammation after myocardial infarction (MI) is a risk factor for recurrent coronary events and whether randomized treatment with pravastatin reduces that risk. METHODS AND RESULTS: A nested case-control design was used to compare C-reactive protein (CRP) and serum amyloid A (SAA) levels in prerandomization blood samples from 391 participants in the Cholesterol and Recurrent Events (CARE) trial who subsequently developed recurrent nonfatal MI or a fatal coronary event (cases) and from an equal number of age- and sex-matched participants who remained free of these events during follow-up (control subjects). Overall, CRP and SAA were higher among cases than control subjects (for CRP P=0.05; for SAA P=0.006) such that those with levels in the highest quintile had a relative risk (RR) of recurrent events 75% higher than those with levels in the lowest quintile (for CRP RR= 1.77, P=0.02; for SAA RR= 1.74, P=0.02). The study group with the highest risk was that with consistent evidence of inflammation (elevation of both CRP and SAA) who were randomly assigned to placebo (RR=2.81, P=0.007); this risk estimate was greater than the product of the individual risks associated with inflammation or placebo assignment alone. In stratified analyses, the association between inflammation and risk was significant among those randomized to placebo (RR=2.11, P=0.048) but was attenuated and nonsignificant among those randomized to pravastatin (RR=1.29, P=0.5). CONCLUSIONS: Evidence of inflammation after MI is associated with increased risk of recurrent coronary events. Therapy with pravastatin may decrease this risk, an observation consistent with a nonlipid effect of this agent.

Aged↗
PubMed2004

Essential role of vascular endothelial growth factor in angiotensin II-induced vascular inflammation and remodeling.

Angiotensin II (Ang II) upregulates vascular endothelial growth factor (VEGF) and activates vascular inflammation. However, the decisive role of VEGF in Ang II-induced vascular inflammation and remodeling has not been addressed. Ang II infusion to wild-type mice increased local expression of VEGF and its receptors in cells of aortic wall and plasma VEGF, and caused aortic inflammation (monocyte infiltration) and remodeling (wall thickening and fibrosis). Hypoxia-inducible factor-1alpha colocalized with VEGF-positive cell types. Blockade of VEGF by the soluble VEGF receptor 1 (sFlt-1) gene transfer attenuated the Ang II-induced inflammation and remodeling. The sFlt-1 gene transfer also inhibited the increased expression of VEGF and inflammatory factors such as monocyte chemoattractant protein-1. In contrast, sFlt-1 gene transfer did not affect Ang II-induced arterial hypertension and cardiac hypertrophy. VEGF is an essential mediator in Ang II-induced vascular inflammation and structural changes through its proinflammatory actions.

Angiotensin II↗
PubMed1999

Chronic obstructive pulmonary disease. Inflammation of small airways and lung parenchyma.

Currently available information suggests that cigarette smoke-induced lung inflammation has a pathogenic role in the development of COPD. Neutrophils, eosinophils, alveolar macrophages, and lymphocytes all appear to participate in the inflammatory process. However, the respective importance of these cells and their level of activation are difficult to quantitate because disease phenotyping, and compartmentalization of inflammation and markers of inflammation in the lung, influence the obtained data and bias their interpretation. Bronchoscopic biopsies are typically obtained from larger, cartilaginous airways containing submucosal glands whereas the site of airflow obstruction in COPD is predominantly the membranous bronchiole, devoid of cartilage and submucosal glands. This makes it difficult to establish structure-function relationships. The proportion of neutrophils has been reported to increase in repeated induced sputum and bronchoalveolar lavage samples. This observation suggests neutrophil recruitment into the airway is induced by the tests or sampling of different airway compartments in subsequent tests. There appears to be a good correlation between the proportions of eosinophils in induced sputum and bronchoalveolar lavage fluid on the one hand and in airway tissue on the other. However, this is not the case for other inflammatory cells, especially T lymphocytes, which are more numerous in airway tissue. Despite these inconsistencies, induced sputum, bronchoalveolar lavage, and bronchial biopsies can be used as markers of inflammation in COPD as long as their limitations are recognized. Cosio MG, Guerassimov A. Chronic obstructive pulmonary disease: inflammation of small airways and lung parenchyma.

Animals↗
PubMed2000

Exercise-induced bronchoconstriction does not cause eosinophilic airway inflammation or airway hyperresponsiveness in subjects with asthma.

The cysteinyl leukotrienes (LT) C(4), D(4), and E(4) may partially mediate eosinophilic airway inflammation in patients with asthma. High- intensity exercise by patients with asthma can result in exercise- induced bronchoconstriction, partly due to leukotriene production, but it is still debated whether this causes airway inflammation. Ten subjects completed a randomized, controlled study to examine the effects of exercise-induced bronchoconstriction on airway inflammatory cells. Subjects completed exercise challenge and methacholine challenge in random order separated by 1 wk. Spirometry was measured for 2 h after challenges, and airway responsiveness was measured the day before and 24 h after each challenge. Blood and sputum samples were obtained before, and 2, 4, 7, and 24 h after each challenge for measurement of inflammatory cells. Nine of the subjects inhaled allergen at least 3 wk before or 1 wk after the study. Sputum samples were collected before, 7 h, and 24 h after challenge. The maximum percentage fall in FEV(1) was 21.3 +/- 1.5% after exercise, 29.9 +/- 1.5% after methacholine, and 28.9+/-2.7% after allergen. Exercise had no effect on airway responsiveness or inflammatory cells measured in blood or sputum, unlike allergen inhalation, which resulted in significant airway hyperresponsiveness and increases in sputum eosinophils (p < 0.05). This study demonstrates that exercise-induced bronchoconstriction does not cause eosinophilic airway inflammation in subjects with asthma who develop airway inflammation with the same degree of allergen-induced bronchoconstriction. We conclude that exercise-induced bronchoconstriction does not cause airway inflammation or airway hyperresponsiveness.

Adolescent↗
PubMed1993

Increased airway inflammation with segmental versus aerosol antigen challenge.

Airway inflammation is increasingly recognized as a pivotal component of asthma. Because allergens provoke bronchial constriction and inflammation in allergic subjects, bronchial antigen challenge has emerged as a powerful technique for evaluating mechanisms involved in this process. In this study, we compare whole lung antigen challenge (WLAC) with segmental bronchoprovocation (SBP) in eight allergic, non-asthmatic, non-smoking subjects, and evaluated the response by bronchoalveolar lavage (BAL) prior to, and 48 h after antigen challenge. Both challenge techniques evoked airway inflammation, manifest as an increase in total cells and eosinophils recovered by BAL, an increase in total protein concentration, and enhanced production of superoxide anion by airspace cells. The degree to which these changes occurred was significantly greater with SBP than WLAC, and only SBP evoked persistent measurable change in alveolar macrophage density and eosinophil granule protein concentrations. Moreover, although both techniques were associated with a comparable immediate fall in FEV1, only WLAC resulted in statistically significant persistent physiologic changes 48 h afterwards. We conclude that, as anticipated, SBP produces more intense airway inflammation in allergic subjects, does not result in late airway obstruction, and offers specific advantages in studying allergen-driven airway inflammation.

Adult↗
PubMed1987

Induction of pulmonary inflammation by components of the pneumococcal cell surface.

Using a rabbit model of experimental pneumonitis, the components on the surface of the pneumococcus that incite pulmonary inflammation were identified. Rabbits were challenged intratracheally with live pneumococci, capsular polysaccharide, purified cell walls, or cell wall subcomponents. Leukocytosis and elevation of protein concentration was quantitated in bronchial lavage fluid during the first 24 h after challenge. Of the pneumococcal surface components tested, cell wall preparations had the highest specific activity in inducing inflammation; abnormalities in bronchial lavage fluid cytochemistry appeared rapidly and in a dose-dependent manner. Cell wall building blocks and the products of penicillin-induced hydrolysis of the cell wall were also highly inflammatory, indicating that inflammation can be generated by disruption of the cell wall during lysis of bacteria by beta-lactam antibiotics. Administration of inhibitors of arachidonic acid metabolism suggested that inhibition of the lipoxygenase pathway reduced inflammation associated with cell walls. We propose that pulmonary inflammation during pneumococcal pneumonia arises in large part from the interaction of the bacterial cell wall with complement and noncomplement-mediated host defenses.

Animals↗
PubMed2004

Treatment of nasal inflammation decreases the ability of subjects with asthma to condition inspired air.

We previously showed that individuals with seasonal allergy have a reduced ability to condition air, which was improved by nasal inflammation. We also showed that subjects with asthma have a reduced ability to condition air. Because individuals with asthma usually have inflammation in the nose, we hypothesized that treatment with an intranasal steroid would reduce nasal inflammation and further decrease nasal conditioning capacity. We performed a randomized, double blind, placebo-controlled, 2-way crossover study on 20 subjects with asthma comparing the effect of treatment with intranasal budesonide for 2 weeks on nasal conditioning. Treatment with budesonide caused no significant effect on nasal conditioning as compared with placebo. When we evaluated the subgroup of nonsmoking subjects, budesonide caused a significant reduction in nasal conditioning. We speculate that nasal inflammation in nonsmoking individuals with asthma increases the conditioning capacity and reducing it with an intranasal steroid worsens the ability of the nose to condition air. In addition, smoking causes an increase in nasal conditioning capacity by non-steroid-dependent factors. These observations help us understand the pathophysiology of nasal conditioning, but do not negate the positive clinical benefits of budesonide on treating nasal inflammation.

Administration, Intranasal↗
PubMed2004

Randomized trials describing lung inflammation after pleurodesis with talc of varying particle size.

We report two trials describing whether talc pleurodesis with a mean particle size of less than 15 microm ("mixed" talc) produces more lung and systemic inflammation than tetracycline or "graded" talc (most particles < 10 microm were removed). First, 20 patients with malignant effusions received tetracycline or mixed talc. Changes in lung and systemic inflammation from lung clearance scans, oxygen saturations, and C-reactive protein from baseline to 48 hours after pleurodesis were recorded. Lung inflammation (change in isotope clearance, talc -9.26, SD 14.3 vs. tetracycline 4.10, SD 13.8 minutes; difference = -13.4; 95% confidence interval [CI], -26.6 to -0.2; p = 0.05) and systemic inflammation (change in C-reactive protein, talc 198 SD 79.2 vs. tetracycline 74 SD 79.4 microg/L; difference = 124; 95% CI, 50 to 199; p = 0.004) were greater after talc. Second, 48 patients received mixed or graded talc, and gas exchange was assessed from changes in the alveolar-arterial oxygen gradient. Mixed talc worsened gas exchange (oxygen gradient change, mixed 2.17 SD 1.74 kPa, 16.3 13.1 mm Hg vs. graded 0.72 SD 2.46 kPa 5.4 18.5 mm Hg, difference = 1.45; 95% CI, 0.2 to 2.7; p = 0.03) and induced more systemic inflammation than graded talc. We conclude that the routine use of graded talc for pleurodesis would reduce the morbidity of this procedure.

Blood Gas Analysis↗
PubMed2006

CXCR2 ligands and G-CSF mediate PKCalpha-induced intraepidermal inflammation.

Transgenic mice overexpressing PKCalpha in the epidermis (K5-PKCalpha mice) exhibit an inducible severe intraepidermal neutrophilic inflammation and systemic neutrophilia when PKCalpha is activated by topical 12-O-tetradecanoylphorbol-13-acetate (TPA). This inducible model of cutaneous inflammation was used to define mediators of skin inflammation that may have clinical relevance. Activation of cutaneous PKCalpha increased the production of the chemotactic factors cytokine-induced neutrophil chemoattractant (KC) and macrophage inflammatory protein 2 (MIP-2) in murine plasma. TPA treatment of cultured K5-PKCalpha keratinocytes also released KC and MIP-2 into culture supernatants through an NF-kappaB-dependent pathway. MIP-2 and KC mediated the infiltration of neutrophils into the epidermis, since this was prevented by ablating CXCR2 in K5-PKCalpha mice or administering neutralizing antibodies against KC or MIP-2. The neutrophilia resulted from PKCalpha-mediated upregulation of cutaneous G-CSF released into the plasma independent of CXCR2. These responses could be inhibited by topical treatment with a PKCalpha-selective inhibitor. Inhibiting PKCalpha also reduced the basal and TNF-alpha- or TPA-induced expression of CXCL8 in cultured psoriatic keratinocytes, suggesting that PKCalpha activity may contribute to psoriatic inflammation. Thus, skin can be the source of circulating factors that have both local and systemic consequences, and these factors, their receptors, and possibly PKCalpha could be therapeutic targets for inhibition of cutaneous inflammation.

Adult↗
PubMed2000

Regulation of inflammation by collagen-binding integrins alpha1beta1 and alpha2beta1 in models of hypersensitivity and arthritis.

Adhesive interactions play an important role in inflammation by promoting leukocyte attachment and extravasation from the vasculature into the peripheral tissues. However, the importance of adhesion molecules within the extracellular matrix-rich environment of peripheral tissues, in which cells must migrate and be activated, has not been well explored. We investigated the role of the major collagen-binding integrins, alpha1beta1 and alpha2beta1, in several in vivo models of inflammation. mAb's against murine alpha1 and alpha2 were found to significantly inhibit effector phase inflammatory responses in animal models of delayed-type hypersensitivity (DTH), contact hypersensitivity (CHS), and arthritis. Mice that were alpha1-deficient also showed decreased inflammatory responses in the CHS and arthritis models when compared with wild-type mice. Decreased leukocyte infiltration and edema formation accompanied inhibition of antigen-specific models of inflammation, as nonspecific inflammation induced by croton oil was not inhibited. This study demonstrates the importance in vivo of alpha1beta1 and alpha2beta1, the collagen-binding integrins, in inflammatory diseases. The study also extends the role of integrins in inflammation beyond leukocyte attachment and extravasation at the vascular endothelial interface, revealing the extracellular matrix environment of peripheral tissues as a new point of intervention for adhesion-based therapies.

Animals↗
PubMed1996

Correlation of hematologic markers of inflammation and lung function: a comparison of asymptomatic smokers and nonsmokers.

Increased inflammation of the peripheral airways has been implicated as a cause of pulmonary function impairment. However, little information is available on the correlation between subclinical decrements of pulmonary function and inflammation in asymptomatic individuals. A relationship between markers of inflammation and lung function may be useful in predicting the early onset of lung function impairment. The purpose of this study was to investigate the correlation of hematologic markers of inflammation and spirometry in asymptomatic smokers and nonsmokers. The specific objectives of this study were twofold. The first objective was to quantify and compare the spirometric measures of lung function in smokers and nonsmokers having similar demographic and lifestyle characteristics. The second objective was to define the correlation between these spirometric measurements and hematologic markers of inflammation (white blood cells, monocytes, basophils, PGE1, IgG, and IgE). Systemic blood samples and spirometric measurements were obtained from 61 age-matched (33 +/- 9 years) healthy, asymptomatic smokers and nonsmokers, with similar self reported lifestyles (i.e., food, alcohol, vitamin consumption and exercise). Both male and female smokers self reported a higher coffee consumption (P < 0.05) compared to nonsmokers. Male smokers self-reported a trend toward current blue-collar versus white-collar occupation when compared with the nonsmokers. Body weight (77.6 +/- 16.6 kg) did not differ between the smokers and nonsmokers. The male nonsmokers were taller than the male smokers (P < 0.05). All subjects were asymptomatic and had clinically normal spirometry. Compared to male nonsmokers, the male smokers had lower FEF25-75% and FEF75-45% values (P < 0.05). No additional spirometric measurements, including FEV1/FVC, FEV1 and FVC were significantly different. The female smokers did not differ from the female nonsmokers (P < 0.05) in any of the spirometric endpoints measured. Thirteen statistically significant (P < 0.05) correlations involving inflammatory (white blood cells, monocytes, basophils, and PGE1) or immunologic endpoints (IgE) and spirometric measurements were observed in female smokers, female nonsmokers and male nonsmokers. No statistically significant correlations involving immunologic or inflammatory endpoints were observed in the male smokers. A better mechanistic understanding of the observed relationship between elevated hematologic inflammatory endpoints and reduced lung function may provide valuable insight into the clinical significance of these correlations.

Adult↗
PubMed2004

NEUROPEPTIDES AND NEUROGENIC MECHANISMS IN ORAL AND PERIODONTAL INFLAMMATION.

It is generally accepted that the nervous system contributes to the pathophysiology of peripheral inflammation, and a neurogenic component has been implicated in many inflammatory diseases, including periodontitis. Neurogenic inflammation should be regarded as a protective mechanism, which forms the first line of defense and protects tissue integrity. However, severe or prolonged noxious stimulation may result in the inflammatory response mediating injury rather than facilitating repair. This review focuses on the accumulating evidence suggesting that neuropeptides have a pivotal role in the complex cascade of chemical activity associated with periodontal inflammation. An overview of neuropeptide synthesis and release introduces the role of neuropeptides and their interactions with other inflammatory factors, which ultimately lead to neurogenic inflammation. The biological effects of the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), and neuropeptide Y (NPY) are summarized, and evidence for their involvement in the localized inflammatory lesions which characterize periodontitis is presented. In this context, the role of CGRP in bone metabolism is described in more detail. Recent research highlighting the role of the nervous system in suppressing pain and inflammation is also discussed.

Journal Article↗
PubMed2006

Ocular permeation and inhibition of retinal inflammation: an examination of data and expert opinion on the clinical utility of nepafenac.

BACKGROUND: The efficacy of topical nonsteroidal anti-inflammatory drugs (NSAIDs) for inflammation in the anterior segment, and pain control after cataract surgery, is well established. However, their effectiveness in the posterior segment has not been as well studied. Nepafenac ophthalmic suspension, 0.1% is a new topical NSAID pro-drug that has been approved by the US Food and Drug Administration (FDA) for the treatment of pain and inflammation after cataract surgery. Preclinical data suggest nepafenac may also provide unique efficacy in the posterior segment. SCOPE: We searched the PubMed database from 1966 to 2005 for various combinations of the search terms 'nepafenac', 'ophthalmic', 'inflammation', 'anterior segment', and 'posterior segment'. We review here the three articles identified in the search, and also include findings from three recent clinical trials. RESULTS: Nepafenac's corneal permeability characteristics are superior to those of ketorolac tromethamine, diclofenac sodium, and bromfenac sodium. Nepafenac is hydrolyzed by intraocular tissues to amfenac, a potent cyclooxygenase inhibitor. In addition to a limited hydrolysis in the cornea, significant bioactivation occurs in the iris/ciliary body and retina/choroid. Nepafenac administration significantly suppresses PGE2 synthesis in the retina/choroid. Topical nepafenac administration also significantly inhibits prostaglandin (PG)-mediated blood-retinal barrier breakdown and concurrent protein extravasation into the vitreous. In these studies, topical ketorolac and diclofenac failed to inhibit these key markers of inflammation. Nepafenac's clinical effectiveness in the posterior segment may be explained by its superior corneal permeation, biodistribution, and bioactivation to amfenac by the target tissues (i.e., iris, ciliary body, retina, and choroid) known to generate PGs. CONCLUSIONS: Nepafenac's ability to inhibit PG synthesis in the retina/choroid following topical administration indicates the drug also targets suppression of PG synthesis in the posterior segment. Nepafenac may therefore have a clinical role in conditions that are caused by PG-mediated vascular leakage, such as anterior chamber inflammation and cystoid macular edema following cataract surgery.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

The effect of refurbishing a UK steel plant on PM10 metal composition and ability to induce inflammation.

BACKGROUND: In the year 2000 Corus closed its steel plant operations in Redcar, NE of England temporarily for refurbishment of its blast furnace. This study investigates the impact of the closure on the chemical composition and biological activity of PM10 collected in the vicinity of the steel plant. METHODS: The metal content of PM10 samples collected before during and after the closure was measured by ICP-MS in order to ascertain whether there was any significant alteration in PM10 composition during the steel plant closure. Biological activity was assessed by instillation of 24 hr PM10 samples into male Wistar rats for 18 hr (n = 6). Inflammation was identified by the cellular and biochemical profile of the bronchoalveolar lavage fluid. Metal chelation of PM10 samples was conducted using Chelex beads prior to treatment of macrophage cell line, J774, in vitro and assessment of pro-inflammatory cytokine expression. RESULTS: The total metal content of PM10 collected before and during the closure period were similar, but on reopening of the steel plant there was a significant 3-fold increase (p < 0.05) compared with the closure and pre-closure samples. Wind direction prior to the closure was predominantly from the north, compared to south westerly during the closure and re-opened periods. Of metals analysed, iron was most abundant in the total and acid extract, while zinc was the most prevalent metal in the water-soluble fraction. Elevated markers of inflammation included a significant increase (p < 0.01) in neutrophil cell numbers in the bronchoalveolar lavage of rats instilled with PM10 collected during the reopened period, as well as significant increases in albumin (p < 0.05). Extracts of PM10 from the pre-closure and closure periods did not induce any significant alterations in inflammation or lung damage. The soluble and insoluble extractable PM10 components washed from the reopened period both induced a significant increase in neutrophil cell number (p < 0.05) when compared to the control, and these increases when added together approximately equalled the inflammation induced by the whole sample. PM10 from the re-opened period stimulated J774 macrophages to generate TNF-alpha protein and this was significantly prevented by chelating the metal content of the PM10 prior to addition to the cells. CONCLUSION: PM10-induced inflammation in the rat lung was related to the concentration of metals in the PM10 samples tested, and activity was found in both the soluble and insoluble fractions of the particulate pollutant.

Air Pollutants↗
PubMed2005

Anti-Fas mAb-induced apoptosis and cytolysis of airway tissue eosinophils aggravates rather than resolves established inflammation.

BACKGROUND: Fas receptor-mediated eosinophil apoptosis is currently forwarded as a mechanism resolving asthma-like inflammation. This view is based on observations in vitro and in airway lumen with unknown translatability to airway tissues in vivo. In fact, apoptotic eosinophils have not been detected in human diseased airway tissues whereas cytolytic eosinophils abound and constitute a major mode of degranulation of these cells. Also, Fas receptor stimulation may bypass the apoptotic pathway and directly evoke cytolysis of non-apoptotic cells. We thus hypothesized that effects of anti-Fas mAb in vivo may include both apoptosis and cytolysis of eosinophils and, hence, that established eosinophilic inflammation may not resolve by this treatment. METHODS: Weeklong daily allergen challenges of sensitized mice were followed by airway administration of anti-Fas mAb. BAL was performed and airway-pulmonary tissues were examined using light and electron microscopy. Lung tissue analysis for CC-chemokines, apoptosis, mucus production and plasma exudation (fibrinogen) were performed. RESULTS: Anti-Fas mAb evoked apoptosis of 28% and cytolysis of 4% of eosinophils present in allergen-challenged airway tissues. Furthermore, a majority of the apoptotic eosinophils remained unengulfed and eventually exhibited secondary necrosis. A striking histopathology far beyond the allergic inflammation developed and included degranulated eosinophils, neutrophilia, epithelial derangement, plasma exudation, mucus-plasma plugs, and inducement of 6 CC-chemokines. In animals without eosinophilia anti-Fas evoked no inflammatory response. CONCLUSION: An efficient inducer of eosinophil apoptosis in airway tissues in vivo, anti-Fas mAb evoked unprecedented asthma-like inflammation in mouse allergic airways. This outcome may partly reflect the ability of anti-Fas to evoke direct cytolysis of non-apoptotic eosinophils in airway tissues. Additionally, since most apoptotic tissue eosinophils progressed into the pro-inflammatory cellular fate of secondary necrosis this may also explain the aggravated inflammation. Our data indicate that Fas receptor mediated eosinophil apoptosis in airway tissues in vivo may cause severe disease exacerbation due to direct cytolysis and secondary necrosis of eosinophils.

Animals↗
PubMed2006

Effects of lipopolysaccharide-induced inflammation on expression of growth-associated genes by corticospinal neurons.

BACKGROUND: Inflammation around cell bodies of primary sensory neurons and retinal ganglion cells enhances expression of neuronal growth-associated genes and stimulates axonal regeneration. We have asked if inflammation would have similar effects on corticospinal neurons, which normally show little response to spinal cord injury. Lipopolysaccharide (LPS) was applied onto the pial surface of the motor cortex of adult rats with or without concomitant injury of the corticospinal tract at C4. Inflammation around corticospinal tract cell bodies in the motor cortex was assessed by immunohistochemistry for OX42 (a microglia and macrophage marker). Expression of growth-associated genes c-jun, ATF3, SCG10 and GAP-43 was investigated by immunohistochemistry or in situ hybridisation. RESULTS: Application of LPS induced a gradient of inflammation through the full depth of the motor cortex and promoted c-Jun and SCG10 expression for up to 2 weeks, and GAP-43 upregulation for 3 days by many corticospinal neurons, but had very limited effects on neuronal ATF3 expression. However, many glial cells in the subcortical white matter upregulated ATF3. LPS did not promote sprouting of anterogradely labelled corticospinal axons, which did not grow into or beyond a cervical lesion site. CONCLUSION: Inflammation produced by topical application of LPS promoted increased expression of some growth-associated genes in the cell bodies of corticospinal neurons, but was insufficient to promote regeneration of the corticospinal tract.

Activating Transcription Factor 3↗
PubMed2003

Acute coronary disease Athero-Inflammation: Therapeutic approach.

Antithrombotic therapy is the cornerstone of the treatment of acute coronary syndromes, but there is now evidence which indicates that by blocking inflammation, thrombosis and thus, acute coronary events, could be lowered. The concept of athero-inflammation emerges as the meeting point of different morbidities; dyslipemia, diabetes, hypertension, obesity, immunity, infection, hyperhomocyteinemia, smoking, etc. usual named as risk factors. Thus, beside specific drugs, earliest treatment, in the stage of inflammation, using anti-inflammatory drugs, should be considered since in patients with increased risk of acute coronary process are likely to have many point of origen throughout the coronary arteries. There are a body of evidences for supporting the potential of anti-inflammatory therapy to the prevention of inflammation and atherosclerosis. COX-2 inhibition may decrease endothelial inflammation reducing monocytes infiltration improving vascular cells function, plaque stability and probably resulting in a decrease of coronary atherothrombotic events.Trials including large numbers of patients in prospective double-blind randomized studies worthwhile to confirm the efficacy of NSAID, mainly, COX-2 inhibitors, together with aspirin in the prevention of coronary events in patients with acute coronary disease.

Journal Article↗
PubMed2005

Spinal cord NR1 serine phosphorylation and NR2B subunit suppression following peripheral inflammation.

BACKGROUND: Spinal cord N-methyl-D-aspartate (NMDA) receptors are intimately involved in the development and maintenance of central sensitization. However, the mechanisms mediating the altered function of the NMDA receptors are not well understood. In this study the role of phosphorylation of NR1 splice variants and NR2 subunits was examined following hind paw inflammation in rats. We further examined the level of expression of these proteins following the injury. RESULTS: Lumbar spinal cord NR1 subunits were found to be phosphorylated on serine residues within two hours of the induction of hind paw inflammation with carrageenan. The enhanced NR1 serine phosphorylation reversed within six hours. No phosphorylation on NR1 threonine or tyrosine residues was observed. Likewise, no NR2 subunit phosphorylation was observed on serine, threonine or tyrosine residues. An analysis of NR1 and NR2 protein expression demonstrated no change in the levels of NR1 splice variants or NR2A following the inflammation. However, spinal cord NR2B expression was depressed by the hind paw inflammation. The expression of NR2B remained depressed for more than one week following initiation of the inflammation. CONCLUSION: These data suggest that NR1 serine phosphorylation leads to an initial increase in NMDA receptor activity in the spinal cord following peripheral injury. The suppression of NR2B expression suggests compensation for the enhanced nociceptive activity. These data indicate that spinal cord NMDA receptors are highly dynamic in the development, maintenance and recovery from central sensitization following an injury. Thus, chronic pain therapies targeted to NMDA receptors should be designed for the exact configuration of NMDA receptor subunits and post-translational modifications present during specific stages of the disease.

Journal Article↗