Acute Inflammation (acute + inflammation)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Refractory Progression of Coronary Aneurysms, a Case of Delayed Onset Kawasaki Disease as Depicted by Cardiac Computed Tomography Angiography

CONGENITAL HEART DISEASE, Issue 3 2010
FACP, Shah Azmoon MD
ABSTRACT Background., Kawasaki disease (KD) is an immune-mediated vasculitis of unknown etiology with self-limited clinical course that was first described in 1967 by Dr. Tomisaku Kawasaki. It is a disease of early childhood and rare past late adulthood but one that can have detrimental consequences when there is a delay in diagnosis and treatment. Cardiovascular complications causing increased morbidity and mortality may include coronary artery aneurysms, myocardial infarction, heart failure, arrhythmias, and peripheral artery occlusion. Case Presentation., Here, we present an atypical case of delayed onset KD in a young teenager. DS had visited three different emergency departments during the course of 2 weeks for unrelenting fevers. Despite multiple treatment protocols including immunoglobulin, steroids, and tumor necrosis factor-alpha antagonists, he continued to have progression of cardiovascular complications. While echocardiographic findings were suspicious for cardiac complications, a cardiac computed tomography (CT) angiography was able to clearly distinguish giant coronary aneurysms. Conclusion., Without prompt therapy, fever and manifestations of acute inflammation can last for several weeks to months with increased risk toward complications. The incidence of coronary artery aneurysms has been noted to be 25% in untreated patients with a mortality rate of up to 2%. Using low-dose protocols along with high spatial and temporal resolution of cardiac CT angiography may provide a useful and complimentary imaging modality in accurate diagnosis and follow-up of patients with KD. [source]


Mycobacterium avium complex infection in a neck abscess: A diagnostic pitfall in fine-needle aspiration biopsy of head and neck lesions

DIAGNOSTIC CYTOPATHOLOGY, Issue 7 2009
Valerie A. Fitzhugh M.D.
Abstract Fine-needle aspiration biopsy (FNAB) is a useful tool in the diagnosis of mycobacterial disease, especially Mycobacterium tuberculosis. However, nontuberculous mycobacterial infection diagnosed with FNAB material is much rarer, with Mycobacterium avium complex being the most common. In this report, we present the case of a 21-year-old HIV positive man, who presented with a unilateral, tender, enlarging cervical neck mass. FNAB had revealed acute inflammation. Mycobacterium avium complex grew in culture from the material that was aspirated and was confirmed by DNA probe. Because of the paucity of articles on this subject in the cytology literature, it is important to reiterate the value of the material aspirated at the bedside and the clinic in the diagnosis of infectious disease. When faced with antibiotic-resistant cellulitis and abscesses, the FNAB material must be sent for acid fast bacteria smears and culture. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source]


Disseminated subcutaneous nocardiosis caused by Nocardia farcinica diagnosed by FNA biopsy and 16S ribosomal gene sequencing

DIAGNOSTIC CYTOPATHOLOGY, Issue 4 2008
Ronald M. Angeles M.D.
Abstract Nocardia is an infrequent but significant cause of infections in the immunocompromised host. Clinical syndromes are varied and ranges from pulmonary, disseminated, cutaneous, and CNS involvement. Here we describe a case of disseminated subcutaneous nodules in a patient with multiple myeloma caused by Nocardia farcinica. The diagnosis was made by FNA biopsy which revealed gram positive filamentous bacilli in background of acute inflammation on smears. This was confirmed by 16S ribosomal gene sequencing. Prompt identification of N. farcinica is important because of its intrinsic resistance to broad spectrum cephalosporins and high risk of dissemination. Diagn. Cytopathol. 2008;36:266,269. © 2008 Wiley-Liss, Inc. [source]


Pancreatic mucinous lesions: A retrospective analysis with cytohistological correlation

DIAGNOSTIC CYTOPATHOLOGY, Issue 11 2006
Jing Zhai M.D., Ph.D.
Abstract The diagnosis of mucinous pancreatic lesions, which include mucinous noncystic adenocarcinoma, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), and mucinous metaplasia, is critical, given different clinical management and prognosis. This retrospective study is done to assess the cytological features and pitfalls associated with these entities in cytological samples. A search for pancreatic cytology specimens with histological confirmation of the various pancreatic mucinous lesions was done from 1988 to 2005: 9 mucinous adenocarcinoma, 14 IPMN, 11 MCN, and 3 mucinous metaplasia. The majority (35/37) had been endoscopic ultrasound-guided fine-needle aspirations. The cellularity, background extracellular mucin, epithelial architecture, mucinous nature of the epithelium, cell shape, and nuclear features were evaluated on the cytology material. Of the 22 cytological features evaluated, the presence of three-dimensional clusters, micropapillary structures, and nuclear atypia, which includes nuclear crowding, increased N/C ratio, anisonucleosis, nuclear membrane contour irregularity, clumpy chromatin, and prominent nucleoli, was found to be consistently associated with mucinous adenocarcinoma. There were no statistically significant cytological features, which helped in differentiating IPMN, MCN, and mucinous metaplasia. There was a relatively high false-positive rate in the IPMN group (5/14, 36%). Review of the histological specimen showed severe dysplastic epithelial change in these cases. One false-positive case of mucinous metaplasia (1/3, 33%) showed marked intraepithelial acute inflammation. The cytological diagnosis of mucinous pancreatic lesions remains challenging, except for mucinous noncystic adenocarcinoma. The findings were largely nonspecific in the differentiation between IPMN, MCN, mucinous metaplasia, and incidentally sampled gastrointestinal epithelium. False-positive diagnosis of adenocarcinoma occurs not infrequently in the setting of IPMN with severe dysplastic epithelial change and in lesions with associated acute inflammation, and can be a pitfall in the diagnosis of these lesions. Diagn. Cytopathol. 2006;34: 724,730. © 2006 Wiley-Liss, Inc. [source]


Low-grade urothelial carcinoma: Reappraisal of the cytologic criteria on ThinPrep®

DIAGNOSTIC CYTOPATHOLOGY, Issue 3 2003
Ph.D., Wei Xin M.D.
Abstract The diagnostic criteria for low-grade urothelial lesions that have been described in the past were based on urinary specimens prepared by the cytospin method. Recognizing the recent popularity of the ThinPrep® methodology and the cytologic alterations it introduces to the cellular features, we sought to evaluate the reproducibility of these criteria in ThinPrep urinary samples. One hundred twenty-six ThinPrep urinary specimens with a tissue diagnosis of low-grade urothelial carcinoma (LGUC) and 45 negative controls were evaluated. Three pathologists blindly reviewed the slides separately and the consensus on each feature was used in the study. Logistic regression analysis was used to determine which criteria in combination were most predictive of low-grade urothelial carcinoma. All specimens were evaluated for the following 18 features: nucleus/cytoplasm ratio, irregular nuclear border, cytoplasm homogeneity, cell clusters, high cellularity, prominent nucleoli, granular nuclear chromatin, hyperchromasia, acute inflammation, vesicular chromatin, nuclear molding, nuclear eccentricity, elongated nuclei, necrosis, anisonucleosis, irregular bordered fragments, absent cytoplasmic collar, and peripheral palisading. High nucleus-to-cytoplasm ratio, irregular nuclear borders, and homogeneous cytoplasm (combination sensitivity of 59% and specificity of 100%) were the best predictive features for LGUC. Minor predictive criteria were eccentric nuclei and nuclear molding. ThinPrep provides well preserved, cleaner specimens without significantly altering the morphology. The three key criteria applied in cytospin specimens to diagnose LGUC were reproducible in ThinPrep specimens. Diagn. Cytopathol. 2003;29:125,129. © 2003 Wiley-Liss, Inc. [source]


A link between neutrophils and chronic disease manifestations of Chlamydia muridarum urogenital infection of mice

FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2010
Hyo Y. Lee
Abstract Vigorous acute inflammatory responses accompany Chlamydia muridarum infections in mice and are positively correlated with adverse urogenital and respiratory tract infection outcomes in the mouse model. Thus, we tested the hypothesis that neutrophils induce an acute inflammatory insult that, in the repair phase, leads to the chronic sequelae of hydrosalpinx , a surrogate marker of infertility in the mouse model. To this end, we induced neutropenia in mice using a neutrophil-depleting monoclonal antibody during acute phases of C. muridarum urogenital infection only (days 2,21 postinfection). To prove induced neutropenia, peripheral blood was monitored for neutrophils during the treatment regimen. Neutropenic mice had a similar infection course as control mice, but had significantly reduced levels of certain histopathological parameters, reduced production of matrix metalloproteinase-9 (MMP-9) and reduced rates of hydrosalpinx following resolution of the infection. We conclude that neutrophils are a major source of MMP-9, a previously proved pathological factor in this model. Further, we conclude that acute inflammation in the form of neutrophils and neutrophil activation products are at least partially responsible for inducing the histological changes that ultimately result in fibrosis and infertility in the mouse model of chlamydial upper genital tract disease. [source]


Changes in chromatin structure and methylation of the human interleukin-1, gene during monopoiesis

IMMUNOLOGY, Issue 3 2010
Inga Wessels
Summary Interleukin-1, (IL-1,) induces the expression of a variety of proteins responsible for acute inflammation and chronic inflammatory diseases. However, the molecular regulation of IL-1, expression in myeloid differentiation has not been elucidated. In this study the chromatin structure of the IL-1, promoter and the impact of methylation on IL-1, expression in monocytic development were examined. The results revealed that the IL-1, promoter was inaccessible in undifferentiated promyeloid HL-60 cells but highly accessible in differentiated monocytic cells which additionally acquired the ability to produce IL-1,. Accessibilities of differentiated cells were comparable to those of primary monocytes. Lipopolysaccharide (LPS) stimulation did not affect promoter accessibility in promyeloid and monocytic HL-60 cells, demonstrating that the chromatin remodelling of the IL-1, promoter depends on differentiation and not on the transcriptional status of the cell. Demethylation via 5-aza-2,-deoxycytodine led to the induction of IL-1, expression in undifferentiated and differentiated cells, which could be increased after LPS stimulation. Our data indicate that the IL-1, promoter is reorganized into an open poised conformation during monopoiesis being a privilege of mature monocytes but not of the entire myeloid lineage. As a second mechanism, IL-1, expression is regulated by methylation acting independently of the developmental stage of myeloid cells. [source]


Classical and alternative pathway complement activation are not required for reactive systemic AA amyloid deposition in mice

IMMUNOLOGY, Issue 2 2004
Winston L. Hutchinson
Summary During induction of reactive systemic amyloid A protein (AA) amyloidosis in mice, either by chronic inflammation or by severe acute inflammation following injection of amyloid enhancing factor, the earliest deposits form in a perifollicular distribution in the spleen. Because the splenic follicular localization of immune complexes and of the scrapie agent are both complement dependent in mice, we investigated the possible complement dependence of AA amyloid deposition. In preliminary experiments, substantial depletion of circulating C3 by cobra venom factor had little effect on experimental amyloid deposition. More importantly, mice with targeted deletion of the genes for C1q or for both factor B and C2, and therefore unable to sustain activation, respectively, of either the classical complement pathway or both the classical and alternative pathways, showed amyloid deposition similar to wild type controls. Complement activation by either the classical or alternative pathways is thus not apparently necessary for the experimental induction of systemic AA amyloid in mice. [source]


Experimental acute respiratory Burkholderia pseudomallei infection in BALB/c mice

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 1 2009
Mark S. Lever
Summary Burkholderia pseudomallei is the causative agent of melioidosis, which is considered a potential deliberate release agent. The objective of this study was to establish and characterise a relevant, acute respiratory Burkholderia pseudomallei infection in BALB/c mice. Mice were infected with 100 B. pseudomallei strain BRI bacteria by the aerosol route (approximately 20 median lethal doses). Bacterial counts within lung, liver, spleen, brain, kidney and blood over 5 days were determined and histopathological and immunocytochemical profiles were assessed. Bacterial numbers in the lungs reached approximately 108 cfu/ml at day 5 post-infection. Bacterial numbers in other tissues were lower, reaching between 103 and 105 cfu/ml at day 4. Blood counts remained relatively constant at approximately 1.0 × 102 cfu/ml. Foci of acute inflammation and necrosis were seen within lungs, liver and spleen. These results suggest that the BALB/c mouse is highly susceptible to B. pseudomallei by the aerosol route and represents a relevant model system of acute human melioidosis. [source]


Three Unusual Neuropathologic-Related Causes of Sudden Death,

JOURNAL OF FORENSIC SCIENCES, Issue 3 2008
Dennis J. Chute M.D.
Abstract:, We discuss the autopsy findings of three medico-legal cases of sudden death associated with uncommon neuropathologic findings of which the general forensic pathologist may not be familiar. Case 1 was a 43-year-old man who died of a seizure due to malignant melanoma of the temporal lobe associated with neurocutaneous melanosis (NCM). Case 2 was a 57-year-old woman with a history of mental retardation and incoordination because of chronic lead poisoning, who died of a pulmonary thromboembolism due to deep venous thrombosis status post left leg fracture after a fall down a staircase. Autopsy revealed atrophy and gliosis of her cerebellum as a result of childhood lead poisoning. The third patient was a 75-year-old woman who died as a result of acute bacterial leptomeningitis at the cervico-medullary junction with acute inflammation of the connective tissue of her upper cervical spinal column associated with subluxation of her atlantoaxial (AA) joint, also known as Grisel's syndrome. [source]


Periodontal therapy: a novel non-drug-induced experimental model to study human inflammation

JOURNAL OF PERIODONTAL RESEARCH, Issue 5 2004
F. D'Aiuto
Background:, Chronic periodontitis causes a low-grade systemic inflammatory response; its standard treatment, however, induces an acute inflammatory response. The aim of this study was to describe the systemic inflammatory reactions to an intensive periodontal treatment regimen. Methods:, Fourteen otherwise healthy subjects suffering from severe chronic periodontitis were enrolled in a 1 month pilot single-blind trial. Intensive periodontal treatment, consisting of full-mouth subgingival root debridement delivered within a 6-h period, was performed. Periodontal parameters were recorded before and 1 month after completion of treatment. Blood samples were taken at baseline and 1, 3, 5, 7 and 30 days after treatment. Interleukin-1 receptor antagonist (IL-1Ra), Interleukin-6 (IL-6) and C-reactive protein (CRP) serum concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Complete blood counts were also performed. Results:, One day after treatment, mild neutrophilia and monocytosis (p < 0.05) and lymphopenia (p < 0.01) were accompanied by a sharp increase in inflammatory markers (IL-1Ra, IL-6, p < 0.01). A 10-fold increase in CRP (p < 0.001) was detected on day 1 and its kinetics followed a pattern of a classical acute phase response (significantly raised concentrations up to 1 week, p < 0.01). At 3,7 days after treatment, subjects presented also with a mild tendency towards a normocytic anaemic state (p < 0.01) and a degree of lympho-thrombocytosis (p < 0.05). The observed changes were similar to those expected following the well-characterized endotoxin-challenge model of inflammation. Conclusions:, Intensive periodontal treatment produced an acute systemic inflammatory response of 1 week duration and might represent an alternative to classic endotoxin-challenge or drug-induced models to study acute inflammation in humans. [source]


The anti-arthritic effect of ursolic acid on zymosan-induced acute inflammation and adjuvant-induced chronic arthritis models

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2008
Suk-Yun Kang
Ursolic acid (UA) is pentacyclic triterpenoic acid that naturally occurs in many medicinal herbs and plants. In this study, we examined the possible suppressive effect of UA extracted from Oldenlandia diffusa on zymosan-induced acute inflammation in mice and complete Freund's adjuvant (CFA)-induced arthritis in rats. UA treatment (per oral) dose-dependently (25,200 mg kg,1) suppressed zymosan-induced leucocyte migration and prostaglandin E2 (PGE2) production in the air pouch exudates. Since the maximal effective dose of UA was 50 mg kg,1 in the zymosan experiment, we used this dose of UA in a subsequent study using an adjuvant-induced rheumatoid arthritis model. UA treatment (50 mg kg,1, per oral, once a day for 10 days) was started from day 12 after adjuvant injection. UA dramatically inhibited paw swelling, plasma PGE2 production and radiological changes in the joint caused by CFA injection. Moreover, UA significantly suppressed the arthritis-induced mechanical and thermal hyperalgesia as well as the spinal Fos expression, as determined by immunohistochemistry, which was increased by CFA injection. In addition, overall anti-arthritic potency of UA was comparable with ibuprofen (100 mg kg,1, oral) while UA did not induce significant gastric lesions as compared with the ibuprofen treatment group. These findings strongly suggest that UA is a useful suppressive compound for rheumatoid arthritis treatment with low risk of gastric problems. [source]


Review article: gastrointestinal sensory and motor disturbances in inflammatory bowel disease , clinical relevance and pathophysiological mechanisms

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2008
H. U. DE SCHEPPER
Summary Background, It is well known that inflammation has a profound impact on the neuromuscular apparatus of the gastrointestinal tract during the inflammatory insult and in periods of remission, at the site of inflammation and at distance from this site. The importance of this interaction is illustrated by the higher prevalence of functional gut disorders in patients with inflammatory bowel disease. Aims, To document the epidemiological and clinical significance of functional alterations of gut motility and sensitivity in patients with inflammatory bowel disease and to formulate potential pathophysiological mechanisms. Results and conclusions, Functional gut disorders occur frequently in patients with inflammatory bowel disease, both during inflammatory episodes and in periods of remission, and have a major impact on their quality of life. The clinical manifestations of these motility and sensitivity disorders vary and are often difficult to treat, mainly because therapeutic guidelines and specific diagnostic tests to distinguish inflammatory bowel disease from functional gut disorders are lacking. Chronic bowel inflammation results in a complicated interaction between neuroendocrine serotonin-predominant cells of the mucosa, inflammatory cells (particularly mast cells) in the submucosa, the intrinsic and extrinsic innervation and the muscular apparatus including the interstitial cells of Cajal. The outcome of this interaction is a perturbation of gastrointestinal motor function, both locally and at distance from the site of inflammation and during both acute inflammation and remission. [source]


Stratum corneum TARC level is a new indicator of lesional skin inflammation in atopic dermatitis

ALLERGY, Issue 9 2010
E. Morita
To cite this article: Morita E, Takahashi H, Niihara H, Dekio I, Sumikawa Y, Murakami Y, Matsunaka H. Stratum corneum TARC level is a new indicator of lesional skin inflammation in atopic dermatitis. Allergy 2010; 65: 1166,1172. Abstract Background:, Management of atopic dermatitis (AD) requires judging the symptoms of local skin lesions and prescribing a suitable treatment. However, no method has been established in which objective measures can be used to evaluate the severity of local symptoms. We established a method for measuring thymus and activation-regulated chemokine (TARC) levels in the stratum corneum (scTARC), and examined whether the scTARC can be used as an indicator of the severity of local skin lesions in patients with AD. Methods:, Stratum corneum was obtained from patients with AD by tape-stripping, and scTARC was evaluated using a TARC-specific antibody followed by image analysis. The scTARC was examined to determine correlation with the severity of local skin lesions (the severity of erythema, edema/papule, oozing/crusts, excoriations, lichenification, and xerosis) as well as with the severity scoring of atopic dermatitis (SCORAD) index, serum TARC level, serum IgE level, serum lactate dehydrogenase (LDH) level, interleukin (IL)-4-producing T cell ratio (Th2 cell ratio), and blood eosinophil count. Results:, The scTARC was correlated with the severity of local skin lesions, especially with the erythema, edema/papule, and oozing/crusts score. The scTARC in the most severe lesions was also correlated with the SCORAD index, serum TARC level, serum IgE level, and blood eosinophil count. The scTARC was not, however, correlated with the serum LDH level and Th2 cell ratio. Conclusion:, An immunofluorescent technique combined with tape-stripping was used to measure scTARC. The scTARC can be used as an indicator of the severity of local acute inflammation in patients with AD. [source]


The Value of Breast Ductoscopy in Radiologically Negative Spontaneous/Persistent Nipple Discharge

THE BREAST JOURNAL, Issue 4 2009
Ercument Tekin MD
Abstract:, Breast ductoscope is a fiberoptic endoscope used for examining the distal breast ducts under direct vision in order to identify the source of pathologic nipple discharge. The purpose of this study was to investigate the reliability of intra-operative breast ductoscopy in patients with pathologic nipple discharge, which could not be identified by radiologic tests. Between April 2002 and March 2007, breast ductoscopy was performed in 34 patients who had pathologic nipple discharge with no radiologic evidence about the source. The procedures were carried out under general anesthesia and ductoscopic findings were as well as the histopathology of the specimens were recorded and documented. In 88%, (30 of 34) of the patients, endoscope was successfully introduced into the external orifice of the ducts at the nipple and proximal breast ducts were successfully visualized. Ductoscopy revealed intraductal lesions (i.e., ductal obstruction, intraductal papilloma, red patches, and erythematoid platter) in 20 patients (66%). Among the 20 patients with visible endoluminal pathology, nine had a papilloma and eight had signs of either acute inflammation (bleeding, erythema) or previous inflammation with healing (adhesions and blocked ducts). In two cases, invasive breast carcinoma was identified, one of which was ductal carcinoma in situ (DCIS) with minimal invasion. In both cases, there had been blocked ducts. In one case DCIS was identified. Breast ductoscopy is a reliable and easy-to-use method to demonstrate the source of pathologic nipple discharge in cases with bleeding and other intraductal lesions. [source]


Inflammation and Epithelial to Mesenchymal Transition in Lung Transplant Recipients: Role in Dysregulated Epithelial Wound Repair

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010
L. A. Borthwick
Epithelial to mesenchymal transition (EMT) has been implicated in the pathogenesis of obliterative bronchiolitis (OB) after lung transplant. Although TNF-, accentuates TGF-,1 driven EMT in primary human bronchial epithelial cells (PBECs), we hypothesized that other acute pro-inflammatory cytokines elevated in the airways of patients with OB may also accentuate EMT and contribute to dysregulated epithelial wound repair. PBECs from lung transplant recipients were stimulated with TGF-,1 ± IL-1,, IL-8, TNF-, or activated macrophages in co-culture and EMT assessed. The quality and rate of wound closure in a standardized model of lung epithelial injury was assessed in response to above stimuli. Co-treatment with TGF-,1 + TNF-, or IL-1, significantly accentuates phenotypic and some functional features of EMT compared to TGF-,1 alone. Co-treatment with TGF-,1 + TNF-, or IL-1, accelerates epithelial wound closure however the quality of repair is highly dysregulated. Co-treatment with TGF-,1 + IL-8 has no significant effect on EMT or the speed or quality of wound healing. Activated macrophages dramatically accentuate TGF-,1-driven EMT and cause dysregulated wound repair. Crosstalk between macrophage-derived acute inflammation in the airway and elevated TGF-,1 may favor dysregulated airway epithelial repair and fibrosis in the lung allograft via EMT. [source]


Neuroplasticity predicts outcome of optic neuritis independent of tissue damage

ANNALS OF NEUROLOGY, Issue 1 2010
Thomas M. Jenkins MRCP
Objectives To determine whether lateral occipital complex (LOC) activation with functional magnetic resonance imaging (fMRI) predicts visual outcome after clinically isolated optic neuritis (ON). To investigate the reasons behind good recovery following ON, despite residual optic nerve demyelination and neuroaxonal damage. Methods Patients with acute ON and healthy volunteers were studied longitudinally over 12 months. Structural MRI, visual evoked potentials (VEPs), and optical coherence tomography (OCT) were used to quantify acute inflammation, demyelination, conduction block, and later to estimate remyelination and neuroaxonal loss over the entire visual pathway. The role of neuroplasticity was investigated using fMRI. Multivariable linear regression analysis was used to study associations between vision, structure, and function. Results Greater baseline fMRI responses in the LOCs were associated with better visual outcome at 12 months. This was evident on stimulation of either eye (p = 0.007 affected; p = 0.020 fellow eye), and was independent of measures of demyelination and neuroaxonal loss. A negative fMRI response in the LOCs at baseline was associated with a relatively worse visual outcome. No acute electrophysiological or structural measures, in the anterior or posterior visual pathways, were associated with visual outcome. Interpretation Early neuroplasticity in higher visual areas appears to be an important determinant of recovery from ON, independent of tissue damage in the anterior or posterior visual pathway, including neuroaxonal loss (as measured by MRI, VEP, and OCT) and demyelination (as measured by VEP). ANN NEUROL 2010;67:99,113 [source]


Detection of human herpesvirus-6 in cerebrospinal fluid of patients with encephalitis,

ANNALS OF NEUROLOGY, Issue 3 2009
Karen Yao MS
Objective Virus infections are the most common causes of encephalitis, a syndrome characterized by acute inflammation of the brain. More than 150 different viruses have been implicated in the pathogenesis of encephalitis; however, because of limitations with diagnostic testing, causative factors of more than half of the cases remain unknown. Methods To investigate whether human herpesvirus-6 (HHV-6) is a causative agent of encephalitis, we examined for evidence of virus infection by determining the presence of viral sequence using polymerase chain reaction and assessed HHV-6 antibody reactivity in the cerebrospinal fluid of encephalitis patients with unknown cause. In a cohort study, we compared virus-specific antibody levels in cerebrospinal fluid samples of patients with encephalitis, relapsing-remitting multiple sclerosis, and other neurological diseases. Results Our results demonstrated increased levels of HHV-6 IgG, as well as IgM levels, in a subset of encephalitis patients compared with other neurological diseases. Moreover, cell-free viral DNA that is indicative of active infection was detected in 40% (14/35) of encephalitis patients, whereas no amplifiable viral sequence was found in either relapsing-remitting MS or other neurological diseases patients. In addition, a significant correlation between polymerase chain reaction detection and anti-HHV-6 antibody response was also demonstrated. Interpretation Collectively, these results suggested HHV-6 as a possible pathogen in a subset of encephalitis cases. Ann Neurol 2009;65:257,267 [source]


Increased p53 immunoreactivity in proliferative inflammatory atrophy of prostate is related to focal acute inflammation

APMIS, Issue 3 2009
WANZHONG WANG
Proliferative inflammatory atrophy (PIA) of prostate has been proposed as a precursor lesion of prostate cancer. The aim of the current study was to evaluate the expression of p53 protein in PIA lesions and to investigate the relationship between p53 staining and Ki-67, glutathione S -transferase-, (GSTP1) and cyclooxygenase-2 (COX-2) immunohistochemical expression. The results revealed that p53 nuclear immunostaining appeared in PIA lesions in 2.1±3.4% (mean±SD) of the basal and 0.9±2.3% of the luminal epithelial cells. Both these values were significantly higher than those in normal-appearing acini (p<0.0001). Increased p53 expression in luminal cells was related to focal infiltration of polymorphonuclear leucocytes. A positive correlation between p53 expression and Ki-67 was found in COX-2-positive PIA lesions (r=0.610, p<0.0001). Half of the p53-positive epithelial cells expressed diffuse GSTP1 immunostaining in the same lesions. The present study demonstrates an increased p53 expression in PIA lesions, and inflammation, especially acute inflammation, may play a role in the induction of p53 over-expression, particularly as cells in PIA lesions are known to have a reduced defence against DNA damage. [source]


Angiogenesis and the persistence of inflammation in a rat model of proliferative synovitis

ARTHRITIS & RHEUMATISM, Issue 7 2010
Sadaf Ashraf
Objective To determine whether blood vessel growth at the onset of resolving synovitis leads to its subsequent persistence and whether inhibiting this angiogenesis at the onset of persistent inflammation leads to its subsequent resolution. Methods Inflammation and angiogenesis were induced by injection of 0.03% carrageenan and/or 6 pmoles of fibroblast growth factor 2 (FGF-2) into rat knees. A brief treatment with the angiogenesis inhibitor PPI-2458 (5 mg/kg orally on alternate days) was administered 1 day before and up to 3 days after synovitis induction. Controls comprised naive and vehicle-treated rats. Synovial angiogenesis was measured using the endothelial cell proliferation index, and inflammation was determined by measuring joint swelling and macrophage percentage area. Data are presented as the geometric mean (95% confidence interval). Results Intraarticular injection of 0.03% carrageenan into rat knees produced acute synovitis, which was not associated with synovial angiogenesis and which resolved within 29 days. Injection of FGF-2 (6 pmoles) induced synovial angiogenesis without significant synovitis. Stimulation of angiogenesis with FGF-2 at the time of carrageenan injection was followed by synovitis that persisted for 29 days. Persistence of carrageenan/FGF-2,induced synovitis was prevented by systemic administration of 3 doses of the angiogenesis inhibitor PPI-2458 during the acute phase. Conclusion Our findings indicate that conversion of acute inflammation to chronic inflammation may be due to the stimulation of angiogenesis, and brief antiangiogenic treatment during the acute phase of synovitis may prevent its subsequent progression. Clinical studies will be needed to determine whether brief antiangiogenic treatment may reduce the burden of inflammatory joint diseases such as rheumatoid arthritis by facilitating the resolution of early synovitis. [source]


META060 inhibits osteoclastogenesis and matrix metalloproteinases in vitro and reduces bone and cartilage degradation in a mouse model of rheumatoid arthritis

ARTHRITIS & RHEUMATISM, Issue 6 2010
Veera Reddy Konda
Objective The multikinase inhibitor META060 has been shown to inhibit NF-,B activation and expression of markers of inflammation. This study was undertaken to investigate the effect of META060 on biomarkers associated with bone and cartilage degradation in vitro and its antiinflammatory efficacy in vivo in both acute and chronic inflammation models. Methods Glycogen synthase kinase 3, (GSK3,),dependent ,-catenin phosphorylation was evaluated in RAW 264.7 macrophages to assess kinase inhibition. The inhibition of osteoclastogenesis and tartrate-resistant acid phosphatase (TRAP) activity was evaluated in RANKL-treated RAW 264.7 cells. The inhibition of interleukin-1, (IL-1,),mediated markers of inflammation was analyzed in human rheumatoid arthritis synovial fibroblasts (RASFs). Mice with carrageenan-induced acute inflammation and collagen-induced arthritis (CIA) were used to assess efficacy. Results META060 inhibited the activity of kinases (spleen tyrosine kinase [Syk], Bruton's tyrosine kinase [Btk], phosphatidylinositol 3-kinase [PI 3-kinase], and GSK3) associated with RA and inhibited ,-catenin phosphorylation. META060 inhibited osteoclastogenesis, as indicated by decreased transformation of RAW 264.7 cells to osteoclasts and reduced TRAP activity, and inhibited IL-1,,activated prostaglandin E2, matrix metalloproteinase 3, IL-6, IL-8, and monocyte chemotactic protein 1 in RASFs. In mice with acute inflammation, oral administration of META060 reduced paw swelling similar to the effect of aspirin. In mice with CIA, META060 significantly reduced the arthritis index and decreased bone, joint, and cartilage degradation. Serum IL-6 concentrations in these mice were inhibited in a dose-dependent manner. Conclusion Our findings indicate that META060 reduces swelling in a model of acute inflammation and inhibits bone and cartilage destruction in a model of chronic inflammation. Its efficacy is associated with the inhibition of multiple protein kinases, including Syk, Btk, PI 3-kinase, and GSK3. These results warrant further clinical testing of META060 for its therapeutic potential in the treatment of inflammatory diseases. [source]


Induction of triggering receptor expressed on myeloid cells 1 in murine resident peritoneal macrophages by monosodium urate monohydrate crystals

ARTHRITIS & RHEUMATISM, Issue 2 2006
Yousuke Murakami
Objective Triggering receptor expressed on myeloid cells 1 (TREM-1) is a cell surface molecule that was recently identified on monocytes and neutrophils. TREM-1 has been implicated in the early inflammatory responses induced by microbes, but its pathophysiologic role in nonmicrobial inflammation remains unknown. In the present study, we investigated the role of TREM-1 in acute inflammation induced by monosodium urate monohydrate (MSU) crystals. Induction of TREM-1 expression by MSU crystal,stimulated murine resident peritoneal macrophages and infiltrating leukocytes in a murine air-pouch model of crystal-induced acute inflammation was determined. The biologic role of TREM-1 in crystal-induced cytokine production by resident peritoneal macrophages was also investigated. Methods TREM-1 expression by resident peritoneal macrophages and infiltrating leukocytes in a murine air-pouch model was determined by quantitative real-time polymerase chain reaction, Western blot analysis, and flow cytometry. Cytokine production by resident peritoneal macrophages after incubation with MSU crystals in the presence or absence of an anti,TREM-1 agonist antibody was determined by enzyme-linked immunosorbent assay. Results TREM-1 expression by resident peritoneal macrophages was significantly induced after stimulation with the crystals. Maximum expression of TREM-1 transcripts and protein occurred at 1 and 4 hours after exposure to the crystals, respectively. Costimulation of resident peritoneal macrophages with MSU crystals and an anti,TREM-1 agonist antibody synergistically increased the production of both interleukin-1, and monocyte chemotactic protein 1 compared with stimulation with the crystals alone. MSU crystals also induced TREM-1 expression in infiltrating leukocytes in a murine air-pouch model of crystal-induced acute inflammation. Conclusion These findings suggest that rapid induction of TREM-1 expression on resident peritoneal macrophages and neutrophils by MSU crystals may contribute to the development of acute gout through enhancement of inflammatory responses. [source]


Rapid induction of peroxisome proliferator,activated receptor , expression in human monocytes by monosodium urate monohydrate crystals

ARTHRITIS & RHEUMATISM, Issue 1 2003
Tohru Akahoshi
Objective Peroxisome proliferator,activated receptor , (PPAR,) is a member of the nuclear hormone receptor superfamily and functions as a key regulator of lipid and glucose metabolism, atherosclerosis, and inflammatory responses. This study was undertaken to evaluate the biologic role of PPAR, in self-limiting episodes of acute gouty arthritis. To do this, we investigated PPAR, expression by monosodium urate monohydrate (MSU) crystal,stimulated monocytes, and we studied the effects of PPAR, ligands on crystal-induced acute inflammation. Methods PPAR, expression by MSU crystal,stimulated human peripheral blood mononuclear cells was determined by reverse transcription,polymerase chain reaction and immunostaining. Expression of CD36 on monocytes was detected by flow cytometric analysis. The effects of PPAR, ligands on in vitro crystal-induced cytokine production and on in vivo cellular infiltration during crystal-induced acute inflammation were also investigated. Results MSU crystals rapidly and selectively induced PPAR, expression by monocytes. Gene expression was detected as early as 2 hours, and maximum expression was observed at 4 hours after stimulation. The induced PPAR, was functional, since a PPAR, ligand was able to up-regulate CD36 expression on monocytes. A natural ligand of PPAR,, 15-deoxy-,12,14 -prostaglandin J2 (15deoxy-PGJ2), significantly reduced the crystal-induced production of cytokines by monocytes. Indomethacin inhibited cytokine production only at high concentrations, and an antidiabetic thiazolidinedione (troglitazone) failed to exert significant effects. Administration of troglitazone and 15deoxy-PGJ2 significantly prevented cellular accumulation in a mouse air-pouch model of MSU crystal,induced acute inflammation. Conclusion Rapid induction of PPAR, expression on monocytes by MSU crystals may contribute, at least in part, to the spontaneous resolution of acute attacks of gout. [source]


Adenosine A2A or A3 receptors are required for inhibition of inflammation by methotrexate and its analog MX-68

ARTHRITIS & RHEUMATISM, Issue 1 2003
M. Carmen Montesinos
Objective Low-dose weekly methotrexate therapy remains a mainstay in the treatment of inflammatory arthritis. Results of previous studies demonstrated that adenosine, acting at one or more of its receptors, mediates the antiinflammatory effects of methotrexate in animal models of both acute and chronic inflammation. We therefore sought to establish which receptor(s) is involved in the modulation of acute inflammation by methotrexate and its nonpolyglutamated analog MX-68 (N -[[4-[(2,4-diaminopteridin-6-yl)methyl]-3,4-dihydro-2H -1,4-benzothiazin-7-yl]-carbonyl]- L -homoglutamic acid). Methods We studied the effects of low-dose methotrexate (0.75 mg/kg intraperitoneally [IP] every week for 5 weeks), MX-68 (2 mg/kg IP 2 days and 1 hour before induction of inflammation), dexamethasone (1.5 mg/kg IP 1 hour before induction of inflammation), or vehicle control on acute inflammation in an air-pouch model in A2A and A3 receptor knockout mice. Results Low-dose weekly methotrexate treatment increased the adenosine concentration in the exudates of all mice studied and reduced leukocyte and tumor necrosis factor , accumulation in the exudates of wild-type mice, but not in those of A2A or A3 receptor knockout mice. Dexamethasone, an agent that suppresses inflammation by a different mechanism, was equally effective at suppressing leukocyte accumulation in A2A knockout, A3 knockout, and wild-type mice, indicating that the lack of response was specific for methotrexate and MX-68. Conclusion These findings confirm that adenosine, acting at A2A and A3 receptors, is a potent regulator of inflammation. Moreover, these results provide strong evidence that adenosine, acting at either or both of these receptors, mediates the antiinflammatory effects of methotrexate and its analog MX-68. [source]


Mechanisms underlying the anti-inflammatory activity and gastric safety of acemetacin

BRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2007
A E Chávez-Piña
Background and purpose: Acemetacin is regarded as a pro-drug of indomethacin and induces significantly less gastric damage but the reasons for this greater gastric safety of acemetacin are unclear. The anti-inflammatory effects of acemetacin have been attributed, at least in part, to its hepatic biotransformation to indomethacin. The aim of this study was to determine the effects of acemetacin and indomethacin in an in vivo model of acute inflammation and to examine the importance of biotransformation of acemetacin (to indomethacin) to its anti-inflammatory actions. Experimental approach: The zymosan airpouch model was used in rats. Indomethacin or acemetacin (2.7,83.8 ,mol kg,1) were administered orally or directly into the pouch. Leukocyte infiltration, prostaglandin (PG) E2 and leukotriene (LT) B4 levels in exudates, and whole blood thromboxane (TX) B2 synthesis were measured. Key results: Acemetacin was rapidly converted to indomethacin after its administration. Both acemetacin and indomethacin elicited comparable, dose-dependent reductions of leukocyte infiltration and of PGE2 and TXB2 synthesis. However, indomethacin induced more gastric damage than acemetacin and elevated LTB4 production in the airpouch. Conclusions and implications: The similar effects of acemetacin and indomethacin on leukocyte infiltration and PG synthesis are consistent with rapid biotransformation of acemetacin to indomethacin. Some of this biotransformation may occur extra-hepatically, for instance in inflammatory exudates. Acemetacin probably exerts actions independent of conversion to indomethacin, given the different effects of these two drugs on LTB4 production. Such differences may contribute to the relative gastric safety of acemetacin compared to indomethacin. British Journal of Pharmacology (2007) 152, 930,938; doi:10.1038/sj.bjp.0707451; published online 17 September 2007 [source]


Inhibition of glycogen synthase kinase-3, attenuates the development of carrageenan-induced lung injury in mice

BRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2006
S Cuzzocrea
Background and purpose: Glycogen synthase kinase-3 (GSK-3) is a ubiquitous serine-threonine protein kinase that participates in a multitude of cellular processes and has recently been implicated in the pathophysiology of a number of diseases. The aim of this study was to investigate the effects of GSK-3, inhibition in a model of acute inflammation. Here, we have investigated the effects of TDZD-8, a potent and selective GSK-3, inhibitor, in a mouse model of carrageenan-induced pleurisy. Experimental approach: 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), prostaglandin E2 (PGE2), tumour necrosis factor-,, (TNF-,) and interleukin-1, (IL-1,). Furthermore, carrageenan induced an upregulation of the adhesion molecules ICAM-1 and P-selectin, iNOS, COX-2 as well as nitrotyrosine as determined by immunohistochemical analysis of lung tissues. Key results: Administration of TDZD-8 (1, 3 or 10 mg kg,1, i.p.), 30 min prior to injection of carrageenan, caused a dose-dependent reduction in all the parameters of inflammation measured. Conclusions and Implications: Thus, based on these findings we propose that inhibitors of the activity of GSK-3,, such as TDZD-8, may be useful in the treatment of various inflammatory diseases. British Journal of Pharmacology (2006) 149, 687,702. doi:10.1038/sj.bjp.0706902 [source]


Nonregenerative stimulation of hepatocyte proliferation in the rat: Variable effects in relation to spontaneous liver growth; a possible link with metabolic induction

CELL PROLIFERATION, Issue 5 2000
C. Nadal
Three procedures were used to stimulate hepatocyte proliferation in the rat without reducing liver mass, resulting in a supplementary growth which differs from the regenerative growth observed after loss of liver mass by hepatectomy or toxic necrosis. They were: (a) the ingestion of cyproterone, a cytochrome P450 inducing drug (b) the injection of an irritant which provokes glycogenesis and synthesis of acute-phase proteins (c) the injection of albumin-bound bilirubin leading to elimination of glucuronated bilirubin in bile. This ensuing supplementary growth was studied in the rat under several conditions of hepatic proliferation: 1In normal adult rats, in which hepatocyte proliferation is very low, the effect on proliferation was either weak or undetectable. 2In suckling rats, with a rapid body and liver growth, all the stimulants provoked a synchronized wave of proliferation with a steep increase of the percentage of S-phase hepatocytes from 4.5% in controls to 15,30% in treated rats. This increase was followed by a compensatory period of low proliferation during which a treatment with a second stimulant was much less effective. 3In 2/3 hepatectomized adult rats, the proliferation induced by cyproterone was higher than the spontaneous regenerative proliferation alone and additional to it during all of the regenerative process. The proliferation induced by acute inflammation was competitive with the synchronous spontaneous proliferation during the early period of synchronized proliferation following surgery, suggesting that both are similar acute responses. Differently, during the late period of lower and unsynchronized regenerative proliferation, the proliferation provoked by acute inflammation was additional to the spontaneous one. A stimulation of proliferation by injection of the albumin-bilirubin complex was observed during the late period after 2/3 hepatectomy. The highest level of stimulation occurred when the liver growth and the hepatocyte proliferation were already high. This suggests that these stimulants are not complete mitogenic stimuli and need cofactors which are present during the spontaneous growth or, alternatively, that the effect of stimulants is opposed by an inhibitory mechanism present in the adult rat. [source]


2213: Herpetic keratitis: Herpes simplex virus versus host

ACTA OPHTHALMOLOGICA, Issue 2010
G VERJANS
Herpes simplex virus type 1 (HSV-1) is an endemic virus worldwide that causes ocular disease in a limited but significant number of infected persons. Corneal HSV-1 infection is clinically classified into herpetic epithelial keratitis (HEK) and herpetic stromal keratitis (HSK). HEK is an acute inflammation and results from viral toxicity of infected corneal epithelial cells. In contrast, HSK is characterized as a chronic immunopathogenic disease in which tissue injury and eventually blindness is due to the complex interplay between cells of the innate and adoptive immune response to viral antigens expressed in the corneal tissue. Studies performed on the experimental HSK mouse model greatly improved our understanding of the pathogenesis of HSK. This talk will recapitulate current insights on the virus-host interactions involved in the initiation and perpetuation of herpetic keratitis in mice and men. [source]


Acute scurvy during treatment with interleukin-2

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 7 2009
D. T. Alexandrescu
Summary The association of vitamin C deficiency with nutritional factors is commonly recognized. However, an acute form of scurvy can occur in patients with an acute systemic inflammatory response, which is produced by sepsis, medications, cancer or acute inflammation. The frequency of acute hypovitaminosis C in hospitalized patients is higher than previously recognized. We report the occurrence of acute signs and symptoms of scurvy (perifollicular petechiae, erythema, gingivitis and bleeding) in a patient hospitalized for treatment of metastatic renal-cell carcinoma with high-dose interleukin-2. Concomitantly, serum vitamin C levels decreased to below normal. Better diets and longer lifespan may result a lower frequency of acute scurvy and a higher frequency of scurvy associated with systemic inflammatory responses. Therefore, increased awareness of this condition can lead to early recognition of the cutaneous signs of acute scurvy in hospitalized patients with acute illnesses or in receipt of biological agents, and prevent subsequent morbidity such as bleeding, anaemia, impaired immune defences, oedema or neurological symptoms. [source]


Selective expansion of CD16highCCR2, subpopulation of circulating monocytes with preferential production of haem oxygenase (HO)-1 in response to acute inflammation

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2005
K. Mizuno
Summary Monocytes are composed of two distinct subpopulations in the peripheral blood as determined by their surface antigen expressions, profiles of cytokine production and functional roles played in vivo. We attempted to delineate the unique functional roles played by a minor CD16highCCR2, subpopulation of circulating monocytes. They produced significant levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-,, but very low levels of IL-10 upon in vitro stimulation. Characteristic profiles of cytokine production were confirmed by stimulating purified subpopulations of monocytes after cell sorting. It was noteworthy that freshly isolated CD16highCCR2, monocyte subpopulations produced significant levels of haem oxygenase (HO)-1, whereas the major CD16lowCCR2+ subpopulation produced little. These results were contrary to the generally accepted notion that the CD16highCCR2, monocyte subpopulation plays a predominantly proinflammatory role in vivo. The CD16highCCR2, subpopulation increased in Kawasaki disease and influenza virus infection. In accord with this, HO-1 mRNA expression by mononuclear cells was significantly increased in these illnesses. These results indicate that CD16highCCR2, subpopulations are of a distinct lineage from CD16lowCCR2+ monocytes. More importantly, they may represent a monocyte subpopulation with a unique functional role to regulate inflammation by producing HO-1 in steady state in vivo. [source]