INTERNATIONAL ENDODONTIC JOURNAL, Issue 7 2003
S. Liapatas
Abstract Aim, To determine the cellular profile of human chronic periradicular lesions using immunohistochemical methods in order to study the differences in the cell infiltrate of periradicular granulomas and cysts. Methodology, The study population consisted of 45 individuals without any systemic disease. Biopsies were obtained during periradicular surgery. Paraffin-embedded sections were stained by the avidin,biotin complex method (ABC), whilst cryostat tissue sections were stained using the alkaline phosphatase antialkaline phosphatase assay (APAAP). These methods are highly valid and sensitive using a panel of specific monoclonal antibodies: CD4, CD8, CD3, CD10, HLADR, CD20, CD45RO, CD68 and CD57. The 45 specimens were characterized by the use of both techniques. Results, The 45 specimens were histologically diagnosed as: 25 periradicular granulomas, 17 periradicular cysts and 3 scar tissues. No statistically significant differences were detected in the inflammatory infiltrate between periradicular granulomas and cysts. Observation of the sections showed that the majority of inflammatory cells consisted of T and B lymphocytes and macrophages. T and B lymphocytes were equally distributed in 60% of the cases. The T4/T8 ratio ranged approximately from 1 to 3 and greater, being consistent with inflammation of periradicular tissues. The final differentiation of B lymphocytes to plasma cells was also detected, whilst natural killer (NK) cells were found in only 10 cases (22%). Moreover, antigen presenting cells and T suppressor/cytotoxic cells were found to be associated with both pre-existing and newly formed epithelium. Conclusions, Periradicular granulomas and cysts represent two different stages in the development of chronic periradicular pathosis as a normal result of the process of immune reactions that cannot be inhibited. [source]

Understanding and Treating Patients With Alcoholic Cirrhosis: An Update

ALCOHOLISM, Issue 7 2009
Giovanni Addolorato
Alcoholic cirrhosis represents the terminal stage of alcoholic liver disease (ALD) and one of the main causes of death among alcohol abusers. The aim of this review was to provide an update on alcoholic cirrhosis, with an emphasis on recent findings. Increased alcohol consumption in developing countries is expected to increase cirrhosis mortality. There is a need, therefore, to develop new approaches to the prevention of ALD, including more attention to co-factors that may increase risk of ALD (i.e., obesity and diabetes, chronic HCV infection, and smoking). Furthermore, a better understanding of the pathological mechanisms on the basis of alcohol cirrhosis represents a cornerstone in order to develop new pharmacological treatments. Inflammatory and immune responses along with oxidative stress and alterations in adipokine secretion might contribute in different ways to the evolution of alcohol-induced fibrosis/cirrhosis. As of this date, patients with severe alcoholic hepatitis with a Maddrey Discriminant Factor (MDF) 32 should be offered pentoxifylline and/or corticosteroids unless contraindications exist. For ambulatory patients, S-adenosylmethionine (SAMe) may be considered in a motivated patient with nutritional support. Current studies do not support use of anti-tumor necrosis factor (TNF)-alpha antibody. Finally, achieving total alcohol abstinence should represent the main aim in the management of patients affected by any stage of cirrhosis. In the last decades, several drugs able to increase abstinence and prevent alcohol relapse have been evaluated and some of them have obtained approval for alcohol dependence. Patients with alcoholic cirrhosis; however, are usually excluded from such treatments. A recent study demonstrated the efficacy and safety of baclofen in inducing and maintaining alcohol abstinence in cirrhotic alcohol-dependent patients with cirrhosis. All together the information available suggests the need of a multimodal approach in the clinical management of these patients. [source]

The use of exclusive enteral nutrition for induction of remission in children with Crohn's disease demonstrates that disease phenotype does not influence clinical remission

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009
E. BUCHANAN
Summary Background, Exclusive enteral nutrition (EEN) achieves variable remission rates in patients with Crohn's disease (CD). Aim, To describe our experience of treating CD with an 8-week course of primary EEN and to study factors affecting treatment outcome. Methods, All CD patients treated with EEN in our centre between 2004 and 2007 were included in the study. Remission was determined by a combination of clinical parameters. Disease phenotype was assigned using published classifications. Inflammatory markers and anthropometry (Z -scores) were calculated before and after treatment. Results, A total of 114 children were treated (four were excluded). Median age at diagnosis was 11.6 years. Fifty-seven (51.8%) were fed orally whilst 53 (48.2%) were fed by tube. Eighty-eight (80%) achieved remission with consequent reductions in erythrocyte sedimentation rate and C-reactive protein (P < 0.001). Patients in remission had comparative improvements in weight (,1.04 cf. ,0.40) and BMI Z -scores (,0.98 cf. ,0.03) by the end of treatment (P < 0.001). Individuals with isolated terminal ileal disease (n = 4) had lower remission rates than other locations (P = 0.02). No other significant differences in remission rates for any other disease locations were found. Conclusions, Exclusive enteral nutrition induces clinical remission, normalization of inflammatory markers and improves weight/BMI Z -scores in most patients. This study demonstrates that disease phenotype should not influence clinicians when commencing patients on EEN. [source]

Quantitative Analysis of Inflammatory and Immune Responses in Dogs with Gastritis and Their Relationship to Helicobacter spp.

JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2005
Infection
The present study sought to quantitatively examine mucosal inflammatory and immune responses in dogs with gastritis and the relationship of these responses to infection with Helicobacter. Gastric biopsies from 30 dogs were evaluated for B- and T-lymphocytes, neutrophils, eosinophils, macrophages, and mast cells. Mucosal atrophy, fibrosis, cellularity, and severity of gastritis were graded qualitatively. Messenger-RNA (mRNA) for actin, interleukin-1, (IL-1,), IL-4, IL-8, and IL-10, transforming growth factor beta (TGF-,), and interferon gamma (IFN-,) was quantified by polymerase chain reaction (PCR). The presence of Helicobacter spp. was determined by urease activity, histology, PCR, and enzyme-linked immunosorbent assay. mRNA for IL-1,, IL-8, IL-10, TGF-,, and IFN-, was detected in most dogs. IL-4 mRNA was detected in only 1 dog. Correlations were observed for IL-1, versus IL-8 and IL-10; IL-8 versus IL-10, IFN-,, and TGF-,; and IL-10 versus IFN-,. Mucosal pathology was related to cytokine mRNA expression (neutrophils to IL-8 and IFN-,, macrophages and lymphocytes to IFN-,, and fibrosis to IL-1,). Gastritis was categorized as lymphoplasmacytic in all dogs, and its histologic severity correlated with atrophy, infiltration with lymphocytes and macrophages, and expression of IL-10 and IFN-,. Of the dogs examined, 76.7% were infected with Helicobacter spp. Infection was associated with increased expression of TGF-, and fibrosis. Circulating anti- Helicobacter immunoglobulin G titers were higher in uninfected than infected dogs. We conclude that lymphoplasmacytic gastritis in dogs is characterized by concurrent activation of proinflammatory and immunomodulatory cytokines, with increased mRNA expression related to mucosal pathology. No significant associations between Helicobacter infection and proinflammatory cytokine expression, severity of gastritis, or differences in the pathogenicity of different Helicobacter spp. were found. [source]

Inflammatory profiles in nasal mucosa of patients with persistent vs intermittent allergic rhinitis

ALLERGY, Issue 9 2010
F. Liu
To cite this article: Liu F, Zhang J, Liu Y, Zhang N, Holtappels G, Lin P, Liu S, Bachert C. Inflammatory profiles in nasal mucosa of patients with persistent vs intermittent allergic rhinitis. Allergy 2010; 65: 1149,1157. Abstract Background:, To date there is little information on the inflammatory profiles of patients suffering from persistent (PER) and intermittent allergic rhinitis (IAR). Also, it is not clear whether differences exist in eosinophilic inflammation and/or T-helper cell sub-populations and their markers. The aim of this study was to primarily evaluate the inflammatory profiles of patients with moderate/severe PER and IAR. Methods:, Inferior nasal turbinate tissue was obtained from 12 PER, 12 IAR and 12 nonallergic nonrhinitic (control) patients, and symptoms (visual analogue scales, VAS) and impairment of life was monitored. All tissues were assessed for eosinophil and mast cell numbers by immunohistochemistry; IL-5, ECP and IgE concentrations by immunoassay; mRNA for transcription factors GATA-3, T-bet, FOXP3 and RORc by quantitative real-time polymerase chain reaction; and IgE-induced release of LTC4/D4/E4 and PGD2in vitro. Results:, Eosinophils and mast cells were significantly increased in patients with PER and patients with IAR compared to control subjects; by patients with PER demonstrating even significantly greater increase of both cell types than patients with IAR. Similarly, ECP IL-5, GATA-3 mRNA expression and IgE-induced release of LTC4/D4/E4 and PGD2 from mast cells were significantly increased in patients with PER compared to patients with IAR. In contrast, the expression of T-bet, FOXP3 or RORc mRNA was not significantly different in the PER, IAR or control patients. Conclusion:, The findings from the present study suggest that PER is characterized by a significantly greater eosinophilic and predominantly Th2 cell-mediated nasal inflammatory profile compared to IAR. [source]

Inflammatory and Hemodynamic Changes in the Cerebral Microcirculation of Aged Rats after Global Cerebral Ischemia and Reperfusion

MICROCIRCULATION, Issue 4 2008
Leslie Ritter
ABSTRACT Effects of aging on inflammation and blood flow in the brain are unclear. Young (three to six months) and aged (19,22 months) male Brown Norway Fisher rats were used to compare (i) leukocyte function in nonischemic conditions and (ii) leukocyte function and hemodynamic changes after ischemia-reperfusion (I-R). In nonischemic studies, polymorphonuclear (PMN) CD11b expression and reactive oxygen species (ROS) production were measured with flow cytometry and PMN chemotaxis was measured with a Boyden chamber (+/-fMLP). In I-R studies, ischemia was induced by bilateral carotid artery occlusion and hypotension (20 minutes). During early reperfusion (30 minutes), leukocyte adhesion and rolling and blood-shear rates were measured using fluorescence microscopy. During late reperfusion (48 hours), mortality, neurological function, and leukocyte infiltration were measured. Stimulated PMN chemotaxis was increased in nonischemic aged rats (p < 0.05). In early reperfusion, there was a significant increase in leukocyte rolling and adhesion in the cerebral microcirculation and a significant decrease in shear rate in aged rats, compared to the young (p < 0.05). During late reperfusion, neurologic function was worse in aged vs. young rats (p < 0.05). These findings suggest that increased intravascular PMN adhesion and vascular dysfunction may contribute to poor neurologic outcome after cerebral I-R in the aged brain. [source]

Cytokine pattern determines the progression of experimental periodontal disease induced by Actinobacillus actinomycetemcomitans through the modulation of MMPs, RANKL, and their physiological inhibitors

MOLECULAR ORAL MICROBIOLOGY, Issue 1 2006
G. P. Garlet
Objective:, Inflammatory and immune reactions raised in response to periodontopathogens are thought to trigger periodontal tissue destruction. We therefore investigated the expression of matrix metalloproteinases (MMPs) and the osteoclastogenic factor RANKL (receptor activator of nuclear factor-,B ligand), their respective inhibitors TIMPs (tissue inhibitors of metalloproteinases) and OPG (osteoprotegerin) and their possible correlation with the expression of inflammatory and regulatory cytokines in the course of experimental periodontal disease in mice. Methods:, We characterized the time course of leukocyte migration and alveolar bone loss in C57BL/6 mice infected with Actinobacillus actinomycetemcomitans. Quantitative polymerase chain reaction (RealTime PCR) and ELISA were performed to determine the expression of MMPs, TIMPs, RANKL, OPG and cathepsin K, interleukin-1,, tumor necrosis factor-,, interferon-,, interleukin-12, interleukin-4 and interleukin-10 in periodontal tissue samples harvested throughout the course of experimental disease. Results:, Oral inoculation of A. actinomycetemcomitans results in an intense and widespread migration of leukocytes to the gingival tissues, besides marked alveolar bone resorption. Our data also demonstrate two distinct patterns of MMP/TIMP and RANKL/OPG expression in the course of experimental periodontal disease. The expression of MMPs (MMP-1, 2 and 9) and RANKL was correlated with the expression of interleukin-1,, tumor necrosis factor-, and interferon-,, in a time period characterized by the intense increase of inflammatory reaction and alveolar bone loss. On the other hand, interleukin-4 and interleukin-10 were associated with higher expression of TIMPs (TIMP 1, 2 and 3) and OPG, with a lower expression of MMPs and RANKL, and with reduced rates of increase of cellular infiltration in periodontal tissues and alveolar bone loss. Conclusions:, It is possible that the pattern of cytokines produced in periodontal tissues determines the progression and the severity of experimental periodontal disease, controlling the breakdown of soft and bone tissues through the balance between MMPs/TIMP and RANKL/OPG expression in gingival tissues. [source]

Minocycline treatment following hypoxic/ischaemic injury attenuates white matter injury in a rodent model of periventricular leucomalacia

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2008
M. Lechpammer
Aims: Periventricular white matter injury in premature infants occurs following hypoxia/ischaemia and systemic infection, and results in hypomyelination, as well as neuromotor and cognitive deficits later in life. Inflammatory infiltrates are seen within human cerebral white matter from periventricular leucomalacia (PVL) cases. Methods: In this study, we examine the time course of CD-68+ microglial cell responses relative to cell death within white matter following hypoxia/ischaemia in a rat model of PVL. We also tested the efficacy of the minocycline, an agent that suppresses microglial activation, in this model when administered as a post-insult treatment. Results: We show that preoligodendrocyte injury in the post-natal day 6 begins within 24 h and continues for 48,96 h after hypoxia/ischaemia, and that microglial responses occur primarily over the first 96 h following hypoxia/ischaemia. Minocycline treatment over this 96 h time window following the insult resulted in significant protection against white matter injury, and this effect was concomitant with a reduction in CD-68+ microglial cell numbers. Conclusions: These results suggest that anti-inflammatory treatments may represent a useful strategy in the treatment of PVL, where clinical conditions would favour a post-insult treatment strategy. [source]

Fractional 1320 nm Nd : YAG laser in the treatment of acne vulgaris: a pilot study

PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 5 2009
Hui Deng
Thirty-five patients with moderate to severe acne were treated with a fractional 1320 nm neodymium : yttrium aluminum garnet (Nd : YAG) laser. These patients received six treatment sessions at a 2-week interval. Inflammatory and non-inflammatory lesions were counted before and after treatment. Fractional 1320 nm Nd : YAG laser therapy was well tolerated, resulting in the reduction of inflammatory lesions by 57% (P<0.05) and the reduction of non-inflammatory lesions by 35% (P<0.05). A significant reduction in the skin sebum level by 30% (P<0.05) was also noted after treatment. [source]

Deficiency of tenascin-C attenuates liver fibrosis in immune-mediated chronic hepatitis in mice,

THE JOURNAL OF PATHOLOGY, Issue 1 2007
A El-Karef
Abstract Tenascin-C (TNC), an extracellular matrix glycoprotein, is upregulated in chronic liver disease. Here, we investigated the contribution of TNC to liver fibrogenesis by comparing immune-mediated hepatitis in wild-type (WT) and TNC-null (TNKO) mice. Eight-week-old BALB/c mice received weekly intravenous injections of concanavalin A to induce hepatitis, and were sacrificed one week after the 3rd, 6th, 9th, and 12th injections. In WT livers, immunohistochemical staining revealed a gradual increase in TNC deposition. TNC mRNA levels also increased sequentially and peaked after the 9th injection. Collagen deposition, stained with picrosirius red, was significantly less intense in TNKO mice than in WT mice, and procollagen I and III transcripts were significantly upregulated in WT mice compared with TNKO mice. Inflammatory infiltrates were most prominent after the 3rd-6th injections in both groups and were less intense in TNKO mice than in WT mice. Interferon- ,, tumour necrosis factor- ,, and interleukin-4 mRNA levels were significantly higher in WT mice than in TNKO mice, while activated hepatic stellate cells (HSCs) and myofibroblasts, a cellular source of TNC and procollagens, were more common in WT livers. Transforming growth factor (TGF)- ,1 mRNA expression was significantly upregulated in WT mice, but not in TNKO mice. In conclusion, TNC can promote liver fibrogenesis through enhancement of inflammatory response with cytokine upregulation, HSC recruitment, and TGF-, expression during progression of hepatitis to fibrosis. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source]

Human inflammatory synovial fibroblasts induce enhanced myeloid cell recruitment and angiogenesis through a hypoxia-inducible transcription factor 1,/vascular endothelial growth factor,mediated pathway in immunodeficient mice

ARTHRITIS & RHEUMATISM, Issue 10 2009
Manuel J. del Rey
Objective Hyperplasia and phenotypic changes in fibroblasts are often observed in chronic inflammatory lesions, and yet the autonomous pathogenic contribution of these changes is uncertain. The purpose of this study was to analyze the intrinsic ability of fibroblasts from chronically inflamed synovial tissue to drive cell recruitment and angiogenesis. Methods Fibroblasts from patients with rheumatoid arthritis (RA) or osteoarthritis (OA), as well as fibroblasts from healthy synovial tissue and healthy skin, were cultured and subcutaneously engrafted into immunodeficient mice. Cell infiltration and angiogenesis were analyzed in the grafts by immunohistochemical studies. The role of vascular endothelial growth factor (VEGF), CXCL12, and hypoxia-inducible transcription factor 1, (HIF-1,) in these processes was investigated using specific antagonists or small interfering RNA (siRNA),mediated down-regulation of HIF-1, in fibroblasts. Results Inflammatory (OA and RA) synovial fibroblasts, compared with healthy dermal or synovial tissue fibroblasts, induced a significant enhancement in myeloid cell infiltration and angiogenesis in immunodeficient mice. These activities were associated with increased constitutive and hypoxia-induced expression of VEGF, but not CXCL12, in inflammatory fibroblasts compared with healthy fibroblasts. VEGF and CXCL12 antagonists significantly reduced myeloid cell infiltration and angiogenesis. Furthermore, targeting of HIF-1, expression by siRNA or of HIF-1, transcriptional activity by the small molecule chetomin in RA fibroblasts significantly reduced both responses. Conclusion These results demonstrate that chronic synovial inflammation is associated with stable fibroblast changes that, under hypoxic conditions, are sufficient to induce inflammatory cell recruitment and angiogenesis, both of which are processes relevant to the perpetuation of chronic inflammation. [source]

Inflammatory rheumatic disease and smoking are predictors of aortic inflammation: A controlled study of biopsy specimens obtained at coronary artery surgery,

ARTHRITIS & RHEUMATISM, Issue 6 2007
Ivana Hollan
Objective Several inflammatory rheumatic diseases are associated with accelerated atherosclerosis. Atherosclerosis may result from systemic and/or local vascular inflammation. The aim of this study was to evaluate the occurrence of chronic inflammatory infiltrates in the aortas of patients with and those without inflammatory rheumatic disease who had undergone coronary artery bypass graft (CABG) surgery, and to assess the relationship between the infiltrates and other factors thought to play a role in atherosclerosis, such as smoking. Methods Aortic specimens routinely removed during CABG surgery in 66 consecutive patients with inflammatory rheumatic disease and 51 control patients without inflammatory rheumatic disease were examined by light microscopy for the occurrence, location, and severity of chronic inflammatory infiltrates and atherosclerotic lesions. Results Mononuclear cell infiltrates in the inner adventitia (apart from those localized along the epicardium) were more frequent in the group of patients with inflammatory rheumatic disease (47% versus 20%; P = 0.002, odds ratio [OR] OR 3.6, 95% confidence interval [95% CI] 1.6,8.5), and the extent of these infiltrates was greater. Multivariate analyses revealed that the occurrence of mononuclear cell infiltrates was associated with inflammatory rheumatic disease (OR 2.99, P = 0.020) and current smoking (OR 3.93, P = 0.012), and they were observed in 6 of 7 patients with a history of aortic aneurysm. Inflammatory infiltrates in the media were seen only in patients with inflammatory rheumatic disease. The frequency of atherosclerotic lesions, inflammation within the plaques, and epicardial inflammatory infiltrates in the 2 groups was equal. Conclusion Among aortic samples collected during CABG surgery, those obtained from patients with inflammatory rheumatic disease had more pronounced chronic inflammatory infiltration in the media and inner adventitia than those obtained from control patients. Current smoking was an independent predictor of chronic inner adventitial infiltrates. The infiltrates may represent an inflammatory process that promotes atherosclerosis and formation of aneurysms. [source]

Neuropathology and Pathogenesis of Encephalitis following Amyloid , Immunization in Alzheimer's Disease

BRAIN PATHOLOGY, Issue 1 2004
Isidre Ferrer
Immunizing transgenic PDAPP mice, which overexpress mutant APP and develop ,-amyloid deposition resembling plaques in Alzheimer's disease (AD), results in a decrease of amyloid burden when compared with non treated transgenic animals im-munization with amyloid , peptide has been initiated in a randomised pilot study in AD. Yet a minority of patients developed a neurological complication consistent with meningoencephalitis and one patient died; the trial has been stopped. Neuropathological examination in that patient showed meningoencephalitis and focal atypically low numbers of diffuse and neuritic plaques but not of vascular amyloid nor regression of tau pathology in neurofibrillary tangles and neuropil threads. The present neuropathological study reports the second case of menigoencephalitis following immunization with amyloid-, peptide in AD, and has been directed toward exploring mechanisms underlying decreased tau pathology in relation- with amyliod deposit regression, and possible molecular bases involved in the inflammatory response following immunization. Inflammatory infiltrates were composed of CD8+, CD3+, CD5+ and, rarely, CD7+ lymphocytes, whereas B lymphocytes and T cytotoxic cells CD16, CD57, TIA and graenzyme were negative. Characteristic neuropathological findings were focal depletion of diffuse and neuritic plaques, but not of amyloid angiopathy, and the presence of small numbers of extremely dense(collapsed) plaques surrounded by active microglia, and multinucleated giant cells filled with dense A,42and A,40, in addition to severe small cerebral blood Reduced amyloid burden was accompanied by low amyloid-associated oxidative stress responses (reduced superoxide dismutase-1:SOD-1 expression) and by local inhibition of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 kinase which are involved in tau phosphorylation. These results support the amyloid cascade of tau phosphorylation in AD regarding phosphorylation of tau in neurofibrillary tangles and ,-amyloid deposition in neuritic plaques, but not of tau in neurofibrillary tangles and threads. Furthermore, amyloid reduction was accompanied by increased expression of the PA28,/, inductor, and of LMP7, LMP2 and MECL1 subunits of the immunopro-teasome in microglial and inflammatory cells surrounding collapsed plaques, and in multinucleated giant cells.Immunoproteasome subunit expression was accompanied by local presentation of MHC class molecules. Release of antigenic peptides derived from ,-amyloid processing may enhance T-cell inflammatory responses accounting for the meningoencephalitis following amyloid-, peptide immunization [source]

Inflammatory and oxidative stress biomarkers in allergic rhinitis: the effect of smoking

CLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2009
K. Tanou
Summary Background Accumulating evidence confirms the presence of pan-airway inflammation in allergic rhinitis patients. Smoking is known to affect the asthmatic airway inflammation. However, no study has evaluated the impact of smoking on airway inflammation of allergic rhinitis patients. Objective The aim of the present study was to evaluate the impact of smoking on inflammatory and oxidative stress biomarkers in patients with seasonal allergic rhinitis, using non-invasive methods for sample collection. Methods Forty patients with seasonal allergic rhinitis (20 smokers and 20 non-smokers) and 30 healthy subjects (15 smokers and 15 non-smokers) were recruited for the study during pollen season. All subjects were submitted to measurement of the fraction of exhaled NO (FeNO), exhaled breath condensate (EBC) collection, nasal lavage collection, pre- and post- bronchodilation spirometry and metacholine bronchial challenge testing. pH, leukotriene B4 (LTB4) and 8-isoprostane were determined in EBC and nasal lavage samples. Results Patients with allergic rhinitis presented higher LTB4 and 8-isoprostane levels in nasal lavage (P<0.0001 for both comparisons), with no significant differences between smokers and non-smokers. Patients with allergic rhinitis also presented higher LTB4 levels and lower pH in EBC (P<0.001 and P=0.004, respectively), with prominent differences between smokers and non-smokers (P<0.0001 and P=0.003, for LTB4 and pH, respectively). A significant correlation between nasal lavage and EBC LTB4 values was observed (rs=0.313, P=0.048). Conclusions Patients with allergic rhinitis present increased LTB4 and 8-isoprostane in their nasal cavity, however, with no significant differences between smokers and non-smokers. In contrast, smokers with allergic rhinitis present higher LTB4 levels and lower pH in EBC, suggesting that these patients may be more susceptible to the deleterious effects of smoking, compared with non-smokers. [source]

Spectroscopic increase in choline signal is a nonspecific marker for differentiation of infective/inflammatory from neoplastic lesions of the brain

JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 1 2001
Sudhakar K. Venkatesh MD
Abstract We report in vivo proton magnetic resonance (MR) spectroscopic findings in three benign infective/inflammatory lesions (one case each of tuberculoma, fungal granuloma, and xanthogranuloma), which showed high choline along with the presence of lipid/lactate, a feature characteristically described in neoplastic lesions. Histopathology of the lesions showed inflammatory cellular infiltrates with areas of necrosis/caseation. The spectroscopic-visible increased choline resonance in these lesions is probably the result of cellularity. We conclude that increased choline, along with the presence of lipid/lactate is a nonspecific finding and may not be of much value in the differentiation of neoplastic from nonneoplastic infective/inflammatory intracranial mass lesions. J. Magn. Reson. Imaging 2001;14:8,15. © 2001 Wiley-Liss, Inc. [source]

Invasive and Noninvasive Correlations of B-Type Natriuretic Peptide in Patients With Heart Failure Due to Chagas Cardiomyopathy

CONGESTIVE HEART FAILURE, Issue 3 2008
Fábio Vilas-Boas MD
Heart failure due to Chagas cardiomyopathy (HFCC) differs from failure with other etiologies because of the occurrence of intense inflammatory infiltrate and right ventricle compromise. This article investigates correlations of B-type natriuretic peptide (BNP) levels with parameters of severity in HFCC. Twenty-eight patients and 8 normal controls underwent heart catheterization and clinical and laboratory analyses. BNP levels were higher in patients with HFCC (P<.0001) and correlated with New York Heart Association (NYHA) class; right atrial pressure; wedge pressure; cardiac output; levels of serum sodium, hemoglobin, urea, and tumor necrosis factor-,; and ejection fraction. Interferon-, and transforming growth factor-, did not correlate with BNP level. The authors conclude that BNP levels are elevated in patients experiencing HFCC, irrespective of NYHA class, and that the occurrence of HFCC correlates with severity of disease. [source]

The calcium-conducting ion channel transient receptor potential canonical 6 is involved in macrophage inflammatory protein-2-induced migration of mouse neutrophils,

ACTA PHYSIOLOGICA, Issue 1 2009
N. Damann
Abstract Aim:, The role of the calcium-conducting ion channel transient receptor potential canonical 6 (TRPC6) in macrophage inflammatory protein-2 (MIP-2) induced migration of mouse neutrophils was investigated. Methods:, Neutrophil granulocytes isolated from murine bone marrow of wild-type (TRPC6+/+) and TRPC6 knockout (TRPC6,/,) mice were tested for the presence of TRPC6 channel expression using quantitative real-time polymerase chain reactions and immunocytochemistry. The effect of different stimuli (e.g. MIP-2, 1-oleoyl-2-acetyl-sn-glycerol, formyl-methionyl-leucyl-phenylalanin) on migration of isolated neutrophils was tested by two-dimensional (2D) migration assays, phalloidin staining and intracellular calcium imaging. Results:, We found that neutrophil granulocytes express TRPC6 channels. MIP-2 induced fast cell migration of isolated neutrophils in a 2D cell-tracking system. Strikingly, MIP-2 was less potent in neutrophils derived from TRPC6,/, mice. These cells showed less phalloidin-coupled fluorescence and the pattern of cytosolic calcium transients was altered. Conclusions:, We describe in this paper for the first time a role for transient receptor potential (TRP) channels in migration of native lymphocytes as a new paradigm for the universal functional role of TRPs. Our data give strong evidence that TRPC6 operates downstream to CXC-type Gq -protein-coupled chemokine receptors upon stimulation with MIP-2 and is crucial for the arrangement of filamentous actin in migrating neutrophils. This is a novel cell function of TRP channel beyond their well-recognized role as universal cell sensors. [source]

Could chronic pain and spread of pain sensation be induced and maintained by glial activation?

ACTA PHYSIOLOGICA, Issue 1-2 2006
E. Hansson
Abstract An injury often starts with acute physiological pain, which becomes inflammatory or neuropathic, and may sometimes become chronic. It has been proposed recently that activated glial cells, astrocytes and microglia within the central nervous system could maintain the pain sensation even after the original injury or inflammation has healed, and convert it into chronic by altering neuronal excitability. Glial cell activation has also been proposed to be involved in the phenomenon of spread of pain sensation ipsilaterally or to the contralateral side (i.e. mirror image pain). Substance P and calcitonin gene-related peptide, released due to an inflammatory process, interact with the endothelial cells of the blood,spinal cord and blood,brain barriers. The barriers open partially and substances may influence adjacent glial cells. Such substances are also released from neurones carrying the ,pain message' all the way from the injury to the cerebral cortex. Pro-inflammatory cytokines may be released from the microglial cells, and astroglial Ca2+ -transients or oscillations may spread within the astroglial networks. One theory is that Ca2+ -oscillations could facilitate the formation of new synapses. These new synapses could establish neuronal contacts for maintaining and spreading the pain sensation. If this theory holds true, it is possible that Ca2+ waves, production of cytokines and growth factors could be modified by selective anti-inflammatory drugs to achieve a balance in the activities of the different intercellular and intracellular processes. This paper reviews current knowledge about glial mechanisms underlying the phenomena of chronic pain and spread of the pain sensation. [source]

NON-GYNAECOLOGICAL CYTOLOGY: THE CLINICIAN'S VIEW

CYTOPATHOLOGY, Issue 2006
I. Penman
There is increased recognition of the importance of accurate staging of malignancies of the GI tract and lung, greater use of neoadjuvant therapies and more protocol-driven management. This is particularly important where regional lymph node involvement significantly impacts on curability. Multidetector CT and PET scanning have resulted in greater detection of potential abnormalities which, if positive for malignancy, would change management. There is also a greater recognition that many enlarged nodes may be inflammatory and that size criteria alone are unreliable in determining involvement. In other situations, especially pancreatic masses, not all represent carcinoma as focal chronic pancreatitis, autoimmune pancreatitis etc can catch out the unwary. A preoperative tissue diagnosis is essential and even if unresectable, oncologists are increasingly reluctant to initiate chemotherapy or enroll patients into trials without this. The approach to obtaining tissue is often hampered by the small size or relative inaccessibility of lesions by percutaneous approaches. As such novel techniques such as endoscopic ultrasound (EUS) guided FNA have been developed. A 120cm needle is passed through the instrument and, under real-time visualisation, through the gastrointestinal wall to sample adjacent lymph nodes or masses. Multiple studies have demonstrated the safety and performance of this technique. In oesophageal cancer, confirmation of node positivity by has a major negative influence on curative resection rates and will often lead to a decision to use neoadjuvant chemotherapy or a non-operative approach. Sampling of lymph nodes at the true coeliac axis upstages the patient to M1a status (stage IV) disease and makes the patient incurable. In NSCLC, subcarinal lymph nodes are frequently present but may be inflammatory. If positive these represent N2 (stage IIIA) disease and in most centres again makes the patient inoperable. Access to these lymph nodes would otherwise require mediastinosocopy whereas this can be done simply, safely and quickly by EUS. Overall the sensitivity for EUS , FNA of mediastinal or upper abdominal lymph nodes is 83,90% with an accuracy of 80,90%. In pancreatic cancer performance is less good but pooled analysis of published studies indicates a sensitivity of 85% and accuracy of 88%. In a recent spin-off from EUS, endobronchial ultrasound (EBUS) instruments have been developed and the ability to sample anterior mediastinal nodes has been demonstrated. It is likely that this EBUS , FNA technique will become increasingly utilised and may replace mediastinoscopy. The development of techniques such as EUS and EBUS to allow FNA sampling of lesions has increased the role of non-gynaecological cytology significantly in recent years. Cytology therefore remains important for a broad range of specialties and there is ongoing need for careful and close co-operation between cytologists and clinicians in these specialties. References:, 1. Williams DB, Sahai AV, Aabakken L, Penman ID, van Velse A, Webb J et al. Endoscopic ultrasound guided fine needle aspiration biopsy: a large single centre experience. Gut. 1999; 44: 720,6. 2. Silvestri GA, Hoffman BJ, Bhutani MS et al. Endoscopic ultrasound with fine-needle aspiration in the diagnosis and staging of lung cancer. Ann Thorac Surg 1996; 61: 1441,6. 3. Rintoul RC, Skwarski KM, Murchison JT, Wallace WA, Walker WS, Penman ID. Endobronchial and endoscopic ultrasound real-time fine-needle aspiration staging of the mediastinum ). Eur Resp J 2005; 25: 1,6. [source]

Borderline nuclear change; can a subgroup be identified which is suspicious of high-grade cervical intraepithelial neoplasia, i.e. CIN 2 or worse?

CYTOPATHOLOGY, Issue 5 2002
J. M. Edwards
Borderline nuclear change; can a subgroup be identified which is suspicious of high-grade cervical intraepithelial neoplasia, i.e. CIN 2 or worse? Only 10% of first borderline smears are associated with a histological high-grade (HG) abnormality, i.e. CIN 2,3, invasive malignancy or glandular neoplasia on subsequent investigation. The advantages of highlighting this subgroup are obvious but is this possible? From 1996 and 1997, 242 borderline smears with histological follow-up were examined by two independent experienced observers (observer 1 and 2) without prior knowledge of further investigation results. For each smear a profile of nuclear details was produced, also noting the type of cell mainly affected by the process; then the observers were asked to assess the degree of worry of HG disease for each smear i.e. whether the smear fell into group 1 borderline changes indicative of low-grade (normal, inflammatory, CIN1/HPV) disease (BL/LG) or group 2 difficult borderline smear, HG disease (CIN 2,3, invasive neoplasia or glandular neoplasia) cannot be excluded (BL/HG). Observer 1 selected a group of BL/HG with a PPV for HG disease of 38%, with observer 2 having a PPV of 50%; this compared with the overall laboratory HG disease PPV for borderline smears of 14%. Both observers found the most useful criterion to be the increase in nuclear:cytoplasmic ratio. Our results show that it is possible to separate a small group of borderline smears which should be classified as ,borderline/high grade lesion difficult to exclude' (BL/HG). Both observers had some success in arriving at this classification although their method of selecting out this group was quite different. [source]

Comparison of acidic fibroblast growth factor on collagen carrier with calcium hydroxide as pulp capping agents in monkeys

DENTAL TRAUMATOLOGY, Issue 5 2007
Zhimei Li
Abstract,,, Acidic fibroblast growth factor (aFGF) has been shown to facilitate wound healing by stimulating fibroblast proliferation and angiogenesis. It has also been reported to possess a powerful anti-apoptotic function This study compared the histological pulp responses to aFGF on collagen carrier and Ca(OH)2 placed on the mechanically exposed dental pulp in monkeys at two observation periods. Thirty-six teeth with pulp exposures were distributed into three groups according to the capping agents used prior to application of the coronal seal: collagen-based matrix carrier (group 1), aFGF on the collagen-based matrix carrier (group 2) and aqueous calcium hydroxide [Ca(OH)2] paste (group 3). Specimens were harvested at 6 and 13 weeks postoperatively and prepared for hematoxylin and eosin, and Gram staining. Histological qualitative evaluation of pulp responses were performed under the light microscope following criteria modified from Cox et al. (17) and Hu et al. (18). Semi-quantitative analysis was also carried out using Kruskal,Wallis and Mann,Whitney U -tests. There was neither negligible inflammatory infiltrates with no bacteria present in the three groups at both timings, nor was there any significant difference in the soft tissue organization among the three groups at or between the 6- and 13-week observation periods. At 6 weeks, the hard tissue barrier produced by Ca(OH)2 group (1.040 ± 0.089) was significantly more superior than aFGF/collagen carrier group (1.930 ± 0.825) (P = 0.030) as well as collagen carrier group (3.142 ± 1.069, P = 0.018). At 13 weeks, both aFGF/collagen carrier group (1.214 ± 0.485) and the collagen carrier group (1.457 ± 0.814) produced significantly better hard tissue barrier (P = 0.040 and P = 0.017, respectively) than earlier timing. However, these two groups did not induce significantly improved hard tissue barrier compared to that produced by aqueous Ca(OH)2 paste which stimulated matrix secretion in a polar tubular dentin-like pattern. [source]

Federal University of Santa Catarina follow-up management routine for traumatized primary teeth , part 1

DENTAL TRAUMATOLOGY, Issue 6 2004
Mariane Cardoso
Abstract,,, The objective of this study was to verify if the follow-up management routine of traumatized primary teeth set up by Federal University of Santa Catarina, which performs clinical and radiographic assessments (15 and 45 days; 4, 8 and 12 months) after the oral trauma, enabled an early diagnosis of sequelae which would indicate the need for endodontic intervention, as well as the influence a type of trauma and the child's age could have in the severity of the sequelae. In this study 52 sets of records were used of patients being seen in the last 6 months, with a total of 70 teeth that were receiving follow-up treatment. Patients returned for regular visits set up by the management routine, where clinical and radiographic examinations were performed to check for sequelae, which justified endodontic intervention. Mobility (51.2%) and crown discoloration (25.6%) were the most common sequelae found in the patient's first appointment. In the follow-up visits, replacement root resorption (22.5%) was the second most common sequela found, suggesting endodontic intervention. No significant association was found between severe sequelae, types of trauma and a child's age (,2 = 0.3, P = 0,8613). During the intervals of the follow-up visits, it was noticed that between 46 days and 8 months a higher number of sequelae were diagnosed (P < 0.05). The diagnosis of sequelae such inflammatory and replacement root resorption, which can lead to an early loss of a primary tooth, are frequent and that the interval between the follow-up visits has to be changed, suggesting the setting up of management routine 2. The study also concluded that the type of trauma and the child's age are not fundamental factors in the diagnosis of severe sequelae. [source]

Review of Fractional Photothermolysis: Treatment Indications and Efficacy

DERMATOLOGIC SURGERY, Issue 10 2009
EMILY P. TIERNEY MD
BACKGROUND Fractional photothermolysis (FP) is one of the most significant milestones in laser technology and resurfacing. METHODS Review of the Medline English literature and recent international conferences regarding FP technology, applications, and indications. RESULTS Successful conditions treated with nonablative FP reported in the literature include acne scarring; dyschromia and fine wrinkling of photoaging on the face, chest, neck, and hands; melasma; poikiloderma of Civatte; nevus of Ota; scars; minocycline hyperpigmentation; telangiectatic matting; residual hemangioma; granuloma annulare; colloid milium; and disseminated superficial actinic porokeratosis. An advance in 2007 was the introduction of ablative FP (AFP), which results in significantly greater improvement in skin laxity and textural abnormalities. Most recently, AFP has demonstrated significantly greater improvement than nonablative FP in reducing acne scarring and skin redundancy and laxity associated with photoaging. CONCLUSIONS Through the induction of microthermal zones of injury, FP technology stimulates a robust and rapid wound healing response resulting in improvement in a diversity of aesthetic, inflammatory, and preneoplastic skin disorders. Further investigation into the technology and diverse array of cutaneous conditions that can benefit from FP is highly needed. [source]

The histopathology of alopecia areata in vertical and horizontal sections

DERMATOLOGIC THERAPY, Issue 4 2001
David A. Whiting
Alopecia areata (AA) is a relatively common disease affecting 1.7% of Americans by the age of 50 years. The diagnosis is usually made on clinical grounds. In some cases the diagnosis is elusive and biopsies are necessary. In other cases biopsies are useful from a prognostic point of view to determine whether there are enough follicles left for possible future regrowth. In view of the active research being conducted into AA, biopsies provide valuable material for further investigation. The diagnosis of AA is improved by the use of horizontal sections in addition to or instead of vertical sections of scalp biopsies. The histopathologic features favoring the diagnosis of AA include peribulbar and intrabulbar mononuclear infiltrates, degenerative changes in the hair matrix, decreased numbers of terminal anagen follicles, increased numbers of terminal catagen and telogen follicles, an increased number of follicular stelae, an increased number of miniaturized vellus hair follicles, and pigment incontinence of hair bulbs and follicular stelae. Follicular counts with horizontal sections are particularly helpful in making the diagnosis of AA when the biopsy has been taken between acute episodes and the characteristic peribulbar inflammatory infiltrate is absent. [source]

Intracerebral large artery disease in Aicardi,Goutières syndrome implicates SAMHD1 in vascular homeostasis

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 8 2010
VENKATESWARAN RAMESH
Aim, To describe a spectrum of intracerebral large artery disease in Aicardi,Goutières syndrome (AGS) associated with mutations in the AGS5 gene SAMHD1. Method, We used clinical and radiological description and molecular analysis. Results, Five individuals (three males, two females) were identified as having biallelic mutations in SAMHD1 and a cerebral arteriopathy in association with peripheral vessel involvement resulting in chilblains and ischaemic ulceration. The cerebral vasculopathy was primarily occlusive in three patients (with terminal carotid occlusion and basal collaterals reminiscent of moyamoya syndrome) and aneurysmal in two. Three of the five patients experienced intracerebral haemorrhage, which was fatal in two individuals. Post-mortem examination of one patient suggested that the arteriopathy was inflammatory in origin. Interpretation, Mutations in SAMHD1 are associated with a cerebral vasculopathy which is likely to have an inflammatory aetiology. A similar disease has not been observed in patients with mutations in AGS1 to AGS4, suggesting a particular role for SAMHD1 in vascular homeostasis. Our report raises important questions about the management of patients with mutations in SAMHD1. [source]

Effect of raisin consumption on oxidative stress and inflammation in obesity

DIABETES OBESITY & METABOLISM, Issue 11 2008
J. W. Rankin
Aim:, Oxidative stress can initiate increased inflammation that elevates risk for cardiovascular disease. The objective of this study was to determine the effects of daily consumption of raisins on markers of oxidative stress, inflammation and endothelial activation in response to an acute high-fat meal in overweight individuals. Methods:, Seventeen overweight men and women consumed 90 g raisins or isocaloric placebo (264 kcal/day) for 14 days in a randomized, crossover design while following a low-flavonoid diet. The oxidative [urinary 8-iso-prostaglandin-F2, (8-epi PGF2,) and serum oxygen radical absorbance capacity (ORAC)], inflammatory (serum C-reactive protein and interleukin-6), endothelial (serum soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1, sVCAM-1) and metabolic [free fatty acids (FFAs), triacylglycerol, glucose and insulin] response to four high-fat (53%) meals was tested pre- and postintervention. Results:, Urinary 8-epi PGF2, decreased (,22%) and fasting ORAC increased (+3%) after both interventions combined. Fasting protein-free ORAC was modestly (+3.5%) higher during the raisin than the placebo intervention. Neither the meals nor the raisins consistently induced fasted markers of inflammation or endothelial dysfunction. Gender influenced postprandial metabolic responses in that males responded with higher serum FFAs, sVCAM-1 and glucose compared with females. Conclusions:, Serum antioxidant capacity was modestly increased by daily raisin consumption, but this did not alter fasted or postprandial inflammatory response in these relatively healthy but overweight individuals. Providing all food in regular pattern reduced measures of oxidative stress. [source]

Somatostatin receptors and autoimmune-mediated diabetes

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2005
Xaio-Ping Wang
Abstract Somatostatin (SST) peptide is produced by various SST-secreting cells throughout the body and acts as a neurotransmitter or paracrine/autocrine regulator in response to ions, nutrients, peptides hormones and neurotransmitters. SST is also widely distributed in the periphery to regulate the inflammatory and immune cells in response to hormones, growth factors, cytokines and other secretive molecules. SST peptides are considered the most important physiologic regulator of the islet cell, gastrointestinal cell and immune cell functions, and the importance of SST production levels has been implicated in several diseases including diabetes. The expression of SST receptors has also been found in T lymphocytes and primary immunologic organs. Interaction of SST and its receptors is also involved in T-cell proliferation and thymocyte selection. SSTR gene-ablated mice developed diabetes with morphologic, physiologic and immunologic alterations in the endocrine pancreas. Increased levels of mononuclear cell infiltration of the islets are associated with the increased levels of antigen-presenting cells located in the islets and peripancreatic lymph nodes. Increased levels of SST were also found in antigen-presenting cells and are associated with a significant increase of CD8 expression levels on CD4+/CD8+ immature thymocytes. These findings highlight the crucial role of this neuroendocrine peptide and its receptors in regulating autoimmune functions. Copyright © 2004 John Wiley & Sons, Ltd. [source]

Bone lesions: Role of sediment cytology

DIAGNOSTIC CYTOPATHOLOGY, Issue 6 2009
Surbhi Shah M.B.B.S.
Abstract This study was conducted to evaluate the role of sediment cytology of biopsy specimen fixatives, which is usually discarded, in early diagnosis of bone lesions. Cytological smears prepared from sediments of biopsy specimen fixatives (sediment cytology) were used to study 65 bone specimens biopsied with suspicion of malignancy. The cytological diagnosis was then compared with histological diagnosis, taking the latter as gold standard. Smears were adequately cellular and showed good preservation of cellular morphology. Some of the smears showed microfragments of tissue. Cytology labeled 29 lesions as malignant, 26 lesions as benign, 3 as inflammatory, and 7 smears as inconclusive because of low cell yield. Sediment cytology was able to correctly diagnose 58 of 65 lesions. There was no false-positive or false-negative case. The sediment cytology could be considered as an easy and effective diagnostic tool that can provide early diagnosis for the lesion of bone. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source]

Epidermal inclusion cyst: Cytomorphological features and differential diagnosis

DIAGNOSTIC CYTOPATHOLOGY, Issue 12 2008
Uma Handa M.D.
Abstract Aspirates from 162 epidermal inclusion cysts (EIC) from 157 patients were analyzed in order to elaborate on specific cytologic features. The most common site involved was the head and neck region (96 cases; 59.2%). The maximum patients were in the 3rd and 4th decades of life. Aspirates from EIC showed a clear background, with high cellularity, and nucleate and anucleate squames. Keratinous material was seen in some cases but the amount was less compared with the cellular elements. In 31 cases, a diagnosis of infected EIC was made on the basis of dense inflammatory infiltrate in addition to the squames. Histopatholgy was available in 56 cases out of which EIC was diagnosed in 45 cases. The remaining 11 cases were dermoid cyst (5 cases), branchial cyst (2 cases), pilomatricoma (2 cases), and sebaceous and thyroglossal cyst (1 case each). Thus, EIC should be differentiated from other squamous cell containing lesions. Diagn. Cytopathol. 2008. © 2008 Wiley-Liss, Inc. [source]