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Chronic Inflammatory (chronic + inflammatory)
Terms modified by Chronic Inflammatory Selected AbstractsMarkedly attenuated acute and chronic pain responses in mice lacking adenylyl cyclase-5GENES, BRAIN AND BEHAVIOR, Issue 2 2007K.-S. Kim Chronic inflammatory and neuropathic pain is often difficult to manage using conventional remedies. The underlying mechanisms and therapeutic strategies required for the management of chronic pain need to be urgently established. The cyclic AMP (cAMP) second messenger system has been implicated in the mechanism of nociception, and the inhibition of the cAMP pathway by blocking the activities of adenylyl cyclase (AC) and protein kinase A has been found to prevent chronic pain in animal models. However, little is known regarding which of the 10 known isoforms of AC are involved in nociceptive pathways. Therefore, we investigated the potential pronociceptive function of AC5 in nociception using recently developed AC5 knockout mice (AC5,/,). We found that AC5,/, mice show markedly attenuated pain-like responses in acute thermal and mechanical pain tests as compared with the wildtype control. Also, AC5,/, mice display hypoalgesic responses to inflammatory pain induced by subcutaneous formalin injection into hindpaws, and to non-inflammatory and inflammatory visceral pain induced by injecting magnesium sulfate or acetic acid into the abdomen. Moreover, AC5,/, mice show strongly suppressed mechanical and thermal allodynia in two nerve injury-induced neuropathic pain models. These results suggest that AC5 is essential for acute and chronic pain, and that AC5 knockout mice provide a useful model for the evaluation of the pathophysiological mechanisms of pain. [source] Vitamin D and calcium deficits predispose for multiple chronic diseasesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2005M. Peterlik Abstract There is evidence from both observational studies and clinical trials that calcium malnutrition and hypovitaminosis D are predisposing conditions for various common chronic diseases. In addition to skeletal disorders, calcium and vitamin D deficits increase the risk of malignancies, particularly of colon, breast and prostate gland, of chronic inflammatory and autoimmune diseases (e.g. insulin-dependent diabetes mellitus, inflammatory bowel disease, multiple sclerosis), as well as of metabolic disorders (metabolic syndrome, hypertension). The aim of the present review was to provide improved understanding of the molecular and cellular processes by which deficits in calcium and vitamin D cause specific changes in cell and organ functions and thereby increase the risk for chronic diseases of different aetiology. 1,25-dihydroxyvitamin D3 and extracellular Ca++ are both key regulators of proliferation, differentiation and function at the cellular level. However, the efficiency of vitamin D receptor-mediated intracellular signalling is limited by the negative effects of hypovitaminosis D on extrarenal 25-hydroxyvitamin D-1,-hydroxylase activity and thus on the production of 1,25-dihydroxyvitamin D3. Calcium malnutrition eventually causes a decrease in calcium concentration in extracellular fluid compartments, resulting in organ-specific modulation of calcium-sensing receptor activity. Hence, attenuation of signal transduction from the ligand-activated vitamin D receptor and calcium-sensing receptor seems to be the prime mechanism by which calcium and vitamin D insufficiencies cause perturbation of cellular functions in bone, kidney, intestine, mammary and prostate glands, endocrine pancreas, vascular endothelium, and, importantly, in the immune system. The wide range of diseases associated with deficits in calcium and vitamin D in combination with the high prevalence of these conditions represents a special challenge for preventive medicine. [source] Megaoesophagus in Rassf1a -null miceINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2009Louise Van Der Weyden Summary Megaoesophagus, or oesophageal achalasia, is a neuromuscular disorder characterized by an absence of peristalsis and flaccid dilatation of the oesophagus, resulting in the retention of ingesta in the dilated segment. The aetiology and pathogenesis of idiopathic (or primary) megaoesophagus are still poorly understood and very little is known about the genetic causes of megaoesophagus in humans. Attempts to develop animal models of this condition have been largely unsuccessful and although the ICRC/HiCri strain of mice spontaneously develop megaoesophagus, the underlying genetic cause remains unknown. In this report, we show that aged Rassf1a -null mice have an enhanced susceptibility to megaoesophagus compared with wild-type littermates (,20%vs. ,2% incidence respectively; P = 0.01). Histological examination of the dilated oesophaguses shows a reduction in the numbers of nerve cells (both ganglia and nerve fibres) in the myenteric plexus of the dilated mid and lower oesophagus that was confirmed by S100 immunohistochemistry. There was also a chronic inflammatory infiltrate and subsequent fibrosis of the myenteric plexus and the muscle layers. These appearances closely mimic the gross and histopathological findings in human cases of megaoesophagus/achalasia, thus demonstrating that this is a representative mouse model of the disease. Thus, we have identified a genetic cause of the development of megaoesophagus/achalasia that could be screened for in patients, and may eventually facilitate the development of therapies that could prevent further progression of the disease once it is diagnosed at an early stage. [source] The interleukin-25 gene located in the inflammatory bowel disease (IBD) 4 region: no association with inflammatory bowel diseaseINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 5 2003C. Büning Summary Genetic predisposition has been suggested to play an important role in the pathogenesis of inflammatory bowel diseases (IBDs). Linkage studies have identified a Crohn's disease susceptibility locus on chromosome 14 (14q11,12; IBD4). Interleukin-25 (IL-25) is a newly identified proinflammatory cytokine that has been shown to promote Th2 responses by inducing cytokines such as IL-4, IL-5 and IL-13. The IL-25 gene is located within this susceptibility region at 14q11.2. As IBDs are characterized by an imbalance of the Th1/Th2 cytokine response, we hypothesized that genetic alterations within the IL-25 gene might contribute to IBD. First, direct sequencing of the coding regions of the IL-25 gene in 40 patients with Crohn's disease or ulcerative colitis revealed only a newly reported polymorphism (c424C/A) in exon 2. Next, the frequency of this polymorphism was further investigated in 151 patients with Crohn's disease, 111 patients with ulcerative colitis, and 119 healthy controls to determine its clinical relevance. The genotypes of the c424C/A polymorphism did not reveal any significant differences between patients with Crohn's disease or ulcerative colitis and controls. Genoytype,phenotype relations in patients with Crohn's disease showed a comparable distribution of the c424C/A polymorphism in all subgroups of the Vienna classification. In summary, our data indicate that genetic alterations in the coding regions of the IL-25 gene are unlikely to play a role in IBDs, but the c424C/A polymorphism in the IL-25 gene should be investigated for a potential association with other chronic inflammatory and inherited disorders such as autoimmune diseases. [source] Absence of leukocyte microchimerism in oral lichen planus (OLP): an in situ hybridisation studyJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 7 2001T. Lombardi Abstract: Oral lichen planus (OLP) is a relatively common chronic inflammatory disease. The majority of patients are between 30 and 50 years of age with a higher incidence in females. The aetiology is unknown and various hypotheses on the pathogenic mechanisms, including autoimmunity, have been proposed over the years. In the present study, we investigated whether leukocyte microchimerism, a biological situation implicated in the aetiology of some autoimmune diseases, might play a role in the pathogenesis of OLP. We used in situ hybridisation to identify Y chromosome DNA in a series of formalin-fixed paraffin-embedded oral mucosa biopsies of women with established clinical and histological disease who had given birth to a male child. The positive control, two mucosal specimens from a man with OLP, showed over 90% of keratinocytes and cells within the inflammatory infiltrate, a positive nuclear signal. The negative control, biopsies from three women having carried only female foetuses and one nulliparous woman, all with OLP, did not show any nuclear signal. In the fifteen selected cases of OLP biopsies from women who had only male offspring, nucleated cells containing the Y chromosome were not detected within the chronic inflammatory infiltrate. These results suggest that unlike some other immunologically mediated diseases, leukocyte microchimerism does not seems to be involved in the pathogenesis of OLP. [source] Delayed immune-mediated adverse effects related to hyaluronic acid and acrylic hydrogel dermal fillers: clinical findings, long-term follow-up and review of the literatureJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2 2008J Alijotas-Reig Abstract Introduction Implantation of dermal filler for cosmetic purposes is becoming increasingly common worldwide. It is thought that hyaluronic acid (HA) alone or combined with acrylic hydrogels (HA-AH) does not have severe nor persistent side-effects. However, recent evidence may show that major, local and/or systemic, immediate or delayed adverse effects may appear in relation with its use. Objective To evaluate the clinical complaints, laboratory data, treatment and follow-up of patients with delayed adverse effects related to HA and HA-AH implant fillers. Design Prospective, case-series study of patients filled with HA and HA-AH compounds. Setting The study has been done in a tertiary, teaching university hospital. Patients We report on a series of 25 patients, 15 of them in prospective manner, with severe, delayed side-effects related to HA-AH. Inclusion criteria have been drawn up. Patients with immediate side-effects were excluded. Patients were submitted to a clinical follow-up, battery of blood tests and thorax X-ray films. Besides, a review of the literature was made. We undertook a computed-assisted (MEDLINE), National Library of Medicine, Bethesda, MD, USA, search of the literature from 1996 up to December 2005. Main outcome Clinical evaluation of granulomas, skin manifestations and other local and systemic immune-mediated disorders possibly related to HA and HA-AH fillers or their cumulative interaction with previously administered fillers. Results Of 25 cases, 16 were filled with HA alone and 9 with a HA-AH compounds. Of 15 cases analysed and with long-term follow-up, 10 were filled with HA alone, and the remaining five were filled with a HA-AH. Time latency average up to beginning of symptoms was 13.7 months. Three of these 15 cases had been filled before with silicone and another one with Artecoll. Tender nodules were seen in 14 patients. Systemic manifestations appeared in three cases. Laboratory abnormalities were noted in all studied cases. After 16-month average follow-up, seven patients seem to be cured, and six have recurrent bouts. Two cases were lost during follow-up. Conclusion Although in some cases, these clinical complications might have been associated with previous fillers or with other unknown foreign bodies, we feel that, although infrequently, delayed and recurrent chronic inflammatory and granulomatous reactions may complicate HA and HA-AH implant fillers. [source] Omega-3 fatty acids inhibit an increase of proinflammatory cytokines in patients with active Crohn's disease compared with omega-6 fatty acidsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11-12 2005A. A. NIELSEN Summary Background :,Crohn's disease is a chronic inflammatory condition affecting the gastrointestinal tract. Polyunsaturated omega-3 fatty acids given orally may reduce the secretion of proinflammatory cytokines and hereby downregulate the inflammatory process. Aim :,To assess the effects of enteral fatty acids, in the form of Impact Powder (Novartis, Switzerland), as adjuvant therapy to corticosteroid treatment on the proinflammatory and anti-inflammatory cytokine profiles in patients with active Crohn's disease. Methods :,The proinflammatory and anti-inflammatory cytokines were measured in plasma from 31 patients with active Crohn's disease. Patients were randomized for oral intake of omega-3 fatty acid (3-Impact Powder) or omega-6 fatty acids (6-Impact Powder). Clinical and biochemical markers of inflammation were studied at baseline and after 5 and 9 weeks. Results :,Within the 3-Impact Powder group, no significant changes in concentrations of interleukin-6, interferon- ,, monocyte chemoattractant protein-1, interleukin-2, interleukin-5 and interleukin-10, whereas a significant differences in concentration of interleukin-1, and interleukin-4 were observed during therapy. Within the 6-Impact Powder group a significant changes in concentrations of interleukin-1,, interleukin-6, interferon- ,, monocyte chemoattractant protein-1, interleukin-2, interleukin-4, interleukin-5 and interleukin-10 were observed. Conclusions :,The 3-Impact Powder showed immunomodulatory properties and might inhibit an increase of proinflammatory cytokines in contrast to the 6-Impact Powder. [source] Genetic differences in oxidative stress and inflammatory responses to diet-induced obesity do not alter liver fibrosis in miceLIVER INTERNATIONAL, Issue 8 2009Wing-Kin Syn Abstract Objective: To determine how genetic factors might influence the progression of nonalcoholic fatty liver disease (NAFLD). Design/Intervention: Beginning in adolescence, male C57BL6 (BL6) and 129/SVJ mice were fed control (n=15/group) or high-fat (HF) diets (n=30/group) for 6 months. Main Outcome Measures: Assessed were body weight, insulin resistance, hepatic production of free radicals, expression of cytokines and fibrosis-related genes and severity of hepatic steatosis, injury and fibrosis. Results: High-fat diets induced comparable obesity, hepatic steatosis and insulin resistance in the two strains. Compared with BL6 mice, 129/SVJ mice had impaired induction of antioxidant genes, generated three- to four-fold more free radicals and exhibited two-fold greater induction of profibrogenic cytokines (interleukin-4 and transforming growth factor-,1) and fibrosis-related genes (fibronectin and tissue inhibitor of metalloproteinase-1) (all P<0.05 for 129 vs BL6). Surprisingly, however, induction of collagen I ,1 mRNA and accumulation of Sirius red-stained fibrils and hepatic hydroxyproline were similar in BL6 and 129/SVJ mice, and although patchy sinusoidal fibrosis emerged in both strains, neither developed bridging fibrosis. Conclusions: Although BL6 and 129/SVJ mice with diet-induced obesity, insulin resistance and steatosis differed with respect to several factors that are thought to influence human NAFLD progression, they developed comparable liver fibrosis. Moreover, none of the risk factors for NAFLD-related cirrhosis in humans, including obesity, insulin resistance, chronic inflammatory and oxidant stress, steatohepatitis or activation of fibrogenic genes, proved to be sufficient to cause cirrhosis in these mice, even when exposure to one or more of these insults was very prolonged. [source] Third ventricular chordoid glioma: clinicopathological study of two cases with evidence for a poor clinical outcome despite low grade histological featuresNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2005K. M. Kurian Chordoid glioma of the third ventricle is a rare glial tumour whose precise histogenesis remains uncertain. We describe two cases that presented recently to our department and review the background literature. The neoplasm tends to occur in women and its clinical presentation is variable, resulting from acute hydrocephalus or impingement upon local structures. However, the radiological appearance is distinct, with an ovoid shape, hyperdensity and uniform contrast enhancement on computerized tomography and magnetic resonance imaging. Intraoperative smear diagnosis is difficult because of the lack of specific features, although the presence of metachromatic extracellular mucin may be useful. The characteristic histological appearance is that of cords and clusters of cohesive, oval-to-polygonal epithelioid cells with abundant eosinophilic cytoplasm and a mucinous background. There is often a mixed chronic inflammatory infiltrate with lymphocytes and plasma cells with Russell bodies. The main differentials for histological diagnosis include chordoid meningiomas, pilocytic astrocytomas and ependymomas. An immunohistochemical panel including antibodies to glial fibrillary acidic protein, CD34, epithelial membrane antigen, pan cytokeratin, S100 and vimentin can be used to distinguish between these possibilities. Ultrastructurally the tumour cells have basal lamina and microvilli, reminiscent of ependymomas. The clinical outcome in our cases was poor because of the location of the lesion and its close relation to the hypothalamus. Limited follow-up after surgery with or without radiotherapy suggests that as-full-as-possible resection favours a better outcome, although surgery in this area carries significant operative risks. [source] Sclerosing encapsulating peritonitis (abdominal cocoon) associated with liver cirrhosis and diffuse large B-cell lymphoma: Autopsy casePATHOLOGY INTERNATIONAL, Issue 9 2009Sohsuke Yamada A case of sclerosing encapsulating peritonitis (SEP) associated with liver cirrhosis (LC) and complicated by diffuse large B-cell lymphoma (DLBCL) is reported herein. A 49-year-old Japanese man had undergone peritoneo-venous shunt against refractory ascites due to hepatitis C virus-positive uncompensated LC for 2 years. After he received a diagnosis of DLBCL of the left neck lymph node 3 months before his death, palliative care was given because of his poor general condition. He developed severe abdominal distention and pain over 1 week and was found to have marked ascites and whole bowel lumped together on abdominal CT. At autopsy, the peritoneum was covered with a thick white membrane and the bowel could not be distinguished, which was macroscopically characterized by a cocoon-like appearance. Histology indicated a proliferation of diffusely thickened or hyalinized fibrocollagenous tissue in the entire peritoneum with a slight chronic inflammatory infiltrate and without remarkable change of mucosa. A diagnosis of SEP, also known as abdominal cocoon, was established based on these features. Additionally, in the abdominal cavity, a large amount of serous ascites and multiple peritoneal nodules or masses involved by DLBCL were recognized. To the authors' knowledge this is the first case report of SEP associated with LC and complicated by the invasion of DLBCL in the abdominal cavity. [source] Lower motor neuron loss in multiple sclerosis and experimental autoimmune encephalomyelitis,ANNALS OF NEUROLOGY, Issue 3 2009Johannes Vogt MD Objective Multiple sclerosis (MS) is considered a chronic inflammatory and demyelinating disease of the central nervous system. Evidence that axonal and neuronal pathology contributes to the disease is accumulating, however, the distribution of neuronal injury as well as the underlying mechanisms have not yet been fully clarified. Here, we investigated the role of neuronal cell loss in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). Methods We performed electrophysiological investigations in MS patients, including assessment of compound muscle action potentials and motor unit numbers and quantified neuronal cell loss in human MS samples and different EAE models by high-precision stereology. Results Both electrophysiological and morphological analyses indicated a massive loss of lower motor neurons in MS patients. We regularly found dying spinal motor neurons surrounded by CD3+ (CD4+ as well as CD8+) T cells expressing tumor necrosis factor,related apoptosis-inducing ligand (TRAIL). We observed a similar degree of damage and immune attack in different variants of EAE; the lower motor neurons were preserved in adoptive transfer EAE induced with TRAIL-deficient T lymphocytes. Interpretation Our study indicates that damage to lower motor neurons and TRAIL-mediated inflammatory neurodegeneration in the spinal cord contribute to MS pathology. Ann Neurol 2009;66:310,332 [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 2007Ivana 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] Glycoproteins of drusen and drusen-like lesionsACTA OPHTHALMOLOGICA, Issue 2007RE BONSHEK Purpose: Drusen are a marker of age-related macular degeneration. Lesions similar to drusen, both in histology and their clinical appearance are also seen in choroidal tumours, chronic inflammatory and degenerative conditions of the eye, and in mesangiocapillary glomerulonephritis type II (MCGN-II). This study aims to compare the saccharide composition of these drusen-like lesions in the various ocular pathological groups and in MCGN-II. Methods: Formalin fixed and paraffin wax embedded tissue from 21 eyes was studied. The histological diagnoses included AMD, retinal detachment, malignant melanoma, long-standing uveitis, glaucoma and MCGN II. Glycosylation was examined using a panel of twenty biotinylated lectins and an avidin-peroxidase-DAB-cobalt revealing system, with and without neuraminidase pre-treatment. Results: High mannose, bi/tri-nonbisected and bisected complex N-glycan, N-acetyl glucosaminyl, galactosyl and sialyl residues were found to be expressed by drusen, while treatment with neuraminidase exposed subterminal N-acetyl galactosamine and galactosyl residues. Similar binding patterns were found in the various pathological groups studied. Conclusions: As there was no significant difference in the lectin-binding pattern in drusen in different pathologies, a common pathogenesis or at least a final common pathway for the elaboration of carbohydrate components of drusen is suggested. [source] Rosacea lymphoedema of the eyelidACTA OPHTHALMOLOGICA, Issue 6 2004Tze Foon Lai Abstract. Purpose:,To present a patient with rosacea lymphoedema of one upper eyelid resulting in unilateral complete ptosis. Methods:,A 51-year-old white man presented with a 12-month history of progressive painless swelling of the left upper eyelid. An incisional biopsy of the upper eyelid was performed. Results:,The biopsy showed dermal oedema with lymphangiectasia and telangiectasia, accompanied by a mild to moderate mixed chronic inflammatory infiltrate of lymphocytes, histiocytes, plasma cells and rare eosinophils. Stains for fungi and mycobacteria were negative. The lack of lichenoid reaction, dermal mucin or lip swelling indicated a lymphoedematous manifestation of rosacea. The patient was treated with minocycline and prednisolone with no effect. Conclusion:,Rosacea lymphoedema involving the eyelid, as in our case, is a rare complication and can present diagnostic and therapeutic challenges to the ophthalmologist. [source] Role of interleukin-17F in chronic inflammatory and allergic lung diseaseCLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2006N. Hizawa Summary IL-17 family members belong to a distinct category of cytokines that coordinate local tissue inflammation by inducing the release of pro-inflammatory and neutrophil-mobilizing cytokines. The importance of the IL-17 family in inflammatory and autoimmune disease is becoming increasingly apparent. IL-17F is a recently discovered member of the IL-17 family that has a number of biological activities through induction of various cytokines, chemokines, and mediators. IL-17A, the founding member of the IL-17 family, and IL-17F are produced by several inflammatory cells, including activated T cells, in response to infectious and antigenic stimuli. Overexpression of IL-17A or IL-17F in the lungs results in induction of CXC chemokines and neutrophil recruitment. In a case,control study of 1125 unrelated Japanese subjects, a His161 to Arg161 (H161R) substitution in the third exon of the IL17F gene was shown to be associated with asthma and chronic obstructive pulmonary disease (COPD). Functionally, this variant failed to induce cytokines and chemokines, and interestingly, was able to antagonize the activity of wild-type IL-17F. These results provide an experimental basis for the observed genetic association with chronic inflammatory lung diseases, and also suggest the potential therapeutic utility of this antagonistic variant of IL-17F. Given that asthma and COPD are complex diseases involving a number of genetic and environmental factors, the genetic impact of IL-17F H161R with regard to the development of chronic airway inflammation likely varies among individuals with different genetic backgrounds and environmental exposures. [source] | |||||||||||||||||||