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Severe Inflammation (severe + inflammation)
Selected AbstractsHepatitis B virus DNA levels, precore mutations, genotypes and histological activity in chronic hepatitis BJOURNAL OF VIRAL HEPATITIS, Issue 4 2000Lindh The present study aimed to clarify how viraemia levels reflect the clinical stages of chronic hepatitis B virus (HBV) infection, in particular studying whether ,healthy carriers' can be identified by analysing HBV DNA levels with a highly sensitive quantitative assay. Histology activity index (HAI), alanine aminotransferase (ALT) level, genotype and precore mutations were compared with the HBV DNA level, as measured using the Amplicor HBV Monitor assay in a prospective study. In 124 hepatitis B e antigen-negative (HBeAg,) patients, the majority with mild liver disease, log HBV DNA levels showed a Gaussian distribution around a geometric mean of 33 000 genome copies ml,1, and increasing HBV DNA level was associated with significantly higher inflammation (HAIinfl) and fibrosis (HAIfibr) scores and higher ALTi (ALT ÷ the upper reference value). Severe inflammation (HAIinfl , 7) was seen in 83% (five of six), 36% (eight of 22) and 3% (one of 37) of HBeAg, patients with HBV DNA > 107, > 2 × 105 and < 104 copies ml,1, respectively. In severe HBeAg, hepatitis, patients with precore wild-type infection had lower HBV DNA levels than those with precore mutants. In 36 HBeAg-positive (HBeAg+) patients, no correlation between HBV DNA level and liver damage was seen. Ninety-six per cent of HBeAg, patients with ALTi < 0.5 had HAIinfl , 3. In HBeAg, carriers with ALTi 0.5,1.0, the relative risk for severe inflammation, comparing HBV DNA > 2 × 105 copies ml,1vs < 2 × 105 copies ml,1, was 14.7. In conclusion, in HBeAg, carriers, HBV DNA < 104 copies ml,1 or ALTi < 0.5 indicates mild inflammation, while > 2 × 105 copies ml,1 of HBV DNA may justify further investigations. Precore status may be relevant for the interpretation of viraemia. [source] Neuromyelitis optica: Pathogenicity of patient immunoglobulin in vivo,ANNALS OF NEUROLOGY, Issue 5 2009Monika Bradl PhD Objective Severe inflammation and astrocyte loss with profound demyelination in spinal cord and optic nerves are typical pathological features of neuromyelitis optica (NMO). A diagnostic hallmark of this disease is the presence of serum autoantibodies against the water channel aquaporin-4 (AQP-4) on astrocytes. Methods We induced acute T-cell,mediated experimental autoimmune encephalomyelitis in Lewis rats and confronted the animals with an additional application of immunoglobulins from AQP-4 antibody,positive and ,negative NMO patients, multiple sclerosis patients, and control subjects. Results The immunoglobulins from AQP-4 antibody,positive NMO patients are pathogenic. When they reach serum titers in experimental animals comparable with those seen in NMO patients, they augment clinical disease and induce lesions in the central nervous system that are similar in structure and distribution to those seen in NMO patients, consisting of AQP-4 and astrocyte loss, granulocytic infiltrates, T cells and activated macrophages/microglia cells, and an extensive immunoglobulin and complement deposition on astrocyte processes of the perivascular and superficial glia limitans. AQP-4 antibody containing NMO immunoglobulin injected into naïve rats, young rats with leaky blood,brain barrier, or after transfer of a nonencephalitogenic T-cell line did not induce disease or neuropathological alterations in the central nervous system. Absorption of NMO immunoglobulins with AQP-4,transfected cells, but not with mock-transfected control cells, reduced the AQP-4 antibody titers and was associated with a reduction of astrocyte pathology after transfer. Interpretation Human anti,AQP-4 antibodies are not only important in the diagnosis of NMO but also augment disease and induce NMO-like lesions in animals with T-cell,mediated brain inflammation. Ann Neurol 2009;66:630,643 [source] The protective and healing effects of a natural antioxidant formulation based on ubiquinol and Aloe vera against dextran sulfate-induced ulcerative colitis in ratsBIOFACTORS, Issue 1-4 2003Ludmila Korkina Abstract Oxygen/nitrogen reactive species (ROS/RNS) are currently implicated in the pathogenesis of ulcerative colitis, drawing attention on the potential prophylactic and healing properties of antioxidants, scavengers, chelators. We evaluated the possible protective/curative effects of a natural antioxidant preparation based on Aloe vera and ubiquinol, against intestinal inflammation, lesions, and pathological alterations of the intestinal electrophysiological activity and motility, in a rat model of DSS-induced colitis. 5% dextrane sulfate (DDS) (3 days), followed by 1% DSS (4 days) was administered in drinking water. The antioxidant formulation (25 mg/kg) was delivered with a pre-treatment protocol, or simultaneously or post-colitis induction. Spontaneous and acetylcholine-stimulated electrical activity were impaired in the small intestine and in distal colon, upon exposure to DSS only. Severe inflammation occurred, with increased myeloperoxidase activity, and significant alterations of the oxidant/antioxidant status in colonic tissue and peritoneal cells. Lipoperoxidation, superoxide production, glutathione peroxidase and glutathione-S-transferase activities, and reduced glutathione content increased, whilst superoxide dismutase and catalase activities were sharply suppressed in colon tissue. ROS/RNS formation in peritoneal cells was strongly inhibited. Inflammation, electrical/mechanical impairment in the gut, and a great majority of oxidative stress parameters were improved substantially by pre-treatment with the antioxidant preparation, but not by simultaneous administration or post-treatment. [source] Autofluorescence spectroscopy for the diagnosis of cervical intraepithelial neoplasiaBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 8 2002Helmut Weingandt Objective To assess the feasibility of autofluorescence spectroscopy in the diagnosis of cervical intraepithelial neoplasia (CIN) using broadband light excitation. Design Feasibility study. Setting Colposcopy clinic of an university hospital. Population Sixty-eight patients at risk for CIN. Methods After excitation with a broadband light between 375 and 440 nm, spectral distribution of native tissue fluorescence (autofluorescence) was acquired from 685 cervical sites for the localisation and differentiation of CIN, and compared with colposcopically directed biopsy and human papillomavirus (HPV) DNA testing. Main outcome measure Detection of CIN. Results The evaluation of spectral measurements revealed significantly lower autofluorescence values for CIN 3 lesions compared with normal tissue (P < 0.001), and compared with CIN 1 or CIN 2 (P < 0.002). High grade CIN lesions (CIN 2/3) presented with a significant reduced autofluorescence compared with CIN 1 (P < 0.002). Patients with a positive HPV DNA testing showed a significantly lower autofluorescence than patients tested negative for HPV DNA (P < 0.05). Severe inflammation such as chronic cervicitis may lead to false positive results. Conclusions Autofluorescence spectroscopy represents an interesting approach for the detection of cervical neoplasia. Using an excitation wavelength band between 375 and 440 nm, significant differences between normal and precancerous lesions of the cervix can be seen. [source] Oral health and oral implant status in edentulous patients with implant-supported dental prostheses who are receiving long-term nursing careGERODONTOLOGY, Issue 4 2009Rita Isaksson Aim:, The aim of this study was to investigate oral health and oral implant status in a group of edentulous patients receiving long-term residential or nursing care (LTC), all of whom had implant-supported fixed or removable dental prostheses. Material and methods:, A dental examination was performed on a total of 3310 patients receiving LTC and from this population 35 edentulous patients in whom dental implants had been placed formed the cohort for this study. All examinations were performed by a specialist in hospital dentistry and took place in the patients' own home environment. Oral health was assessed by means of a protocol which evaluated oral hygiene status, possible oral mucosal inflammation and oral mucosal friction levels. Any problems with the implant-supported prosthesis, implant mobility or other complications were also assessed. In addition, patients were asked about any oral symptoms and their usual oral hygiene procedures. Results:, About half of the subjects (17/35) were registered as having no/mild inflammation with 18 of 35 having moderate/severe inflammation. Twelve of the 35 patients had good/acceptable oral hygiene and 23 of 35 had poor/bad oral hygiene. Twenty-one of the 35 patients depended on help from the nursing personnel for their daily oral hygiene procedures. Obvious problems with food impaction were noted in 11 patients. A total of 229 implants had been placed in 43 jaws supporting 40 full arch-fixed prostheses and three implant-borne overdentures. There was no evidence of mobility or fractures of either the implants or the prostheses. Fifteen implants showed some exposed screw threads. Pus was exuding from one implant site and general peri-implant gingival hyperplasia was noted in two patients. Twenty-four patients were completely satisfied with the function and appearance of their implant-supported prostheses. Two patients were totally dissatisfied. Conclusion:, This study indicates that oral implant therapy can be considered as a treatment of choice in elderly patients, even if oral hygiene is sub-optimal. [source] The role of free fatty acids, pancreatic lipase and Ca2+ signalling in injury of isolated acinar cells and pancreatitis model in lipoprotein lipase-deficient miceACTA PHYSIOLOGICA, Issue 1 2009F. Yang Abstract Aim and methods:, Recurrent pancreatitis is a common complication of severe hypertriglyceridaemia (HTG) often seen in patients carrying various gene mutations in lipoprotein lipase (LPL). This study investigates a possible pathogenic mechanism of cell damage in isolated mouse pancreatic acinar cells and of pancreatitis in LPL-deficient and in wild type mice. Results:, Addition of free fatty acids (FFA) or of chylomicrons to isolated pancreatic acinar cells caused stimulation of amylase release, and at higher concentrations it also caused cell damage. This effect was decreased in the presence of the lipase inhibitor orlistat. Surprisingly, pancreatic lipase whether in its active or inactive state could act like an agonist by inducing amylase secretion, increasing cellular cGMP levels and converting cell damaging sustained elevations of [Ca2+]cyt to normal Ca2+ oscillations. Caerulein increases the levels of serum amylase and caused more severe inflammation in the pancreas of LPL-deficient mice than in wild type mice. Conclusion:, We conclude that high concentrations of FFA as present in the plasma of LPL-deficient mice and in patients with HTG lead to pancreatic cell damage and are high risk factors for the development of acute pancreatitis. In addition to its enzymatic effect which leads to the generation of cell-damaging FFA from triglycerides, pancreatic lipase also prevents Ca2+ overload in pancreatic acinar cells and, therefore, counteracts cell injury. [source] T-cell-specific deletion of gp130 renders the highly susceptible IL-10-deficient mouse resistant to intestinal nematode infectionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2009Nicolas Fasnacht Abstract Gp130 is the common receptor of the IL-6 family of cytokines and is involved in many biological processes, including acute phase response, inflammation and immune reactions. To investigate the role of gp130 under inflammatory conditions, T-cell-specific conditional gp130 mice were first bred to the IL-10-deficient background and were then infected with the gastrointestinal nematode Trichuris muris. While IL-10,/, mice were highly susceptible to T. muris, developed a mixed Th1/Th17 response and displayed severe inflammation of the caecum, infection of mice with an additional T-cell-specific deletion of gp130 signalling completely reversed the phenotype. These mice showed an accelerated worm expulsion that was associated with the rapid generation of a strong Th2 immune response and a significant increase in Foxp3-expressing Treg. Therefore, gp130 signalling in T cells regulates a switch between proinflammatory and pathogenic Th1/Th17 cells and regulatory Th2/Treg in vivo. Taken together, the data demonstrate that gp130 signalling in T cells is a positive regulator of inflammatory processes, favouring the Th1/Th17 axis. [source] Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 8 2005Craig A Solem MD Abstract Introduction: We sought to examine the relationship between C-reactive protein (CRP) and clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease (IBD). Methods: All IBD patients at our institution between January 2002 and August 2003 who had a CRP, colonoscopy, and either small bowel follow-through (SBFT) or CT enterography (CTE) performed within 14 days were identified. Clinical activity was assessed retrospectively through review of the medical record. Logistic regression was used in Crohn's disease (CD) patients to estimate the odds ratio (OR) with 95% confidence intervals for an elevated CRP. Associations were assessed using Fisher exact test in ulcerative colitis (UC) patients due to small sample size. Results: One-hundred four CD patients (46% males) and 43 UC and indeterminate colitis patients (44% males) were identified. In CD patients, moderate-severe clinical activity (OR, 4.5; 95% CI, 1.1-18.3), active disease at colonoscopy (OR, 3.5; 95% CI, 1.4-8.9), and histologically severe inflammation (OR, 10.6; 95% CI; 1.1-104) were all significantly associated with CRP elevation. Abnormal small bowel radiographic imaging was not significantly associated with CRP elevation. In UC patients, CRP elevation was significantly associated with severe clinical activity, elevation in sedimentation rate, anemia, hypoalbuminemia, and active disease at ileocolonoscopy, but not with histologic inflammation. Conclusions: CRP elevation in IBD patients is associated with clinical disease activity, endoscopic inflammation, severely active histologic inflammation (in CD patients), and several other biomarkers of inflammation, but not with radiographic activity. [source] Safety and therapeutic efficacy of undenatured type-ii collagen (UC-II) in comparison to glucosamine and chondroitin in arthritic horsesJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 2 2009R. C. Gupta Osteoarthritis (OA) is the most common form of arthritis, which causes severe inflammation and loss of cartilage. It is a debilitating disease that commonly affects thousands of horses each year. Recently, we assessed the anti-arthritic and anti-inflammatory potential of undenatured type II collagen (UC-II) in horses. This comparative investigation evaluated arthritic pain in horses receiving daily placebo, UC-II 320 mg/day (providing 80 mg active UC-II), 480 mg/day (providing 120 mg active UC-II), or 640 mg/day (providing 160 mg active UC-II), and glucosamine and chondroitin (5.4 g/day and 1.8 g/day, respectively, bid for the first month, and thereafter once daily) for 150 days. Pain in each leg was evaluated using the flexion test and the lameness-grading system after the initial two strides. Average pain of all four legs represented the pain for each horse. Horses receiving placebo showed no change in arthritic condition, while those receiving 320, 480, or 640 mg UC-II exhibited significant reduction in arthritic pain (P < 0.05). UC-II at 480 mg dose provided optimal effects. With this dose, reduction in overall pain was from 5.7 ± 0.0.42 (100%) to 0.7 ± 0.42 (12%); and in pain upon limb manipulation from 2.35 ± 0.37 (100%) to 0.52 ± 0.18 (22%). In regards to glucosamine and chondroitin treated group, although reduction in pain was significant compared to pretreated values, the efficacy was significantly less compared with that observed with UC-II. UC-II was found to be twice as effective as glucosamine and chondroitin in arthritic horses. Clinically, physical condition, and liver (ALP, GGT, and bilirubin), kidney (BUN and creatinine), and heart (CK) functions remained unchanged, suggesting that these supplements were well tolerated. Overall, these results demonstrate that UC-II was significantly more efficacious than glucosamine and chondroitin in arthritic horses. [source] Sulfur mustard induced cytokine production and cell death: Investigating the potential roles of the p38, p53, and NF-,B signaling pathways with RNA interference,JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2010Albert L. Ruff Abstract Cutaneous and ocular injuries caused by sulfur mustard (SM; bis-(2-chloroethyl) sulfide) are characterized by severe inflammation and death of exposed cells. Given the known roles of p38MAPK and NF-,B in inflammatory cytokine production, and the known roles of NF-,B and p53 in cell fate, these pathways are of particular interest in the study of SM injury. In this study, we utilized inhibitory RNA (RNAi) targeted against p38,, the p50 subunit of NF-,B, or p53 to characterize their role in SM-induced inflammation and cell death in normal human epidermal keratinocytes (NHEK). Analysis of culture supernatant from 200 ,M SM-exposed cells showed that inflammatory cytokine production was inhibited by p38, RNAi but not by NF-,B p50 RNAi. These findings further support a critical role for p38 in SM-induced inflammatory cytokine production in NHEK and suggest that NF-,B may not play a role in the SM-induced inflammatory response of this cell type. Inhibition of NF-,B by p50 RNAi did, however, partially inhibit SM-induced cell death, suggesting a role for NF-,B in SM-induced apoptosis or necrosis. Interestingly, inhibition of p53 by RNAi potentiated SM-induced cell death, suggesting that the role of p53 in SM injury, may be complex and not simply prodeath. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:155,164, 2010; Published online inWiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20321 [source] Histopathological observations of human periimplantitis lesionsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 5 2004Tord Berglundh Abstract Objective: The aim of the present study was to analyze some characteristics of advanced and progressive periimplantitis lesions in man. Material and methods: Soft tissue biopsies were obtained from 12 implants in six patients. The implants had been in function between 4 and 21 years and were, with one exception, located in the maxilla. The radiographic examination performed prior to biopsy revealed that all sites exhibited advanced bone loss. Further, clinical signs of severe inflammation, such as suppuration, swelling and/or fistula formation were detected in the majority of sites and seven of the 12 implants were found to be mobile at biopsy. Each biopsy was following fixation embedded in epoxy resin and sections were prepared for histometric and morphometric analysis. Results and conclusion: It was demonstrated (i) that all soft tissue units harbored large inflammatory cell infiltrates (ICT) that extended to a position apical of a pocket epithelium and (ii) that about 60% of the lesions were occupied by inflammatory cells, among which plasma cells dominated. Numerous amounts of PMN cells occurred not only in the pocket epithelium and adjacent connective tissue areas, but were also present in peri-vascular compartments in more central areas of the ICT. [source] Atypical Response of Xeroderma Pigmentosum to 5-Fluorouracil: A Histopathological Image Analysis Study Reveals New Insight into EtiopathogenesisJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005S.A. Centurion Xeroderma pigmentosum (XP) is a recessively inherited genodermatosis associated with extreme sun sensitivity, defective repair of several types of sunlight induced adducts in cellular DNA, and numerous, early-onset skin cancers. The dry, rough skin corresponds to progressive cytologic atypia and loss of polarity in the underlying epidermis. Associated with these changes are immune deficiencies against ultraviolet radiation-induced skin cancer. 5-Fluorouracil (5-FU) is a DNA synthesis antimetabolite used against several types of cancers. Applied topically in normal subjects it is associated with moderate to severe inflammation in areas where actinic keratoses have arisen followed by ablation of the actinic keratoses which is dependent on the inflammation. We applied 5-FU to the sun-exposed skin of two patients with XP, a 14 year-old light complected black male and a 14 year-old Caucasian female. No inflammation was observed, but marked improvement in the clinical presentation of the skin was seen, as well as an absence of new malignancies. This change was confirmed histopathologically and correlated with normalization of polarity and cytologic changes in the epidermal cells. These histologic findings were quantitated using computerized image analysis. These results may be due to activation of alternative DNA repair pathways in these nucleotide excision repair deficient cells. [source] Differential expression of CCR5 and CRTH2 on infiltrated cells in colonic mucosa of patients with ulcerative colitisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2003KOJI MATSUZAKI Abstract Background and Aim:, The pathogenesis of ulcerative colitis (UC) is unclear, but abnormal infiltration of T lymphocytes in the colonic mucosa has been implicated in the mucosal tissue damage. The abnormal cytokine production because of a T helper (h)1/Th2 imbalance may play an important role in continuing inflammation in the colonic mucosa. In the present study, the expression of chemokine receptor 5 (CCR5) as a Th1 marker and a chemoattractant receptor-homologs molecule expressed on Th2 cells (CRTH2) were investigated in order to analyze impaired Th1/Th2 responses in the colonic mucosa of UC patients. Methods:, Tissue samples were obtained by colonic biopsies from patients with UC or colonic polyps, with informed consent. Immunohistochemical analysis was performed on periodate, lysine-paraformaldehyde-fixed serial cryostat sections using the labeled streptavidin biotin method. Monoclonal antibodies against CD4, CCR5 or CRTH2 were used as primary antibodies. The number of cells expressing CD4, CCR5 or CRTH2 per unit area was calculated by using an image analyzer. Results:, In the patients with UC, the numbers of CD4- and CCR5-positive cells were significantly increased in inflamed mucosa, and appeared to be correlated with the disease activity. The infiltration of CRTH2-positive cells was predominantly observed in the mildly inflamed or the margin of inflamed mucosa of UC patients. Conclusion:, There is a possibility that Th1 responses significantly occur in colonic mucosa with severe inflammation, while Th2 responses mainly occur with mild inflammation in UC patients. The Th1/Th2 imbalance in colonic mucosa may be related to the disease progression of UC. [source] Disorder-specific changes in innervation in oral lichen planus and lichenoid reactionsJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2000Sirkku Niissalo Abstract: The peripheral nervous system was analysed in the oral mucosa of eight patients with oral lichen planus (OLP), five with a lichenoid reaction (LR) and three with mild chronic inflammation (MCI), by morphometric analysis of nerve fibres containing immunoreactive PGP 9.5, substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), or C-flanking peptide of neuropeptide Y (CPON). Overall nerve fibre density was higher in OLP (P=0.039) and LR (P=0.026) compared with healthy oral mucosa and was compatible with sprouting and collateral formation. In contrast to the innervation visualized with structural nerve fibre-marker PGP 9.5, the densities of neuropeptide-immunoreactive nerves were low in inflamed tissue. This is consistent with depletion via local release. Retraction and local loss of innervation were found in areas coinciding with the most severe inflammation and basal membrane (BM) damage. Interestingly, LR showed a twenty-eight-fold loss of post-ganglionic CPON-ir sympathetic nerve fibres (P=0.044). In LR, CPON-ir innervation was markedly lower than in OLP. Finally, the pattern of innervation in relation to inflammatory cell infiltrates and tissue structures differed between OLP and LR. In conclusion, the peripheral nervous system is implicated in the immunopathogenesis of lichen planus and lichenoid reactions, with a disorder-specific difference in this involvement. [source] Adiponectin changes in HCV-Genotype 4: relation to liver histology and response to treatmentJOURNAL OF VIRAL HEPATITIS, Issue 10 2009M. Derbala Summary., Recently, attention has been focussed on adiponectin and its changes in different types of chronic liver disease. Its relation to hepatic fibrosis and insulin resistance in post-hepatitis liver disease is not clear. The aim of this study was to clarify the adiponectin changes in genotype 4 hepatitis C virus (HCV)-infected patient in relation to liver histology and insulin resistance, and its usefulness as a predictor of hepatic fibrosis and response to treatment. Total adiponectin and its high molecular weight (HMW) form as well as insulin levels were studied in 92 chronic HCV, genotype 4 and 66 healthy control volunteers. Neither total adiponectin (r = 0.101, P = 0.220) nor HMW adiponectin (r = 0.081, P = 0.328) correlated with viral load. Total and not HMW adiponectin was significantly correlated with hepatic fibrosis and inflammation (r = 0.267, P = 0.002, r = 0.278, P < 0.001, respectively). In addition, total adiponectin (r = 0.224, P = 0.002) and HMW adiponectin (r = 0.266, P < 0.0006) significantly correlated with insulin resistance. As fibrosis did not correlate with insulin resistance (r = 0.081, P = 0.204), the correlation between total adiponectin and fibrosis was not mediated by insulin resistance. Multivariable regression analysis, (including pretreatment cases and controls) revealed that total adiponectin was significantly associated with gender, being lower among male subjects (X2 = 13.04, P = 0.0001). The multivariable regression model supported the lack of association between insulin resistance and total adiponectin levels (X2 = 1.88, P = 0.171), while non cirrhotics had significantly lower total adiponectin levels than cirrhotics (X2 = 10.90, P = 0.004) and lower level of inflammation significantly lower total adiponectin levels than more severe inflammation (X2 = 8.95, P = 0.003). Total or HMW adiponectin did not yield receiver operating characteristic (ROC) curves with area under the curve (AUC) >75%, thus the cutoff points have poor sensitivity/specificity as predictors of fibrosis. However, as a predictor of end-of-treatment response, the ROC curve of adiponectin index gave yield an AUC = 81.4%. We can conclude that total adiponectin level, in HCV genotype 4 patients, increases with progression of hepatic fibrosis regardless of insulin resistance. Its high molecular form does not have such correlation. The adiponectin changes are not related to viral load, insulin resistance or other demographic data suggesting that this change is histologically related. In spite of this, no adiponectin cutoff level had reasonable sensitivity/specificity for predicting hepatic fibrosis stage, while this may be used as a predictor for antiviral response possibly reflecting improvement in hepatic inflammation post treatment. [source] Hepatitis B virus DNA levels, precore mutations, genotypes and histological activity in chronic hepatitis BJOURNAL OF VIRAL HEPATITIS, Issue 4 2000Lindh The present study aimed to clarify how viraemia levels reflect the clinical stages of chronic hepatitis B virus (HBV) infection, in particular studying whether ,healthy carriers' can be identified by analysing HBV DNA levels with a highly sensitive quantitative assay. Histology activity index (HAI), alanine aminotransferase (ALT) level, genotype and precore mutations were compared with the HBV DNA level, as measured using the Amplicor HBV Monitor assay in a prospective study. In 124 hepatitis B e antigen-negative (HBeAg,) patients, the majority with mild liver disease, log HBV DNA levels showed a Gaussian distribution around a geometric mean of 33 000 genome copies ml,1, and increasing HBV DNA level was associated with significantly higher inflammation (HAIinfl) and fibrosis (HAIfibr) scores and higher ALTi (ALT ÷ the upper reference value). Severe inflammation (HAIinfl , 7) was seen in 83% (five of six), 36% (eight of 22) and 3% (one of 37) of HBeAg, patients with HBV DNA > 107, > 2 × 105 and < 104 copies ml,1, respectively. In severe HBeAg, hepatitis, patients with precore wild-type infection had lower HBV DNA levels than those with precore mutants. In 36 HBeAg-positive (HBeAg+) patients, no correlation between HBV DNA level and liver damage was seen. Ninety-six per cent of HBeAg, patients with ALTi < 0.5 had HAIinfl , 3. In HBeAg, carriers with ALTi 0.5,1.0, the relative risk for severe inflammation, comparing HBV DNA > 2 × 105 copies ml,1vs < 2 × 105 copies ml,1, was 14.7. In conclusion, in HBeAg, carriers, HBV DNA < 104 copies ml,1 or ALTi < 0.5 indicates mild inflammation, while > 2 × 105 copies ml,1 of HBV DNA may justify further investigations. Precore status may be relevant for the interpretation of viraemia. [source] Risk factors for recurrence of autoimmune hepatitis after liver transplantation,,LIVER TRANSPLANTATION, Issue 10 2009Aldo J. Montano-Loza Autoimmune hepatitis has been reported to recur after liver transplantation. The aim of our study was to evaluate the risk factors associated with recurrence of autoimmune hepatitis. Forty-six patients that underwent liver transplantation because of end-stage liver disease secondary to autoimmune hepatitis were studied. Recurrence of autoimmune hepatitis was diagnosed in 11 of the 46 (24%) patients, and the overall 5-year probability of recurrence was 18%. By univariate Cox analysis, the features before liver transplantation associated with a higher risk of recurrence were concomitant autoimmune disease [hazard ratio (HR), 3.74; 95% confidence interval (CI), 1.05,13.36; P = 0.04], high aspartate aminotransferase (HR, 1.09; 95% CI, 1.03,1.14; P = 0.002), high alanine aminotransferase (HR, 1.09; 95% CI, 1.03,1.20; P = 0.003), and high immunoglobulin G (IgG; HR, 1.25; 95% CI, 1.11,1.41; P = 0.0003). Moreover, patients with recurrence had a higher frequency of moderate to severe inflammatory activity (HR, 5.3; 95% CI, 1.55,18.79; P = 0.008) and plasma cell infiltration in the liver explant (HR, 5.8; 95% CI, 1.52,22.43; P = 0.01). In the multivariate Cox analysis, only the presence of moderate to severe inflammation (HR, 6.9; 95% CI, 1.76,26.96; P = 0.006) and high IgG levels before liver transplantation (HR, 7.5; 95% CI, 1.45,38.45; P = 0.02) were independently associated with the risk of autoimmune hepatitis recurrence. In conclusion, patients with concomitant autoimmune disease, high aspartate aminotransferase, alanine aminotransferase, and IgG before the transplant, or moderate to severe inflammatory activity or plasma cell infiltration in the liver explant have a higher risk of recurrent disease. These findings suggest that recurrence of autoimmune hepatitis may reflect incomplete suppression of disease activity prior to liver transplantation. Liver Transpl 15:1254,1261, 2009. © 2009 AASLD. [source] Remote Liver Injury is Attenuated by Adenovirus-Mediated Gene Transfer of Heme Oxygenase-1 During the Systemic Inflammatory Response SyndromeMICROCIRCULATION, Issue 7 2004SARAH D. MCCARTER ABSTRACT Objectives: Adenovirus-mediated gene therapy is being investigated with increasing success for future treatment of autoimmune diseases. However, the use of adenoviruses is still limited by inflammatory and immune responses in the target organ. Previous work by the authors' laboratory established that the adenovirus encoding inducible heme oxygenase (Ad-HO-1) does not elicit the acute hepatic inflammation normally caused by adenoviruses, inviting further investigation in models of severe inflammation. Concurrently, there is increasing evidence for an endogenous protective role for heme oxygenase (HO) in the liver during the systemic inflammatory response syndrome (SIRS). Building on our previous results, this study investigated the effect of Ad-HO-1 pretreatment on remote liver injury during normotensive SIRS, induced by bilateral hind limb ischemia and reperfusion. Methods: Microvascular perfusion and hepatocyte death were quantified using established intravital videomicroscopy techniques. Hepatocellular injury and liver function were assessed using blood-borne indicators. Results: Microvascular perfusion deficits and increased hepatocyte death occurred following limb ischemia and 3 h of reperfusion in vehicle-pretreated animals; however, Ad-HO-1 pretreatment prevented these deficits. In contrast, the increase in serum alanine transaminase levels was unaffected by Ad-HO-1 pretreatment. Serum bilirubin levels were increased during systemic inflammation, predominantly in the conjugated form; and, this increase was prevented by administration of Ad-HO-1. Conclusions: These data indicate that gene transfer of inducible HO is an effective method to protect the liver during SIRS, providing incentive for further investigation into gene therapy strategies exploiting this anti-inflammatory enzyme. [source] Increased expression of epidermal fatty acid-binding protein by alveolar macrophages during acute rejection of rat lungsAPMIS, Issue 10 2010JULIA HOLLER Holler J, Zakrzewicz A, Garn H, Hirschburger M, Kummer W, Padberg W, Grau V. Increased expression of epidermal fatty acid-binding protein by alveolar macrophages during acute rejection of rat lungs. APMIS 2010; 118: 791,800. In the lung, epidermal fatty acid-binding protein (E-FABP) is expressed by alveolar macrophages (AM) and alveolar epithelial cells type II (AEII). E-FABP may regulate macrophage activation and is involved in the metabolism of surfactant phospholipids. As macrophage activation and surfactant dysfunction are associated with rejection, we hypothesize that E-FABP expression is changed during acute rejection of pulmonary grafts. Orthotopic left lung transplantations were performed in the Dark Agouti to Lewis and in the isogeneic Lewis to Lewis rat strain combinations. E-FABP expression was analyzed in the lung by immunohistochemistry, immunoblotting and quantitative reverse transcription-polymerase chain reaction (RT-PCR). Alveolar leukocytes obtained by bronchoalveolar lavage were analyzed by RT-PCR. Immunohistochemistry of isografts revealed strong E-FABP immunoreactivity in AEII and a moderate immunoreactivity in AM. In allografts undergoing acute rejection, AM exhibiting increased E-FABP immunoreactivity accumulated. Immunoblots revealed a single band at 15 kDa, which corresponds to the expected molecular mass of E-FABP. The levels of E-FABP mRNA were higher in allografts than in isografts and control lungs. Furthermore, alveolar leukocytes isolated by bronchoalveolar lavage from allografts displayed higher E-FABP mRNA expression levels than leukocytes from isografts and controls. In conclusion, we demonstrate for the first time upregulation of E-FABP expression in AM during severe inflammation. [source] Novel experimental Pseudomonas aeruginosa lung infection model mimicking long-term host,pathogen interactions in cystic fibrosisAPMIS, Issue 2 2009CLAUS MOSER The dominant cause of premature death in patients suffering from cystic fibrosis (CF) is chronic lung infection with Pseudomonas aeruginosa. The chronic lung infection often lasts for decades with just one clone. However, as a result of inflammation, antibiotic treatment and different niches in the lungs, the clone undergoes significant genetic changes, resulting in diversifying geno- and phenotypes. Such an adaptation may generate different host responses. To experimentally reflect the year-long chronic lung infection in CF, groups of BALB/c mice were infected with clonal isolates from different periods (1980, 1988, 1997, 1999 and 2003) of the chronic lung infection of one CF patient using the seaweed alginate embedment model. The results showed that the non-mucoid clones reduced their virulence over time, resulting in faster clearing of the bacteria from the lungs, improved pathology and reduced pulmonary production of macrophage inflammatory protein-2 (MIP-2) and granulocyte colony-stimulating factor (G-CSF). In contrast, the mucoid clones were more virulent and virulence increased with time, resulting in impaired pulmonary clearing of the latest clone, severe inflammation and increased pulmonary MIP-2 and G-CSF production. In conclusion, adaptation of P. aeruginosa in CF is reflected by changed ability to establish lung infection and results in distinct host responses to mucoid and non-mucoid phenotypes. [source] Important role of interleukin-3 in the early phase of collagen-induced arthritisARTHRITIS & RHEUMATISM, Issue 5 2009Hilke Brühl Objective Activation of basophils contributes to memory immune responses and results in exacerbation of collagen-induced arthritis (CIA). We undertook the present study to analyze the production and biologic effects of interleukin-3 (IL-3), a strong activator of basophils, in CIA. Methods Arthritis was induced by immunization with type II collagen. Mice were treated with blocking monoclonal antibodies against IL-3 or with recombinant IL-3. Clinical scoring, histologic analysis, fluorescence-activated cell sorter analysis, enzyme-linked immunosorbent assay, and cell culturing were performed to assess disease activity and IL-3 production. Results IL-3 was produced in large quantities by collagen-specific CD4+ T cells in the spleen and was present in the synovial tissue during onset of arthritis, but was down-regulated in paws with severe inflammation. Blockade of IL-3 during the time of arthritis onset resulted in profound improvement of the disease, with reductions in synovial leukocyte and cytokine levels, peripheral blood basophil levels, and anticollagen antibody titers. Blockade of IL-3 during the late phase of arthritis had no beneficial effect. Administration of recombinant IL-3 during onset of arthritis induced a marked exacerbation of the disease, with increased peripheral blood basophil and plasma IL-6 levels and increased titers of anticollagen antibody. In studies of the regulation of IL-3 expression in CD4+ T cells, IL-6 and IL-4 suppressed the release of IL-3 by activated CD4+ T cells, whereas lipopolysaccharide and CpG DNA up-regulated IL-3 secretion in activated CD4+ T cells by acting on costimulatory cells. Conclusion Taken together, the present results demonstrate for the first time that IL-3 has an important role in the early phase of CIA. [source] Inflammation and angiogenesis in osteoarthritisARTHRITIS & RHEUMATISM, Issue 8 2003L. Haywood Objective To quantify the relationship between inflammation and angiogenesis in synovial tissue from patients with osteoarthritis (OA). Methods Hematoxylin and eosin staining and histologic grading for inflammation were performed for 104 patients who met the American College of Rheumatology criteria for OA and had undergone total joint replacement or arthroscopy. A purposive sample of synovial specimens obtained from 70 patients was used for further analysis. Vascular endothelium, endothelial cell (EC) proliferating nuclei, macrophages, and vascular endothelial growth factor (VEGF) were detected by immunohistochemical analysis. Angiogenesis (EC proliferation, EC fractional area), macrophage fractional area, and VEGF immunoreactivity were measured using computer-assisted image analysis. Double immunofluorescence histochemical analysis was used to determine the cellular localization of VEGF. Radiographic scores for joint space narrowing and osteophyte formation in the knee were also assessed. Results Synovial tissue samples from 32 (31%) of 104 patients with OA showed severe inflammation; thickened intimal lining and associated lymphoid aggregates were often observed. The EC fractional area, EC proliferation, and VEGF immunoreactivity all increased with increasing histologic inflammation grade and increasing macrophage fractional area. In the synovial intimal lining, VEGF immunoreactivity was localized to macrophages and increased with increasing EC fractional area and angiogenesis. No inflammation or angiogenic indices were significantly correlated with radiographic scores. Conclusion Inflammation and angiogenesis in the synovium are associated with OA. The angiogenic growth factor VEGF generated by the inflamed synovium may promote angiogenesis, thereby contributing to inflammation in OA. [source] Bowel obstruction associated with endoscopic tattooing of the colon with India inkASIAN JOURNAL OF ENDOSCOPIC SURGERY, Issue 3 2010Y Seki Abstract During a laparoscopic resection of small colorectal lesions, preoperative endoscopic marking with India ink is useful for identifying the location of the lesion. India ink has been thought to be a safe agent with few adverse effects. We herein report a case who suffered from postoperative abdominal pain resulting in bowel obstruction, due to massive adhesion around the area with India ink. A 61-year-old man with early transverse colon cancer underwent a laparoscopy-assisted transverse colon resection. Prior to the operation, endoscopic tattooing with India ink was performed. At the operation, spillage of India ink into the peritoneal cavity was observed. Many small black spots were thereafter seen on the peritoneum, mesentery and omentum, but neither severe inflammation nor any adhesion was noticed. The operation was performed without any difficulty. Though his immediate postoperative course was uneventful, a bowel obstruction gradually developed from a week postoperatively. Finally, he had to undergo a re-operation, and was found to have diffuse and massive adhesion around areas with India ink. Especially, severe omental adhesion involved and squeezed the transverse colon. A resection of the omentum with stenotic colon and re-anastomosis was performed. India ink can cause severe inflammation and adhesion when it accidentally leaks into the peritoneal cavity. [source] Inhibition of LPS-induced chemokine production in human lung endothelial cells by lipid conjugates anchored to the membraneBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2002G Ch Beck In acute respiratory distress syndrome (ARDS) induced by endotoxins, a high production of inflammatory mediators by microvascular lung endothelial cells (LMVEC) can be observed. Activation of cells by endotoxins may result in elevated secretion of phospholipase A2 (sPLA2) which is thought to contribute to tissue damage. The present study was undertaken to investigate the role of sPLA2 in chemokine production in human lung microvascular endothelial cells (LMVEC) stimulated with the endotoxins lipopolysaccharide (LPS) and lipoteichoic acid (LTA). In particular, we investigated the effects of sPLA2 inhibitors, specifically, the extracellular PLA2 inhibitors (ExPLIs), composed of N-derivatized phosphatidyl-ethanolamine linked to polymeric carriers, and LY311727, a specific inhibitor of non-pancreatic sPLA2. ExPLIs markedly inhibited LPS and LTA induced production and mRNA expression of the neutrophile attracting chemokines IL-8, Gro-, and ENA-78, as well as of the adhesion molecules ICAM-1 and E-selectin. Concomitantly, ExPLIs inhibited the LPS-induced activation of NF-,B by LPS but not its activation by TNF-, or IL-1. Endotoxin mediated chemokine production in LMVEC seems not to involve PLA2 activity, since LPS stimulation was not associated with activation of intracellular or secreted PLA2. It therefore seems that the inhibitory effect of the ExPLIs was not due to their PLA2 inhibiting capacity. This was supported by the finding that the LPS-induced chemokine production was not affected by the selective sPLA2 inhibitor LY311727. It is proposed that the ExPLIs may be considered a prototype of potent suppressors of specific endotoxin-induced inflammatory responses, with potential implications for the therapy of subsequent severe inflammation. British Journal of Pharmacology (2002) 135, 1665,1674; doi:10.1038/sj.bjp.0704618 [source] 2332: Pathological changes of anatomical structure and markers of limbal stem cell niche due to inflammationACTA OPHTHALMOLOGICA, Issue 2010C CURCIO Purpose It's known that severe inflammatory processes may cause limbal stem cell (SC) deficiency decreasing the number of SC niches and changing the microanatomy of these structures. Methods The aim of this study was to evaluate the expression of different SC markers in normal human limbus and to study how an inflammatory conditions can modulate these antigens. To understand the pathological changes in limbal crypts structure due to severe inflammation, a case of corneal melting and perforation in advanced herpes simplex (HSV) disease, two cases of endophthalmitis and a case of fungal infection were analyzed.Samples were examined by immunohistochemistry or immunofluorescence for p63, vimentin, laminin5, integrin (Int) ,6, int ,1, int ,4, ABCG2, desmoglein 3, connexin43, N-cadherin and cytokeratin (K) 12 positivity. We evaluated the anatomical structure of limbal crypts in each case and the positivity for SC marker used to identify SC. Results In normal limbus, the investigated SC markers were positive. In the HSV we didn't observe presence of crypts, whereas in both cases of endophthalmitis crypts were still present but they had an atypical structure: the basal cells in the crypts were "stretched" and endowed by inflammatory cells. In the pathological cases, we observed positivity for K12 while, among SC markers, p63, ABCG2 and connexin43 were still present; the others antigens were variably expressed. Conclusion Different pathologies involving the limbus may result in marked chenges of expression of SC markers within the crypts. [source] Fetal inflammatory response in women with proteomic biomarkers characteristic of intra-amniotic inflammation and preterm birthBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 2 2009CS Buhimschi Objective, To determine the relationship between presence of amniotic fluid (AF) biomarkers characteristic of inflammation (defensins 2 and 1 and calgranulins C and A) and fetal inflammatory status at birth. Design, Prospective observational cohort. Setting, Tertiary referral University hospital. Population, One hundred and thirty-two consecutive mothers (gestational age, median [interquartile range]: 29.6 [24.1,33.1] weeks) who had a clinically indicated amniocentesis to rule out infection and their newborns. Methods, Intra-amniotic inflammation was diagnosed by mass spectrometry surface-enhanced-laser-desorption-ionization time of flight (SELDI-TOF). The AF proteomic fingerprint (mass-restricted [MR] score) ranges from 0,4 (none to all biomarkers present). The intensity of intra-amniotic inflammation was graded based on the number of proteomic biomarkers: MR score 0: ,no' inflammation, MR score 1,2: ,minimal' inflammation and MR score 3,4: ,severe' inflammation. At birth, cord blood was obtained for all women. Severity of histological chorioamnionitis and early-onset neonatal sepsis (EONS) was based on established histological and haematological criteria. Interleukin-6 (IL-6) levels were measured by sensitive immunoassays. The cord blood-to-AF IL-6 ratio was used as an indicator of the differential inflammatory response in the fetal versus the AF compartment. Main outcome measures, To relate proteomic biomarkers of intra-amniotic infection to cord blood IL-6 and to use the latter as the primary marker of fetal inflammatory response. Results, Women with intra-amniotic inflammation delivered at an earlier gestational age (analysis of variance, P < 0.001) and had higher AF IL-6 levels (P < 0.001). At birth, neonates of women with severe intra-amniotic inflammation had higher cord blood IL-6 levels (P = 0.002) and a higher frequency of EONS (P = 0.002). EONS was characterised by significantly elevated cord blood IL-6 levels (P < 0.001). Of the 39 neonates delivered by mothers with minimal intra-amniotic inflammation, 15 (39%) neonates had umbilical cord blood IL-6 levels above the mean for the group and 2 neonates had confirmed sepsis. The severity of the neutrophilic infiltrate in the chorionic plate (P < 0.001), choriodecidua (P = 0.002), umbilical cord (P < 0.001) but not in the amnion (P > 0.05) was an independent predictor of the cord blood-to-AF IL-6 ratio. Relationships were maintained following correction for gestational age, birthweight, amniocentesis-to-delivery interval, caesarean delivery, status of the membranes, race, MR score and antibiotics and steroid exposure. Conclusions, We provide evidence that presence of proteomic biomarkers characteristic of inflammation in the AF is associated with an increased inflammatory status of the fetus at birth. Neonates mount an increased inflammatory status and have positive blood cultures even in the context of minimal intra-amniotic inflammation. [source] | ||||||||||||||||||||||||||||