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Local Inflammation (local + inflammation)
Selected AbstractsLowered albumin extravasation rate in heart but not in other organs in ,3-integrin-deficient miceACTA PHYSIOLOGICA, Issue 4 2009Ř. S. Svendsen Abstract Aim:, The vascular protein permeability is dependent on the integrity of the vascular wall. The heart capillaries in male mice lacking ,3 integrins have an immature phenotype. Previously, we have demonstrated a role for ,v,3 integrins in control of interstitial fluid pressure (Pif) and thereby in the fluid flux during inflammation. We wanted to explore a possible role for ,v,3 integrins in controlling capillary protein permeability during control situation and inflammation. Methods:, We performed double-tracer and microdialysis experiments on ,3-integrin-deficient mice and wild type control mice. We also measured blood pressure and heart rate in the two mice strains. Results:, We found reduced albumin extravasation (during 25 min) in the heart capillaries (0.053 ± 0.003 vs. 0.087 ± 0.009 mL g,1 dw, P < 0.05), and an increased cardiac mass/body weight (5.3 × 10,3 ± 0.3 × 10,3 vs. 3.8 × 10,3 ± 0.1 × 10,3, P < 0.01) in the ,3-integrin-deficient mice (n = 6) compared with the controls (n = 6). Heart rate and blood pressure were the same in mice with and without ,3-integrins. No difference in permeability was found in other tissues studied, or under local inflammation. Conclusion:, These results show a function for the ,v,3 integrin in the regulation of protein permeability, selective for the heart capillaries. [source] Rosiglitazone combined with insulin preserves islet , cell function in adult-onset latent autoimmune diabetes (LADA)DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2005Zhiguang Zhou Abstract Background LADA is thought to result from the chronic autoimmune destruction of the insulin-producing pancreatic , cells. In addition to antidiabetic effects, the newly developed insulin sensitizer-thiazolidinediones have the potential to increase the insulin content of islet cells by downregulating local inflammation and autoimmune response. Therefore, we hypothesized that LADA patients might benefit from thiazolidinediones treatment. Methods LADA patients, with a fasting C-peptide (FCP) of 0.3 nmol/L or more, were enrolled and randomly assigned to receive subcutaneous insulin alone (insulin group, n = 12) or rosiglitazone plus insulin (insulin + RSG group, n = 11) to compare the impacts on islet , cell function. Plasma glucose, HbA 1c, fasting C-peptide (FCP) and C-peptide after 2 h 75-g glucose load (PCP) were determined every 6 months. GAD-Ab and C-peptide were measured with radioimmune assays. Islet , cell function was evaluated by PCP and ,CP(,CP = PCP-FCP). Results All of the 23 patients have been followed up for 6 months, 17 cases for 12 months and 14 for 18 months. (1) During 6 months' follow-up, there were no significant changes for ,CP and PCP levels in both groups. (2) PCP and ,CP levels in insulin + RSG group patients stayed steady during the 12 months' observation (P = 0.161 for both PCP and ,CP), while in the insulin alone group, both FCP (P = 0.021) and PCP (P = 0.028) levels decreased significantly. Furthermore, PCP (P = 0.004) and ,CP(P = 0.015) differences between 12th month and baseline were higher in insulin + RSG group than those in the insulin group. (3) When observed up to 18 months, PCP and ,CP levels in insulin + RSG group patients still stayed steady, while PCP and ,CP levels decreased more in the insulin alone group. Conclusions This pilot study suggests that rosiglitazone combined with insulin may preserve islet , cell function in LADA patients. Copyright © 2004 John Wiley & Sons, Ltd. [source] The ability to mount multiple immune responses simultaneously varies across the range of the tree swallowECOGRAPHY, Issue 1 2007Daniel R. Ardia Variation in immune responses is an important part of life history variation. When correlations between multiple immune measures are reported, studies report different patterns. I tested whether the correlation between levels of immune response was consistent across a species range. The ability of tree swallows Tachycineta bicolor to simultaneously produce immune responses to both a humoral immune response and T-cell mediated local inflammation to PHA was tested at three sites that span the breeding range. Females in Tennessee maintained stronger PHA responses than did females in either New York or Alaska. In New York and Alaska, individuals that produced strong PHA responses produced low levels of antibodies to a humoral challenge of sheep red blood cells (SRBC). However, in Tennessee, individuals that showed strong local PHA inflammation also mounted strong responses to SRBC. Increasing daily daytime temperatures led to increased PHA response, but there were no differences in the effect of temperature among sites. These results indicate spatial and/or temporal variation occurs in the ability to produce multiple immune responses simultaneously; this pattern suggests important geographic (or temporal) differences in factors driving investment in immune activity. In addition, these results suggest that studies extrapolating results across populations should be careful to consider geographic variation in immune activity. [source] Intracutaneous injection of the macrophage-activating lipopeptide-2 (MALP-2) which accelerates wound healing in mice , a phase I trial in 12 patientsEXPERIMENTAL DERMATOLOGY, Issue 12 2008Margarete Niebuhr Abstract:, Chronic skin ulcers, such as leg ulcers, pressure sores and diabetic foot ulcers, are a challenge to physicians and medical personnel and a cause of tremendous discomfort and ensuing loss of quality of life to the patients. Wound healing involves production and action of various growth factors. A novel approach, distinct from the application of single growth factors, is the administration of the macrophage stimulator macrophage-activating lipopeptide-2 (MALP-2). The rationale is based on the finding that macrophages are the main source of several growth factors required for wound healing, which are sequentially released during this process. MALP-2 has previously been shown to be effective in an established animal model with diabetic mice. The purpose of the present phase I study was to establish tolerability of MALP-2 when applied into small cutaneous wounds in human beings. Twelve patients (six females and six males; mean age 66.8 years; range 52,87 years) with different diagnoses were enrolled into the study. An artificial wound was created with a 2-mm diameter skin biopsy punch and a volume of 30 ,l MALP-2 (0.125,1 ,g) or vehicle control, respectively, was injected intracutaneously into the wound and closed with a water-resistant transparent adhesive. Photos were taken daily from every patient up to 6 days, and skin biopsies were performed after 1 week from six patients. We could show in the present study for the first time that MALP-2 caused a transient erythema and was tolerated without any systemic side effects up to a dose of 1 ,g per wound in human beings. In healthy as well as in diabetic patients, MALP-2 induced local inflammation that faded after 48 h. The effectiveness of MALP-2 in the healing of chronic wounds in humans, e.g. in chronic skin ulcers, such as leg ulcers, pressure sores and diabetic foot ulcers, could now be addressed in further studies. [source] Fucosyltransferase VII-positive, skin-homing T cells in the blood and skin lesions of atopic dermatitis patientsEXPERIMENTAL DERMATOLOGY, Issue 3 2008Yoshiko Mizukawa Abstract: Patients with atopic dermatitis (AD) have an abnormally increased frequency of cutaneous lymphocyte antigen (CLA)+ Th2 cells responsible for local inflammation; however, this is paradoxical, given the well-recognized defective capacity of Th2 cells to migrate to the skin sites of inflammation. These discrepant observations would stem from the ambiguity of CLA+ T cells, because CLA does not represent the epitope required for binding to E-selectin but the epitope generated by fucosyltransferase VII (Fuc-TVII) and because skin-homing T cells are composed of three distinct subpopulations; Fuc-TVII+ E-selectin ligand (ESL)+ CLA,, Fuc-TVII+ ESL+ CLA+ and Fuc-TVII, ESL, CLA+ cells. We therefore asked which subpopulations of skin-homing Th2 cells could be increased in the blood and skin lesions of AD. We analysed the frequencies of the three subpopulations in purified CD4+ peripheral blood T cells from AD patients and healthy controls by immunohistochemistry and flow cytometry. The Fuc-TVII+ CLA+ or CLA+ ESL+ CCR4+ cells were dramatically increased in frequency not only in the blood but also in the skin lesions of AD patients and this increase was related to the severity of the clinical symptoms. Our data indicate the clinical importance of identifying skin-homing T cells with the potent capacity to migrate into the skin by analysing their Fuc-TVII expression and E-selectin binding ability in patients with AD. [source] Development of colonic stenosis following severe acute pancreatitisHPB, Issue 3 2003F Maisonnette Background Colonic necrosis after acute pancreatitis is rare. When it does occur, it is commonly due to ischaemia or inflammation and may necessitate early colonic resection. Case outline A 72-year-old man developed colonic necrosis 6 weeks after severe acute pancreatitis. CT scan revealed a bulky mass near the left colon. Barium enema and colonoscopy revealed stenosis of the left colonic flexure, and this segment of bowel was successfully resected. Discussion Severe acute pancreatitis must be recognised as a cause of colonic ischaemia and necrosis. The possible pathogenic mechanisms include severe local inflammation and an ischaemic process. This complication is associated with a very poor prognosis despite surgical intervention, but a timely resection may prevent further problems. [source] Anti-inflammatory effects in the skin of thymosin-,4 splice-variantsIMMUNOLOGY, Issue 1 2003Michael Girardi Summary The intraepithelial lymphocyte (IEL) network of T-cell receptor ,,+ (V,5+) dendritic epidermal T cells (DETC) in murine skin down-regulates cutaneous inflammation, although the mechanism is unknown. Thymosin-,4 (T,4), identified by serial analysis of gene expression as a predominant transcript in gut IEL, encodes both a ubiquitous actin-binding protein (UT,4) with demonstrated capacity to inhibit neutrophilic infiltration, and a splice-variant limited to lymphoid tissue (LT,4) with unknown bioactivity. Freshly isolated V,5+ DETCs expressed both forms, while only LT,4 was preferentially up-regulated after cellular activation in vitro. To compare the anti-inflammatory properties of LT,4 and UT,4 in the skin in vivo, the biological activities of synthesized polypeptides were assessed using three different strategies: neutrophil infiltration by footpad ,-carrageenan injection; irritant contact dermatitis to 12-O-tetradecanoylphorbol 13-acetate; and allergic contact dermatitis to 2,4-dinitrofluorobenzene. These studies clearly showed that the anti-inflammatory activities of LT,4 were broader and most often stronger than those of UT,4. Thus, the activation-responsive expression of the lymph-specific form of T,4 may be one mechanism by which DETC, and possibly other IELs, down-regulate local inflammation. [source] The immunological basis of B-cell therapy in systemic lupus erythematosusINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 1 2010Mo Yin MOK Abstract Loss of B-cell tolerance is a hallmark feature of the pathogenesis in systemic lupus erythematosus (SLE), an autoimmune disease that is characterized by hypergammaglobulinemia and autoantibody production. These autoantibodies lead to formation of immune-complex deposition in internal organs causing inflammation and damage. Autoreactive B-cells are believed to be central in the pathophysiology of SLE. Other than its role in the production of antibodies that mediate humoral immune response, B-cells also function as antigen-presenting cells and are capable of activating T-cells. Activated B-cells may also produce pro-inflammatory cytokines that aggravate local inflammation. Abnormal B-cell homeostasis has been described in SLE patients. This may occur as a result of intrinsic B-cell defect or from aberrant regulation by maturation and survival signals. B-cell-based therapy is the current mainstream of research and development of novel therapies in SLE patients with severe and refractory disease. Potential cellular and molecular targets for B-cell therapies include cell surface molecules such as CD20 (rituximab) and CD22 (epratuzumab); co-stimulatory molecules involved in B-cell,T-cell interaction such as CTLA4 and B7 molecules (abatacept); maturation and growth factors such as B-cell activating factor and a proliferation-inducing ligand (belimumab, briobacept, atacicept) and B-cell tolerogen (abetimus). This article provides an overview on normal B-cell physiology and abnormal B-cell biology in SLE that form the immunological basis of B-cell-targeted therapy in the treatment of these patients with refractory diseases. [source] Improved outcome of EAN, an animal model of GBS, through amelioration of peripheral and central inflammation by minocyclineJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2009Zhi-Yuan Zhang Abstract Experimental autoimmune neuritis (EAN) is a widely used animal model of the human acute inflammatory demyelinating polyradiculoneuropathy, which is the most common subtype of Guillain-Barré Syndrome. EAN is pathologically characterized by breakdown of the blood-nerve barrier, infiltration of reactive immune cells, local inflammation, demyelination in the peripheral nervous system and mechanical allodynia. Minocycline is known to have neuroprotective and anti-inflammatory effects. Furthermore, relieve of neuropathic pain following minocycline administration was observed in a variety of animal models. Here, we investigated the effects of minocycline on rat EAN. Suppressive treatment with minocycline (50 mg/kg body weight daily immediately after immunization) significantly attenuated the severity and duration of EAN. Macrophage and T-cell infiltration and demyelination in sciatic nerves of EAN rats treated with minocycline were significantly reduced compared to phosphate-buffered saline (PBS)-treated EAN rats. mRNA expressions of matrix metallopeptidase-9, inducible nitric oxide synthase and pro-inflammatory cytokines interleukin-1 , and tumour necrosis factor-, in EAN sciatic nerves were greatly decreased by administration of minocycline as well. Furthermore, minocycline attenuated mechanical allodynia in EAN rats and greatly suppressed spinal microglial activation. All together, our data showed that minocycline could effectively suppress the peripheral and spinal inflammation (immune activation) to improve outcome in EAN rats, which suggests that minocycline may be considered as a potential candidate of pharmacological treatment for autoimmune-mediated neuropathies. [source] Critical role of the vascular endothelial cell in health and disease: a review articleJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 2 2004Todd C. Duffy DVM Abstract Objective: To review the human and veterinary literature on the role of the vascular endothelial cell in health, as well as during hypoxic and inflammatory disease states. Data sources: Data from human and veterinary literature were reviewed through a Pubmed search and a manual search of the references listed in articles covering some aspect of vascular endothelial cell function. Human data synthesis: The development of techniques that allow the maintenance and growth of endothelial cells in culture has produced an explosion of new research in the area of endothelial cell physiology. This plethora of data has revealed the critical role that vascular endothelial cells play in both health and disease states. Interspecies variations can occur with respect to the vascular endothelial cell physiology and its response to pathologic conditions. Veterinary data synthesis: There is a paucity of information regarding the role of the vascular endothelial cell in health or disease of small animals. Many human studies use species cared for by veterinarians, providing information that may be applied to small animals and that may be used to construct future studies. Conclusion: An organ system itself, the vascular endothelium is an essential component of all organs in the body. The endothelial cell lining functions to maintain selective permeability between the blood and the tissue it supplies, regulate vascular tone, sustain blood fluidity through regulation of coagulation, and modulate interaction of leukocytes with the interstitium and inflammatory reactions. During disease states, the endothelial cell functions locally to limit the boundaries of the disease process. If these functions are not controlled, they can become a part of the pathogenic process, contributing to blood stasis and thrombosis, potentiation of local inflammation and interstitial edema formation, subsequent tissue hypoxia, and multiple organ dysfunction. Pharmacological investigations targeting the modulation of endothelial function during disease states have not yet advanced treatment protocols. Since all critically ill animals are at risk for some degree of endothelial cell dysfunction, treatment regimens should focus on promoting capillary blood flow and tissue oxygen delivery. [source] Long-term reduction in local inflammation by a lipid raft molecule in atopic dermatitisALLERGY, Issue 9 2010S. Dölle To cite this article: Dölle S, Hoser D, Rasche C, Loddenkemper C, Maurer M, Zuberbier T, Worm M. Long-term reduction in local inflammation by a lipid raft molecule in atopic dermatitis. Allergy 2010; 65: 1158,1165. Abstract Background:, The complex pathogenesis of atopic dermatitis (AD) is guided by cell surface receptor-mediated signal transduction regulated in lipid rafts. Miltefosine is a raft-modulating molecule targeting cell membranes. With this controlled clinical study, the clinical and immunomodulatory efficacy of miltefosine was investigated in patients with AD in comparison with a topical corticosteroid treatment. Methods:, Sixteen patients with AD were treated topically with miltefosine and hydrocortisone localized on representative AD target lesions for 3 weeks. To assess the clinical efficacy, the three item severity (TIS) score was evaluated before, during and after treatment as well as after 4-week-follow-up period. To study the anti-inflammatory effect of miltefosine on the cellular T cell pattern, skin biopsies were analysed before and after treatment. Results:, The TIS score dropped in both groups significantly after treatment. A carry-over effect was exclusively seen for miltefosine after discontinuing the treatment. These findings were substantiated by thermographic imaging with a significant decrease in the maximum temperature (Tmax) after miltefosine application (P = 0.034, ,Tmax = 1.7°C [2.1,3.9]). Immunohistochemically, a reduction in lesional CD4+ -infiltrating T cells was observed in both treatments. Moreover, increased FoxP3+ cells were present in the skin after miltefosine treatment (before 5.4% [1.9,9.8], after 6.2% [3.5,9.5]). Conclusion:, We demonstrate that miltefosine is locally active in patients with AD and led to a sustained clinical improvement in local skin inflammation. Moreover, the increased frequency of FoxP3+ cells in the skin of patients with AD suggests its immunomodulatory properties. [source] Glial reactions in Parkinson's diseaseMOVEMENT DISORDERS, Issue 4 2008Patrick L. McGeer MD Abstract Dopaminergic neurons of the substantia nigra are particularly vulnerable to oxidative and inflammatory attack. Such processes may play a crucial role in the etiology of Parkinson disease (PD). Since glia are the main generators of these processes, the possibility that PD may be caused by glial dysfunction needs to be considered. This review concentrates on glial reactions in PD. Reactive astrocytes and reactive microglia are abundant in the substantia nigra (SN) of PD cases indicating a robust inflammatory state. Glia normally serve neuroprotective roles but, given adverse stimulation, they may contribute to damaging chronic inflammation. Microglia, the phagocytes of brain, may be the main contributors since they can produce large numbers of superoxide anions and other neurotoxins. Their toxicity towards dopaminergic neurons has been demonstrated in tissue culture and various animal models of PD. The MPTP and ,-synuclein models are of particular interest. Years after exposure to MPTP, inflammation has been observed in the SN. This has established that an acute insult to the SN can result in a sustained local inflammation. The ,-synuclein model indicates that an endogenous protein can induce inflammation, and, when overexpressed, can lead to autosomal dominant PD. Less is known about the role of astrocytes than microglia, but they are known to secrete both inflammatory and anti-inflammatory molecules and may play a role in modulating microglial activity. Oligodendrocytes do not seem to play a role in promoting inflammation although, like neurons, they may be damaged by inflammatory processes. Further research concerning glial reactions in PD may lead to disease-modifying therapeutic approaches. © 2007 Movement Disorder Society [source] Static orthoses in the prevention of hand dysfunction in rheumatoid arthritis: a review of the literatureMUSCULOSKELETAL CARE, Issue 2 2005DipCOT Lecturer in Occupational Therapy, Jo Adams MSc Abstract Static orthoses are recommended for individuals who have early rheumatoid arthritis (Scottish Intercollegiate Guidelines Network, 2002; College of Occupational Therapists, 2003). These orthoses aim to rest and immobilize weakened joint structures and decrease local inflammation (Janssen et al., 1990; Nicholas et al., 1982); correctly position joints (Nordenskiöld, 1990; Ouellette, 1991); minimize joint contractures (McClure et al., 1994); increase joint stability (Kjeken et al., 1995); relieve pain (Feinberg, 1992; Callinan and Mathiowetz, 1996; Kjeken et al., 1995) and improve function (Janssen et al., 1990; Pagnotta et al., 1998; Nordenskiöld, 1990). Wrist and hand orthoses have been routinely prescribed for individuals with rheumatoid arthritis (RA) for the last 30 years with limited evidence that they are effective in achieving their purported aims. This article reviews the possible deterioration in hand structure that can occur in RA and discusses the theoretical basis for the application of static orthoses in RA. The evidence for the effectiveness of four commonly used static orthoses is then examined. Copyright © 2005 Whurr Publishers Ltd. [source] Monitoring acute inflammatory processes in mouse muscle by MR imaging and spectroscopy: a comparison with pathological resultsNMR IN BIOMEDICINE, Issue 3 2002Jesús Ruiz-Cabello Abstract We have studied an animal model of acute local inflammation in muscle induced by Aspergillus fumigatus by using magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We have compared our data to those found using histopathology and segmentation maps obtained by the mathematical processing of three-dimensional T2 -weighted MRI data via a neural network. The MRI patterns agreed satisfactorily with the clinical and biological evidence of the phases of acute local infection and its evolution towards chronicity. The MRS results show a statistically significant increase in inorganic phosphate and a significant decrease in phosphocreatine levels in the inflamed region. Image segmentation made with a self-organizing, neural-network map yielded a set of ordered representatives that remained constant for all animals during the inflammatory process, allowing a non-invasive, three-dimensional identification and quantification of the inflamed infected regions by MRI. Copyright © 2002 John Wiley & Sons, Ltd. [source] Does orthodontic loading influence bone mineral density around titanium miniplates?ORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 1 2010An experimental study in dogs To cite this article: Cornelis MA, Mahy P, Devogelaer JP, De Clerck HJ, Nyssen-Behets C: Does orthodontic loading influence bone mineral density around titanium miniplates? An experimental study in dogs Orthod Craniofac Res 2010;13:21,27 Structured Abstract Authors,,, Cornelis MA, Mahy P, Devogelaer JP, De Clerck HJ, Nyssen-Behets C Objectives,,, To evaluate whether orthodontic loading has an effect on miniplate stability and bone mineral density (BMD) around the screws supporting those miniplates. Setting and Sample Population,,, Two miniplates were inserted in each jaw quadrant of 10 dogs. Material and Methods,,, Two weeks later, coil springs were placed between the miniplates of one upper quadrant and between those of the contralateral lower quadrant. The other miniplates remained non-loaded. The dogs were sacrificed 7 or 29 weeks after surgery, and the jaws were scanned with peripheral Quantitative Computed Tomography (pQCT) to assess BMD. Results,,, The success rate was not significantly different for the loaded and the non-loaded miniplates, but was significantly higher for the maxillary compared to the mandibular ones. Mobility, associated with local inflammation, most often occurred during the transition between primary and secondary stability. pQCT showed higher BMD around mandibular vs. maxillary screws, without significant difference between loaded and non-loaded ones. Furthermore, load direction did not lead to any significant difference in BMD. Conclusion,,, Miniplate stability and BMD of the adjacent bone did not appear to depend significantly on orthodontic loading, but rather on the receptor site anatomy. [source] Efficacy of 1.25% and 1% topical cyclosporine in the treatment of severe vernal keratoconjunctivitis in childhoodPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 7 2006Laura Spadavecchia Cyclosporine eyedrops 2% have been used for treatment of corticosteroid-resistant vernal keratoconjunctivitis (VKC) cases. The purpose of our study was to verify the efficacy of 1.25% vs. 1% topical cyclosporine in improving severe form of VKC in childhood. Twenty children with severe VKC, were enrolled in a double-blind, placebo-controlled study and received cyclosporine 1.25% in one eye for 2 wk. Then an open trial was conducted during the next 3 months and 2 wk. Thirty-two more patients were recruited the next year into a new open trial and they received cyclosporine 1% for 4 months. Ocular subjective symptoms and objective signs were scored in all children at entry, 2 wk and 4 months. Skin prick tests and conjunctival scraping tests were also performed; serum immunological and biochemical markers were assessed. The mean score values for severity of subjective symptoms and objective signs were significantly decreased after 2 wk, and 4 months, compared with those at entry (p < 0.001), in both groups of children who received cyclosporine eyedrops 1.25% and 1%, respectively. Serum markers did not differ from the beginning to the end of treatment. Conjunctival eosinophils and cyclosporine serum levels were not detectable at the end of therapy, nor were endothelial corneal cells damaged. Our findings suggest that 1% cyclosporine concentration might be the minimal effective treatment regimen to control symptoms and local inflammation in severe forms of VKC. [source] Safety of anthrax vaccine: an expanded review and evaluation of adverse events reported to the Vaccine Adverse Event Reporting System (VAERS),,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 12 2004John L. Sever Abstract Purpose To assess the safety of a licensed anthrax vaccine (AVA) given to more than 500,000 US military personnel, through review and medical evaluation of adverse events (AEs) reported to the Vaccine Adverse Event Reporting System (VAERS). Methods AEs were summarized by person, vaccine lot, type, frequency and impact. A Delphic approach was used to tentatively assess causality in an effort to detect serious AEs (SAEs) or other medically important AEs (OMIAEs) possibly attributable to AVA. Results The Anthrax Vaccine Expert Committee (AVEC) reviewed 1841 reports describing 3991 AEs (9.4 reports/10,000 doses of AVA) that were submitted to VAERS from 1Q1998 through 4Q2001. One hundred forty-seven reports described an SAE or OMIAE, of which 26 were tentatively rated as possible, probable or certain consequences of vaccination (injection-site reaction [12], ,anaphylactic-like reaction' [5] and eight other systemic AEs [1,2 each]). Conclusions This review produced no evidence for an unusual rate of any SAE or OMIAE attributable to AVA. It supported an earlier impression that AVA may cause significant local inflammation and should be administered over the deltoid rather than the triceps to avoid direct or compression injury to the ulnar nerve. The subjects of VAERS reports tended to be older than all recipients of AVA. Females generally had and/or reported AEs more often than males, but transient articular reactions were surprisingly more common in males. Variations in the frequency or severity (as judged by hospitalization and/or loss of duty) of reported AEs did not suggest a significant problem with (1) a particular lot of AVA, (2) recurrent AEs after multiple doses or (3) vaccination of persons with a concomitant illness or those given other vaccines or medications. Copyright © 2004 John Wiley & Sons, Ltd. [source] Safety of anthrax vaccine: a review by the Anthrax Vaccine Expert Committee (AVEC) of adverse events reported to the Vaccine Adverse Event Reporting System (VAERS)PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 3 2002John L. Sever Abstract Purpose To assess the safety of a licensed anthrax vaccine given to nearly 400,000 US military personnel, reports of adverse events (AEs) submitted to the Vaccine Adverse Event Reporting System (VAERS) were reviewed and evaluated medically. Methods The Anthrax Vaccine Expert Committee (AVEC), a civilian panel of private-sector physicians and other scientists, reviewed 602 VAERS reports using a Delphic approach (structured expert consensus) to assess the causal relationship between vaccination and the reported AEs and sought to identify unexpected patterns in the occurrence of medically important events. Reports were entered into a database and used to profile AEs with respect to person, type/location, relative frequency, severity/impact, concomitant illness or receipt of other drugs or vaccines, and vaccine lot. Results Nearly half the reports noted a local injection-site AE, with more than one-third of these involving a moderate to large degree of inflammation. Six events qualified as serious AEs (SAEs), and all were judged to be certain consequences of vaccination. Three-quarters of the reports cited a systemic AE (most common: flu-like symptoms, malaise, rash, arthralgia, headache), but only six individual medically important events were judged possibly or probably due to vaccine (aggravation of spondyloarthropathy (2), anaphylactoid reaction, arthritis (2), bronchiolitis obliterans organizing pneumonia) Conclusions Since some cases of local inflammation involved distal paresthesia, AVEC recommends giving subcutaneous injections of AVA over the inferior deltoid instead of the triceps to avoid compression injury to the ulnar nerve. At this time, ongoing evaluation of VAERS reports does not suggest a high frequency or unusual pattern of serious or other medically important AEs. Copyright © 2002 John Wiley & Sons, Ltd. [source] Adaptation of the Human Skin by Chronic Solar-simulating UV Irradiation Prevents Ultraviolet-B Irradiation-induced Rise in Serum C-Reactive Protein Levels,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2005Jarmo K. Laihia ABSTRACT Exposure of the skin to UV radiation induces local inflammation. We hypothesized that inflammation induced by erythemal UV-B irradiation could elevate levels of serum C-reactive protein (CRP) and that suberythemal repeating doses of solar-simulating UV radiation (SSR) would produce photoadaptation to such inflammation. Separation-free high-sensitivity assays of CRP show an increase by 42% (P= 0.046) in CRP concentrations in healthy human subjects 24 h after a 3 minimal erythemal dose (MED) dose of UV-B delivered onto a 100 cm2 skin area. Preceding daily suberythemal doses of whole-body SSR for 10 or 30 consecutive days completely prevented the CRP increase. UV-B-induced skin erythema was partially attenuated by 30 preceding days of SSR only (P= 0.00066). After 10 daily SSR doses, the mean baseline CRP concentrations (0.24 ± 0.21 mg/L) declined by 35% (P= 0.018). Using high-sensitivity analysis of serum CRP as the endpoint marker for cutaneous inflammation, we show that acute exposure of even a relatively small skin area to erythemal UV-B induces skin inflammation detectable also at the systemic level and that photoadaptation by preceding repeating suberythemal doses of SSR reduces signs of inflammation. Our data complement the view given by previous studies in that local photoadaptation also has systemic manifestations. [source] Frequency of sister chromatid exchanges in the lymphocytes of patients with atopic dermatitisTHE JOURNAL OF DERMATOLOGY, Issue 9 2006Ali KARAMAN ABSTRACT The combination of genetic susceptibility and environmental factors can induce allergic sensitization and subsequent local inflammation, resulting in atopic dermatitis (AD). Sister chromatid exchange (SCE) is a sensitive method that may reflect an instability in DNA or a deficiency in DNA repair. The aim of the present study was to investigate whether patients with AD have defects in DNA repair and whether SCE frequency can be used as a genetic marker in the pathogenesis of AD. Between September 2004 and July 2005, SCE was analyzed in the peripheral blood lymphocyte chromosomes of 32 patients with AD and 28 control subjects at the Dermatology Unit of Erzurum State Hospital. This study found that the SCE frequency was significantly increased in patients with AD (P < 0.00001). The prevalence of SCE was not correlated with patient age, sex, disease duration or AD disease severity. Our results indicate that increased chromosome instability may play an important role in the etiology of AD. [source] Microbiology of Stents in Laryngotracheal Reconstruction,THE LARYNGOSCOPE, Issue 2 2004Payman Simoni MD Abstract Objectives: Granulation tissue often forms around a laryngotracheal stent, tracheostomy tube, or other airway prosthesis, especially if infection occurs. We studied the types and frequency of organisms colonizing stents used in pediatric laryngotracheal reconstruction. Study Design: This prospective study included 21 patients undergoing 23 consecutive laryngotracheal reconstructions with stents between 1991 and 1999. Methods: After endoscopic removal, each laryngotracheal stent was placed immediately in a sterile container and transported to the laboratory. Specimens for culture were obtained from biofilms on the stents and plated on agars for growth of aerobic, anaerobic, and fungal organisms. Culture results were analyzed with regard to patient age, duration of stenting, and graft type. Results: All stents were colonized with more than one pathogen (range 2,7). The most frequent aerobic isolates were Streptococcus viridians, Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenza, and Neisseria species. Anaerobic organisms were isolated in 26% of cases. Candida species were isolated in 57% of the cases; patients whose stents were colonized with Candida were significantly (P = .007) older (mean 77.5 months) than those not colonized with this organism (mean 26.1 months) Conclusions: The antibiotic agents currently used for children undergoing laryngotracheal reconstruction target mainly aerobic organisms. Despite prophylactic measures, the incidence of granulation tissue formation is clinically significant, and the prevalence of anaerobic, including fungal, pathogens is high. Antibiotic therapy directed toward controlling anaerobic and fungal organisms could help in controlling local inflammation and thus granulation tissue formation. [source] T Cell-mediated Rejection of Kidney Transplants: A Personal ViewpointAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010P. F. Halloran In kidney allografts, T cell mediated rejection (TCMR) is characterized by infiltration of the interstitium by T cells and macrophages, intense IFNG and TGFB effects, and epithelial deterioration. Recent experimental and clinical studies provide the basis for a provisional model for TCMR. The model proposes that the major unit of cognate recognition in TCMR is effector T cells engaging donor antigen on macrophages. This event creates the inflammatory compartment that recruits effector and effector memory CD4 and CD8 T cells, both cognate and noncognate, and macrophage precursors. Cognate T cells cross the donor microcirculation to enter the interstitium but spare the microcirculation. Local inflammation triggers dedifferentiation of the adjacent epithelium (e.g. loss of transporters and expression of embryonic genes) rather than cell death, via mechanisms that do not require known T-cell cytotoxic mechanisms or direct contact of T cells with the epithelium. Local epithelial changes trigger a response of the entire nephron and a second wave of dedifferentiation. The dedifferentiated epithelium is unable to exclude T cells, which enter to produce tubulitis lesions. Thus TCMR is a cognate recognition-based process that creates local inflammation and epithelial dedifferentiation, stereotyped nephron responses, and tubulitis, and if untreated causes irreversible nephron loss. [source] The infrapatellar fat pad in knee osteoarthritis: An important source of interleukin-6 and its soluble receptorARTHRITIS & RHEUMATISM, Issue 11 2009Emilie Distel Objective Obesity is a potent risk factor in knee osteoarthritis (OA). It has been suggested that adipokines, secreted by adipose tissue (AT) and largely found in the synovial fluid of OA patients, derive in part from the infrapatellar fat pad (IFP), also known as Hoffa's fat pad. The goal of this study was to characterize IFP tissue in obese OA patients and to compare its features with thigh subcutaneous AT to determine whether the IFP contributes to local inflammation in knee OA via production of specific cytokines. Methods IFP and subcutaneous AT samples were obtained from 11 obese women (body mass index ,30 kg/m2) with knee femorotibial OA. Gene expression was measured by real-time quantitative polymerase chain reaction. Cytokine concentrations in plasma and in conditioned media of cultured AT explants were determined by enzyme-linked immunosorbent assay or by Luminex xMAP technology. Results In IFP tissue versus subcutaneous AT, there was a decrease in the expression of genes for key enzymes implicated in adipocyte lipid metabolism, whereas the expression levels of genes for AT markers remained similar. A 2-fold increase in the expression of the gene for interleukin-6 (IL-6), a 2-fold increase in the release of IL-6, and a 3.6-fold increase in the release of soluble IL-6 receptor (sIL-6R) were observed in IFP samples, compared with subcutaneous AT, but the rates of secretion of other cytokines in IFP samples were similar to the rates in subcutaneous AT. In addition, leptin secretion was decreased by 40%, whereas adiponectin secretion was increased by 70%, in IFP samples versus subcutaneous AT. Conclusion Our results indicate that the IFP cytokine profile typically found in OA patients could play a role in paracrine inflammation via the local production of IL-6/sIL-6R and that such a profile might contribute to damage in adjacent cartilage. [source] Association of interleukin-18 expression with enhanced levels of both interleukin-1, and tumor necrosis factor , in knee synovial tissue of patients with rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 2 2003Leo A. B. Joosten Objective To examine the expression patterns of interkeukin-18 (IL-18) in synovial biopsy tissue of patients with rheumatoid arthritis (RA), and to determine whether expression of this primary cytokine is related to the expression of other cytokines and adhesion molecules and related to the degree of joint inflammation. Methods Biopsy specimens of knee synovial tissue either without synovitis (n = 6) or with moderate or severe synovitis (n = 11 and n = 12, respectively) were obtained from 29 patients with active RA. Paraffin-embedded, snap-frozen sections were used for immunohistochemical detection of IL-18, tumor necrosis factor , (TNF,), IL-1,, IL-12, and IL-17. Furthermore, adhesion molecules, such as intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin, and cell markers CD3, CD14, and CD68 were stained. Results IL-18 staining was detectable in 80% of the RA patients, in both the lining and sublining of the knee synovial tissue. IL-18 expression in the synovial tissue was strongly correlated with the expression of IL-1, (in the sublining r = 0.72, in the lining r = 0.71; both P < 0.0001) and TNF, (in the sublining r = 0.59, P < 0.0007, and in the lining r = 0.68, P < 0.0001). In addition, IL-18 expression in the sublining correlated with macrophage infiltration (r = 0.64, P < 0.0007) and microscopic inflammation scores (r = 0.78, P < 0.0001), and with the acute-phase reaction as measured by the erythrocyte sedimentation rate (r = 0.61, P < 0.0004). Interestingly, RA synovial tissue that coexpressed IL-18 and IL-12 demonstrated enhanced levels of the Th1-associated cytokine IL-17. Conclusion Our results show that expression of IL-18 is associated with that of IL-1, and TNF, and with local inflammation in the synovial tissue of patients with RA. In addition, synovial IL-18 expression correlates with the acute-phase response. These data indicate that IL-18 is a primary proinflammatory cytokine in RA that drives the local production of IL-1, and TNF,. [source] Gene expression in actinic keratoses: pharmacological modulation by imiquimodBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2004B. Lysa Summary Background, Actinic keratoses (AKs) are premalignant lesions that can progress into squamous cell carcinoma. Imiquimod, which belongs to the new class of immune-response modifiers, was recently shown to be effective in the treatment of AKs. The underlying mechanisms are not fully understood. Objectives, To study the expression of individual genes in uninvolved skin and AKs before therapy and to elucidate the way in which the expression of these genes is influenced by imiquimod therapy. Methods, We treated 13 patients with AK with imiquimod and compared gene expression before, during (five patients) and after (eight patients) therapy with that in uninvolved skin. We analysed genes coding for inflammatory cytokines or their receptors, adhesion molecules, anti-apoptotic proteins, p53 and toll-like receptors (TLRs) by reverse-transcriptase polymerase chain reaction. Results, Comparing uninvolved skin and untreated AK, we found significant differences in the expression of interleukin (IL)-6, hurpin, TLR7 and TLR8. During imiquimod therapy, we detected a further upregulation of interferon-,, IL-6, IL-10 receptor 1 and TLR7. In contrast, two anti-apoptotic genes, hurpin and HAX-1, were downregulated. We did not detect significant differences in gene expression for p53, tumour necrosis factor-, and ,- and ,-catenins. Clinically, the upregulated expression of the proinflammatory cytokines correlated with the local inflammation induced by imiquimod. Conclusions, Our results indicate that specific differences in gene expression are detectable between AK and uninvolved skin. Imiquimod influenced the expression of most genes analysed in this study. This work extends previous findings on the effects of imiquimod on gene regulation in AKs. [source] Complement factor H and factor B expression in RPE cellsACTA OPHTHALMOLOGICA, Issue 2008Purpose Age-related macular degeneration (AMD) is the leading cause of untreatable blindness in the developed world. The pathogenesis of AMD is not fully understood. Recent evidence suggests that local inflammation in particular complement activation plays an important role. We aim to understand how complement activation is regulated at retina/choroidal interface. Methods The expression and distribution of complement factor H (CFH) and factor B (CFB) in mouse ocular tissues were examined by immunohistochemistry. Regulation of CFH and CFB gene expression by various cytokines or photoreceptor outer segments (POS) was investigated in vitro in cultured RPE cells. Changes in CFH or CFB gene expression after treatment were evaluated by RT-PCR. Results In normal mouse eyes, CFH was detected in corneal epithelial cells, ciliary body, RPE cells, Bruch's membrane and choroidal vessels. There is no significant change in either the expression level or the distribution pattern of CFH in ocular tissues of different ages of mice. CFB was exclusively detected in RPE cells in normal mice. The expression of CFB in RPE cells increases with age. In vitro in RPE cultures, the expression of CFH was negatively regulated by cytokine TNF-alpha and IL-6, whereas the expression of CFB was positively regulated by TNF-alpha and IFN-gamma. Short-term incubation of RPE cells with POS did not alter the expression of CFH or CFB, whereas long-term incubation of RPE cells with POS significantly down-regulated CFH expression but up-regulated CFB expression. Conclusion Complement regulatory factors CFH and CFB are produced locally in the retina/choroidal interface by RPE cells. The production of CFH and CFB in RPE cells is regulated differently by various cytokines and oxidized POS. [source] Fibronectin concentrations in catheter sepsisCLINICAL MICROBIOLOGY AND INFECTION, Issue 3 2000B. Nemet Objectives To investigate the role of fibronectin in the pathogenesis of biomaterial-related infections and the influence of catheter sepsis on the concentration of plasma fibronectin during various stages of bacteremia. Methods Plasma fibronectin concentrations were determined by the simple radial immunodiffusion method. Four groups of subjects were used: one group comprised patients with catheter sepsis, the second patients with local inflammation of the catheter insertion site caused by slime-positive, coagulase-negative staphylococci, the third patients with slime-negative, coagulase-negative staphylococci isolated from the catheter, and the fourth demonstrably healthy persons. Results In patients with catheter sepsis, fibronectin concentrations were found after the disappearance of catheter sepsis and 3,5 days after the removal of the catheter. A statistically significant decrease in fibronectin concentration was detected in the plasma of patients with catheter sepsis compared with other groups of patients and control subjects. Conclusions The above results indicate a pathogenic role for fibronectin in biomaterial-related infections. [source] | ||||||||||||||||||||||||||||