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Biomedical subjects

L Magrini

Publications and source records attributed to L Magrini.

At least 19 recordsLinked to original sources
PubMed2006

Overlapping humoral autoimmunity links rheumatic fever and the antiphospholipid syndrome.

OBJECTIVE: Rheumatic fever (RF) and the antiphospholipid syndrome (APS) are autoimmune diseases that share similar cardiac and neurological pathologies. We assessed the presence of shared epitopes between M protein, N-acetyl-beta-D-glucosamine (GlcNAc) and beta2 glycoprotein-I (beta2GPI), the pathogenic molecules engaged in these autoimmune conditions. METHODS: Sera from the APS patients were affinity-purified on beta2GPI and beta2GPI-related peptide columns. Sera from RF patients were affinity-purified on protein G column. The beta2GPI and M protein-related peptides were prepared by conventional solid-phase peptide synthesis. The enzyme-linked immunosorbent assay direct binding and inhibition studies were performed on the RF and APS sera for the presence, and cross-reactivity, of antibodies against beta2GPI, beta2GPI-related peptides, streptococcal M protein, M-derived peptides and GlcNAc. RESULTS: Antibodies (Abs) to beta2GPI were found in 24.4% of 90 RF patients. Antibodies against various beta2GPI-related peptides were found in 1.1-36.7% of the patients. The immunoglobulin G sera from RF patients possessed significant anti-beta2GPI activity, while sera from APS patients contained a considerable anti-streptococcal M protein as well as anti-GlcNAc activity. Furthermore, affinity-purified anti-beta2GPI and anti-beta2GPI-related peptide Abs from APS patients cross-reacted with streptococcal M protein and M5 peptide, while beta2GPI and beta2GPI-related peptides inhibited anti-streptococcal M protein activity from RF patients. The results were confirmed by immunoblot analyses. The beta2GPI also inhibited anti-GlcNAc activity from APS patients with chorea. CONCLUSIONS: The results of our study, showing a considerable overlap of humoral immunity in RF and APS, support a hypothesis that common pathogenic mechanisms underlie the development of cardiac valve lesions and Central Nervous System abnormalities in both diseases.

Acetylglucosamine↗
PubMed2004

Inflammatory status and cartilage regenerative potential of synovial fibroblasts from patients with osteoarthritis and chondropathy.

OBJECTIVES: To evaluate the inflammatory status and the cartilage regenerative potential of pathological synovial fibroblasts from patients with osteoarthritis (OA) compared with non-inflamed synovium (NS)-derived cells from patients with chondropathy. METHODS: The inflammatory cell phenotype was investigated based on the constitutive and inducible surface expression and secretion of various effector molecules using flow cytometry or ELISA assays. The capacity of cells to produce cartilage-like extracellular matrix was assessed using acid Alcian blue staining and type II collagen immunostaining after treatment with transforming growth factor beta1 (TGF-beta1). RESULTS: OA and NS fibroblasts consistently expressed CD29, CD44, CD49e, CD54, CD90 and CD106. Expression of high-affinity receptors for IL-4, IL-15, CXCL8 and CXCL12 was also detected but only intracellularly. All types of fibroblasts spontaneously released abundant amounts of CXCL12, CCL2, IL-6 and tissue inhibitor of metalloproteinase 1, while the production of IL-11, TGF-beta1, matrix metalloproteinase 1 (MMP-1) and MMP-9 was detected at moderate levels. Several other secreted factors remained undetectable. No statistically significant differences were noted between the two groups of fibroblasts. Treatment with the proinflammatory cytokine tumour necrosis factor alpha (TNF-alpha) up-regulated the same set of surface and secreted molecules, including CD54, CD106, membrane IL-15, CCL2 and CCL5. Under TGF-beta1 treatment and adipogenic culture conditions, both OA and NS fibroblasts displayed chondrogenic and adipocytic activities that were reduced in OA compared with NS cells. CONCLUSIONS: OA synovial fibroblasts did not display a distinct activated inflammatory phenotype compared with NS cells. However, they did differ in their reduced ability to produce cartilage-like matrix. This difference may be an additional important factor contributing to OA pathogenesis.

Adipocytes↗
PubMed2004

Libman-Sacks endocarditis associated with antiphospholipid syndrome and infection.

INTRODUCTION: Antiphospholipid syndrome (APS) is a systemic autoimmune disease, associated not only with a hypercoagulable state and recurrent fetal loss but with many diverse clinical manifestations including heart involvement, neurological manifestations, as well as skin, kidney and hematologic abnormalities. Cardiac manifestations include coronary by-pass graft and angioplasty occlusions, cardiomyopathy, cyanotic congenital heart disease, intracardiac thrombus and complications of cardiovascular surgery. The valvular heart disease was defined as Libman-Sacks nonbacterial endocarditis. Previously, we have shown a linear subendothelial deposition of anti-cardiolipin/beta2 glycoprotein I (beta2GPI) antibodies in the valve specimens derived from APS patients. The involvement of complement C3c in the pathogenesis was documented. We assessed the beta2GPI-related target epitope recognized by the anti-beta2GPI Abs on the valves. MATERIALS AND METHODS: In order to find the beta2GPI-related target epitopes recognized by the anti-beta2GPI antibodies on the valves, we used beta2GPI-related synthetic peptides. The presence of anti-beta2GPI Abs on the studied valves was detected by anti-idiotypic antibody, followed by immunoperoxidase analysis. Biotin attached to the N-terminal of beta2GPI-related synthetic peptides and control peptide were used to identify the epitope addressed by the anti-beta2GPI Abs deposited on the patient's valve. The binding was probed by streptavidin-peroxidase and appropriate substrate. The specificity was confirmed by competition assays with control peptide and anti-idiotypic antibody. RESULTS: Among the beta2GPI-related synthetic peptides, two peptides were found in previous studies to mimic common pathogens either bacteriae or viruses, which raised a possible infectious origin for APS. One of these peptides, TLRVYK, is a specific target for anti-beta2GPI Abs deposited on the APS valves. This synthetic peptide was able to displace the anti-anti-beta2GPI anti-idiotypic Abs for binding the anti-beta2GPI Abs on the valve by a competition assay. CONCLUSION: We point to the possibility that Libman-Sacks nonbacterial endocarditis may have an infectious origin.

Antibodies, Anticardiolipin↗
PubMed2004

Decrease of anti-cyclic citrullinated peptide antibodies and rheumatoid factor following anti-TNFalpha therapy (infliximab) in rheumatoid arthritis is associated with clinical improvement.

OBJECTIVE: To investigate the effect of infliximab treatment on anti-cyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) in patients with rheumatoid arthritis. METHODS: 43 patients with rheumatoid arthritis not responding to disease modifying anti-rheumatic drugs (DMARD) received intravenous infliximab at a dose of 3 mg/kg at baseline and after two and six weeks, and subsequently bimonthly, in combination with methotrexate. Serum samples were collected at baseline and at week 24. A commercial enzyme linked immunosorbent assay was used to test for anti-CCP antibodies; RF were detected using a quantitative nephelometric assay. RESULTS: At baseline, 38 of the 43 patients (88%) were positive for anti-CCP antibodies, and 41 (95%) were positive for RF. The serum titre of anti-CCP and RF decreased significantly after six months of treatment (p = 0.0001 and p<0.0001, respectively). When the patients were grouped on the basis of their clinical response to infliximab, a significant decrease in serum anti-CCP antibodies and RF was observed only in patients who had clinical improvement (ACR 20 and ACR 50). CONCLUSIONS: Anti-TNFalpha treatment in rheumatoid arthritis results in a decrease in the serum titres of RF and anti-CCP antibodies in patients showing clinical improvement, suggesting that these measurements may be a useful adjunct in assessing treatment efficacy.

Adult↗
PubMed2003

Polymorphism of the Duffy erythrocyte chemokine receptor in Italian patients with Behçet's disease.

This study examined the hypothesis that the polymorphism of Duffy antigen receptor for chemokines (DARC) predisposes to and/or influences the clinical manifestations of Behçet's disease. The serum levels of IL-8 and monocyte chemotactic peptide (MCP)-1, two DARC-binding chemokines, were investigated and related to this polymorphism. Twenty-eight patients with Behçet's disease and 30 healthy blood donors were included in the study. No null phenotypes were found among the patients studied, and the frequencies of the other phenotypes (Fy((a+b-)), Fy((a+b+)), and Fy((a-b+))) did not significantly differ from those found in the blood donor group or reported in the general Caucasian population. No difference was found between the single phenotypes in terms of IL-8 and MCP-1 serum levels, and no relevant association between the clinical characteristics, Behçet's disease-associated human leukocyte antigen (HLA)-B51, and single phenotypes was observed. This investigation indicates that DARC is not a genetic trait significantly associated with or predisposing to Behçet's disease, at least in Caucasian Italians. However, the role of this polymorphism in the development and in the clinical course of the disease awaits further investigation.

Adult↗
PubMed2003

Pro-inflammatory and anti-inflammatory circulating cytokines and periprosthetic osteolysis.

We investigated the circulating levels of the main cytokines involved in bone resorption (IL-1beta, IL-6, TNF-alpha), prostaglandins (PGE2) and metalloproteases (MMP-1), as possible early markers of osteolysis, in the serum of eight patients with periprosthetic osteolysis and ten patients without osteolysis. All had received a cementless hip prosthesis (ABG-1). We also assessed the serum levels of IL-1 and TGF-beta anti-inflammatory cytokines exerting protective effect on bone resorption. The mean serum levels of IL-1beta, IL-6, TNF-alpha, TGF-beta, MMP-1, and PGE2 in patients with periprosthetic osteolysis did not differ significantly from those of patients without osteolysis or from those of normal controls. IL-11 serum levels were not detectable at all in any of the patients, while they were detected within normal reference values in the control subjects (significant inverse correlation). We believe that circulating cytokines cannot be regarded as markers of osteolysis, a condition characterised by a local inflammation without systemic signs of inflammation. On the contrary, the undetectable levels of IL-11 in implanted patients could provide evidence for a lack of balance between pro- and anti-inflammatory cytokines in these patients.

Aged↗
PubMed2001

Mast cell activation in acquired chronic urticaria-angioedema.

Mast cells play a central role in the pathogenesis of many allergic disorders. They can be activated in different ways. The present study was focused to evaluate the role of mast cells in acquired chronic urticaria-angioedema induced by gastroesophageal reflux. Tryptase, an important marker of mast cell activation, was detected with UniCap Tryptase Fluoroenzymeimmunoassay (Pharmacia & Upjohn AB, Uppsala, Sweden). Eight subjects were studied: four males and four females, aged between 29 and 71 years (mean age: 45 yrs.), suffering from acquired chronic urticaria-angioedema. Results were compared with the results of seven healthy control subjects. Moreover, data were compared with those of 13 subjects (10 males and 3 females, mean age: 24.7 years) suffering from allergic rhinitis. In acquired chronic urticaria-angioedema, serum tryptase levels (mean +/- S.D.: 9.6 +/- 4.3 microg/l) were significantly higher (P < 0.007) than those of the controls (mean +/- S.D.: 3.0 +/- 1.2 microg/l) and higher also than in allergic rhinitis (mean +/- S.D.: 6.1 +/- 2.4 microg/l, P < 0.03). The results underline the central role of mast cells in the inflammation of acquired chronic urticaria-angioedema.

Adult↗
PubMed2001

Increase in free radicals on UHMWPE hip prostheses components due to inflamed synovial cell products.

Oxidative degradation of artificial UHMWPE joint implants caused by gamma-ray sterilization is thought to be responsible for the production of wear debris resulting in adverse tissue responses. On the other hand, it is well known that inflammation is associated with generation, by inflammatory cells, of free radicals (H(2)O(2) and NO) and destructive proteolytic enzymes (collagenases), which creates a strong oxidative environment. We hypothesized that when an UHMWPE implantation was performed in an inflammatory joint environment, the oxidative substances produced by inflamed synoviocytes could increase oxidative degradation of the polyethylene insert. We measured the amount of free radicals on conventional and on Duration-treated polyethylene samples by the electron spin resonance (ESR) technique before and after exposure of the samples to (1) inflamed synovial cell cultures; (2) normal synovial cell cultures; and (3) medium alone. We observed an increase in the number of free radicals on polyethylene samples after their immersion in cell cultures. Furthermore, it was observed that the increase of free radicals on polyethylene correlated with the degree of inflammation of synovial cells in culture.

Arthroplasty, Replacement, Hip↗
PubMed2000

Vernal keratoconjunctivitis revisited: a case series of 195 patients with long-term followup.

OBJECTIVE: This study aimed at revisiting vernal keratoconjunctivitis (VKC) on the basis of anamnestic, clinical, immunologic, histopathologic, and followup data of 195 patients. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: One hundred and ninety-five patients with VKC. METHODS: Clinical evaluation and outcome in 151 of 195 patients with a median followup of 47 months. Evaluation was by telephone survey in 69 patients. MAIN OUTCOME MEASURES: (1) Demographic, clinical, and immunologic features of VKC and their influence on the course of the disease; (2) conjunctival and corneal complications and efficacy of treatment observed during the followup period. RESULTS: VKC is a chronic disease. More than 60% of patients had repeated recurrences all year round. Males had an earlier presentation of symptoms than females and the male/female ratio decreased with age. Major (greater than 80%) and minor (up to 80%) diagnostic criteria were defined for clinical signs and symptoms of the disease. Negative skin test or radioallergosorbent test was present in approximately 50% of patients, whereas eosinophil infiltration was a constant histopathologic finding. A marked conjunctival sensitivity to nonspecific stimuli was noted in more than one third of patients. In 6% of cases, a reduction of visual acuity resulted from corneal scarring, and in 2% of patients, steroid-induced glaucoma was observed. The large size of giant papillae indicates poor prognosis for the persistence of the disease and its evolution into a chronic, perennial condition. CONCLUSIONS: VKC is a chronic eosinophilic disease of the ocular surface involving IgE, non IgE-mediated mechanisms, and age-sex-related influences. Although the disease has a good prognosis, severe visual impairments may result from long-standing inflammation.

Adolescent↗
PubMed1997

Efficacy of lodoxamide eye drops on mast cells and eosinophils after allergen challenge in allergic conjunctivitis.

PURPOSE: The purpose of the study is to evaluate in a double-blind, randomized study the efficacy of lodoxamide tromethamine 0.1% versus placebo. METHODS: Signs and symptoms, tear tryptase, and tear fluid cytology were evaluated in 20 asymptomatic subjects with allergic conjunctivitis. The study included three allergen challenges in skin test-positive patients. At the first visit, a threshold dose of allergen was established. At the second visit, a bilateral ocular challenge was performed without pretreatment. At the third visit, either lodoxamide or placebo eye drops were used for 1 week before ocular challenge. RESULTS: Lodoxamide significantly reduced tryptase levels (P < 0.01), neutrophils (P < 0.04), and eosinophils (P < 0.01) in the tear fluid and significantly inhibited ocular itching (P < 0.02) when compared with that of placebo. CONCLUSIONS: Lodoxamide is effective in reducing tryptase levels and the recruitment of inflammatory cells in the tear fluid after allergen challenge.

Administration, Topical↗
PubMed1997

Markers of connective tissue activation in aseptic hip prosthetic loosening.

The fundamental role played by macrophages and fibroblasts of the synovial-like membrane in aseptic hip prosthesis loosening (AHPL) has recently been confirmed by numerous studies. In this study, the activity of these cells in patients with prosthetic loosening was analyzed by evaluating the main markers of fibroblast and macrophage activation in sera and in supernatants of cultured fibroblasts obtained from AHPL patients who underwent revision of a loose total hip arthroplasty implant. In these patients interleukin-1, hyaluronic acid (HA), and type III procollagen peptide were evaluated. The results were compared with those obtained in 13 patients with firmly fixed implants and 13 patients with osteoarthritis. Serum HA levels were significantly higher (779.3 +/- 951.6 micrograms/L) in patients with AHPL as compared with patients with firmly fixed implants (112.9 +/- 84.9 micrograms/L) and osteoarthritis (115.3 +/- 107.8 micrograms/L). Type III procollagen peptide levels were elevated in only 33.3% of patients with AHPL, whereas interleukin-1-beta (IL-1 beta) was detectable in 4 patients with AHPL but not in patients with firmly fixed implants or osteoarthritis. In supernatants, IL-1 beta was measurable in 4 of 6 fibroblast cultures, whereas type III procollagen peptide and HA were measurable in all cultures. The data confirm the existence of an inflammatory process in AHPL patients in which macrophages and fibroblasts play a key role. The detection, in these patients, of high circulating levels of IL-1 beta and HA is very important from a clinical point of view because they could be considered specific markers of inflammation.

Aged↗
PubMed1997

The eosinophil and the eye.

Personal studies in allergic eye diseases reviewed in this paper indicate that: 1. An increased number and an abnormal distribution of eosinophils is present in conjunctival biopsies of patients with vernal keratoconjunctivitis (VKC). 2. Eosinophil and eosinophil products, such as ECP, are also increased in tears of VKC patients and, in hay fever conjunctivitis, accumulate during the late-phase of allergic reaction following specific allergen challenge. 3. Circulating eosinophils of VKC patients show a typical activation phenotypic profile which is associated with increased serum level of eosinophil cationic protein and eosinophil-derived neurotoxin/protein X. A clinical study of the modulatory effect of cetirizine on the early and late phase of the allergic reaction as well as on the eosinophil activation and tissue recruitment following conjunctival allergen challenge is reported as an example of the need to evaluate eosinophil functions when investigating anti-allergic drugs. Drugs modulating various aspects of eosinophil function could play a primary role in the treatment of allergic eye disease.

Cetirizine↗
PubMed1997

Increased plasma levels of substance P in vernal keratoconjunctivitis.

PURPOSE: The increase of nerve growth factor (NGF) plasma levels in vernal keratoconjunctivitis (VKC) patients has been demonstrated previously. Results of numerous studies in vitro and in vivo have shown that NGF modulates the synthesis of substance P (SP), a neuropeptide involved in the pathogenesis of human allergic diseases. In this study the involvement of SP in this allergic conjunctivitis is investigated, along with its relationship with NGF and other systemic and local markers of VKC. METHODS: Competitive radioimmunoassays were used to detect the levels of SP in plasma, the levels of eosinophil cationic protein, and the total and specific immunoglobulin E in the serum of 11 patients with VKC and in 11 healthy matched controls. Plasma levels of nerve growth factor (NGF) were measured in all VKC patients and controls using an immunoenzymatic assay. Histologic evaluation was performed in tarsal and bulbar conjunctival specimens obtained in biopsies from 8 VKC patients and 4 control subjects. RESULTS: Patients with VKC show a significant increase of SP and NGF plasma levels (P < 0.003 and P < 0.001, respectively), and an increase of eosinophil cationic protein and immunoglobulin E levels in the serum (P < 0.001 and P < 0.002, respectively). Mast cells, eosinophils, and lymphocytes were also significantly increased in the conjunctiva of VKC patients. Interestingly enough, VKC patients with the highest NGF plasma levels also showed the highest SP levels. CONCLUSIONS: The data show the involvement of SP in VKC and suggest that SP with NGF could modulate the allergic response in this disease, probably through an interaction with inflammatory cytokines.

Adolescent↗
PubMed1996

Circulating nerve growth factor levels are increased in humans with allergic diseases and asthma.

Nerve growth factor (NGF) serum levels were measured in 49 patients with asthma and/or rhinoconjunctivitis and/or urticaria-angioedema. Clinical and biochemical parameters, such as bronchial reactivity, total and specific serum IgE levels, and circulating eosinophil cationic protein levels, were evaluated in relation to NGF values in asthma patients. NGF was significantly increased in the 42 allergic (skin-test- or radioallergosorbent-test-positive) subjects (49.7 +/- 28.8 pg/ml) versus the 18 matched controls (3.8 +/- 1.7 pg/ml; P < 0.001). NGF levels in allergic patients with asthma, rhinoconjunctivitis, and urticaria-angioedema were 132.1 +/- 90.8, 17.6 +/- 6.1, and 7.6 +/- 1.8 pg/ml (P < 0.001, P < 0.002, and P < 0.05 versus controls), respectively. Patients with more than one allergic disease had higher NGF serum values than those with a single disease. When asthma patients were considered as a group, NGF serum values (87.6 +/- 59.8 pg/ml) were still significantly higher than those of control groups (P < 0.001), but allergic asthma patients had elevated NGF serum levels compared with nonallergic asthma patients (132.1 +/- 90.8 versus 4.9 +/- 2.9 pg/ml; P < 0.001). NGF serum levels correlate to total IgE serum values (rho = 0.43; P < 0.02). The highest NGF values were found in patients with severe allergic asthma, a high degree of bronchial hyperreactivity, and high total IgE and eosinophil cationic protein serum levels. This study represents the first observation (that we know of) that NGF is increased in human allergic inflammatory diseases and asthma.

Adolescent↗
PubMed1996

Serum levels of eosinophil cationic protein in allergic diseases and natural allergen exposure.

BACKGROUND: Eosinophil cationic protein (ECP) is a cytotoxic performed mediator stored in eosinophil granules and released under various in vitro and in vivo conditions. OBJECTIVE: This study was carried out to evaluate the clinical value of ECP as a marker of allergic inflammation. METHODS: ECP was measured by a competitive radioimmunoassay in serum samples from 265 patients and 45 matched control subjects and related to the type of allergic disease (asthma, rhinitis, conjunctivitis) and to the type of allergic sensitization. RESULTS: All the patient groups studied showed significantly higher levels of serum ECP than control groups (p < 0.001). The type of sensitization was shown to be the only variable influencing ECP serum levels. In fact, subjects sensitized to perennial allergens had significantly higher ECP values than subjects with seasonal allergy (p < 0.001), whereas in patients with seasonal allergy ECP levels were significantly increased only during the pollen season. Differences in ECP values between various allergic diseases or age groups were only due to a nonhomogeneous distribution of the type of sensitization or to time of sera collection. CONCLUSIONS: Results obtained indicate that persistent natural exposure to a sensitizing allergen is responsible for a measurable increase in serum ECP levels in patients with allergy.

Adolescent↗
PubMed1996

Tear tryptase levels and allergic conjunctivitis.

We measured tryptase, a neutral protease stored in the secretory granules of mast cells, by solid-phase radioimmunoassay in tears of 12 subjects with vernal keratoconjunctivitis (VKC) during remission phases, nine subjects with seasonal or perennial allergic conjunctivitis, and eight healthy controls. Mean values of tear tryptase levels were significantly (P < 0.02) increased in VKC patients (14.5 +/- 13 micrograms/l) when compared to those measured in patients with seasonal or perennial allergic conjunctivitis (0.6 +/- 0.1 microgram/l) and in controls (3.3 +/- 3.2 micrograms/l). In subjects with allergic conjunctivitis, the levels of tryptase, almost undetectable before allergen conjunctival challenge, showed a significant increase in the challenged eye 20 min-but not 6 h-after provocation in 5/9 cases. Our results indicate that VKC a severe ocular disease characterized by an increased number and abnormal distribution of mast cells in the conjunctiva, also shows elevated levels of tryptase in tears even during remission phases. Evidence of mast-cell activation, as revealed by a significant increase of tryptase levels in tears, in documented during the early-phase reaction, but not during the late-phase reaction, of allergic conjunctivitis patients challenged topically by specific allergen.

Adolescent↗