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Chemerin/ChemR23 pathway: a system beyond chemokines
Florenzo Iannone, Giovanni Lapadula
Arthritis Research & Therapy , 2011, DOI: 10.1186/ar3273
Abstract: Knowledge of the pathophysiology of articular cartilage is crucial in understanding the mechanisms underlying joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). In a previous issue of Arthritis Research and Therapy, Berg and colleagues [1] have provided new insights in this field by showing for the first time that chondrocytes express chemerin and its cognate receptor, ChemR23, and that this system may be involved in cartilage degradation.Chemerin is a secreted protein that exerts its functions by binding the G protein-coupled receptor ChemR23. It was first discovered as a chemotactic peptide directing macrophages and dendritic cells expressing ChemR23 toward sites of inflammation, being involved in both adaptive and innate immunity [2]. As often happens, regulatory proteins have pleiotropic functions. ChemR23 is also expressed by endothelial cells, where it is up-regulated by pro-inflammatory cytokines, and chemerin strongly induces angiogenesis in vitro by promoting endothelial cell proliferation and remodeling through stimulation of matrix metalloproteinase (MMP) activity [3]. Interest in chemerin has grown since it was discovered in fat tissue as a novel adipokine secreted by adipocytes, which also express ChemR23. Chemerin is up-regulated in white fat cells upon IL-1β stimulation in vitro and chemerin serum levels are increased in obese patients; thus, chemerin may be the functional link between chronic inflammation and obesity, and obesity-related disorders such as type 2 diabetes and cardio-vascular diseases [4].There is evidence that chemokines may play an important role in recruiting inflammatory cells into the joints and contribute to chronic synovitis in OA and RA [5]. Additionally, chemokines exert catabolic effects on cartilage. Functional chemokine receptors (CCR-1, CCR-2, CCR-3, CCR-5, CXCR-1, and CXCR-2) are detectable on human articular chondrocytes and up-regulated in OA cartilage. The interactions of these receptors with the
Update on subcutaneous methotrexate for inflammatory arthritis and psoriasis
Florenzo Iannone,Gino Antonio Vena,Nicoletta Cassano
- , 2018, DOI: 10.2147/TCRM.S154745
Abstract: Methotrexate (MTX) is one of the mainstays of treatment for several immune-mediated inflammatory joint and skin diseases, especially rheumatoid arthritis (RA) and moderate-to-severe psoriasis. Oral MTX has been used for the treatment of such diseases for decades for many reasons. There is, however, a relevant interpatient variability of clinical and safety outcomes that can also be related to differences in patients’ individual pharmacogenomic profile. Orally administered MTX has been found to have a saturable intestinal absorption and nonlinear pharmacokinetics, with significant consequences on drug bioavailability and clinical efficacy. The current evidence shows that parenterally administered MTX results in rapid and complete absorption, higher serum levels, and less variable exposure than oral dosing. The use of parenteral MTX, particularly when administered as a subcutaneous (SC) injection, has recently raised great interest in order to overcome the limitations of oral MTX. The effectiveness and safety of SC MTX have mostly been assessed in rheumatological settings, especially in patients with RA. There are only a limited number of data on SC MTX in juvenile idiopathic arthritis and even fewer in psoriatic disease. Various clinical experiences have suggested that SC MTX is more effective than oral MTX and may provide significant benefit even in patients in whom oral MTX proved to be inadequate. The increased efficacy of SC MTX resulting from higher drug exposure compared with oral MTX has been associated with a similar safety profile and in various reports even with a lower frequency of gastrointestinal complaints. The aim of this article was to review the available literature data on SC MTX treatment of inflammatory arthritis, with special emphasis on RA and psoriasis, examining differences with oral MTX treatment. A brief mention of pharmacokinetics, pharmacodynamic features and pharmacoeconomic considerations is also given
Extracorporeal shock waves down-regulate the expression of interleukin-10 and tumor necrosis factor-alpha in osteoarthritic chondrocytes
Biagio Moretti, Florenzo Iannone, Angela Notarnicola, Giovanni Lapadula, Lorenzo Moretti, Vittorio Patella, Raffaele Garofalo
BMC Musculoskeletal Disorders , 2008, DOI: 10.1186/1471-2474-9-16
Abstract: Human adult articular cartilage was obtained from 9 patients (6 male and 3 females), with primary knee osteoarthritis (OA), undergoing total joint replacement and from 3 young healthy donors (HD) (2 males, 1 female) with joint traumatic fracture. After isolation, chondrocytes underwent ESW treatment (electromagnetic generator system, MINILITH SL1, STORZ MEDICAL) at different parameters of impulses, energy levels and energy flux density. After that, chondrocytes were cultured in 24-well plate in DMEM supplemented with 10% FCS for 48 hours and then beta1 integrin surface expression and intracellular IL-10 and TNF-alpha levels were evaluated by flow-cytometry.At baseline, osteoarthritic chondrocytes expressed significantly lower levels of beta1 integrin and higher levels and IL-10 and TNF-alpha levels. Following ESW application, while beta1 integrin expression remain unchanged, a significant decrease of IL-10 and TNF-alpha intracellular levels was observed both in osteoarthritic and healthy chondrocytes. IL-10 levels decreased at any impulses and energy levels, while a significant reduction of TNF-alpha was mainly found at middle energies.Our study confirmed that osteoarthritic chondrocytes express low beta1 integrin and high TNF-alpha and IL-10 levels. Nonetheless, ESW treatment application down-regulate the intracellular levels of TNF-alpha and IL-10 by chondrocytes, suggesting that ESW might restore TNF-alpha and IL-10 production by osteoarthritic chondrocytes at normal levels. However, further in vivo and in vitro studies are necessary to establish if ESW can represent a viable option in the treatment of OA.Extra-corporeal shock waves (ESW) are expanding their applications from urinary calculi treatment to orthopaedic settings. Recent studies have provided some evidence that ESW may be useful in treating osteoarthritis (OA) in animals, such as dogs [1], and horses [2]. In humans, ESW therapy is widely used for the treatment of several medical disorders such as plan
A Case of Osteonecrosis of the Jaw in a Patient with Crohn’s Disease Treated with Infliximab
Angela Tempesta,Eugenio Maiorano,Florenzo Iannone,Gianfranco Favia,Giovanni Lapadula,Luisa Limongelli,Vito Crincoli
- , 2017, DOI: 10.12659/AJCR.905355
Abstract:
Possible role of adipocytokines in systemic sclerosis–associated small pericardial effusion
Angela Chialà,Cinzia Rotondo,Dorotea Natuzzi,Emanuela Praino,Fabio Cacciapaglia,Florenzo Iannone
- , 2018, DOI: 10.1177/2397198318762893
Abstract: Pericardial effusion is a common manifestation of systemic sclerosis, but its pathogenesis has been poorly investigated. Adipokines and interleukins may play a role in the pathophysiology of pericardial effusion. This study aimed at evaluating serum levels of adipokines and interleukins in systemic sclerosis patients with and without pericardial effusion. A total of 87 systemic sclerosis patients (age 52.6？±？14？years; disease duration 8.2？±？6.7 years) were recruited in this study. Demographics, body mass index, and clinical characteristics were recorded in each patient. Pericardial effusion was considered pathologic when ≥50？mL was detected by echocardiography. Serum levels of adiponectin, leptin, resistin, visfatin, tumor necrosis factor-α, interferon-γ, interlueukin-2, interlueukin-10, and interlueukin-17 were measured using Multiplex Immunoassay (Bioplex 200 System). In all, 11 (13%) systemic sclerosis patients had pericardial effusion. Systemic sclerosis patients with and without pericardial effusion did not differ in age, sex, and body mass index. Systemic sclerosis patients with pericardial effusion had significantly higher levels of visfatin (median/interquartile range: 1546？pg/mL (interquartile range: 8590) vs 388？pg/mL (interquartile range: 103), p？=？0.03) and interlueukin-17 (1.33？pg/mL (interquartile range: 3.5) vs 0.05？pg/mL (interquartile range: 0.56), p？=？0.04), but lower levels of adiponectin (2,845,000？pg/mL (interquartile range: 4,132,900) vs 5,272,100？pg/mL (interquartile range 8,243,600), p？=？0.02) than patients without pericardial effusion. Interstitial lung disease, pulmonary arterial hypertension, and “limited” or “diffuse” cutaneous subset did not correlate to adipokines or interleukin levels. Visfatin and adiponectin may play an important role in the pathogenesis of systemic sclerosis–related pericardial effusion. Further longitudinal studies are needed to unravel a possible role of these molecules as biomarkers of pericardial effusion in systemic sclerosis patients
HBV Reactivation in Patients Treated with Antitumor Necrosis Factor-Alpha (TNF-α) Agents for Rheumatic and Dermatologic Conditions: A Systematic Review and Meta-Analysis
Fabrizio Cantini,Stefania Boccia,Delia Goletti,Florenzo Iannone,Emanuele Leoncini,Nikola Panic,Francesca Prignano,Giovanni Battista Gaeta
International Journal of Rheumatology , 2014, DOI: 10.1155/2014/926836
Abstract: Introduction. Antitumor necrosis factor-alpha (TNF-α) agents are widely used for treatment of rheumatic and dermatological diseases. We conducted the systematic review and meta-analysis to assess the prevalence of HBV reactivation among patients treated with anti-TNF-α. Methods and Findings. A comprehensive literature search of MEDLINE, Scopus, and ISI Web of Knowledge databases was conducted. From 21 studies included in the systematic review, 9 included patients with occult chronic HBV infection and 6 included patients with overt infection while 6 addressed both groups. Based on 10 studies eligible for meta-analysis we report pooled estimate of HBV reactivation of 4.2% (95% CI: 1.4–8.2%, : 74.7%). The pooled prevalence of reactivation was 3.0% (95% CI: 0.6–7.2, : 77.1%) for patients with occult infection, and 15.4% (95% CI: 1.2–41.2%, : 79.9%) for overt infection. The prevalence of reactivation was 3.9% (95% CI: 1.1–8.4%, : 51.1%) for treatment with etanercept and 4.6% (95% CI: 0.5–12.5%, : 28.7%) for adalimumab. For subgroup of patients without any antiviral prophylaxis the pooled reactivation was 4.0% (95% CI: 1.2–8.3%, : 75.6%). Conclusion. Although HBV reactivation rate is relatively low in patients treated with anti-TNF-α for rheumatic and dermatological conditions, the antiviral prophylaxis would be recommended in patients with overt chronic HBV infection. 1. Introduction Antitumor necrosis factor-alpha (TNF-α) agents are widely used for effective treatment of autoimmune rheumatic and dermatological diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (SA), psoriasis (Ps), or psoriatic arthritis (PsA). Nevertheless, anti-TNF-α agents have been associated with growing number of adverse events, particularly infections [1, 2] of which some can be life threatening. TNF-α is an important proinflammatory cytokine in the host defense mechanism against many intracellular pathogens. It suppresses hepatitis B virus (HBV) replication and promotes HBV eradication by stimulating HBV-specific cytotoxic T-cell response [3–5]. It has been reported that reactivation of HBV infection may occur directly due to lack of TNF-α or indirectly via diminishing T-cell activation [6, 7]. TNF-α inhibitors are therefore likely to induce HBV replication and reactivation in cases when chronic infection is present. HBV is regarded as a leading cause of acute hepatitis, cirrhosis, and hepatocellular carcinoma [8], being responsible for about 600000 deaths every year [8]. Chronic HBV infection is defined as an overt when hepatitis B surface antigen (HBsAg) is
Pain Processing and Vegetative Dysfunction in Fibromyalgia: A Study by Sympathetic Skin Response and Laser Evoked Potentials
Anna Montemurno,Eleonora Vecchio,Florenzo Iannone,Giuseppe Libro,Giuseppe Lopalco,Katia Ricci,Marianna Delussi,Marina de Tommaso
- , 2017, DOI: 10.1155/2017/9747148
Abstract:
Orofacial Manifestations and Temporomandibular Disorders of Sj？gren Syndrome: An Observational Study
Angela Rinaldi,Angela Tempesta,Florenzo Iannone,Gianfranco Favia,Giovanni Lapadula,Luisa Limongelli,Mariasevera Di Comite,Mariateresa Guerrieri,Rossana Patricia Rotolo,Vito Crincoli
- , 2018, DOI: 10.7150/ijms.23044
Abstract: AIMS: Sj？gren Syndrome is a disorder involving oral tissues, with xerostomia, dysgeusia, dysphagia, tooth decay, gingivitis, angular cheilitis and glossitis. Temporomandibular disorders are a generic term referred to clinical conditions involving the jaw muscles and temporomandibular joint. The aim of this study was to investigate the prevalence of oral manifestations and temporomandibular disorders (TMD) in Sj？gren Syndrome (SS) patients compared with healthy people.
A research agenda for Italian emergency medicine
Primiano Iannone
Emergency Care Journal , 2010, DOI: 10.4081/ecj.2010.2.4
Abstract: Not available
Ameliorating the emergency department workflow by involving the observation unit: effects on crowding | Emergency Care Journal
Primiano Iannone
- , 2015, DOI: https://doi.org/10.4081/ecj.2015.4957
Abstract: Crowding adversely affects the performance of emergency departments (EDs) by worsening efficiency, timeliness of care, clinical outcomes and patients’ satisfaction. We describe in this study our attempt at improving crowding by modifying the roles and workflow of the ED physicians. The observation unit physician was given the additional duty of prioritizing admissions and managing unclear, complex cases, which were previously under the responsibility of front line emergency physicians. We analyzed two corresponding periods, both before the intervention (9897 ED attendances) in 2012 and after the intervention (10,297 attendances) in 2013. Most of the crowding indices improved significantly, including timeliness of triage, of first medical contact, access to resus area, and overall length of stay in ED. Also, emergency hospital admissions, average specialist consultations and imaging studies per patient decreased significantly. The observation unit workload increased. There was no significant excess of adverse events
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