A Caraffa

Università degli Studi di Perugia, Perugia, Umbria, Italy

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Publications (116)164.07 Total impact

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    ABSTRACT: Inflammatory mediators, such as cytokines, chemokines and arachidonic acid compounds, lead to vascular permeability and dilation and increase sensitization and pain receptors. Proinflammatory cytokines, including tumor necrosis factor, are involved in the etiology of clinical neurological disorders. These cytokines activate nuclear factor-kappa B (NF-kappa B) which leads to the activation of different inflammatory genes. TNF implicated in neurological disorders has an important role in the activation of micro glia and astrocytes. The inhibition of TNF may lead to the decrease of microglia activation and can be useful for therapeutic intervention. TNF, at the site of nerve injury may activate mast cells (MCs) which mediate pathologic events such as headache and pain. TNF is the only cytokine stored in mast cells and can be rapidly released along with biogenic amines after MC stimulation. Activation of MCs leads to NF-kappa B and AP1 generation with release of many cytokines including TNF, IL-33 and IL-1. In this paper we discuss the role of TNF in MC activation, mediating pain and neurological disorders.
    No preview · Article · Oct 2015 · Journal of biological regulators and homeostatic agents
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    ABSTRACT: Vitamin D has a major role in calcium absorption and maintenance of healthy bones. Vitamin D is also involved in cancer, cardiovascular system, allergic diseases, immune regulation and immune disor¬ders. Irradiation of food as well as animals produces vitamin D and more than 90% of previtamin D3 synthesis in the skin occurs in the epidermis. Vitamin D receptor has been found in many cells including T and B lymphocytes, macrophages, mast cells, NK cells and Tregs, and it selectively binds with high affinity to its ligand. Vitamin D binds its receptor VDR, resulting in transcription of a number of genes playing a role in inhibition of MAPK. Its effect may be also mediated by the direct activation of PKC. Vitamin D has the ability to suppress inflammatory cytokines such as TNF, IL-1, IFN-gamma and IL-2; while it increases the generation of anti-inflammatory cytokines IL-4 and IL-10. In B cells, vitamin D3 have also been shown to suppress IgE antibody class switch partly through the inhibition of NF-kB. Here we discuss the relationship between vitamin D, immunity and skin disorders.
    No preview · Article · Sep 2015 · Journal of biological regulators and homeostatic agents
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    ABSTRACT: Neuropeptides are involved in neurogenic inflammation where there is vasodilation and plasma protein extravasion in response to this stimulus. Nerve growth factor (NGF), identified by Rita Levi Montalcini, is a neurotrophin family compound which is important for survival of nociceptive neurons during their development. Therefore, NGF is an important neuropeptide which mediates the development and functions of the central and peripheral nervous system. It also exerts its proinflammatory action, not only on mast cells but also in B and T cells, neutrophils and eosinophils. Human mast cells can be activated by neuropeptides to release potent mediators of inflammation, and they are found throughout the body, especially near blood vessels, epithelial tissue and nerves. Mast cells generate and release NGF after degranulation and they are involved in iperalgesia, neuroimmune interactions and tissue inflammation. NGF is also a potent degranulation factor for mast cells in vitro and in vivo, promoting differentiation and maturation of these cells and their precursor, acting as a co-factor with interleukin-3. In conclusion, these studies are focused on cross-talk between neuropeptide NGF and inflammatory mast cells.
    No preview · Article · Jul 2015 · International journal of immunopathology and pharmacology
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    ABSTRACT: Existing techniques for operative treatment of hallux rigidus commonly combine skeletal and soft tissue interventions to obtain long-lasting relief of pain. To date, operative treatments include implant arthroplasty, cheilectomy, various osteotomies, nonimplant arthroplasty, and arthrodesis. We assessed a technique that respects the anatomy and joint function and used a shortening osteotomy of the head of the first metatarsal. We evaluated a series of 40 consecutive patients affected by grade II and III hallux rigidus, aged 32 to 79 years, who had undergone surgery from January 2010 to January 2014. All patients were evaluated clinically and radiographically, preoperatively and postoperatively, and underwent a final follow-up at a mean of 35.4 (range = 12-51) months. For the clinical evaluation, the American Orthopaedic Foot & Ankle Society (AOFAS) clinical rating scale for the hallux metatarsophalangeal-interphalangeal joints was used. A patient survey revealed excellent and good overall satisfaction in 90% of the sample. Postoperative results included a significant increase (P < .001) in the median global AOFAS score, from 39 (range = 25-60) to 84 (range = 78-94). The technique of a shortening osteotomy of the first metatarsal head appeared to be useful for the correction of stiffness, pain relief, and an improvement in range of motion. Other advantages were that it preserved the integrity of the metatarsophalangeal joint and led to a rapid functional recovery. Level IV, retrospective case series. © The Author(s) 2015.
    No preview · Article · Jul 2015
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    ABSTRACT: A care gap exists between the health care needs of older persons with fragility fractures and the therapeutic answers they receive. The Fracture Prevention Service (FPS), a tailored in-hospital model of care, may effectively bridge the osteoporosis care gap for hip-fractured older persons. The purpose of this study was to evaluate the efficacy of the FPS in targeting persons at high risk of future fracture and to improve their adherence to treatment. This was a prospective observational study conducted in a teaching hospital with traumatology and geriatric units, and had a pre-intervention and post-intervention phase. The records of 172 participants were evaluated in the pre-intervention phase, while data from 210 participants were gathered in the post-intervention phase. All participants underwent telephone follow-up at 12 months after hospital discharge. The participants were patients aged ≥65 years admitted to the orthopedic acute ward who underwent surgical repair of a proximal femoral fracture. A multidisciplinary integrated model of care was established. Dedicated pathways were implemented in clinical practice to optimize the identification of high-risk persons, improve their evaluation through bone mineral density testing and blood examinations, and initiate an appropriate treatment for secondary prevention of falls and fragility fractures. Compared with the pre-intervention phase, more hip-fractured persons received bone mineral density testing (47.62% versus 14.53%, P<0.0001), specific pharmacological treatments (48.51% versus 17.16%, P<0.0001), and an appointment for evaluation at a fall and fracture clinic (52.48% versus 2.37%, P<0.0001) in the post-intervention phase. Independent of some confounders, implementation of the FPS was positively associated with recommendations for secondary fracture prevention at discharge (P<0.0001) and with 1-year adherence to pharmacological treatment (P<0.0001). The FPS is an effective multidisciplinary integrated model of care to optimize identification of older persons at highest risk for fragility fracture, to improve their clinical management, and to increase adherence to prescriptions.
    Full-text · Article · Jun 2015 · Clinical Interventions in Aging
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    ABSTRACT: Atraumatic avulsion of the tibial attachment of patellar tendon in adults is a very rare injury with only few published case reports. Here we are sharing the successful management and follow-up of a similar case with a different suture material for repair of the tendon, the FiberWire.We believe that the management we are discussing allows for early return to activity with good functional outcome.
    Full-text · Article · Jun 2015
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    ABSTRACT: Atraumatic avulsion of the tibial attachment of patellar tendon in adults is a very rare injury with only few published case reports. Here we are sharing the successful management and follow-up of a similar case with a different suture material for repair of the tendon, the FiberWire. We believe that the management we are discussing allows for early return to activity with good functional outcome.
    Full-text · Article · Jun 2015
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    ABSTRACT: Vitamins are natural components of foods and are organic compounds distinct from fat, carbohydrates and proteins. Vitamin A is the generic descriptor for compounds with the qualitative biological activity of retinol. Unlike beta-carotene, vitamin A is not an antioxidant and its benefit is related to possible boosting of immune reactions. The effect of vitamin A on immune function is wide-reaching and its deficiency appears to affect immunity in several ways. Innate and adaptive immune responses are affected in some way by lack of vitamin A. Retinoids seem to act on differentiation of lymphocytes, antibody production, phagocytosis of macrophages, NK, Treg, and T helper cell activity. In addition, in humans, signs of a vitamin A deficiency also include the dysregulation of cytokine/chemokine generation and release. However, excess of vitamin A has been demonstrated to have toxic effects in most species studied. Here we summarize some important effects of vitamin A in immunity and inflammation.
    Full-text · Article · Apr 2015 · Journal of biological regulators and homeostatic agents
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    ABSTRACT: Vitamin B1 (thiamin) is considered to be the oldest vitamin and in 1936 R.R. Williams and colleagues determined its chemical structure and were able to synthesize this vitamin. Vitamin B1 influences pro-apoptotic proteins, mitochondrial membrane potential, cytochrome C release, protein kinases, p38-MAPK, suppresses oxidative stress-induced NF-kappaB and has anti-inflammatory properties. Deficiency of vitamin B1 may cause beriberi, dysfunction of the nervous system, neuroinflammation, T cell infiltration, chemokine CCL2 activation, over expression of proinflammatory cytokines, such as IL-1, TNF, IL-6, and arachidonic acid products, and induces expression of CD40 by the microglia and CD40L by astrocytes which provoke the death of neurons. Here we report the relationship between vitamin B complex and immunity.
    Full-text · Article · Apr 2015 · Journal of biological regulators and homeostatic agents
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    ABSTRACT: Existing techniques for surgical treatment of hammer toe commonly combine skeletal and soft tissues interventions to obtain a durable correction of the deformity, balance the musculotendinous forces of flexion and extension of the toe, and normalization of the relations between interosseous muscles and metatarsal bones. The most common surgical techniques can provide the correction of the deformity through arthroplasty with resection of the head of the proximal phalanx or arthrodesis of the proximal interphalangeal joint. In most cases, these have been associated with elongation of the extensor apparatus, capsulotomy of the metatarsophalangeal joint, and stabilization with a Kirschner wire. To experiment with a technique that respects the anatomy and joint function, we used a distal subtraction osteotomy of the proximal phalanx neck. We evaluated a series of 40 patients, aged 18 to 82 years, who underwent surgery from January 2008 to December 2010. All patients were evaluated clinically and radiographically pre- and postoperatively and underwent examination at a mean final follow-up point of 24.4 (minimal 12, maximal 36) months. For the clinical evaluation, we used the American Orthopaedic Foot and Ankle Society score. The rate of excellent and good results was >90%. Compared with other techniques, this technique led to considerable correction, restoration of the biomechanical and radiographic parameters, and an adjunctive advantage of preserving the integrity of the proximal interphalangeal joint. Thus, our results have caused us to prefer this technique. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Mar 2015 · The Journal of foot and ankle surgery: official publication of the American College of Foot and Ankle Surgeons
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    ABSTRACT: Inflammation, neurodegeneration, imbalance of neurotransmitter systems, oxidative stress and depression are all risk factors for obesity. There is evidence regarding the cross-talk between adipose tissue and the immune system and obese patients may show an alteration of immune functions with major depression, including immune suppression with reduced T-cell and macrophage activity. Obesity is mediated by inflammatory cells such as lymphocytes, macrophages and mast cells which release pro-inflammatory cytokines and chemokines. Obesity-induced leukocyte infiltrations in adipose tissue cause cytokine/chemokine release and inflammation. Here, we report the relationship between obesity, neurological alterations and inflammation.
    Full-text · Article · Dec 2014 · European Journal of Inflammation
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    ABSTRACT: Atherosclerosis is an inflammatory disease and hyperlipidaemia is one of the main risk factors for aging, hypertension and diabetes. Variance in plasma LDL cholesterol concentration may be associated with differences in cardiovascular disease risk and high levels of lipids are associated with increased risk of developing atherosclerosis. Macrophages, which generate pro-inflammatory cytokines, mainly interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-alpha), are deeply involved in atherosclerosis, as well as mast cells which generate several cytokines, including IL-6 and IFN-gamma, and chemokines such as eotaxin, MCP-1 and RANTES involved in monocyte recruitment and differentiation in the arterial wall. In addition, mast cells participate in lipid retention and vascular cell remodeling, and are mediators of innate and adaptive immunity during atherosclerosis. Mast cells which accumulate in the human arterial intima and adventitia during atherosclerotic plaque progression, release vasoactive and angiogenic compounds, and pro-inflammatory mediators, such as arachidonic acid metabolites, histamine, cytokines/chemokines, platelet activating factor (PAF) and proteolytic enzymes. Mast cells can be activated by pro-inflammatory stimuli, including cytokines, hypercholesterolemia, and hyperglycemia, and trigger the endothelial expression of adhesion molecules such as P-selectin, vascular cell adhesion molecule-1 (VCAM-1) and chemokines which mediate the recruitment and adhesion of leukocytes. The participation of mast cells in atherosclerosis is still an enigma and it may be of therapeutic interest to clarify this process.
    Full-text · Article · Oct 2014 · International journal of immunopathology and pharmacology
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    ABSTRACT: Purpose Chin-on-chest deformity is a rare and severe condition mostly related with ankylosing spondylitis, traumas and/or cervical spine surgery. We present a case of 69 years old woman with a rare form of chin-on-chest secondary to dropped head syndrome (DHS), developed after radiotherapy for Hodgkin disease. In addition, we reviewed the few publications about this specific condition; management and surgical treatment of DHS are discussed. Methods We performed a pedicle subtraction osteotomy (PSO) and stabilization through a posterior approach. Intraoperative monitoring using motor and somatosensory evoked potentials and wake-up test were carried out. Results At 19th month follow-up, the patient reported a significant improvement of cervical pain, dysphagia and respiratory difficulty and a complete restoration of the neurological impairment. The achieved correction was successful and the patient was very satisfied by the restoration of forward gaze. Conclusions DHS is a very rare post-radiotherapy complication; there is lack of evidences in literature about its management. The only definitive treatment seems to be surgical intervention. PSO is a valid therapeutic option when fixed chin-on-chest deformity occurs; although it is a demanding technique and it presents high rate of complications, the actual neurological monitoring methods provide more intraoperative safety.
    No preview · Article · Sep 2014 · European Spine Journal
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    ABSTRACT: Microglia derive from mononuclear myeloid progenitors and are a major glial complement of the central nervous system. When microglia are activated they secrete inflammatory cytokines and toxic mediators which amplify the inflammatory response. In addition, the microglia inflammatory products are implicated in the neuronal destruction usually observed in various neurodegenerative diseases. Microglia cells express corticotropin releasing hormone (CRH) receptors, and activation of microglia by CRH releases bioactive molecules which have a biological effect in the brain and regulate several neurological diseases. CRH plays a pivotal role in stress responses and is a key mediator of the hypothalamic-pituitary-adrenocortical system. CRH is expressed in human mast cells, leading to autocrine effects and participates in inflammatory response together with neuropeptides, and stimulates mast cells. IL-33-activated mast cells release vascular endothelial growth factor in response to CRH and act synergistically to increase vascular permeability. CRH also up-regulates IL-18 expression by increasing intracellular reactive oxygen in microglia cells. Here we report the relationship between CRH, microglia and mental disorders.
    No preview · Article · Jul 2014 · International journal of immunopathology and pharmacology
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    ABSTRACT: Serotonin (5-HT) is an important neurotransmitter that acts in both central and peripheral nervous system, and has an impact on cell proliferation, migration and apoptosis. 5HT exerts its effects via several receptors. Treatment with anti-5-HT receptors diminish the severity of contact allergy in experimental animals, an effect mediated by mast cells; while an agonist reduces the stress level and relieves pruritus in patients with atopic dermatitis. Mast cells are important for both innate and adaptive immunity and they are activated by cross-linking of FceRI molecules, which are involved in the binding of multivalent antigens to the attached IgE molecules, resulting in a variety of responses including the immediate release of potent inflammatory mediators. Serotonin is present in murine mucosal mast cells and some authors reported that human mast cells may also contain serotonin, especially in subjects with mastocytosis. Here we report the interrelationship between mast cells, serotonin and its receptor inhibitor.
    No preview · Article · Jul 2014 · Journal of biological regulators and homeostatic agents
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    ABSTRACT: Mast cells (MCs) derive from a distinct precursor in the bone marrow and are predominantly found in tissues at the interface between the host and the external environment where they can secrete mediators without overt degranulation. Mast cells mature under local tissue microenvironmental factors and are necessary for the development of allergic reactions, through crosslinking of their surface receptors for IgE (FcεRI), leading to degranulation and the release of vasoactive, pro-inflammatory and nociceptive mediators that include histamine, pro-inflammatory and anti-inflammatory cytokines and proteolytic enzymes. Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demylination within the central nervous system. MCs are involved in the pathogenesis of MS by generating various vasoactive mediators and cytokines and participate in the destruction of the myelin sheath and the neuronal cells. The process of the development of demyelinating plaques in MS is probably linked with the rupture of the blood-brain barrier by MC products. The effects of natalizumab, which is a very effective drug in reducing the annualized relapse rate and other relapse-based endpoints, are discussed. Here, we report the relationship between MCs and MS.
    No preview · Article · Jul 2014 · International journal of immunopathology and pharmacology
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    ABSTRACT: Human mast cells (first described in 1879 by Paul Ehrlich) develop from committed precursors in the bone marrow expressing the differentiation marker CD34+ and distinct from the three other myeloid cells. Mast cells are present in various tissues especially near blood vessels, epithelia and nerves and they are activated by cross-linking of FcεRI, but also by a number of neuropeptides. NGF mediates a number of inflammatory and autoimmune states in conjunction with an increased accumulation of mast cells which appear to be involved in neuroimmune interactions and tissue inflammation. Here we report some relationships between mast cells and nerve growth factor (NGF).
    Full-text · Article · Jul 2014 · International journal of immunopathology and pharmacology
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    ABSTRACT: Asthma is a chronic inflammatory disease of the lung and its pathophysiology is initiated by mast cell activation in response to the antigen binding to IgE receptor as well as by TH2 cell activation. Mast cells are well established effector cells in asthma where they exacerbate the inflammatory response, playing a key role in early phase, degranulating and increasing histamine. Human mast cells possess high affinity IgE receptors and are ubiquitous but predominantly localized in mucosal and connective tissue and are distributed along blood vessels. There are two types of mast cells: connective tissue mast cells (TC) and mucosal mast cells (T mast cells). TC mast cells contain more heparin, whereas T mast cells contain more chondroitin sulfate. In asthma, mast cell activation can trigger degranulation, releasing secretory granule complex and preformed mediators, such as histamine and proteases, along with the synthesis of leukotrines and prostaglandins, and induction of cytokines and chemokines. Leukotrine inhibitors and omalizumab, which inhibits IgE, both relieve the asthma exacerbation when administered to humans and permit to reduce the use of other drugs. The release of cytokines by mast cells, such as TNF-alpha, IL-1, IL-6 and IL-33, participate in the pathogenesis of asthma. Stress worsens asthma, and this effect is also mediated by mast cell activation through the release of cytokines. Administration of IL-33 in experimental animals provokes pathological effects in the mucosal tissues and augments antibody IgE and IgA in blood vessels. Here, we report the impact of mast cell biology in asthma pathogenesis.
    No preview · Article · May 2014 · European Journal of Inflammation
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    ABSTRACT: It is well established that mast cells, which are found in the tissues in the proximity of small blood vessels and post-capillary venules, play a key role in the early phase of IgE-mediated allergic reactions. A greatly expanded understanding of the biology of IL-3 has emerged since the early 1980s. IL-3 is a specific factor that stimulates the growth of hematopoietic stem and progenitor cells of a variety of lineages and can promote the proliferation of certain classes of lymphocytes distinct from those that are dependent on IL-2. IL-3 has been identified among the most important cytokines for regulation of mast cell growth and differentiation, migration and effector function activities of many hematopoietic cells. IL-3 termed multi colony-stimulating-factor (multi-CSF) or mast cell growth factor (MCGF) is a haematopoietic growth factor which stimulates the formation of colonies for erythroid, megakaryocytic, granulocytic and monocytic lineages. It is predominantly produced by activated T cells, natural killer (NK) cells and mast cells and supports the growth-promoting effects of SCF on mast cell precursors. IL-3 causes severe hypersensivity reactions and plays a pivotal role in exacerbating the inflammatory response in vivo. Here we report the interrelationship between IL-3 and mast cells.
    No preview · Article · Apr 2014 · Journal of biological regulators and homeostatic agents
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    ABSTRACT: IgE is an important marker for allergy and plays a central role in the induction of allergic diseases through its binding of the high affinity receptor on mast cells. Mast cells can influence B cell survival, proliferation and differentiation into CD138+ cells. Among TH2 cytokines, interleukin (IL)-4 and IL-13 are responsible for class-switching in B cells which resolves in production of allergen-specific IgE antibodies that bind to specific receptor on mast cells. IgE synthesis by B cells is regulated by CD40 ligand, IL-4 and interferon-gamma, therefore inhibition of B cell antigen-specific IgE may prevent the cleavage of CD23 from B cells, having a therapeutic impact which also includes the removal of circulating free IgE, omalizumab, corticosteroids, mast cell stabilizers, leukotriene receptor antagonist, and others. B cell differentiation into IgE-producing cells requires two signals provided by TH2 cells and IL-4, however IL-4, IL-1 and IL-10 as well as several hormones are critical for the development of TH2 cells, while cytokines, such as interferon (IFN)-alpha, IFN-gamma, IL-12 and transforming growth factor (TGF)-beta play a negative role. However, the exact mechanism of this process has not yet been defined.
    No preview · Article · Jan 2014 · European Journal of Inflammation