bluuebunny/crossref_metadata_2025 huggingface dataset:
Delayed Allergy to Aminopenicillins: Clinical and Immunological Findings
Authors: Schiavino D. , Nucera E. , De Pasquale T. , Roncallo C. , Pollastrini E. , Lombardo C. , Giuliani L. , Larocca L.M. , Buonomo A. , Patriarca G.
Published: January 2017

Aminopenicillins are the most used β-lactam antibiotics. Morbilliform or maculopapular rashes are rather frequent during therapy with aminopenicillins. The pathogenesis of these reactions is often due to a cell-mediated allergy. The aim of this work is to characterize patients with cell-mediated allergy to aminopenicillins and to identify alternative β-lactam drugs that can be safely administered to these patients. We studied 27 subjects affected by cell-mediated allergy to aminopenicillins. The diagnosis was made on the basis of positivity of patch tests with aminopenicillins. These patients then underwent an allergological evaluation (skin and patch tests, oral and/or intramuscular challenge tests) with a wide spectrum of β-lactam antibiotics. Our work highlights the following main characteristics of cell-mediated allergy to aminopenicillins: time elapsing between drug administration and onset of symptoms of about 2 days; the maculopapular rash and delayed appearance of urticaria/angioedema were the most typical symptoms (82.8% of cases); a cross-reactivity with aminocephalosporins is usually absent, or it is limited to cephalexin (in our study, in fact, just 3 out of 20 patients challenged with cephalexin showed a positive oral challenge test); all the β-lactams, other than aminopenicillins, are well tolerated. Patch tests represent a specific diagnostic tool with a good predictive value of identifying alternative drugs that can be safely administered to patients with β-lactam allergy. Our patients could tolerate other β-lactam drugs after a complete allergological evaluation. On the basis of our study, cell-mediated allergy to aminopenicillins should be considered a well-defined nosologic entity.
Risk Factors for Sensitization to Anisakis Simplex: A Multivariate Statistical Evaluation
Authors: Foti C. , Fanelli M. , Mastrandrea V. , Buquicchio R. , Cassano N. , Conserva A. , Nettis E.
Published: January 2017

Anisakis simplex is a nematode belonging to the Anisakidae family. The ingestion of third stage larvae in uncooked or undercooked seafood may cause human diseases known as anisakiasis and anisakidosis. A total of 400 (159 atopic and 241 non-atopic) subjects living in an area of southern Italy (Bari district) were consecutively evaluated to identify the association of some factors (sex, age, atopy, consumption of uncooked seafood and sensitization to dust mites) with the risk of Anisakis simplex sensitization. Patients were investigated on history of atopy and allergic diseases and were skin prick tested with commercial allergen extracts of Anisakis simplex, Acarus siro, Lepidoglyphus destructor, Tyrophagus putrescentiae, Glycyphagus domesticus, Euroglyphus maynei, Dermatophagoides pteronyssinus and Dermatophagoides faunae. Our results suggest that atopic subjects have a lower risk of Anisakis allergy than non-atopic subjects and show the association of Anisakis simplex sensitization with the consumption of uncooked seafood (anchovies and squid), increasing age and sensitization to Glycyphagus domesticus.
Antiphospholipid Antibodies in Patients with Cancer
Authors: Pugliese L. , Bernardini I. , Pacifico E. , Viola-Magni M. , Albi E.
Published: January 2017

Antiphospholipid antibodies are generally associated with Antiphospholipid Syndrome, which can occur as a primary disorder or may be secondary to connective tissue disease or tumour. The presence of antiphospholipid antibodies in patients with tumour disease is responsible for thrombotic complications. In a population of 53 tumor patients with positive carcinoembryonic antigen CEA, carbohydrate antigen CA19.9, CA125 and CA15.3 markers, IgM and IgG anticardiolipin and antiphosphatidylinositol were detected by solid-phase immunoassays. Our results show that moderate or high levels of antiphospholipid antibodies are present in a great number of patients with CEA and CA19.9 markers, suggesting a specific association with gastroenteric tumors. By testing for antiphosphatidylinositol antibodies, many patients not evidenced by the standard anticardiolipin assay were found to be antiphospholipid-positive. The analysis of antiphosphatidylinositol antibodies as a diagnostic tool in gastroenteric cancer to highlight patients with the risk of thromboembolic complications is discussed.
Psychiatric Manifestations as a Primary Symptom in Antiphospholipid Syndrome
Authors: Manna R. , Ricci V. , Curigliano V. , Pomponi M. , Adamo F. , Costa A. , De Socio G. , D'Onofrio F. , Gasbarrini G. , Bria P.
Published: January 2017

Antiphospholipid syndrome is a disorder characterised by recurrent venous or arterial thrombosis and/or foetal losses associated with typical laboratory abnormalities. The initial manifestation of anthiphospholipid syndrome can involve many organ systems either singly or in combination. We describe the case of a 62 year old female showing schizophrenia-like symptoms in which further evaluations allowed us to diagnose the antiphospolipid syndrome.
Listeria Monocytogenes in a Young Patient with Non Hodgkin's Lymphoma: Case Report
Authors: Fioriti D. , Penta M. , Suraci S. , Chiriacò D. , Cacchione A. , Schippa S. , Conte M.P. , Nicosia R. , Chiarini F. , Pietropaolo V.
Published: January 2017

Listeria monocytogenes is an intracellular food-borne pathogen, widely distributed in the environment, which rarely causes clinical infection in healthy people, but may cause severe disease in immunocompromised patients. A case of listeriosis is certified in an immunocompromised patient, thus confirming this microorganism to be an opportunistic human pathogen.
High Intracytoplasmatic Levels of IL-4 and IL-5 in a Patient with Gleich's Syndrome: Case Report
Authors: Novembre E. , Mori F. , Arcangeli F. , Cianferoni A. , Bernardini R. , Pucci N. , Annunziato F. , Parronchi P. , De Martino M. , Vierucci A.
Published: January 2017

Gleich's syndrome is characterized by recurrent localized angioedema, hypereosinophilia, elevated levels of IgM, rapid weight gain, itchy urticaria and fever. Little is known about the pathogenesis of this disease. Increased serum levels for IL5, IL6 and C5a have been reported before and during clinical exacerbations. In order to better understand the role of the T cells in Gleich's syndrome we analyzed the intracellular cytokine expression in CD3+ cells of a patient affected by the disease. As hypereosinophilia was documented, we asked whether IL-4 and IL-5 levels were increased, and the intracytoplasmatic expression of these Th2-cytokines was determined. The percentage of T lymphocytes (CD3-gated cells) of both CD8− and CD8+ phenotype expressing different cytokines showed an unusually high percentage of Th2-related cytokine (IL-4, IL-5 and IL-13) expressing T lymphocytes. The two new variants (myeloproliferative and lymphoproliferative) seem to account for hypereosinophilia in patients with hypereosinophilic syndrome (HES). In the lymphroliferative variant, the presence of a clonal CD3-CD4+ Th2 like lymphocyte secreting IL-4 and IL-5 in peripheral blood, may explain the hypereosinophilia and the hyper-IgE. In our study we show that the patient had a lymphoproliferative variant and her T cell had a Th2 type phenotype. Moreover, we suggest that Th2 lymphocytes may play a role in the pathogenesis of Gleich's syndrome. Further studies are needed to evaluate the possibility that a polyclonal aspecific activation of Th2 type cells can lead to hypereosinophilia, IgE production and the other manifestations typical of Gleich's syndrome.
Acute Impact of Volcanic Ash on Asthma Symptoms and Treatment
Authors: Shimizu Y. , Dobashi K. , Hisada T. , Ono A. , Todokoro M. , Iijima H. , Utsugi M. , Kakegawa S. , Iizuka K. , Ishizuka T. , Morikawa A. , Mori M.
Published: January 2017

Information about the impacts of disasters on health is useful for establishing hazard prediction maps and action plans of disaster management. This study aims at learning effective asthma management from the volcano disaster of Mount Asama eruption in Japan on September 1, 2004. We conducted a cross-sectional study to assess the acute impact of volcanic ash on asthma symptoms and their treatment changes by using a questionnaire completed by 236 adult asthmatic patients and their physicians. In the ashfall over 100g/m2 area, 42.9% of asthma patients suffered exacerbations, PEF decreased, asthma treatments increased, and inhalation of β2 stimulants was used most for exacerbated asthma. Compared to severe asthma patients, mild and moderate asthma patients were most at risk. Severe asthma patients were not affected since most of them knew their asthma status was severe, and did not go outside and kept windows closed. Deteriorated asthma symptoms of wheezing, chest tightness and cough appeared in the ashfall over 100g/m2 area. Ash contained inhalable 10μm diameter particles, and included high concentrations of airway toxic substrates of silica. These data suggest that ashfall over 100 g/m2 is harmful, access to these areas by asthma patients needs to be restricted, and these areas need to improve asthma treatment. In addition, the increase in the proportion of asthma patients with wheeze and cough are diagnostic clues for ash-induced asthma in affected areas, and can be used by doctors to tell whether patients are receiving sufficient asthma treatment.
A Proposal for Guideline for Prevention of Allergic Occupational Asthma-in Conformity with the Globally Harmonized System of Classification and Labelling of Chemicals (GHS)
Authors: Sato K. , Kusaka Y.
Published: January 2017

The use of chemical products to enhance and improve life is a widespread worldwide practice. Alongside the benefits of these products, there is also the potential of chemicals for adverse effects to people or the environment. As a result, a number of countries or organizations have developed laws or regulations over the years that require information to be prepared and transmitted to those using chemicals, through labels or Safety Data Sheets (SDS). Their differences are significant enough to result in different labels or SDS for the same product in different countries. In July 2003, United Nations (UN) recommended the globally harmonized system of classification and labelling of chemicals (GHS). We, special committee of Japanese Society of Occupational and Environmental Allergy proposed a guideline for prevention of allergic occupational asthma and sensitizers (n=60) causing occupational asthma or contact dermatitis in conformity with respiratory and skin sensitization criteria of GHS. We should propose these 60 sensitizers to the chemical industry association and governments to control, regulate and label them in each country.
Occupational Contact Dermatitis (Drug-Induced Medicamentosa): Six Case Reports
Authors: Zou J. , Liu L. , Sun S. , Zhao Y. , Pei Y. , Liu G.
Published: January 2017

We report six patients who had dermatitis after contacting certain chemical substances (one worker with contact 1-chloromethyl naphthalene and five with contact Hydroxy-phthalimide). They appeared like drug-induced erythma multiforme, bullosa epidermalysis from the point of contact gradually spreading to the whole body, combining high temperature, digestive system dysfunction, such as liver dysfunction etc. We can call this occupational drug-induced medicamentosa. The course of dermatosis diseases is 1–2 months. Hormone and sustaining treatment may be effective. We discuss chemistry substance, clinical presentation, diagnoses, treatment and relevant prognosis.
Case Study of Volatile Organic Compounds in Indoor Air of a House before and after Repair where Sick Building Syndrome Occurred
Authors: Harada K. , Hara K. , Wei C.N. , Ohmori S. , Matsushita O. , Ueda A.
Published: January 2017

A housewife in her late thirties, mother of two children, had an indefinite complaint about the indoor air quality of her house. Inspectors from a public health center treating the housewife's complaint quantified formaldehyde (FA) in high concentration exceeding Japanese national guideline of FA in some rooms of the house. We also determined FA and total volatile organic compounds (TVOCs) in higher concentrations more than the national guidelines. Remodeling of the house was performed to improve the air quality as follows. Vinyl wallpaper was exchanged to plant made paper, plywood made doors were exchanged to pure wood made doors, plywood stairs were covered with plant cork and so on. After remodeling the house, we measured the concentrations of FA and TVOCs again. The concentrations of the chemicals in the indoor air decreased which approve effectiveness of the remodeling. Moreover complaints of the housewife lessened. This also proved the effectiveness of the remodeling. Four years after the inspection, we visited the house again and found that the concentration of FA in the house was still lower than that of national guideline. The housewife was evaluated in a good healthy condition by her answers to our questions related to indoor air quality, daily life, physical condition, and so on.
Benzene Metabolites Inhibit the Release of Proinflammatory Mediators and Cytokines from Human Basophils
Authors: Borrelli I. , Loffredo S. , Staiano R.I. , Frattini A. , Bergamaschi A. , Marone G. , Triggiani M.
Published: January 2017

Benzene and its metabolites have been involved in the pathogenesis of chronic lung inflammation and allergic disorders such as bronchial asthma. However, the effects of these xenobiotics on human basophils, key cells in the development of respiratory allergy, have not been investigated. We examined the effects of hydroquinone (HQ) and benzoquinone (BQ), two important chemicals implicated in benzene toxicity, on the release of preformed (histamine) and de novo synthesized mediators (cysteinyl leukotriene C4, LTC4, and IL-4) from human basophils. Preincubation of basophils purified from normal donors with HQ (3–100 μM) inhibited up to 30% histamine release induced by anti-IgE and up to 55% of that induced by the Ca2+ ionophore A23187. HQ had no effect on histamine release induced by formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe). Preincubation of basophils with BQ (3–100 μM) resulted in the concentration-dependent inhibition of histamine release (up to 70%) induced by anti-IgE, A23187 and f-Met-Leu-Phe. HQ completely suppressed the de novo synthesis of LTC4 from basophils challenged with anti-IgE or f-Met-Leu-Phe and the production of IL-4 in cells stimulated with anti-IgE. These results indicate that two major benzene metabolites, HQ and BQ, inhibit the release of proinflammatory mediators and Th2-promoting cytokines from basophils activated by different stimuli. These results suggest that benzene metabolites interfere with multiple intracellular signals involved in the activation of human basophils.
A Study of Adenosine-Deaminase Genetic Polymorphism in Rheumatoid Arthritis
Authors: Sebastiani G.D. , Bottini N. , Greco E. , Saccucci P. , Canu G. , Lucarelli P. , Gloria-Bottini F. , Fontana L.
Published: January 2017

Recent investigations suggest that Adenosine Deaminase (ADA) could play a role in susceptibility to rheumatoid arthritis (RA). The purpose of our study is to investigate the possible role of genetic variability of ADA in the susceptibility to RA. We studied three intragenic ADA polymorphisms, ADA1, ADA2 and ADA6, in a sample of 91 subjects with RA and in 246 healthy subjects from the same Caucasian population and compared genotype and pairwise haplotype distributions between cases and controls. No statistically significant differences between RA and controls are observed for ADA genotypes. A border line difference for ADA1-ADA2 haplotype distribution is observed due to a decreased proportion of ADA1*2/ADA2*2 haplotype in RA compared to controls. Our data indicate a border line effect of ADA gene polymorphism on susceptibility to RA that need to be confirmed in other clinical settings.
In Vitro Activity of Cefditoren versus other Antibiotics against S. Pneumoniae Clinical Strains Isolated in Italy
Authors: Tempera G. , Furneri P.M. , Ferranti C. , Genovese C. , Ripa S. , Ungheri S. , Nicoletti G.
Published: January 2017

Over the last twenty years there has been an alarming increase in isolation of Streptococcus pneumoniae strains with a reduced susceptibility not only to penicillin, but also to other betalactams and macrolides. This phenomenon justifies the great interest in new antibiotics. Cefditoren, a new aminothiazolyl oral cephalosporin, recently commercialized in Italy, is characterized by an extended activity against penicillin-resistant S. pneumoniae. The aim of this study is to evaluate the incidence of the resistance/susceptibility to various antibiotics in 1000 strains of S. pneumoniae (678 SPSS, 219 SPPI and 103 SPPR), clinically isolated during 2009. The data obtained by our in vitro study show that cefditoren is the most active agent against S. pneumoniae. In fact, the MIC90 values of 0.5 fig/ml obtained could be particularly significant in terms of therapeutic predictivity.
Attention-Deficit Hyperactivity Disorder and Intellectual Disability: A Study of Association with Brain-Derived Neurotrophic Factor Gene Polymorphisms
Authors: Aureli A. , Del Beato T. , Sebastiani P. , Marimpietri A. , Melillo C.V. , Sechi E. , Di Loreto S.
Published: January 2017

Symptoms of attention-deficit hyperactivity disorder (ADHD) have been found in several studies of children with intellectual disabilities (ID) but the two diseases are not always associated. Several lines of evidence implicate the involvement of brain-derived neurotrophic factor (BDNF) in ADHD, and it may also be relevant in ID due to its known involvement in the development of the central nervous system (CNS) and in learning/memory functions. We genotyped paediatric patients with ADHD and ID for the Val66Met and 270 C/T polymorphisms in BDNF. Diagnosis of ADHD and ID was confirmed by the clinicians in accordance with DSM-IV criteria. The G/A genotype of the Val66Met SNP was associated with both ADHD and ID, and the G allele was significantly associated with ADHD. The C/C genotype of the C270T SNP was significantly overrepresented in both ADHD and ID groups compared with the controls. Data suggest that both BDNF polymorphisms could play a role in the etiology of ADHD. In addition, we present the first results suggesting that these BDNF SNPs are significantly associated with ID.
Serum Proteome of Patients with Systemic Sclerosis: Molecular Analysis of Expression and Prevalence of Haptoglobin Alpha Chain Isoforms
Authors: Guerranti R. , Bertocci E. , Fioravanti A. , Papakostas P. , Montella A. , Guidelli G.M. , Cortelazzo A. , Nuti R. , Giordano N.
Published: January 2017

Haptoglobin (Hpt) is an acute phase protein characterized by three major phenotypes (Hpt 1-1, Hpt 2-1 and Hpt 2-2). The Hpt 2-2 phenotype is associated with increased prevalence of various systemic diseases, including autoimmune disorders. Moreover, the Hpt 2-2 phenotype induces a shift from Th1 to Th2 response and increases fibrotic processes. On this basis, we performed serum proteomic analysis of with Systemic Sclerosis (SSc), a connective tissue disorder associated with Th2-type immune response and characterized by interstitial and perivascular fibrosis due to different factors (including genetic, environmental, immunological and microchimeric factors). Serum of 23 SSc outpatients (4 males, 19 females, mean age 54±5.3 years) diagnosed according to the American Rheumatism Association (ARA) criteria, were considered for the proteomic analysis and compared to serum of 21 control subjects. Serum depleted of HAP was analyzed by 2-DE, and Hpt chain spots were identified by WB. The expression frequency of each Hpt a chain in SSc patients and controls was compared and quantitative analysis of spot expression (% Vol) was performed. Above all, our study amplifies the limited data in the literature on proteomic analysis in SSc, also confirming previous data that revealed a significant increase of haptoglobin type 2-2 and a concomitant decrease of the 1-1 phenotype in SSc patients. Moreover, our results demonstrate that c spots are more prevalent in SSc patients than in controls (91.3% vs 55.5%, p<0.05), while the expression frequency of a and b spots does not change. In patients Hpt 2-1 or Hpt 1-1 e spot is less abundant. According to our results, the c and e spots can be considered markers for SSc and thus be of use for the early diagnosis of connective tissue disorders and in establishing appropriate treatment.
Apelin Plasma Levels Predict Arrhythmia Recurrence in Patients with Persistent Atrial Fibrillation
Authors: Falcone C. , Buzzi M.P. , D'Angelo A. , Schirinzi S. , Falcone R. , Rordorf R. , Capettini A. C. , Landolina M. , Storti C. , Pelissero G.
Published: January 2017

Low levels of the regulatory peptide apelin have been reported in patients with lone atrial fibrillation (AF). We evaluate the potential utility of assessing apelin plasma levels as a predictor of AF recurrence in individuals presenting for electrical cardioversion. Plasma levels of apelin, brain natriuretic peptide (BNP) and high-sensitivity C-reactive protein were measured in 93 patients, with persistent AF before successful external electrical cardioversion. Significantly lower apelin plasma levels were found in patients with AF recurrence as respect to population with persistence of sinus rhythm during a six months follow-up. The hazard increased with duration of AF, left atrial dimension, BNP concentrations. Subjects with apelin levels below the median had a hazard ratio of 3.1 of arrhythmia recurrence with respect to those with high apelin levels (p< 0.05). A significant difference in BNP levels was found between patients with and without AF recurrence during the follow-up. After adjusting for potential confounders, both BNP and apelin retained their statistical significance as independent predictors of arrhythmia recurrence. Patients with both low apelin and elevated BNP had a worse prognosis compared with those with either low apelin or elevated BNP alone. Low plasma apelin levels before external electrical cardioversion are an independent prognostic factor for arrhythmia recurrence in patients with AF treated with antiarrhythmic drugs. Apelin may be of particular value for the identification of high-risk patients in addition to BNP.
The Clinical Efficacy of a Sublingual Monomeric Allergoid at Different Maintenance Doses: A Randomized Controlled Trial
Authors: Marogna M. , Colombo F. , Cerra C. , Bruno M. , Massolo A. , Canonica G.W. , Falagiani P. , Passalacqua G.
Published: January 2017

Sublingual immunotherapy is widely recognized as a viable treatment for allergic rhinitis and asthma, but the optimal dosage is still under debate, expecially with modified allergens. We assessed the clinical effects of a monomeric allergoid across 3 different maintenance doses in mite-monosensitized patients with rhinitis and intermittent asthma. Eighty-nine patients allergic to HDM were randomized to 3 maintenance doses of monomeric allergoid (Lais®, Lofarma) or medications only. All the patients recorded their symptoms and rescue drug consumption in a diary card from November to February. Additionally, nasal eosinophil count, spirometry and methacholine bronchial challenge were performed at the beginning of the study and after 3 years. The symptom scores showed a clear improvement in all the three active arms versus baseline and versus the controls, irrespective of the dose. Likewise, a similar improvement versus baseline was seen for nasal inflammation and bronchial hyperreactivity. The SLIT with monomeric allergoids produces clinically significant results across a wide range of doses. The absence of significant side effects, even at high doses, is probably due to their low level of allergenicity.
Large Granular Lymphocyte Leukemia with Pure Red Cell Aplasia Associated with Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy: An Unfortuitous Association?
Authors: Hervier B. , Rimbert M. , Maisonneuve H. , Hamidou Ma.
Published: January 2017

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a recessively inherited monogenic disease caused by a mutation in the autoimmune regulator (AIRE) gene. AIRE plays a major role in central (thymic) immune tolerance. In the absence of AIRE, autoimmunity develops that is especially targeted at endocrine tissues. T-cell large granular lymphocyte (T-LGL) leukemia is a monoclonal lymphoproliferative disease characterized by persistent and indolent lymphocytosis. Autoimmune manifestations, such as rheumatoid arthritis or autoimmune cytopenia, are also common. We report the case of a patient with APECED, who presented with pure red cell aplasia associated with T-LGL leukemia. The association of T-LGL leukemia and APECED is very rare and may not be fortuitous. The immunological mechanisms of this association are discussed.
Immunopathogenetic and Pharmacological Aspects of Interstitial Lung Diseases
Authors: Mazzoccoli G. , De Cata A. , De Pinto G.D. , De Matthaeis A. , Vendemiale G.
Published: January 2017

Interstitial lung diseases (ILDs) are inflammatory diseases characterized by slow and progressive destruction of alveolar-capillary functional units, often leading to respiratory failure and death. A first stage of alveolitis and a following stage of fibrosis provoke an anatomical distortion of the peripheral airways and the interstitium, and for their smoldering evolution and non-specificity of symptoms ILDs may remain undiagnosed and untreated for a long time. In this review we exploited the immunopathogenetic aspects and the therapeutical approaches to this frequently unrecognized and severe disease.
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An Update
Authors: Capelli E. , Zola R. , Lorusso L. , Venturini L. , Sardi F. , Ricevuti G.
Published: January 2017

Chronic Fatigue Syndrome (CFS), also referred to as Myalgic Encephalomyelitis (ME), is a disease of unknown origin. It is classified as Post Viral Fatigue Syndrome (PVFS) in the WHO International Classification of Diseases (ICD) and listed as sub-category at G93.3 under chapter G93, “other disorders of the brain“. ME/CFS is primarily an endemic disorder but occurs in both epidemic and sporadic forms. It affects all racial/ethnic groups and is seen in all socioeconomic strata. A diagnosis of CFS is a diagnosis of exclusion, meaning other medical conditions, including psychiatric disorders, must be first ruled out. CFS is diagnosed if there is no other explanation for the fatigue and if the other symptoms did not develop before the fatigue. The estimated worldwide prevalence of CFS is 0.4–1%. The disease predominantly affects young adults, with a peak age of onset of between 20 and 40 years, and women, with a female to male ratio of 6:1. Mean illness duration ranges from 3 to 9 years. The patho-physiological mechanism of CFS is unclear but the immunological pattern of CFS patients gleaned from various studies indicates that the immune system is chronically activated. Besides the role of environmental insults (xenobiotics, infectious agents, stress) the genetic features of patients are studied to evaluate their role in triggering the pathology. At present there are no specific pharmacological therapies to treat the disease but a variety of therapeutic approaches have been described as benefiting patients. Treatment programs are directed at relief of symptoms, with the goal of the patient regaining some level of preexisting function and well-being.
Vitamins and Mast Cells
Authors: Anogeianaki A. , Castellani M.L. , Tripodi D. , Toniato E. , De Lutiis M.A. , Conti F. , Felaco P. , Fulcheri M. , Theoharides T.C. , Galzio R. , Caraffa A. , Antinolfi P. , Cuccurullo C. , Ciampoli C. , Felaco M. , Cerulli G. , Pandolfi F. , Sabatino G. , Neri G. , Shaik-Dasthagirisaheb Y.B.
Published: January 2017

The immune system is a highly complex, intricately regulated group of cells whose integrated function is essential to health. The mast cell inflammatory response is characterized by an early phase with massive discharge of mediators stored in cytoplasmic secretory granules. Through multigranular/compound exocytosis and a late phase that involves generation of arachidonic acid metabolites and de novo synthesis of cytokines/chemokines and growth factors. Vitamins have been shown to have a protective effect on the body's immune cells. Vitamin C and E are necessary in allergic disease treatment where mast cells are involved. In addition, ascorbic acid and pyridoxine are useful compounds for the treatment of inflammatory disorder of the respiratory airways. Here we revisited the inter-relationship between vitamins and mast cells.
Limited Joint Mobility in Diabetes and Ageing: Recent Advances in Pathogenesis and Therapy
Authors: Abate M. , Schiavone C. , Pelotti P. , Salini V.
Published: January 2017

Limited joint mobility is frequently observed in elderly people and in patients suffering from diabetes, who represent a growing segment of the population of western countries. Our review wishes to offer the “state of art” about this interesting topic, which may have important clinical implications, leading to impairment of both basic and instrumental activities of daily living. The main causes of a reduced range of motion are degenerative joint diseases and increased stiffness of collagen tissue. The main biochemical abnormality, common to aging and diabetes, is the non-enzymatic glycosilation of collagen, with advanced glycation end product (AGE) formation, which in turn leads to an increase of collagen cross-links. The most extensive accumulation of AGEs occurs in tissues that contain proteins with low turnover, such as the collagen in the extracellular matrix of articular capsule, ligaments and muscle-tendon units. The increase in collagen cross-linking alters the mechanical properties of these tissues with a decrease in elasticity and tensile strength, and an increase in mechanical stiffness. Besides this, AGEs react with specific cell surface receptors (RAGEs). The engagement of the ligand by RAGEs triggers cell-specific signalling, resulting in enhanced generation of reactive oxygen species and sustained up-regulation of pro-inflammatory mediators and adhesion molecules. An appropriate control of the glucose levels and a diet rich in antioxidant agents are recommended in patients with diabetes. Stretching and strengthening programmes are widely used, in order to prevent and to reduce joint stiffness, but the improvements with physiotherapy are little and short-lasting. Several drugs, which can interfere with AGE formation and removal, or with the cellular effects of AGEs, are under study (among them pyridoxamine, an active form of Vitamin B6, AGE-breaker compounds, glucosamine, rutin and derivatives, soluble RAGE isoforms, and statins). In experimental animal models, these drugs are effective in reducing diabetic complications due to AGE formation; however, further study is necessary before their extensive use in the clinical setting.
Infection following Bone Tumor Resection and Reconstruction with Tumoral Prostheses: A Literature Review
Authors: Graci C. , Maccauro G. , Muratori F. , Spinelli M.S. , Rosa M.A. , Fabbriciani C.
Published: January 2017

Bone resection is the choice treatment of malignant bone tumors. Tumor prosthesis is one of the most common solutions of reconstruction following resection of bone tumor located to the metaphysis of long bones. Periprosthetic infections are a frequent complication of limb-salvage surgery which is largely due to prolonged and repeated surgeries, as well as to the immunocompromised condition of these patients due to neoplastic treatment. Furthermore, the large exposure of tissues during this type of surgery and the dissection across vascular distributions also contributes to the high risk of infection. The authors reviewed the literature discussing the incidence of infections of tumor prosthesis implanted following resection of bone tumors, taking into account the different sites of implantation. In the English literature, the highest risk of infection which led to limb amputation was observed after proximal tibia resection and this difference was considered to be due to the poor condition of soft tissue and also after pelvic resection due to huge dead space after sarcoma resection not filled by implant. Independent of the location, the management of infected prosthesis is similar. That is, after one or more attempts at debridement and antibiotic therapy, it consists of implant removal and insertion of a new implant in a one- or two-stage procedure, with a decreased risk of failure with the two-stage procedure.
Luteolin and Thiosalicylate Inhibit HGCL2 and Thimerosal-Induced VEGF Release from Human Mast Cells
Authors: Asadi S. , Zhang B. , Weng Z. , Angelidou A. , Kempuraj D. , Alysandratos K.D. , Theoharides T.C.
Published: January 2017

HgCl2 is a known environmental neurotoxin, but is also used as preservative in vaccines as thimerosal containing ethyl mercury covalently linked to thiosalicylate. We recently reported that mercury chloride (HgCl2) can stimulate human mast cells to release vascular endothelial growth factor (VEGF), which is also vasoactive and pro-inflammatory. Here we show that thimerosal induces significant VEGF release from human leukemic cultured LAD2 mast cells (at 1 μM 326±12 pg/106 cells and 335.5±12 pg/106 cells at 10 μM) compared to control cells (242±21 pg/106 cells, n=5, p<0.05); this effect is weaker than that induced by HgCl2 at 10 μM (448±14 pg/106 cells) (n=3, p<0.05). In view of this finding, we hypothesize that the thiosalicylate component of thimerosal may have an inhibitory effect on VEGF release. Thimerosal (10 μM) added together with the peptide Substance P (SP) at 2 μM, used as a positive control, reduced VEGF release by 90%. Methyl thiosalicylate (1 or 10 μM) added with either SP or HgCl2 (10 μM) inhibited VEGF release by 100%, while sodium salicylate or ibuprofen had no effect. Pretreatment for 10 min with the flavonoid luteolin (0.1 mM) before HgCI2 or thimerosal completely blocked their effect. Luteolin and methyl thiosalicylate may be useful in preventing mercury-induced toxicity.
Effects of TNF-α and IL-1β on the Activation of Genes Related to Inflammatory, Immune Responses and Cell Death in Immortalized Human HaCat Keratinocytes
Authors: Nisticò S. , Paolillo N. , Minella D. , Piccirilli S. , Rispoli V. , Giardina E. , Biancolella M. , Chimenti S. , Novelli G. , Nisticò G.
Published: January 2017

The present experiments were designed to characterize by microarray analysis the transcriptional responses of human keratinocytes (HaCat) to TNF-α and IL-1β, given alone or in combination, in order to better understand the mechanisms underlying inflammatory, immune responses and cell death in which both cytokines play a pathophysiological role. Significant differences in the percentage and quality of genes dysregulated by TNF-α and IL-1β were shown. Both cytokines activated a series of genes involved in inflammatory, immune response as well as in cell death. In our experimental conditions, TNF-α, in contrast to IL-1β, did not induce a significant level of apoptosis in keratinocytes. However, given together both cytokines produced a significant decrease in apoptotic cells and synergistic transcriptional response which was due to the activation of several specific genes occurring after application of each cytokine. TNF-α and IL-1β evoked apoptotic effect and transcriptional responses were linked to the stimulation of their specific receptors since a pre-treatment with monoclonal antibodies vs TNF-α and/or IL-1β receptors was able to significantly reduce them.
Cafeteria Diet Increases Prostaglandin E2 Levels in Rat Prostate, Kidney and Testis
Authors: Brunetti L. , Leone S. , Chiavaroli A. , Orlando G. , Recinella L. , Ferrante C. , Di Nisio C. , Verratti V. , Vacca M.
Published: January 2017

Nutrient composition, particularly the omega-6/omega-3 polyunsaturated fatty acids ratio, may differently affect inflammatory mediators production in tissues, which could be causally related to increased cancer incidence in obesity. We evaluated prostaglandin E2 levels in male Wistar rat prostate, kidney and testicle tissues after 15 days of either a high fat, cafeteria-style diet (5.50 Kcal/g, 30% calories from fat, omega-6/omega-3 ratio 2.33) or a standard laboratory chow diet (3.35 Kcal/g, 3% calories from fat, omega-6/omega-3 ratio 0.56). In the cafeteria diet compared to standard laboratory diet rats, we found both an increase in weight gain and increased prostaglandin E2 (PGE2) levels in prostate, kidney and testicle tissues. The increased levels of PGE2 induced by the cafeteria diet could drive an inflammatory process leading to increased incidence of prostate, kidney and testicular cancer in overweight patients.
Ethyl Pyruvate Therapy Attenuates Experimental Severe Arthritis Caused by Type II Collagen (CII) in the Mouse (CIA)
Authors: Di Paola R. , Mazzon E. , Galuppo M. , Esposito E. , Bramanti P. , Fink M.P. , Cuzzocrea S.
Published: January 2017

This study tested the hypothesis that ethyl pyruvate (EP), a simple aliphatic ester with anti-inflammatory effects, can reduce type II collagen-induced mouse arthritis (CIA). DBA/1J mice were used for the study, developing erosive hind paw arthritis when immunized with CII in an emulsion in complete Freund's adjuvant (CFA). The incidence of CIA was 100% by day 28 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period with radiographic evaluation revealing focal resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint margins. EP-treatment (40 mg/kg/day i.p.) starting at the onset of arthritis (day 25) ameliorated the clinical signs at days 26–35 and improved histological status in the joint and paw. Immunohistochemical analysis for nitrotyrosine, poly (ADP-ribose) (PAR), inducible nitric oxide synthase (iNOS) revealed a positive staining in inflamed joints from mice subjected to CIA, while no staining was observed for HO-1 and Nrf-2 in the same group. The degree of staining for nitrotyrosine, PAR, iNOS, was significantly reduced in CII-challenged mice treated with the EP. Immuno-positive-staining for HO-1 and Nrf-2 was observed instead, in joints obtained from the EP-treated group. Plasma levels of TNF-α, IL-6 and the joint tissue levels of macrophage inflammatory protein (MlP)-1α and MIP-2 were also significantly reduced by EP treatment. Thirty-five days after immunization, EP-treatment significantly increased plasma levels of IL-10. These data demonstrate that EP treatment exerts an anti-inflammatory effect during chronic inflammation and is able to ameliorate the tissue damage associated with CIA.
Effects of Toluidine Blue-Mediated Photodynamic Therapy on Periopathogens and Periodontal Biofilm: In Vitro Evaluation
Authors: Nastri L. , Donnarumma G. , Porzio C. , De Gregorio V. , Tufano M.A. , Caruso F. , Mazza C. , Serpico R.
Published: January 2017

Photodynamic therapy (PDT) is a selective modality of killing targeted cells, mostly known for its application in neoplasms. PDT can be considered to be an alternative method for the elimination of periodontal bacteria from the pocket without harms for the resident tissues. Therefore, PDT may replace systemic antibiotics and enhance the effect of mechanical treatments of periodontal defects. This effort focused on the in vitro sensitization of periopathogens ( Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum and Prevotella intermedia) Toluidine Blue mediated and on the use of a Diode laser emitting source. The objective of this research was to evaluate the bactericidal in vitro effect of laser diodes 830 nm (as the light source) after photosensitization with Toluidine Blue (TBO) on the following periopathogenic bacteria: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum and Prevotella intermedia. After evaluating the effect on the single bacterial strain, the ability of Diode Laser to disrupt the structure of biofilms produced by A. actinomycetemcomitans after photosensitization with TBO was also analyzed. The study suggests that the association of TBO and diode laser light 830 nm is effective for the killing of bacteria strains and determines the photoinactivation of Aggregatibacter biofilms. In summary, photodynamic therapy has effectively shown its capabilities and, therefore, it can be considered a valid alternative approach to antimicrobial therapy of periodontitis.
Psoriasis Relapse Evaluation with Week-End Cyclosporine a Treatment: Results of a Randomized, Double-Blind, Multicenter Study
Authors: Colombo D. , Cassano N. , Altomare G. , Giannetti A. , Vena G.A.
Published: January 2017

Cyclosporine A (CsA) effectively controls psoriasis, however, its long-term continuous use is not recommended. This study aims to evaluate the efficacy and tolerability of week-end CsA microemulsion for the reduction of relapse rate in patients with chronic plaque psoriasis who had achieved clinical remission following continuous CsA therapy. The PREWENT (Psoriasis Relapse Evaluation with Week-End Neoral Treatment) study was a 24-week, randomized, double-blind, multicenter study, carried out in 22 Italian hospital or university Dermatology units. CsA was discontinued for 8 days previous to the patients being randomized to oral CsA 5 mg/kg/day or placebo for two consecutive days/week, for a total period of 24 weeks. The primary endpoint was clinical success rate at week 24, defined as the proportion of patients with no clinical worsening (no relapse or a Psoriasis Area and Severity Index [PASI] <75% of pre-treatment PASI). A total of 162 patients were randomized to CsA and 81 to placebo. Clinical success rates at 24 weeks were 66.9% and 53.2% with CsA and placebo, respectively (p = 0.072). Time to first relapse was significantly prolonged with CsA versus placebo (p = 0.023), and PASI was significantly lower from weeks 4 to 16 in CsA recipients. In patients with moderate-severe psoriasis, the clinical success rate was significantly increased with CsA compared to placebo (69.9% vs 46.3%; p = 0.011), and significantly lower increases in PASI were observed from week 4 to week 24 (p < 0.05 vs placebo). CsA was well tolerated, with no differences in mean blood creatinine or blood pressure between CsA and placebo recipients. However, the high withdrawal rate (22.2% of randomized patients), which was not related to side effects, may have led to an overestimation of efficacy, but the study had a good statistical power (88% greater than that observed in similar studies, i.e. 80%). Week-end CsA administration was shown to prolong safely and effectively the time to first relapse in psoriasis patients.
The Clinical Impact of a Cardiologic Follow-up in Breast Cancer Survivors: An Observational Study
Authors: Gallucci G. , Coccaro M. , Storto G. , Lapadula L. , Tartarone A. , Nappi A. , Cammarota A. , Buonerba C. , Di Lorenzo G. , Fusco V. , Aieta M.
Published: January 2017

Anthracycline-containing chemotherapy (A-CHT) can induce late cardiotoxicity adding a considerable burden to cardiovascular risk. Irradiation of left breast cancer has also been associated to an increased risk of cardiovascular disease. The aim of this observational study is to prove the usefulness of an accurate cardiovascular evaluation in left breast cancer survivors treated with radiotherapy (RT) and A-CHT. Patients with left breast cancer, on follow-up after treatment with A-CHT plus RT in an adjuvant setting, were eligible for this observational study. Patients underwent cardiovascular assessment with myocardial perfusion imaging. Thirty patients were enrolled in the study: mean age at diagnosis 55.8 years; stage: I/III; Er and/or pgR status: positive in 24/30 pts; 3 patients in pre-menopausal status. Twenty-two patients (73.3%) had normal perfusion imaging, 1 patient (3.3%) had a fixed myocardial perfusion defect, 7 patients (23.3%) had reversible myocardial perfusion defects; 1 patient (3%) with normal perfusion scan showed depressed rest and stress LVEF. Only 1 patient had a large defect and underwent coronary angiography and percutaneous coronary intervention. Five patients with small defect showed normal coronary arteries at Multislice Computed Tomography. Cardiovascular follow-up may reveal signs of A-CHT or RT-induced cardiotoxicity. A stress test combined with MPI- and GATED-derived data of ventricular systolic performance after stress can give information on the coronary reserve and the contractile reserve and allow early appropriate treatment.
Streptococcus Mutans and Streptococcus Sobrinus are Able to Adhere and Invade Human Gingival Fibroblast Cell Line
Authors: Berlutti F. , Catizone A. , Ricci G. , Frioni A. , Natalizi T. , Valenti P. , Polimeni A.
Published: January 2017

Streptococcus mutans and Streptococcus sobrinus, the principal etiologic agents of caries decay of teeth, are generally acquired in oral cavity at the moment of tooth eruption. However, as S. mutans has been detected in oral cavity of predentate children, the eruption of teeth seems not to be a necessary prerequisite, suggesting that this species may be not confined to dental plaque. Here, we evaluate the ability of S. mutans and S. sobrinus in planktonic and biofilm lifestyle to adhere, invade and survive within human gingival fibroblast (HGF-1) cells. Planktonic and biofilm streptococci adhered and invaded host cells to different extents, showing higher efficiencies of biofilm than planktonic counterparts. Moreover, planktonic and biofilm streptococci showed the same percentage of survival within host cells. Transmission electron and confocal microscopy observations confirmed intracellular localization of planktonic and biofilm bacteria. The adhesion, invasion and survival abilities within human oral cells may be considered S. mutans and S. sobrinus virulence mechanisms to colonize and persist in the oral cavity in the absence of tooth surface.
Severe Giant Cell Arteritis Associated with Essential Thrombocythaemia
Authors: Montalto M. , Biolato M. , Gallo A. , Racco S. , Marrone G. , Manna R. , Grieco A. , Gasbarrini G.
Published: January 2017

Giant-cell arteritis (GCA) is a chronic vasculitis of the elderly usually involving the ophthalmic arteries, which can result in visual loss. High platelet counts may have some pathogenic significance in the obstruction of the ophthalmic circulation and a few cases of associated essential thrombocythaemia and GCA have been described. Here we report a case of severe temporal arteritis associated with essential thrombocythaemia.
Paraneoplastic Sensitive Neuropathy Associated with Anti-Hu Antibodies in a Neuroendocrine Tumor of Duodenum: A Case Report
Authors: Nappi L. , Formisano L. , Damiano V. , Matano E. , Bianco R. , Tortora G.
Published: January 2017

Paraneoplastic sensitive neuropathy is one of the most common presentations among a group of cancer-related disorders known as Paraneoplastic Neurological Syndromes (PNS). PNS likely have an autoimmune etiology since they have been associated with the presence of antibodies against neuronal antigens expressed by tumor cells (such as anti-Hu, anti-Ri and anti-Yo). The tumors most frequently associated with PSN and onconeural antibodies are lung cancer, lymphomas and gynaecological tumors; however, they have also been described in other tumors. We report, for the first time, a case of neuroendocrine tumor of duodenum and PNS associated with anti-Hu antibodies. Moreover, we analyze and discuss the clinical implications that PNS and anti-Hu could have in patients with tumors.