bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement of Clinical Response in Allergic Rhinitis Patients Treated with an Oral Immunostimulating Bacterial Lysate: In Vivo Immunological Effects
Authors: Banche G. , Allizond V. , Mandras N. , Garzaro M. , Cavallo G.P. , Baldi C. , Scutera S. , Musso T. , Roana J. , Tullio V. , Carlone N.A. , Cuffini A.M.
Published: January 2017

Allergic rhinitis is known to be one of the most common chronic diseases in the industrialized world. According to the concept that allergic rhinitis patients generally suffer from an immune deficit, in order to stimulate specifically or aspecifically their immune system, immunomodulating agents from various sources, such as synthetic compounds, tissue extracts or a mixture of bacterial extracts, have been used. The aim of the present trial is to evaluate the efficacy of the treatment with an immunostimulating vaccine consisting of a polyvalent mechanical bacterial lysate (PMBL) in the prophylaxis of allergic rhinitis and subsequently to analyze its in vivo effects on immune responses. 41 allergic rhinitis patients were enrolled: 26 patients were randomly assigned to the group for PMBL sublingual treatment and 15 others to the group for placebo treatment. For all 26 patients blood samples were drawn just before (T0) and after 3 months of PMBL treatment (T3) to evaluate plasma IgE levels (total and allergen-specific) and the cytokine production involved in the allergic response (IL-4, IFN-γ). The results of our study indicate that PMBL is effective in vivo in the reduction or in the elimination of the symptoms in rhinitis subjects during the treatment period in comparison to a non-immunostimulating treatment. A significant and clinically relevant improvement was found in 61.5%, a stationary clinical response was registered in 38.4% and no negative side effects associated with the medication or worsening were recorded. At the end of a 3-month follow up period the clinical picture remained the same as that observed at T3. PMBL treatment did not affect the serum IgE levels (either total or allergen-specific) and did not induce significant changes in IFN-γ concentration. In contrast, PMBL therapy may be accompanied, in some patients, by a potential immunomodulating activity by decreasing IL-4 cytokine expression.
IL-8 and pH Values in Exhaled Condensate after Antibiotics in Cystic Fibrosis Children
Authors: Bodini A. , D'Orazio C. , Peroni D.G. , Corradi M. , Zerman L. , Folesani G. , Assael B.M. , Boner A.L. , Piacentini G.L.
Published: January 2017

Interleukin (IL)-8 is a major factor in inflammatory response and the IL-8 levels in exhaled breath condensate (EBC) may be used as a marker of airway inflammation. Airway acidification is implicated in the pathophysiology of obstructive airway diseases and pH EBC values have been used as a marker of airway acidification. The aim of our study is to investigate whether IL-8 and pH levels in EBC of cystic fibrosis (CF) children with respiratory exacerbations change after antibiotic treatment. Lung function, IL-8 and pH EBC values were measured in fifteen CF children (mean age 11 years) with acute exacerbation before (T0) and after two weeks (T1) of antibiotic treatment. IL-8 and pH values were compared by paired t-test. A p<0.05 was considered significant. IL-8 EBC levels decreased after antibiotic treatment (TO 0.36±0.03pg/ml vs T1 0.28±0.03pg/ml; p=0.03) and pH values increased (TO 7.3610.09 vs T1 7.61±0.08; p=0.04). Results suggest possible application of EBC as a non-invasive tool to monitor efficacy of antibiotic treatment in CF patients.
Molecular Characterization of Virulence Determinants of Stenotrophomonas Maltophilia Strains Isolated from Patients Affected by Cystic Fibrosis
Authors: Di Bonaventura G. , Prosseda G. , Del Chierico F. , Cannavacciuolo S. , Cipriani P. , Petrucca A. , Superti F. , Ammendolia M.G. , Concato C. , Fiscarelli E. , Casalino M. , Piccolomini R. , Nicoletti M. , Colonna B.
Published: January 2017

Stenotrophomonas maltophilia is an emerging nosocomial bacterial pathogen which is currently isolated with increasing frequency from the airways of cystic fibrosis (CF) patients. In this study 13 S. maltophilia strains (11 isolated from the airways of independent CF patients, and two non-CF respiratory reference strains) have been characterized for the expression of several virulence-associated factors. In particular, the ability to form biofilm on abiotic surfaces has been determined and correlated with different features, such as motility, adherence and the ability to invade A549 respiratory epithelial cells. Moreover, the presence of a flagellum-associated gene as well as that of the StmPr1 gene, which encodes an extra-cellular protease, have been determined by Southern blot hybridization. Our data indicate that the different degree of biofilm formation exhibited by the 11 CF isolates does not correlate with motility, ability to adhere to and invade A549 cells, or with the presence of flagella. On the other hand, among the CF isolates the StmPr1 gene was found only in two strains, both able to establish chronic lung infections in CF patients. Moreover, only four of the strains analyzed show a temperature-independent antibiotic-resistance profile, suggesting either a different origin of these strains or an intervening adaptation to host tissues.
Re-Induction as a Possible Alternative Modality of Dose Escalation of Infliximab: A Prospective Evaluation in a Small Series of Psoriatic Patients
Authors: Cassano N. , Guerra A. Puglisi , Malara C. , Loconsole F. , Galluccio A. , Pezza M. , Vena G.A.
Published: January 2017

Infliximab is an anti-tumour necrosis factor-alpha chimeric monoclonal antibody which is highly effective in psoriasis, as well as in other indications. In clinical practice, some patients may require dose escalation to overcome a reduction of the extent and/or duration of response during regular maintenance treatment, possibly due to the loss of stable serum concentrations of the drug. Common strategies of dose escalation are the increase of dose per infusion and the decrease of interval between infusions. Here we report the results of re-induction therapy with infliximab used as a dose escalation strategy in 9 patients whose psoriasis relapsed during maintenance treatment with infliximab 5 mg/kg every 8 weeks. Re-induction was well tolerated and capable of restoring response in 8 of these patients.
B Cell-Ablative Therapy: Where are We Now?
Authors: Bordron A. , Mankaï A. , Bendaoud B. , Saraux A. , Devauchelle V. , Ghedira I. , Jamin C. , Pers J.C. , Berthou C. , Youinou P.
Published: January 2017

Based on their multifaceted functions, B cells participate in several pathological settings such as lymphoproliferative disorders, autoimmune diseases and graft rejection. B cell-ablative therapy has thus emerged as a mainstay in these diseases. A number of anti-B cell antibodies (Abs) have been generated, among which anti-CD20 Abs appear to be efficient. Rituximab (RTX) is one of these anti-CD20 monoclonal Abs. Originally approved for the treatment of non-Hodgkin lymphoma, RTX is now being administered in other malignant proliferations, applied to an increasing number of autoimmune diseases and required to prevent rejection of a graft. Although this medication is remarkably safe, a handful of laboratory tests have been proposed to monitor RTX-treated patients. The efficacy in different diseases, and the emergence of new anti-CD20 Abs raise many questions. Thus, their detailed understanding can lead to a better issue for inhibition of immune responses.
Azithromycin May Reduce Cholestasis in Primary Sclerosing Cholangitis: A Case Report and Serendipitous Observation
Authors: Boner A.L. , Peroni D. , Bodini A. , Delaini G. , Piacentini G.
Published: January 2017

The newer macrolides have been shown to exert additional anti-inflammatory effects. We report the possible effect of azithromycin on primary sclerosing cholangitis in a patient treated with the drug for severe asthma. A 45-year-old woman with Crohn's disease and primary sclerosing cholangitis, also suffering from severe asthma, was treated with azithromycin 500 mg OD for 3 consecutive days a week because of the clinical suspicion of bronchiectasis and the severity of her asthma. When the therapy was discontinued, her urine again became darker, pruritus reappeared with the usual severity and laboratory parameters, evaluated after 6 weeks without azithromycin, also worsened. For these reasons macrolide treatment was re-established. Cholestasis-related symptoms and the dark colour of the urine were again reduced 6 weeks later and laboratory parameters were again reversed. We are therefore tempted to speculate that azithromycin may have an effect on primary sclerosing cholangitis on the basis of its anti-inflammatory properties.
Lymphoepithelioma-like Carcinoma of the Skin
Authors: Cavalieri S. , Feliciani C. , Massi G. , Addolorato G. , Gasbarrini G. , Amerio P. , Rotoli M.
Published: January 2017

The term lymphoepithelioma-like carcinoma identifies a group of nasopharingeal epithelial tumors characterized by aggregates of malignant undifferentiated cells surrounded by a dense reactive lymphoplasmacellular infiltrate. Primary cutaneous localization is rare, with approximately 30 cases reported in literature. We describe a case of primary lymphoepithelioma-like carcinoma of the skin in a 92-year-old woman. Immunohistochemical examination was positive for cytokeratine (KL1 and EMA) as regards epithelial cells, while the lymphocitic infiltrate was positive for LCA and CD3. In situ hybridization for Epstein Barr virus in tumor cells was negative. Electron microscopy showed rounded and occasionally spindle-shaped poorly-differentiated squamous epithelial cells, and a lymphoid stroma consisting mostly of normal-appearing small lymphocytes. Examination of the nasopharynx did not show any tumoral mass and after a 7 years follow-up the patient is free of local and distant recurrences. This tumor affects people aged over 50 years and is localized to the face, but scalp, shoulder and forearm may be involved. Research of Epstein-Barr virus is always negative in this tumor, unlike nasopharingeal epithelial carcinoma. The differential diagnosis of lymphoepithelioma-like carcinoma of the skin may present some difficulties and includes squamous cell carcinoma. Lymphoepithelioma-like carcinoma of the skin is a malignant neoplasm which tends to relapse locally and has a moderate tendency to metastatize.
Anti-TNF-α Treatment and Bile Duct Drainage Restore Cellular Immunity and Prevent Tissue Injury in Experimental Obstructive Jaundice
Authors: Padillo F.J. , Cruz A. , Segura-Jiménez I. , Ruiz-Rabelo J. , Vázquez-Ezquerra M.R. , Perea-álvarez M.D. , Peña J. , Briceño J. , Muntané J.
Published: January 2017

Several experimental studies of obstructive jaundice (OJ) have shown the presence of immunosuppressive state associated with the rise of tumor necrosis factor-α (TNF-α) concentration in plasma. The present study evaluates the impact of anti-TNF-α administration or bile duct drainage on the inflammatory response, liver injury and renal insufficiency in obstructed rats. OJ was induced by the ligation of bile duct in Wistar rats. The parameters were determined at 14 and 21 days after OJ. Two additional groups of animals were treated with anti-TNF-α antibodies or submitted to bile duct drainage at 14 days, and sacrificed 21 days after OJ. Cholestasis decreased glucose, and enhanced urea, Creatinin, bilirubin and transaminases. Cholestasis increased the number of different inflammatory cells (T and B lymphocytes, and monocytes-macrophages) but reduced the expression of the corresponding cellular activation markers. This low responsiveness of the inflammatory cells was related to a decreased free radical production and phagocytic activity of cells. Anti-TNF-α and bile duct drainage reduced tissue injury, and prevented the reduction of the number and activity of T lymphocytes and phagocytic cells observed at the advanced stages of cholestasis. In conclusion, anti-TNF-α and bile duct drainage improved cell immunodeficiency, and reduced liver injury, cholestasis and renal insufficiency in experimental OJ.
A New Diagnostic Approach to Better Identify Antiphospholipid Syndrome
Authors: Faricelli R. , Esposito S. , Toniato E. , Flacco M. , Conti P. , Martinotti S. , Robuffo I.
Published: January 2017

Antiphospholipid syndrome is an autoimmune disorder in which the body produces antibodies to its own phospholipids or plasma proteins. Antiphospholipid syndrome (APS) is associated with many pathologies with several clinical manifestations. It can occur as a primary disorder or may be secondary to connective tissue disorder or tumor. Anti-phospholipid antibodies were detected in two categories of patients: in one group with many clinical manifestations (such as thrombotic events, thrombocytopenia and miscarriages) and in the other group with few clinical manifestations. In the first group high levels of IgG and IgA antibodies resulted, in the other group low levels of IgM. The ratio male:female was 1:3.5. Out of the 700 patients examined, 12 resulted positive for anti-cardiolipin (aCL) and aβ2-GPI (affected by APS), and 15 patients positive for aCL (with middle-high values) but negative for aβ2-GPI. At this point, according to the guidelines, we could have stopped examining. Only by continuing diagnostic investigation for these 15 patients has it been possible to observe:2 patients positive for anti-thrombin (important first marker in the diagnosis of venose and arterial thromboses), anti-phosphatidylserine and anti-phosphatidylinositol (markers for cerebral diseases and recurrent miscarriages); 1 patient positive for anti- phosphatidylserine; 1 patient positive for anti-phosphatidylinositol antibody; 1 patient positive for both anti-phosphatidylserine and anti-phosphatidylinositol; 10 patients positive only for anti-cardiolipin. According to the results obtained, and considering that a more accurate investigation permitted to better identify APS syndrome, we propose a new diagnostic procedure.
Potential Role of Culture Mediums for Successful Isolation and Neuronal Differentiation of Amniotic Fluid Stem Cells
Authors: Orciani M. , Emanuelli M. , Martino C. , Pugnaloni A. , Tranquilli A.L. , Di Primio R.
Published: January 2017

In recent years, the use of stem cells has generated increasing interest in regenerative medicine and cancer therapies. The most potent stem cells derive from the inner cell mass during embryonic development and their use yields serious ethical and methodological problems. Recently, a number of reports suggests that another suitable source of multipotent stem cells may be the amniotic fluid. Amniotic fluid mesenchymal stem cells (AFMSCs) are capable of extensive self-renewal, able to differentiate in specialized cells representative of all three germ layers, do not show ethical restriction, and display minimal risks of teratomas and a very low immunogenity. For all these reasons, amniotic fluid appears as a promising alternative source for stem cell therapy. Their recent discovery implies a lack of knowledge of their specific features as well as the existence of a protocol universally recognized as the most suitable for their isolation, growth and long-term conservation. In this study, we isolated stem cells from six amniotic fluids; these cells were cultured with three different culture mediums [Mesenchymal Stem Cell Medium (MSCGM), PC-1 and RPMI-1640], characterized by cytofluorimetric analysis, and then either frozen or induced to neuronal differentiation. Even if the immunophenotype seemed not to be influenced by culture medium (all six samples cultured in the above-mentioned mediums expressed surface antigens commonly found on stem cells), cells showed different abilities to differentiate into neuron-like cells and to re-start the culture after short-long-term storage. Cells isolated and cultured in MSCGM showed the highest proliferation rate, and formed neuron-like cells when sub-plated with neuronal differentiation medium. Cells from PC-1, on the contrary, displayed an increased ability to re-start culture after short-long term storage. Finally, cells from RPMI-1640, even if expressing stem cells markers, were not able to differentiate in neuron-like cells. Further studies are still needed in order to assess the effective role of culture medium for a successful isolation, growth, differentiation and storage of AFMSCs, but our data underline the importance of finding a universally accepted protocol for the use of these cells.
Inhaled Thiamphenicol and Acetilcysteine in Children with Acute Bacterial Rhinopharyngitis
Authors: Varricchio A. , Capasso M. , Di Gioacchino M. , Ciprandi G.
Published: January 2017

Antibiotic abuse for treating rhinopharyngitis induces the occurrence of resistant bacteria. As topical drugs might reduce this phenomenon, the aims of our study are to evaluate inhaled thiamphenicol associated with acetylcysteine in children with acute bacterial rhinopharyngitis and to compare it with the use of saline solution. The trial was conducted as randomized, parallel group, and single blind. Children, aged 3–6 years, with acute bacterial rhinopharyngitis were treated with aerosolized thiamphenicol associated with acetylcysteine (250 mg: ½ vial in the morning and ½ vial in the evening) (Group A) or saline solution twice daily (Group B), both of them for 5 days. Both treatments were administered using a new device: Rinowash. The following parameters were assessed: nasal obstruction, mucopurulent rhinorrhea, post-nasal drip, cough, sore throat, fever, and cultures. Of 104 patients screened, 90 children, median age 3.7 years (44 females and 46 males), completed the study: 60 in Group A and 30 in Group B. Actively-treated children achieved a significant improvement of all parameters, but fewer than the control group. In conclusion, inhaled thiamphenicol associated with acetylcysteine may represent a valid treatment for acute bacterial rhinopharyngitis in children, as it is effective, safe, economic, and simple to use.
Prevalence of Atopic Symptoms among Blood Donor Carriers of Mannose-Binding Lectin Variant Alleles
Authors: Cardinale F. , Chinellato I. , Marseglia G.L. , Nettis E. , Polizzi A. , Loffredo M.S. , Santostasi T. , Tesse R. , Trerotoli P. , Di Monte D. , Armenio L.
Published: January 2017

Mannose-binding lectin (MBL) is a C-type soluble collectin involved in the innate immune response. Carriers of MBL gene variant alleles (MBLva) have decreased plasma concentrations of MBL and increased susceptibility to bacterial and viral infections. The aim of the present study is to test the hypothesis that carriers of MBLva could have a different frequency of atopic symptoms as compared to wild-type carriers. A total of 385 consecutively enrolled Caucasian blood donors were studied. Blood specimens underwent genomic analysis and genotyping for MBLva by polymerase chain reaction (PCR). MBLva carrier status was associated with a reduced frequency of allergic rhinitis (OR 0.41 [95% CI 0.2 to 0.8], χ2= 6.98, p=.008). No relationship was found between MBLva carrier status and asthma or atopic skin symptoms. MBLva might be one of the host-related genetic factors involved in atopic disorders, namely allergic rhinitis.
N-Oleoyl-Dopamine Decreases Muscle Rigidity Induced by Reserpine in Rats
Authors: Konieczny J. , Przegaliński E. , Pokorski M.
Published: January 2017

N-oleoyl-dopamine (OLDA), a product of condensation of oleic acid and dopamine (DA), is a bioactive compound that crosses the blood-brain barrier after systemic administration. The possibility arises that OLDA could have a potential role in treating DA-related disorders, such as Parkinson's disease (PD). In the present study we seek to determine whether OLDA would affect muscle tone and akinesia in two rat models of PD: the reserpine-evoked muscle rigidity and the reserpine- and haloperidol-induced catalepsy. We found that OLDA (20 mg/kg) significantly decreased muscle rigidity induced by reserpine (2.5 mg/kg), measured as an increased mechanical muscle resistance (MMG) in response to a passive extension and flexion of a rat hind limb at the ankle joint. Moreover, OLDA potently decreased the reserpine-enhanced tonic and reflex electromyographic (EMG) activities recorded before and during the movement, respectively. A lower dose of OLDA (10 mg/kg) failed to have appreciable effects. The reference compound L-DOPA (25 mg/kg) also attenuated the reserpine-increased MMG and EMG activities; the effects were, however, observed much later and were less prominent than those characteristic of OLDA. In contrast to the effects on muscle tone, OLDA (20 and 40 mg/kg) did not influence catalepsy induced by either reserpine (1.25 mg/kg) or haloperidol (0.5 mg/kg). In conclusion, the study demonstrates a novel biological action of N-oleoyl-dopamine consisting of lowering the reserpine-induced muscle rigidity. However, the lack of influence on akinesia suggests that the compound has myorelaxant rather than anti-Parkinsonian properties.
CXCR4+FOXP3+CD25+ Lymphocytes Accumulate in CXCL12-Expressing Malignant Pleural Mesothelioma
Authors: Shimtzu Y. , Dobashi K. , Imai H. , Sunaga N. , Ono A. , Sano T. , Hikino T. , Shimizu K. , Tanaka S. , Ishizuka T. , Utsugi M. , Mori M.
Published: January 2017

CXCL12 is a chemokine that binds to a G-protein-coupled receptor (CXCR4). CXCL12 is expressed in various tumors and is considered as playing an important role in tumor growth and invasion. The aim of this study is to investigate the expression of CXCL12 in human malignant mesothelioma (MM), the chemotactic effect of CXCL12 derived from MM, and the expression of CXCR4 in MM tissues in relation to regulatory T cells. CXCL12 expression was examined by immunostaining of tissue specimens from malignant pleural mesothelioma (MPM) and malignant peritoneal mesothelioma (MPEM). The MM group comprised 6 patients (4 men/2 women, MPM=4, MPEM=2, aged 56.0 ± 12.4 years) and the control (non-mesothelioma) group also had 6 patients (4 men/2 women aged 65.0 ± 6.7 years). CXCL12 mRNA expression was also examined by RT-PCR in MPM cell lines (H28, H2052, and H2058), while CXCR4 mRNA expression was examined by in situ hybridization in MPM tissue. CXCL12 was expressed in the cytoplasm of MM cells from all patients, but was not expressed in the control group. H2052 and H2058 cells expressed CXCL12 mRNA, but H28 cells did not. CXCL12 in MM tissue homogenate supernatant had a chemotactic effect on CXCR4-expressing THP-1 cells. CXCR4 mRNA was expressed by a part of LCA+CD3+ Foxp3+CD25+ T cells that were located adjacent to the border of CXCL12-expressing epithelioid MPM. These findings suggest that CXCL12 contributed to tumor-related inflammation by inducing the accumulation of CXCR4-expressing cells with regulatory T cell markers around MM.
Quantity, Distribution and Immunophenotypical Modification of Dendritic Cells upon Biological Treatments in Psoriasis
Authors: Prignano F. , Ricceri F. , Bianchi B. , Lotti T.
Published: January 2017

Psoriasis is an immune-mediated disease which affects a large world population.

It has long been considered a dermatological disorder in which keratinocytes and lymphocytes play a relevant pathogenic role. The aim of our study is to more closely observe and better define the role of dendritic cells (DCs) in psoriasis. We made a comparative analysis of the antigenic profile and the number, by immunohistochemical and electron microscopical study, of skin biopsy samples from psoriatic patients before and 4 months after biological treatments. Our results demonstrate an abundant distribution of activated DCs in lesional skin of psoriatic plaques and a marked decrease after biological therapies [a decrease of 70% for Langerhans cells (LCs) and mature myeloid dendritic cells (mDCs) and of 50% for plasmocytoid dendritic cells (pDCs)]. Both previous reports and the results of the present study support an underlying persistent immune response involving DCs in the onset and persistence of psoriasis. As DCs play a pivotal role in pathogenesis of psoriasis by presenting antigens via major histocompatibility complex class (MHC) II molecules, the present study supports the view that biological therapies are also effective in clearing psoriatic lesions as well as in reducing the number of DCs.
Imaging Progression despite Clinical Remission in Early Rheumatoid Arthritis Patients after Etanercept Interruption
Authors: Laganà B. , Diamanti A. Picchianti , Ferlito C. , Germano V. , Migliore A. , Cremona A. , Argento G. , David V. , Salemi S. , D'Amelio R.
Published: January 2017

The aim of this preliminary study is to evaluate clinical and imaging response in twenty patients with early Rheumatoid Arthritits (eRA) treated with Etanercept (Etn) + Methotrexate (Mtx) and to investigate whether clinical and MRI remission may be maintained after biological therapy interruption. Assessment included: radiography, Visser score and anti-CCP antibodies at baseline; disease activity score in 44 joints (DAS44), rheumatoid factor (RF), Magnetic Resonance Imaging (MRI) of hands and wrists at baseline (T0), 12 (T1), and 24 months (T2). MRI was scored for synovitis, bone oedema and erosions (OMERACT study); patients who reached clinical and imaging remission at T1 were considered eligible for interrupting Etn. At T1 8/20 (40%) patients showed a total remission [DAS44 from 5 (T0) to 1.4 (T1); p<0.02], whereas the other 12/20 (60%) showed an improvement, without complete remission [DAS44 from 4.8 (T0) to 2.8 (T1); p<0.05]. Etn was therefore interrupted in the first group of patients (group A), whereas it was continued in the other group (group B). At T2, group A maintained clinical remission and group B showed further not significant DAS44 reduction from T1. At T1, a significant reduction in synovitis, bone oedema and total score (p<0.01) was observed both in group A and in group B. At T2, group A showed an increase in all the MRI scores that was significant for the synovitis and total score, whereas group B exhibited a further not significant reduction. This preliminary study reports an excellent clinical and imaging response in eRA patients treated with Etn with total remission in 40% of them after a 1-year therapy period. However, it indicates that joint damage may progress, despite a sustained clinical remission, after Etn suspension
Enhancement of Fibroblast Proliferation, Collagen Biosynthesis and Production of Growth Factors as a Result of Combining Sodium Hyaluronate and Aminoacids
Authors: Mariggiò M.A. , Cassano A. , Vinella A. , Vincenti A. , Fumarulo R. , Muzio L. Lo , Maiorano E. , Ribatti D. , Favia G.
Published: January 2017

Fibroblasts play a key role in tissue healing by producing the majority of extracellular matrix components, favouring granulation tissue formation, and stimulating re-epithelialization. Hyaluronan is a component of ECM and its anti-inflammatory effects and properties in enhancing wound closure are well known. In this study, we examined the effects of Aminogam® gel, a new pharmacological preparation suggested to improve wound healing, composed of hyaluronic acid, proline, lysine, glycine and leucine, on human fibroblasts. Results show that fibroblasts treated with hyaluronic acid plus aminoacid solution increased their proliferative activity, collagen I and III, and fibronectin synthesis. Moreover, HA plus aminoacid solution increased the expression of transforming growth factor beta, connective tissue growth factor, interleukin-6 and −8, assayed by RT-PCR. These results suggested that Aminogam® gel, involved in several stages of wound healing, as fibroblast proliferation, granulation tissue formation, ECM component deposition, and production of cytokines, may be a useful device to favour and accelerate wound closure.
Successful Lamivudine Monotherapy in an Elderly Patient Suffering from HBV-Related Decompensated Cirrhosis Associated with Widespread Leukocytoclastic Vasculitis
Authors: Conca P. , Riccio A. , Tarantino G.
Published: January 2017

Hepatitis B virus (HBV) infection is known to be responsible for both hepatic and extrahepatic manifestations including dermatitis, polyarthralgias and arthritis, pulmonary disease, aplastic anemia, glomerulonephritis and vasculitis. The mechanism of these extrahepatic disorders is thought to be linked to immune complex disease, but their pathogenesis is poorly clarified. Immunosuppressive treatment could promote viral load and impair hepatic disease, also worsening the vasculitis by enhancing viral antigenemia. Lamivudine is a nucleoside analogue approved for treating chronic hepatitis B, that decreases the amount of viral antigens by suppressing HBV replication. Several reports have suggested lamivudine in the treatment of vasculitis associated with HBV infection, but, although significant inhibition of HBV is achieved in the short term, resistance develops in 15–32% annual risk rating. We report an elderly patient whose chronic hepatitis B decompensated cirrhosis with associated refractory hepatic hydrothorax and extensive leukocytoclastic vasculitis was successfully treated with ongoing long-term lamivudine monotherapy.
Detection of Different Borrelia Burgdorferi Genospecies in Serum of People with Different Occupational Risks: Short Report
Authors: Santino I. , Sessa R. , Pantanella F. , Tomao P. , Di Renzi S. , Martini A. , Nicoletti M. , Del Piano M.
Published: January 2017

This study is aimed at applying a previously described PCR-based method to detect B. burgdorferi sensu lato and different Borrelia genospecies in total DNA preparations of serum samples collected from people with different occupational risks for tick bite and with serological evidence of borreliosis. Among the seropositive samples, the PCR for B. burgdorferi confirmed the positivity in 65% of the forestry workers and in 60% of the subjects living in the same area. None of the seronegative subjects belonging to the control group showed the presence of B. burgdorferi sensu lato DNA. Results on genospecies distribution show that B. afzelii was the predominant species, followed by B. garinii and finally by B. valaisiana.
Anti-TNF-α Inhibitors: A New Therapeutic Approach for Inflammatory Immune-Mediated Diseases: An Update upon Efficacy and Adverse Events
Authors: Murdaca G. , Colombo B.M. , Puppo F.
Published: January 2017

The ongoing progresses in the knowledge of the pathogenic mechanisms of various inflammatory or immune-mediated diseases and the availability of innovative biotechnological approaches have lead to the development of new drugs which add to conventional treatments. TNF-α inhibitors (Infliximab, Adalimumab and Etanercept) have demonstrated efficacy either as monotherapy or in combination with other anti-inflammatory or disease modifying anti-rheumatic drugs (DMARDs). The efficacy and safety profile of the TNF-α inhibitors can be considered, in general, as a class effect. Nevertheless, some differences may exist among the three agents. In this paper, we will briefly review the indications for the use of the three TNF-α inhibitors, the pre-treatment considerations and the reported adverse events.
Tumor Necrosis Factor-Alpha Antagonists: Differential Clinical Effects by Different Biotechnological Molecules
Authors: Licastro F. , Chiappelli M. , Ianni M. , Porcellini E.
Published: January 2017

Inhibitors of tumor necrosis factor-alpha (TNF-α) have deeply changed the therapy of several inflammatory human diseases. For instance, clinical management of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis have profoundly benefited after the introduction of new therapeutic tools, such as antagonist of TNF-α molecule. These drugs include etanercept, a soluble TNF-α receptor antagonist, three anti-TNF-α antibodies, adalimumab, infliximab, golimumab and certolizumab a humanized Fab fragment combined with polyethylene glycol. These compounds efficiently inhibit several TNF-α biological- mediated effects, however, they have also shown differential clinical efficacy in several trials from different autoimmune diseases. It is of clinical relevance that non-responders to one of these drugs often positively responded to another. Different mechanisms of action and diversity in pharmacokinetics of these three compounds may partially explain different clinical effects. However, partially diverse pathogentic mechanisms in different diseases also contribute to differential therapeutic responses. Therefore, these apparently homogeneous agents can not be considered equivalent in their clinically efficacy. Differential therapeutic actions of these drugs may be advantageously used in clinical practice and further improve the great potential of individual TNF-α inhibitors.
A New Compound, 1H,8H-Pyrano[3,4-C]Pyran-1,8-Dione, Suppresses Airway Epithelial Cell Inflammatory Responses in a Murine Model of Asthma
Authors: Lee H. , Han A.R. , Kim Y. , Choi S.H. , Ko E. , Lee N.Y. , Jeong J.H. , Kim S.H. , Bae H.
Published: January 2017

Clinical and experimental studies have established eosinophilia as a sign of allergic disorders. Activation of eosinophils in the airways is believed to cause epithelial tissue injury, contraction of airway smooth muscle and increased bronchial responsiveness. As part of the search for new anti-asthmatic agents produced by medicinal plants, the effects of 270 standardized medicinal plant extracts on cytokine-activated A549 human lung epithelial cells were evaluated. After several rounds of activity-guided screening, the new natural compound, 1H,8H-Pyrano[3,4-c]pyran-1,8-dione (PPY), was isolated from Vitex rotundifolia L. To elucidate the mechanism by which the anti-asthmatic responses of PPY occurred in vitro, lung epithelial cells (A549 cell) were stimulated with TNF-α, IL-4 and IL-1β to induce the expression of chemokines and adhesion molecules involved in eosinophil chemotaxis. PPY treatments reduced the expression of eotaxin, IL-8, IL-16 and VCAM-1 mRNA significantly. Additionally, PPY reduced eotaxin secretion in a dose-dependent manner and significantly inhibited eosinophil migration toward A549 medium. In addition, PPY treatment suppressed the phosphorylation of p65 and ERK1/2, suggesting that it can inhibit the MAPK/NF-κβ pathway. To clarify the anti-inflammatory and anti-asthmatic effects of PPY in vivo, we examined the influence of PPY on the development of pulmonary eosinophilic inflammation in a murine model of asthma. To accomplish this, mice were sensitized and challenged with ovalbumin (OVA) and then examined for the following typical asthmatic reactions: an increase in the number of eosinophils in BALF; the presence of Th2 cytokines such as IL-4 and IL-5 in the BALF; the presence of allergen-specific IgE in the serum; and a marked influx of inflammatory cells into the lung. Taken together, our results revealed that PPY exerts profound inhibitory effects on the accumulation of eosinophils into the airways while reducing the levels of IL-4, IL-5, and IL-13 in the BALF. Therefore, these results suggest that PPY may be useful as a new therapeutic drug for the treatment of allergic asthma.
Interferon-γ-Release Assays Detect Recent Tuberculosis Re-Infection in Elderly Contacts
Authors: Ferrara G. , Losi M. , D'Amico R. , Cagarelli R. , Pezzi A.M. , Meacci M. , Meccugni B. , Dori I. Marchetti , Rumpianesi F. , Roversi P. , Casali L. , Fabbri L.M. , Richeldi L.
Published: January 2017

The tuberculin skin test (TST) does not discriminate between recent and remote latent tuberculosis infection (LTBI). This study was carried out to test two interferon-γ (IFN-γ)-based blood assays in recent contacts with high prevalence of remote LTBI. We performed a contact tracing investigation in a nursing home for the elderly, where elderly patients were exposed to a case of pulmonary tuberculosis. TST, QuantiFERON-TB Gold (QFT-G) and T-SPOT.TB (TS.TB) were performed 8 weeks after the end of potential exposure. IFN-γ measurements were recorded and correlation with exposure was evaluated. Twenty-seven (37.5%), 32 (44.4%) and 16 (22.2%) subjects were TST, TS.TB and QFT-G positive, respectively; agreement between TS.TB and QFT-G was good among exposed subjects only (κ=0.915, 0.218 in unexposed, p<0.001). When amounts of IFN-γ were corrected for the number of producing T cells, specific IFN-γ production was significantly different between exposed and unexposed individuals (16.75±5.40 vs 2.33±0.71 IFN-γ IU/1000 SFC, p=0.0001). QFT-G and TS.TB provided discordant results among elderly contacts. Unlike TST, the specific IFN-γ response might discriminate between recent and long-lasting tuberculosis infection.
Abnormal Expression of C3ORF9 Gene in Patients with Myelodysplastic Syndromes
Authors: Karadonta A-V. , Alexandrakis M.G. , Kourelis T.V. , Manola A. , Garlemou K. , Stathakis N.E. , Kyriakou D.
Published: January 2017

Myelodysplastic Syndrome (MDS) cells present genetic instability and dysregulation of the gene C30RF9, which was isolated from an MDS cDNA library and codes for a putative protein. We studied the expression of C30RF9 in MDS syndromes to contribute to the understanding of the pathophysiology of MDS. One hundred and thirty-one patients and 35 healthy controls were involved in our study. Bone marrow aspirates and isolated CD34+ cells were used. Gene expression was estimated by quantitative PCR. C3ORF9 was found to be down-regulated in patients with CMML compared to the controls (p<0.01). There was no difference between RARS and the controls (p=0.1), while increased expression was found in RA, RAEB and RAEB-T (p< 0.01 for all). No mutations or polymorphism were detected in our population. CD34+ cells expressed higher levels of C30RF9 (p<0.01) in patients. The gene expression was correlated to the percentage of + cells in RAEB and RAEB-T (r= 0.64). The altered C30RF9 expression was possibly due to different gene regulation in these patients and/or to the increased CD34+ cells.
Transcription Profile Analysis of Vastus Lateralis Muscle from Patients with Chronic Fatigue Syndrome
Authors: Pietrangelo T. , Mancinelli R. , Toniolo L. , Montanari G. , Vecchiet J. , Fanò G. , Fulle S.
Published: January 2017

Chronic fatigue syndrome (CFS) is a disabling condition characterized by unexplained chronic fatigue that impairs normal activities. Many body systems are affected and etiology has not yet been identified. In addition to immunological and psychological aspects, skeletal muscle symptoms are prominent in CFS patients. In an effort to establish which pathways might be involved in the onset and development of muscle symptoms, we used global transcriptome analysis to identify genes that were differentially expressed in vastus lateralis muscle of female and male CFS patients. We found that the expression of genes that play key roles in mitochondrial function and oxidative balance, including superoxide dismutase 2, were altered, as were genes involved in energy production, muscular trophism and fiber phenotype determination. Importantly, the expression of a gene encoding a component of the nicotinic cholinergic receptor binding site was reduced, suggesting impaired neuromuscular transmission. We argue that these major biological processes could be involved in and/or responsible for the muscle symptoms of CFS.
Analysis of MGMT Promoter Methylation Status on Intraoperative Fresh Tissue Section from Frameless Neuronavigation Needle Biopsy of 25 Patients with Brain Tumor
Authors: Iaccarino C. , Nicoli D. , Serra S. , Froio E. , Pisanello A. , De Berti G. , Ghadirpour R. , Marcello N. , Servadei F. , Carinci F.
Published: January 2017

Formalin fixation under conditions that adversely affected the quality of the DNA, or indeterminant assay, or extensive tumor necrosis can compromise the genetic analysis of a brain bioptic sample. The success of DNA extraction and Methyl Guanine Methyl Transferase (MGMT) promoter methylation testing could be improved by freezing of fresh tumor tissue at the moment of biopsy. To ensure an increased concentration of the DNA samples the withdrawal should be performed in an area with high probability of neoplastic cells. From May 2007 to January 2011 fifty-two frameless neuronavigation brain needle biopsy were performed at the Neurosurgery Unit of the “Arcispedale Santa Maria Nuova” City Hospital of Reggio Emilia. The “image-guided” neuronavigated protocol sampling provided withdrawal specimens highly correlated with neuroimaging characteristics of the lesions. In this study the Authors report the genetic analysis on 24 cases of freezing fresh tissue from brain needle bioptic sample starting from July 2008. The molecular determination of MGMT promoter was assessed with the Nested-Methylation Specific-Polymerase Chain Reaction on fresh or cryopreserved needle bioptic tissue. The genetic characterization was feasible in all the bioptic samples. The MGMT promoter was methylated in eleven patients, including a brain infection. The diagnostic yield of brain biopsy could be increased by the neuronavigated trajectories and the intraoperative frozen sections. In the future the availability of the molecular-genetic characterization of a brain tumor before open surgery will provide important information for the optimal treatment. The MGMT promoter status analysis on needle bioptic fresh tissue could be available also for that patient not eligible for surgical remotion of the tumor.
Assessment of Pain Associated with Insertion Torque of Dental Implants. A Prospective, Randomized-Controlled Study
Authors: Scarano A. , Piattelli A. , Assenza B. , Sollazzo V. , Lucchese A. , Carinci F.
Published: January 2017

This study investigated pain experience following dental implant placement in relation to insertion torque using questionnaires. A total 80 implants were placed in 20 patients. Each patient received 4 implants at different times. One implant was inserted and, then, after 40 days was placed the second implant, after 80 days was placed the third implant and after 120 days was placed the fourth implant. At each time the peri-implant bone levels were evaluated on intraoral radiographs taken with the paralleling technique. The implants were placed with a dynamometric key at 35N, 50N, 65N, 85N. Patients were asked to evaluate their pain experience during surgery, 24 hours after surgery, and at 2 days, 4 days, 1, 2, and 4 weeks after surgery on special pain assessment forms. A separate form was used for each time point. Pain was assessed using a descriptive numerical rating scale of 0 to 10, with 0 indicative of no pain and 10 representing the worst pain imaginable. Patients were instructed that a score of 1 to 3 was indicative of mild pain, 4 to 6 was indicative of moderate pain, and 7 to 10 was indicative of severe pain. A significant correlation pain scores and insertion torque was found between group III and group IV vs group II and group I during surgery, at 24 hours, 2 days, 4 days, 1 week, 2 weeks p⩽0.05. No statistical difference was found between group I vs. group II during surgery, at 24 hours, 2 days, 4 days, 1 week, 2 weeks p⩾0.05. In conclusion, elevated insertion torque values produces pain and resoption of the crestal bone around the implants.
Perioperative Anaphylaxis: Epidemiology
Authors: Caimmi S. , Caimmi D. , Bernardini R. , Caffarelli C. , Crisafulli G. , Pingitore G. , Marseglia G.L.
Published: January 2017

The clinical diagnosis of an anesthesia-related immediate hypersensitivity reaction is a difficult task for clinicians. Anaphylaxis may present as cardiovascular collapse or airway obstruction, associated or not with cutaneous manifestations. Drug hypersensitivity reactions that occur during anesthesia are responsible for significant morbidity and mortality and socio-economic costs. Perioperative anaphylaxis is becoming more common, probably because of the more frequent use of anesthesia and the increasing complexity of the drugs used. However, despite increased awareness of anaphylactic reactions to drugs and compounds used in anesthesia, their incidence remains poorly defined. Moreover, current epidemiological data should be carefully evaluated since the various studies published concerned non-homogeneous populations and gave differing definitions of drug hypersensitivity.
Antibiotic-Coated Nails in Orthopedic and Trauma Surgery: State of the Art
Authors: Nizegorodcew T. , Palmieri G. , Marzetti E.
Published: January 2017

Optimal management of deep infections in orthopedic and trauma surgery is often challenging. Traditional prophylactic and treatment approaches are based on the systemic administration of relatively high doses of antibiotics, which may result in a number of side effects. Furthermore, systemically administered antimicrobials may not reach adequate concentration at the desired site. Finally, traditional approaches are based on two-step protocols, thus delaying definite fixation. In recent years, antibiotic-coated intramedullary nails (ACINs) have been introduced, which offer the advantage of delivering antibiotics locally, thus increasing their local concentrations and length of action. In addition, ACINs offer the great advantage of combining antimicrobial prophylaxis / treatment and stabilization in a single step. Preliminary evidence by small clinical studies appears to support the effectiveness of ACINs in the management of chronic osteomyelitis and infected non-unions, with high rates of infection eradication and bone union. However, randomized clinical trials are needed to definitely establish ACINs' effectiveness and safety.
Angiogenesis in Hand Chondroma: An Immunohistochemical Study
Authors: Ricciardella M.L. , Rossi E. D. , Fadda G. , Graci C. , Spinelli M. S. , Falcone G. , Rosa M.A. , Maccauro G.
Published: January 2017

Hand chondroma is a particular cartilagineous tumour, being clinically benign, but morphologically malignant. This study investigates the expression of VEGF together with other growth factors and proliferation markers such as TGF&bT2, Ki-67, TNF, FGF1, P53 in 8 cases of hand chondroma treated with courettage, in order to define the ethiopathogenesis of this tumour and the clinical significance of the resulting immunohistochemical profile, with particular respect to angiogenesis. VEGF was expressed in all cases; 5 cases were positive for TFGβ2 and 3 for PDGF. None of the other factors was expressed. On the basis of histologic results a specific model of tumour progression based on the indicators of angiogenesis could be related to hand tumours, in which VEGF expression should be the first stadium of the tumour aggressiveness, and the following PDGF, TGF 2 expression should be accompanied with a morphological outline worsening. Nevertheless the non constant expression of these indicators and the absent expression of proliferated indicators can explain the scant tendency to the relapse in presence of accurate curettage. It is important to remember that the cellular polymorphism typical of the cartilaginous tumours does not allow the application of an only oncogenesis model.
Why Glucocorticosteroids Should Remain in the List of Prohibited Substances: A Sports Medicine Viewpoint
Authors: Pigozzi F. , Di Gianfrancesco A. , Zorzoli M. , Bachl N. , Donagh D. Mc , Cummiskey J. , Di Luigi L. , Pitsiladis Y. , Borrione P.
Published: January 2017

In addition to their therapeutic applications, glucocorticosteroids have been widely used and abused in the belief that these substances may enhance athletic performance. Analysis of athlete urine samples by antidoping laboratories around the world support this conclusion. It is commonly accepted in medical practice to use local glucocorticosteroid injections in the treatment of non-infectious local musculotendinous inflammatory conditions conveying symptom relief and often a speedier return to sporting activity. This practice is not to be considered illicit, but sports physicians must accept that such an intervention is not in itself an immediate cure and that an athlete will still require a period of recuperation before continuing sporting activity. How long such a period of recuperation should last is a matter of conjecture and there is little concrete data to support what is, or what is not, an acceptable period of inactivity. In the interest of athlete safety, we would propose to maintain systemic glucocorticosteroids on the World Anti-Doping Agency's (WADA) list of prohibited substances, both in and out-of-competition as well as a mandatory period of 48 hours of rest from play after receiving a local glucocorticosteroid injection.