bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycogen Synthase Kinase-3β Inhibition Attenuates the Development of Bleomycin-Induced Lung Injury
Authors: Cuzzocrea S. , Genovese T. , Mazzon E. , Esposito E. , Muià C. , Abdelrahman M. , Di Paola R. , Bramanti P. , Thiemermann C.
Published: January 2017

Glycogen synthase kinase-3 (GSK-3) is an ubiquitous serine-threonine protein kinase that participates in a multitude of cellular processes and has recently been implicated in the pathophysiology of a number of diseases. The aim of this study is to investigate the effects of TDZD-8, a potent and selective GSK-3β inhibitor, on the development of lung injury caused by administration of bleomycin (BLM). Mice subjected to intra-tracheal administration of BLM developed significant lung injury characterized by marked neutrophil infiltration and tissue edema. An increase in immunoreactivity to nitrotyrosine, iNOS, TNF-α and IL-1β was also observed in the lungs of BLM-treated mice. In contrast, administration of BLM-treated mice with TDZD-8 (1 mg/kg daily) significantly reduced (I) the degree of lung injury, (II) the increase in staining (immunohistochemistry) for myeloperoxidase (MPO), nitrotyrosine, iNOS, TNF-α and IL-1β and (III) the degree of apoptosis, as evaluated by Bax and Bcl-2 immunoreactivity and TUNEL staining. Taken together, these results clearly demonstrate treatment with the GSK-3β inhibitor TDZD-8 reduces the development of lung injury and inflammation induced by BLM in mice.
Metallic Nanoparticles Exhibit Paradoxical Effects on Oxidative Stress and Pro-Inflammatory Response in Endothelial Cells in Vitro
Authors: Peters K. , Unger R.E. , Gatti A.M. , Sabbioni E. , Tsaryk R. , Kirkpatrick C.J.
Published: January 2017

Particulate matter is associated with different human diseases affecting organs such as the respiratory and cardiovascular systems. Very small particles (nanoparticles) have been shown to be rapidly internalized into the body. Since the sites of internalization and the location of the detected particles are often far apart, a distribution via the blood stream must have occurred. Thus, endothelial cells, which line the inner surface of blood vessels, must have had direct contact with the particles. In this study we tested the effects of metallic nanoparticles (Co and Ni) on oxidative stress and proinflammatory response in human endothelial cells in vitro. Exposure to both nanoparticle types led to a concentration-dependent cytotoxic effect. However, the effects on oxidative stress and pro-inflammatory response differed dramatically. Due to the nanoparticle-induced effects, a comparison between metallic nanoparticle- and metal ion-treatment with the corresponding ions was made. Again, divergent effects of nanoparticles compared with the ions were observed, thus indicating differences in the signaling pathways induced by these compounds. These paradoxical responses to different metallic nanoparticles and ions demonstrate the complexity of nanoparticle-induced effects and suggest the need to design new strategies for nanoparticle toxicology.
Apoptic Renal Carcinoma Cells are Better Inducers of Cross-Presenting Activity than Their Primary Necrotic Counterpart
Authors: D'Hooghe E. , Buttiglieri S. , Bisignano G. , Brusa D. , Camussi G. , Matera L.
Published: January 2017

Vaccination with tumor-loaded dendritic cells (DC) is a promising treatment strategy for patients with renal cell carcinoma (RCC). Cells undergoing cell death proved useful as a source of tumor antigen for DC loading. Both apoptotic and necrotic tumor cells have been shown to efficiently load RCC-tumor antigens on DC. However, no direct comparison of these two kinds of death has been attempted in the same RCC. We compared DC pulsed with apoptotic cells, whole cell lysates or their supernatants of the cell line K1, derived from a patient with clear cell RCC, to determine their ability to activate T cells. Monocyte-derived DCs were pulsed with the different sources of tumor antigen, matured and co-cultured with autologouos peripheral blood lymphocytes. After three weekly re-stimulations with DCs, generation of cytotoxic T lymphocytes CTL was assessed by IFN-γ release in an ELISpot assay in the presence of the sensitizing target. By comparison with lysate, apoptotic tumor cells induced a higher frequency of MHC class I-restricted IFN-γ releasing lymphocytes. A higher CTL response was induced by pulsing DCs with cell lysate supernatant compared with whole cell lysate. These results indicate that, although necrotic death has been regarded as highly permissive when compared to apoptotic death, the immunogenicity of the death treatment may vary from one tumor to another.
Differential Effects of All-Trans Retinoic Acid on the Growth of Human Keratinocytes and Mouth Carcinoma Epidermoid Cultures. Involvement of GRIM-19 and Complex I of the Respiratory Chain
Authors: Papa F. , Delia M. , Trentadue R. , Panelli D. , Bellomo F. , Serpico R. , Petruzzi M. , De Benedittis M. , Scacco S.
Published: January 2017

Squamous cell carcinoma (SSC) is the most frequent malignant tumor of the oral cavity. A study on the effect of all-trans retinoic acid (RA) on cell growth, expression of GRIM-19 and content and activity of complex I of the mitochondrial respiratory chain in normal human keratinocytes (NHEK) and mouth carcinoma cells with low (HN) and high (KB) transformation grade was carried out. In NHEK cells, RA treatment resulted in growth suppression, significant overexpression of GRIM-19 protein, enhanced content of complex I but depressed activity of NADH-UQ oxidoreductase activity of the complex. In HN cells, RA treatment depressed cell growth, inhibited the enzymatic activity of complex I but had no significant effect on the levels of GRIM-19 and complex I. In KB cells RA had no effect on cell growth, GRIM-19 expression, content and activity of complex I.
Eosinophil Recruiting Chemokines are Down-Regulated in Peripheral Blood Mononuclear Cells of Allergic Patients Treated with Deflazocort or Desloratadine
Authors: Di Sciascio M.B. , Vianale G. , Verna N. , Petrarca C. , Perrone A. , Toniato E. , Muraro R. , Conti P. , Di Gioacchino M.
Published: January 2017

Chemokines are cytokines with chemotactic properties on leukocyte subsets whose modulation plays a key role in allergic inflammatory processes. To better understand the possible anti-inflammatory effects of histamine-1 receptor antagonists in allergic asthma, we studied the mRNA expression of a set of chemokines known to be involved in the eosinophil/basophil activation as well as recruitment and T-cell signaling events, before and after corticosteroid or antihistamine treatment in PBMCs from allergic/asthmatic patients ex vivo. Twelve patients were enrolled, all of whom were allergic to Parietaria judaica and suffering for mild persistent asthma: six were treated with desloratadine (10 mg/day), and six with deflazacort (12 mg/day). Before and after the treatment, PBMC samples were collected from each patient and analyzed for the expression of encoding mRNAs for several chemokines, 1–309 (CCL1), MCP-1 (CCL2), MIP1-α (CCL3), MIP1-β (CCL4), RANTES (CCL5), IL-8 (CXCL8), IP-10 (CXCL10), Lymphotactin (XCL1). Clinical and functional improvements were seen after 3 weeks of therapy; this was associated with a reduced expression in the mRNA levels for the chemokines RANTES, MIP1-α and MIP1-β with either the corticosteroid or the antihistamine, compared to the pre-treatment levels. Chemokine downregulation was statistically significant in both groups of patients. These findings suggest that certain antihistamines may act as down-modulators of allergic inflammation, possibly through a negative regulation of the chemokines involved in activation and attraction of eosinophils. Our results suggest that clinical trials with long follow-ups may be useful in evaluating histamine-1 receptor antagonists as add-on therapy to steroids in the treatment of asthma.
Neuroendocrine Immunophenotype as Predictor of Clinical Recurrence in 110 Patients with Prostate Cancer
Authors: Autorino R. , Lamendola M.G. , De Luca G. , De Sio M. , Giugliano F. , D'Armiento M. , De Placido S. , Conti P. , Di Lorenzo G.
Published: January 2017

We evaluated the relationship between NE expression and well-known prognostic factors and assessed whether tumor relapse after radical surgery correlates with the extent of NE differentiation. Radical prostatectomy specimens from 110 patients with clinically localized prostate cancer were assessed. Patients were followed up every three months for the first two years after surgery and six monthly for 5 additional years until failure, or for a mean of 48 months from the time of surgery for those who did not experience failure. The percentage of cells showing CgA immunoreactivity was evaluated using a visual quantitative method. Tumor staining was categorized as positive if >10% and negative if <10% of tumor cells were stained, to ensure that only cases with significant positivity were included in the positive group. The median follow-up was 5.4 years (range 1.8 to 7.2). The median time to clinical recurrence was 7.5 years and the median time to biochemical recurrence was 2.8 years. Of 31 patients (28%) who experienced a PSA recurrence, 15 developed a clinical recurrence. The mean preoperative PSA level was 9 ng/ml (range 2.7 to 25). Most cases were well differentiated (Gleason score <7), intraprostatic (≤pT2) tumors. Immunoreactivity in ≥10% of the cells was seen in 17.2% (n=19) of the tumor specimens. The preoperative PSA level, Gleason score, use of neoadjuvant or adjuvant therapy, lymphnode positivity were not statistically associated with NE expression. Only the primary pathologic stage appeared to be associated with CgA staining in the primary tumor (p=0.001). On the univariate analysis NE expression did not predict biochemical recurrence free survival, whereas it was associated with clinical recurrence. NE differentiation in clinically localized prostate cancer can be associated with failure after definitive surgical treatment, even if no conclusions can be drawn regarding its value as an independent prognostic factor.
Human Gastric Epithelium Produces IL-4 and IL-4δ2 Isoform Only upon Helicobacter Pylori Infection
Authors: Orsini B. , Vivas J.R. , Ottanelli B. , Amedei A. , Surrenti E. , Galli A. , Milani S. , Pinzani P. , Del Prete G. , Surrenti C. , Baldari C.T. , Touati E. , D'Elios M.M.
Published: January 2017

Recent evidence suggests that interleukin-4 (IL-4) is related to mucosal tolerance by which an injurious immune response is prevented, suppressed or shifted to a non-injurious response. We investigated the expression of IL-4 and its splice variant isoform IL-4δ2 in gastric epithelial cells of healthy subjects and gastritis patients infected with Helicobacter pylori (H. pylori) with or without the cag pathogenicity island ( cag-PAI). IL-4 and IL-4δ2 mRNAs were evaluated in microdissected gastric epithelium and in AGS cell lines co-cultured with H. pylori B128 or SSI strains. IL-4 mRNA was consistently detected in microdissected gastric epithelial cells from healthy subjects. The IL-4 mRNA expression was low in H. pylori-infected patients, and markedly reduced in cag-PAI-positive ones. IL-4δ2 mRNA was expressed on gastric epithelium of H. pylori-infected patients, but not in healthy subjects. The IL-452 expression was lower in cag-PAI-positive than in cag-PAI-negative H. pylori infected patients. AGS cells also produced IL-4 mRNA upon SSI strain stimulation, whereas IL-4δ2 mRNA expression was detected in AGS co-cultured with either SSI or B128 strains. An inverse correlation was documented between IL-4 and IL-482 mRNA expression by microdissected gastric epithelial cells and the score of gastritis. IL-4, but not IL-452, is expressed by gastric epithelium of healthy subjects, whereas IL-452 and lesser IL-4 mRNA are detectable in the gastric epithelium of H. pylori-infected patients. Data suggest that gastric epithelial cells might regulate the balance between tolerance and immune response by the fine tuning of IL-4 and IL-4δ2 expression.
Morphostructural Analysis of Human Follicular Stem Cells on Highly Porous Bone Hydroxyapatite Scaffold
Authors: Tetè S. , Mastrangelo F. , Carone L. , Nargi E. , Costanzo G. , Vinci R. , Burruano F. , Tortorici S. , Dadorante V. , Caciagli F. , Traini T. , Gherlone E. , Caraffa A. , Salini V. , Conti P. , Ciccarelli R.
Published: January 2017

In this study we investigated the in vitro behaviour, morphostructure and extracellular matrix synthesis of human dental follicular stem cells (hDFSCs) isolated from human dental bud, which resulted to be positive for mesenchymal markers (CD29, CD90, CD146 and CD166) by FACS analysis. Cells were analysed by light and electronic microscopy to evaluate their biological response either at week 1, that is before differentiation, or at weeks 3–6, when they had been cultured in osteogenic medium onto a highly porous natural scaffold material (Bio-Oss®). Microscopy analysis of primary culture cells showed they had a mesenchymal stem cell-like morphostructure, spindle shaped, similar to the culture of mesenchymal stem cells derived from adult bone marrow. Also, after osteogenic differentiation, these analyses indicate typical osteoblast morphostructure and reveale a tri-dimensional organization of the cells and deposition of extracellular matrix (ECM) in close contact with biomaterial. This approach would allow to personalize the scaffold for bone tissue engineering in order to accelerate the process of osteogenesis.
Exaggerated Immune Reactions Predict the Outcome of Interferon Therapy in Patients with Chronic Hepatitis C
Authors: Tarantino G. , Conca P. , Ariello M. , Arena A.
Published: January 2017

HCV plays a key role as chronic antigenic driver in inducing a clonal expansion of B-lymphocytes. The hypothesis that previous immunological pattern, when expression of an exaggerated immune reaction, could affect the response to IFN therapy was tested. Using a longitudinal database, the outcomes of 124 HCV-positive patients, genotype 1b only, with circulating HCV RNA, were analyzed by a retrospective cohort design. Immunological disorder-related clinical features and visceral organ involvement were thoroughly investigated in addition to laboratory data focusing on the presence of cryoglobulins, rheumatoid factor, antinuclear antibody, complement, circulating immunocomplexes and mono-oligoclonal gamma-globulin expansion. Eighty-four patients with and forty patients without abnormal immunological status, presenting a low fibrosis score, were identified. The whole naive population was treated by IFN monotherapy at the classical schedule for six or, alternatively, up to twelve months. Of the 124 patients, 28 showed a sustained response while 50 were non-responders and 46 were relapsers. Particularly, among the 84 patients with abnormalities of the immunological status, skin involvement was detected in 71 patients and hypocomplementemia was found in 69 patients, emerging as independent predictors for the lack of response. Conclusively, a peculiar immunological phenotype, ascertained by clinical and/or laboratory findings, is associated to a lack of IFN response and could be considered a further predictive factor.
Biology of Neurotensin: Revisited Study
Authors: Katsanos G.S. , Anogianaki A. , Castellani M.L. , Ciampoli C. , De Amicis D. , Orso C. , Pollice R. , Vecchiet J. , Tetè S. , Salini V. , Caraffa A. , Patruno A. , Shaik Y.B. , Kempuraj D. , Doyle R. , Antinolfi P.L. , Cerulli G. , Conti C.M. , Fulcheri M. , Neri G. , Sabatino G.
Published: January 2017

The tridecapeptide neurotensin (NT) acts in the mammalian brain as a primary neurotransmitter or neuromodulator of classical neurotransmitters. Morphological and functional in vitro and in vivo studies have demonstrated the existence of close interactions between NT and dopamine both in limbic and in striatal brain regions. Additionally, biochemical and neurochemical evidence indicates that in these brain regions NT also plays a crucial role in the regulation of the aminoacidergic signalling. Immune cells, such as lymphocytes, macrophages and mast cells are reported to be activated by neuropeptides, such as neurotensin; this activation leads to cytokine and immunoglobulin production. In addition, neurotensin increases calcium level and the production of nitric oxide, therefore neurotensin is deeply involved in immunity and inflammation but its real function still remains to be elucidated.
Antibodies as Predictors of Complex Autoimmune Diseases
Authors: Vojdani A.
Published: January 2017

Emerging evidence has suggested environmental factors such as infections and xenobiotics and some dietary proteins and peptides in the pathogenesis of many autoimmune diseases. Considering the fact that autoantibodies can often be detected prior to the onset of a disease, in this study an enzyme immunoassay was used for measurement of antibodies against different highly purified antigens or synthetic peptides originating not only from human tissue, but also from cross-reactive epitopes of infectious agents, dietary proteins and xenobiotics. The measurement of antibodies against a panel of antigens allows for identification of patterns or antibody signatures, rather than just one or two markers of autoimmunity, thus establishing the premise for increased sensitivity and specificity of prediction, as well as positive predictive values. This panel of different autoantibodies was applied to 420 patients with different autoimmune diseases, including pernicious anemia, celiac disease, thyroiditis, lupus, rheumatoid arthritis, osteoarthritis, Addison's disease, type 1 diabetes, cardiovascular disease and autoimmunity, which are presented in this article. In all cases, the levels of these antibodies were significantly elevated in patients versus controls. Antibody patterns related to neuroautoimmune disorders, cancer, and patients with somatic hypermutation will be shown in a subsequent article. We believe that this novel 96 antigen-specific autoantibody or predictive antibody screen should be studied for its incorporation into routine medical examinations. Clinicians should be aware that the detection of antibodies should not automatically mean that a patient will definitely become ill, but would rather give a percentage of risk for autoimmune disease over subsequent months or years.
Cacao Liquor Proanthocyanidins Inhibit Lung Injury Induced by Diesel Exhaust Particles
Authors: Yasuda A. , Takano H. , Osakabe N. , Sanbongi C. , Fukuda K. , Natsume M. , Yanagisawa R. , Inoue K. , Kato Y. , Osawa T. , Yoshikawa T.
Published: January 2017

Epidemiological and experimental studies have suggested that diesel exhaust particles (DEPs), which generate reactive oxygen species, may be involved in the recent increase in the prevalence of lung diseases. Cacao liquor proanthocyanidins (CPs) are naturally occurring polyphenols with antioxidative activities. We carried out a study in mice to investigate the effects of dietary supplementation of CPs on lung injury induced by intratracheal administration of DEPs (500 μg/body). Dietary supplementation with 1.0% CPs inhibited DEP-induced lung injury, characterized by neutrophil sequestration and edema. Immunohistochemical analyses showed that CPs prevented enhanced expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 caused by DEPs in the lung injury. Numerous adducts of nitrotyrosine, N-(hexanonyl) lysine, 4-hydroxy-2-nonenal, and 8-OHdG were also observed immunohistochemically in the lungs of mice treated with DEPs. However, these indicators of oxidative stress were barely visible in mice pretreated with CP supplementation. In addition, the level of thiobarbituric acid reactive substances in the lung was decreased by CP supplementation in the presence of DEPs. These results suggest that CPs inhibit DEP-induced lung injury by reducing oxidative stress, in association with a reduction in the expression of adhesion molecules.
Non-Allergic Rhinitis with Eosinophils and Mast Cells Constitutes a New Severe Nasal Disorder
Authors: Gelardi M. , Del Giudice A. Maselli , Fiorella M.L. , Fiorella R. , Russo C. , Soleti P. , Di Gioacchino M. , Ciprandi G.
Published: January 2017

Three main types of inflammatory Non-Allergic Rhinitis (NAR) have been defined: NAR infiltrated by eosinophils (NARES), by mast cells (NARMA), and by neutrophils (NARNE). A new particular type has been characterized with current infiltration by eosinophils and mast cells (NARESMA). The aim of this study is to evaluate the clinical and functional characteristics in patients with NARES, NARMA, NARNE, and NARESMA and to define the latter. One hundred and seventy-six NAR patients were prospectively and consecutively evaluated:52 patients with NARES, 38 with NARMA, 36 with NARNE, and 50 with NARESMA. Clinical features, Quality of Life (QoL), and rhinomanometry were evaluated in all of them. QoL was significantly different in the 4 groups. NARESMA patients had the worst QoL. Nasal function and QoL in NARESMA patients were significantly correlated. Significant associations were shown with both nasal polyps and asthma in NARESMA patients. This study provides the first evidence that NARESMA constitutes a new type of NAR and is a particularly severe disorder.
Tolerability of Aztreonam in Patients with IgE-Mediated Hypersensitivity to Beta-Lactams
Authors: Patriarca G. , Schiavino D. , Lombardo C. , Altomonte G. , Decinti M. , Buonomo A. , Nucera E.
Published: January 2017

Cross-reactivity between aztreonam and penicillins is poor, but clinical tolerance of aztreonam has been assessed, by means of tolerance challenge tests, only in a few groups of penicillin-allergic patients. The aim of this study is to evaluate the tolerability of aztreonam in a large group of betalactam-allergic patients. We studied all patients (> 14 years of age), with a clinical history of immediate reactions to any betalactam and with positive immediate-type skin tests and/or positive specific IgE to any of the studied betalactam; they were studied by means of: skin prick and intradermal tests with penicilloyl polysine, minor determinant mixture, semisynthetic penicillins, cephalosporins, aztreonam and imipenem; detection of specific IgE to penicillin G, penicillin V, ampicillin, amoxicillin, cefaclor and ceftriaxone. Patients with negative immediate-type skin tests with aztreonam then underwent a graded intramuscular challenge. Forty-five patients (mean age 46.1 ± 15.2 years), 27 females and 18 males, had positive skin tests and/or specific IgE to at least one of the studied betalactams. The most involved drugs were amoxicillin (23 cases), ampicillin (9 cases), penicillin G (8 cases) and other betalactams in the remaining cases. The most frequent reactions were anaphylaxis (27 cases) and urticaria (15 cases). All patients had negative intradermal tests with aztreonam and all patients tolerated the intramuscular graded challenge. Our data confirm the lack of cross-reactivity between betalactams and aztreonam. Immediate-type skin tests with aztreonam represent a simple and rapid diagnostic tool to establish tolerability in betalactam-allergic patients who urgently need this drug.
Effects of Holder Pasteurization on Human Milk Oligosaccharides
Authors: Bertino E. , Coppa G.V. , Giuliani F. , Coscia A. , Gabrielli O. , Sabatino G. , Sgarrella M. , Testa T. , Zampini L. , Fabris C.
Published: January 2017

The benefits of human milk have been confirmed for preterm infants, due to its nutritional aspects and to its biologically active compounds. Oligosaccharides play an emerging leading role among these compounds. Mother's milk can sometimes be lacking for preterm infants; pasteurized donor milk represents therefore an important alternative. The aim of this study is to evaluate the effects of Holder pasteurization on the concentration and pattern of oligosaccharides in preterm human milk. Our results indicate that pasteurization does not affect the concentration or pattern of analyzed oligosaccharides.
The Usefulness of 111Indium-Oxine Autologous Platelet Gel Graft Imaging to Evaluate Osteoinduction in Patients Undergoing Surgery of Jaw Bone Defects
Authors: Sammartino G. , Celentano L. , Tia M. , D'Agostino E. , Fusco A. , Tetè S. , Ottiero M.
Published: January 2017

Autologous platelet gel (AGP) is a source of concentrated growth factors contained in the platelet granules used to enhance bone quality and, especially, quicken bone formation in regeneration techniques, and also ameliorate the haemostasis in anti-coagulated patient management. The purpose of this study is to describe a technique to perform labelling of autologous platelet-gel with 111In -Oxine and to evaluate its usefulness, as a marker of bone osteoinduction by means of scintigraphy, after in vivo application in patients with jaw bone defects following cystic lesion enucleation and the extraction of deeply impacted lower third molar. All patients included in the study presented mandible bone defects following cyst enucleation or deeply impacted lower third molar extraction. In sterile conditions, 111In-Oxine AGP was added during the bone-milling phase of the graft preparation and then applied to the bone defects. The scintigraphy was performed 2 hours after the application of labelled AGP (early scan) and at 24, 48, 72, 384 hours (delayed scan). At early scan all the patients presented a high concentration of 111In-Oxine AGP, which was easily recognized at the level of jaw defect. Limited diffusion of AGP was seen in the tissue surrounding the bone defect; this activity was attributed to the presence, in the PRP, of a quote of autologous granulocytes, as marker of inflammatory process, which was labelled with 111In-Oxine. In order to demonstrate the persistence and stability of labelling AGP, abdominal scintigraphies were performed to assess the presence of activity in the liver, spleen and bone marrow. None of the patients presented appreciable activity in these organs. The labelled AGP topically applied showed high uptake values, without statistically significant activity in the surrounding tissues or in critical organs during the early phase, as well as in delayed controls, and confirmed a very low grade of loss of 111In-Oxine from the bone defect. The scintigraphy represents a useful method of assessing the success of surgical procedure for jaw bone defects performed with autogenous grafts. It is well accepted by the patients, offering at the same time a sensitive method of studying uptake of topically applied AGP and to follow up kinetics of AGP in order to correlate quantitative data of the platelet gel life span with evolution of the bone remodelling process. Finally, the labelled granulocytes around the bone defect allow to assess the inflammatory process evolution derived from the surgical technique.
Effect of Efalizumab on Neutrophil and Monocyte Functions in Patients with Psoriasis
Authors: Capsoni F. , Ongari A.M. , Frigerio E. , Taglioni M. , Altomare G.F.
Published: January 2017

We evaluated the effect of efalizumab on neutrophil and monocyte functions. The in vitro preincubation with efalizumab concentrations similar to those reached during in vivo therapy almost completely saturated CD11a binding sites without affecting the membrane expression of CD11b, CD128a or CD128b. There was a significant reduction in the chemotactic activity of the pre-treated cells toward three different chemo-attractants, whereas their phagocytic capacity and production of oxygen radicals remained unchanged. One month after the administration of efalizumab to five patients with psoriasis (T1) circulating neutrophil counts increased by 34% from pre-therapy (T0) with no change in the number of monocytes. In the same patients the CD11a binding sites on phagocytes were >90% saturated, and there was also a significant down-modulation on neutrophils (44% of T0) and monocytes (63% of T0). In line with in vitro results, efalizumab treatment caused a significant deficiency in the chemotactic properties of neutrophils and monocytes, but no changes in phagocytosis, oxidative burst, production of pro-inflammatory cytokines or the membrane expression of CD11b, CD128a and CD128b. Our findings suggest that neutrophils and monocytes may be among the targets of efalizumab activity in patients with psoriasis.
Prognostic Role of Tumor Necrosis, Microvessel Density, Vascular Endothelial Growth Factor and Hypoxia Inducible Factor-1α in Patients with Clear Cell Renal Carcinoma after Radical Nephrectomy in a Long Term Follow-up
Authors: Minardi D. , Lucarini G. , Filosa A. , Milanese G. , Zizzi A. , Di Primio R. , Montironi R. , Muzzonigro G.
Published: January 2017

Angiogenesis is a critical step in the growth, invasive progression and metastatic spread of solid tumors. We investigated the importance of tumor necrosis, and microvessel density (MVD), vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1α (HIF-1α) immunohistochemical expression in a large series of clear cell renal carcinomas treated with radical nephrectomy and assessed the prognostic value of their expression in terms of patient survival at long-term follow up. Fifty patients with clear cell RCC were examined. The features considered when evaluating the patients were age, tumor size and grade, intratumoral vascular and renal capsula invasion, histological necrosis, and MVD, vascular and tumoral cell VEGF, and vascular, tumoral cytoplasmic and nuclear HIF-1α expression on the histologic specimens. All considered parameters were correlated with patient specific survival. Mean age was 62.06 ± 6.8 years. Median follow-up was 191.66 months; median survival was 120.86 months. Twenty-one patients developed metastases in the follow-up. Tumor necrosis, microvascular invasion and renal capsula infiltration are more likely to occur in high stage and grade RCC; cytoplasmic HIF-1α is highly expressed in high grade RCC. Survival is dependent upon tumor stage and grade, the presence of intratumoral vascular invasion and capsular infiltration, and tumor necrosis; MVD also resulted as being an important prognostic factor. VEGF and HIF-1α correlate with prognosis in high stage tumors where VEGF is the most important independent prognostic factor for cancer specific death. The histological and immunohistochemical parameters considered in our study can influence disease recurrence and survival in RCC.
A Cutaneous Infection Caused by Brevundimonas Vesicularis: A Case Report
Authors: Panasiti V. , Devirgiliis V. , Mancini M. , Curzio M. , Rossi M. , Fioriti D. , Pietropaolo V. , Nicosia R. , Gallinelli C. , Chiarini F. , Pecorini G. , Calvieri S.
Published: January 2017

Brevundimonas vesicularis is a non-fermenting gram-negative bacillus, aerobic and motile. This microrganism is ubiquitous in the environment and has rarely been implicated in human infections. We present the second case of cutaneous infection caused by B. vesicularis in an immunocompetent patient.
Cutaneous Cryptococcosis in a Patient Affected by Chronic Lymphocytic Leukaemia: A Case Report
Authors: Devirgiliis V. , Panasiti V. , Borroni R.G. , Rossi M. , Curzio M. , Riggio R. , Fioriti D. , Nicosia R. , Pietropaolo V. , Tecca M. , Chiarini F. , Innocenzi D. , Calvieri S.
Published: January 2017

Cryptococcosis is an opportunistic infection, the incidence of which is increased in the immunocompromised patients. Cryptococcus neoformans is an encapsulated fungus that mainly infects the lungs and the central nervous system, possibly involving different organs. Cutaneous cryptococcosis is classified into localized infection, usually occurring after traumatic inoculation (primary cutaneous cryptococcosis) and cutaneous manifestation due to hematogenous dissemination (secondary cutaneous cryptococcosis), mostly in patients with underlying immunosuppression. We report a case of cutaneous cryptococcosis in a patient affected by chronic lymphocytic leukaemia.
Comparison between Continuous or Intermittent Schedules of Sublingual Immunotherapy for House Dust Mites: Effects on Compliance, Patients' Satisfaction, Quality of Life and Safety
Authors: Cadario G. , Ciprandi G. , Di Cara G. , Fadel R. , Incorvaia C. , Marcucci F. , Marengo F. , Puccinelli P. , Sensi L. , Strazzeri L. , Frati F.
Published: January 2017

Sublingual immunotherapy (SLIT) is indicated in the treatment of allergic rhinitis and asthma. However, an issue scantly investigated is the patient's satisfaction and the consequent compliance. This study is aimed at evaluating the possible differences of SLIT administered continuously or intermittently on several parameters: clinical efficacy, Quality of Life (QoL), satisfaction, compliance and safety. Forty allergic patients were treated for 12 months. The treatment was carried out by sublingual administration of an allergen extract of a 50% mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae at 10 and 300 IR/ml concentrations. Patients were randomly treated continuously or intermittently (i.e. 2 month treatment alternate to 2 month suspension). Both schedules were significantly effective in reducing allergic symptoms and improving QoL. Compliance and satisfaction were good in both groups. Local and systemic reactions were few, self-resolving, and mild in both schedules. Intergroup analysis did not reveal any difference between the two groups regarding these parameters. In conclusion, this preliminary study provides the evidence that also intermittent SLIT is as effective and safe as traditional continuous treatment. In addition, compliance and satisfaction are super-imposable in the two groups.
Severe Tramadol Addiction in a 61 Year-Old Woman without a History of Substance Abuse
Authors: Pollice R. , Casacchia M. , Bianchini V. , Mazza M. , Conti C.M. , Roncone R.
Published: January 2017

We describe here the first case of Tramadol addiction and withdrawal in an elderly female patient in apparently good physical health. We report successful treatment with mirtazapine and clonidine. We believe that patients must be advised to take Tramadol regularly and to stop gradually especially after long treatment periods; moreover physicians must consider the potential physical dependence when they prescribe Tramadol for pain. Hence, we are observing some patients who continue to take Tramadol in order “to achieve a feeling of well-being,” even though their pain is controlled after disease regression. Finally, the establishing of an evidence-based Tramadol detoxification protocol would be highly desirable
The Duration of Clinical Remission of Photochemotherapy and Narrow-Band UV-B Phototherapy in the Treatment of Psoriasis: A Retrospective Study
Authors: Brazzelli V. , Barbagallo T. , Trevisan V. , Muzio F. , De Silvestri A. , Borroni G.
Published: January 2017

PUVA and UVB-NB phototherapy have an established role in the treatment of moderate-to-severe psoriasis. Even though psoriasis patients often require continuous treatments, inadequate attention is devoted to the duration of remission after the treatment. The purpose of this retrospective study is to assess which phototherapeutic regimen induces a longer remission. Twenty patients with psoriasis were included:10 patients received PUVA and 10 patients received UVB-NB. We consider as a “cycle” the therapeutic period needed to reach clinical remission. The comparison between the average number of days in remission revealed that PUVA induces a longer remission period than UVB-NB: PUVA 386 days (ds ±321), UVB-NB 298 days (ds ± 257). Although the difference of the duration of remission is not statistically significant, a trend is seen and patients treated with PUVA remain clear for a period about 88 days longer than that of patients treated with UVB-NB. The differences in the duration of remission of psoriasis therapies must be considered in planning a patient's course of treatment.
Strategies to Overcome Obstacles to Successful Immunotherapy of Melanoma
Authors: Pandolfi F. , Cianci R. , Lolli S. , Dunn I.S. , Newton E.E. , Haggerty T.J. , Boyle L.A. , Kurnick J.T.
Published: January 2017

The immunogenicity of malignant melanomas has been recognized by the observed recruitment of tumor-specific cytotoxic T-cells (CTL), leading to the identification of several melanoma associated antigen (MAA). However, numerous strategies to treat melanoma with immunotherapy have resulted in only partial success. In this editorial, we discuss recent data related to the ability of tumors to elude immune responses. We therefore discuss different strategies to induce a clinically effective immune response. These approaches include 1) immunostimulation: including peptide/protein based vaccines, dendritic cell vaccines, and adoptive cell transfer; and 2) overcoming immunosuppression, including targeting of checkpoint molecules such as CTLA-4, circumventing the activity of Tregs, and assuring antigen expression by tumor cells (thwarting antigen silencing). Finally, we discuss recent advances in gene therapy, including adoptive therapy with engineered T cell receptors (TCRs). These issues lead to the conclusion that successful immunotherapy in malignant melanoma requires a combination of strategies aimed at both inducing immunostimulation and blocking immunosuppression.
A Quercetin Containing Supplement Reduces Niacin-Induced Flush in Humans
Authors: Kalogeromitros D. , Makris M. , Chliva C. , Aggelides X. , Kempuraj D. , Theoharides T.C.
Published: January 2017

Coronary artery disease is associated with increased serum levels of cholesterol, triglycerides and LDL, but low levels of HDL. The most potent agent capable of reversing this trend is the vitamin nicotinic acid (niacin). However, compliance even with extended-release preparations and addition of acetylsalicylic acid (ASA) is hampered by the development of a feeling of erythema and burning (“flush”), especially on the face. We recently showed that the natural flavonoids quercetin and luteolin can eliminate “flush”, as well as inhibit both niacin-induced plasma prostaglandin D2 (PGD2) and serotonin increase in an animal model. We conducted a pilot clinical study in humans. Four normal male subjects received (a) 1 g immediate release niacin either alone or after (b) the dietary formulation (Algonot-plus®) containing 150 mg quercetin per capsule. Subjects completed a visual scale (1=no, 5=worst response) symptom assessment. Erythema and burning sensation scores were both 4.75±0.50 and lasted for 3.63±1.11 hours. After Algonot-plus® administration, both scores were reduced to 2.5±0.58 and lasted for only 1.68±0.70 hours. Quercetin also inhibited methylnicotinate-induced human mast cell PGD2 release. These preliminary results suggest that quercetin could reduce niacin-induced “flush” in humans.
In-Air Micro-Particle Induced X-ray Emission Analysis of Asbestos and Metals in Lung Tissue
Authors: Shimizu Y. , Dobashi K. , Kusakbe T. , Nagamine T. , Oikawa M. , Satoh T. , Haga J. , Ishii Y. , Ohkubo T. , Kamiya T. , Arakawa K. , Sano T. , Tanaka S. , Shimizu K. , Matsuzaki S. , Utsugi M. , Mori M.
Published: January 2017

Inhalation of asbestos increases the risk of lung cancer and pulmonary fibrosis. It is difficult to directly assess the distribution and content of inhaled particles in lung tissue sections. The purpose of this study is to employ an in-air micro particle induced X-ray emission (in-air micro-PIXE) system for assessment of the spatial distribution and content of asbestos and other metals in lung tissue. A proton ion-microbeam from this system was applied to irradiate lung tissue of patients with or without asbestosis, tumor tissue from both groups, and asbestos fibers ( in vitro). The content of each element composing asbestos and those of other metals were calculated and their distribution was assessed from the characteristic X-ray pattern for each element obtained after irradiation. This in-air micro-PIXE system could identify the location of asbestos bodies composed of Si, Mg, and Fe in lung tissue sections. Macrophage and lymphocytes accumulated in that area. This new system also revealed deposits of titanium, nickel, and cobalt in the lung tissues, in addition to asbestos bodies. The Si and Fe content were higher in lungs with asbestosis than in lungs without asbestosis or in tumor tissue. Analysis of asbestos fibers composed of chrysotile, crocidolite, and amosite showed that the ratios of Si, Fe, and Mg corresponded with those for the chemical structures. In-air micro-PIXE analysis is useful for assessing the distribution and quantities of asbestos bodies and also other metals in lung tissue comparing to immune-related cell localizations, and is also useful for analysis of standard asbestos fibers.
Antibodies to Carbonic Anhydrase in Patients with Connective Tissue Diseases: Relationship with Lung Involvement
Authors: Caccavo D. , Afeltra A. , Rigon A. , Vadacca M. , Zobel B.B. , Zennaro D. , Arcarese L. , Buzzulini F. , Pellegrino N.M. , Amoroso A.
Published: January 2017

The aim of this study is to evaluate the presence of antibodies to carbonic anhydrase I and/or II (ACAI and ACAII) in patients affected by connective tissue diseases (CTD) and to investigate their association with lung involvement evaluated by High resolution CT scan (HRCT). Ninety-six patients affected by CTD were studied, i.e. 33 rheumatoid arthritis (RA), 8 psoriatic arthritis (PA), 8 ankylosing spondilitis (AS), 23 Systemic Lupus Erythematosus (SLE), 10 Sjogren Syndrome (SS), and 14 Systemic Sclerosis (SSc). ACA were detected by ELISA. The lung involvement was evaluated by means of a previously described HRCT score. According to a receiver operator characteristic curve, patients were divided into those with HRCT score ≥ 10 and those with HRCT score < 10, where HRCT score ≥ 10 was predictive of interstitial lung disease. ACAI and/or ACAII were detected in 30/96 patients (31.2%) (P<0.0001 in comparison with controls). In particular, the prevalence of ACAI and/or ACAII was significantly higher in patients with RA (P = 0.002), PA (P < 0.0001), SLE (P = 0.0003) and SSc (P<0.0001). A positive correlation was found between HRCT scores and CRP or ACAI levels (P=<0.0001 and P=0.004, respectively). Thirty-nine of 96 patients (40.6%) showed a HRCT score ≥ 10 and both their CRP and ACAI levels were significantly higher when compared with patients showing a HRCT score < 10 (P<0.0006 and P = 0.0009, respectively). Moreover, C3 and C4 complement fractions inversely correlated with HRCT scores (P = 0.0004 and P<0.0001, respectively) and lower values of C3 and C4 complement fractions were found in patients with HRCT score ≥ 10 than in those with HRCT score < 10 (P = 0.014 and P = 0.007, respectively). Due to the lower levels of complement fractions detected in patients with HRCT score ≥ 10, a possible immune-complex-mediated pathogenic mechanism of lung involvement could be suggested.
Virulence Traits in Escherichia Coli Strains Isolated from Outpatients with Urinary Tract Infections
Authors: Longhi C. , Cossu A. , Iebba V. , Massaro M.R. , Cipriani D. , Chiarini F. , Conte M.P. , Seganti L. , Osborn J. , Schippa S.
Published: January 2017

This study aims to characterize phenotypic and genotypic virulence traits in Escherichia coli strains, isolated from outpatients with urinary tract infections, comparing with those obtained from inpatients. Information on the pathogenic behavior of the uropathogenic strains was obtained by monitoring different biological properties, such as autoagglutination, hemagglutination, adhesiveness to and invasion of human bladder (HT1376) cells, biofilm formation, phylogenetic grouping, and virulence-related genes. The results show similar behavior in the two groups concerning autoagglutination, hemagglutination, and biofilm formation. None of the strains examined was invasive. However, in strains from outpatients there was an increased adhesion to HT1376 cells compared with clinical strains, a significant higher presence of genes codifying for adhesins and cell protection factors, and a lower proportion of strains belonging to B1 group. These findings add further information on the pathogenic traits of community E. coli, since strains isolated from the outpatients' group were differently “armed” in comparison with those of clinical cases, and more suitable to infect healthy individuals.
Characterization of a Staphylococcus Aureus Strain Showing High Levels of Biofilm Formation Isolated from a Vascular Graft: Case Report
Authors: Petrelli D. , Repetto A. , Di Luca M.C. , Parente B. , Tavolini V. , Cao P. , Ripa C. , Prenna M. , Vitali L.A.
Published: January 2017

A methicillin-susceptible Staphylococcus aureus strain, SA-DZ1, was isolated from an infected bypass crossover graft. Its general microbiological features were reminiscent of those previously described for the wound Wiley strain. Removal of the prosthetic device was necessary to resolve the infection. SA-DZ1 grown under different conditions showed a very strong and distinctive biofilm-producing phenotype, which was also visualized by confocal laser scanning microscopy. The biofilm extracellular matrix was essentially polysaccharidic, as determined by differential growth and physicochemical tests. By Multi Locus Sequence Typing (MLST), SA-DZ1 was classified as st94, a single locus variant of st8. Several other genetic traits assayed by PCR, such as agr-type and the presence of gene encoding proteins involved in adhesion and virulence (e.g. ica operon), confirmed the identifying features of this clinical isolate.
Chlamydia Pneumoniae and Atherosclerosis: Current State and Future Prospectives
Authors: Sessa R. , Nicoletti M. , Di Pietro M. , Schiavoni G. , Santino I. , Zagaglia C. , Del Piano M. , Cipriani P.
Published: January 2017

Chlamydia pneumoniae, an intracellular bacterial pathogen, is known as a leading cause of human respiratory tract infections worldwide. Over the last decade, several reports in the literature have suggested that infection with C. pneumoniae may contribute to the pathogenesis of atherosclerosis. In order to play a causative role in chronic disease, C. pneumoniae would need to persist within infected tissue for extended periods of time, thereby stimulating a chronic inflammatory response. C. pneumoniae has been shown to disseminate systemically from the lungs through infected peripheral blood mononuclear cells and to localize in arteries where it may infect endothelial cells, vascular smooth muscle cells, monocytes/macrophages and promote inflammatory atherogenous process. The involvement of C. pneumoniae in atherosclerosis was investigated by seroepidemiological and pathological studies, in vivo and in vitro studies, and in clinical antibiotic treatment trials. This review will provide an update on the role of C. pneumoniae in atherosclerosis focusing on the recent insights and suggesting areas for future research.