bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced Function of CD4+25+ Regulatory T Cell Fraction in Silicosis Patients
Authors: Wu P. , Miura Y. , Hyodoh F. , Nishimura Y. , Hatayama T. , Hatada S. , Sakaguchi H. , Kusaka M. , Katsuyama H. , Tomita M. , Otsuki T.
Published: January 2017

The quality and quantity of CD4+25+ regulatory T cells (Treg) in silicosis patients (SIL) were examined and compared with results from healthy donors (HD) because SIL often develop autoimmune diseases along with pulmonary disorders. Peripheral blood mononuclear cells from 57 SIL and 50 HD were analyzed for Treg. Treg frequency and clinical parameters were subjected to a factor analysis. Treg and CD4+25- T cells (Tneg) from five HD and five SIL, sorted by flow-cytometer, were used for functional assays of Treg, the expression pattern of Treg specific genes (FoxP3, GITR and CTLA-4) and activation-related genes (CD122 and CD123;. Although the actual frequency of Treg did not differ between SIL and HD, the age-corrected level was reduced in SIL. The factor analysis showed that Treg frequency was positively associated with the serum level of IL-2. The inhibitory effect of Treg on Tneg activation was decreased when the Treg:Tneg ratio was 1:¼ to ½. In addition, Treg dominancy of FoxP3 and CTLA-4 expression and Tneg dominancy of CD132 expression found in HD were lost in SIL. These results indicated that the Treg fraction in SIL may be substituted with chronically activated T cells due to recurrent exposure to silica, resulting in a reduction in the frequency and function of Treg. Since the reduction of Treg may precede the clinical manifestation, as silicosis may be a pre-clinical status for autoimmune diseases, control of Treg function using cell and/or gene therapy may be a good way to manage autoimmune disease.
Inhibition of Maturation of Human Monocyte-Derived Dendritic Cells in a Patient with Mycobacterium Avium Infection
Authors: Di Renzo M. , Pasqui A.L. , Rubegni P. , D'Ascenzo G. , De Aloe G. , Auteri A. , Fimiani M.
Published: January 2017

Mycobacterium avium complex is a facultative intracellular pathogen that can cause pulmonary disease in immunocompromised individuals. Dendritic cells (DCs) play a central role in protective immunity against mycobacteria. Mycobacterium avium complex infects DCs but does not impair in vitro infected monocytes' differentiation into DCs. A 54-year old woman affected by chronic graft-versus-host-disease (cGVHD) was referred to our Division of Dermatology. Immature DCs were generated from her monocytes. One week later she was hospitalized due to a lung infection with Mycobacterium avium complex. Monocyte-derived DCs during Mycobacterium avium infection expressed low levels of CD1a and CD80 as determined by flow cytometry. They also expressed high levels of CD83 and CD86, and when stimulated with LPS for 24 hrs they slightly up-regulated CD83 and did not produce IL12. When monocyte-derived DCs were obtained from the patient after having recovered from the Mycobacterium avium complex infection, they expressed normal levels of CD1a and CD80 and were negative both for CD83 and for CD86. IL12 production in response to LPS was restored. Inhibition of DC maturation by the in vivo infection with Mycobacterium avium may be an immune-evasion mechanism used by the pathogen because incompletely matured DCs may not activate effector T cells efficiently in vivo.
The N-Terminal Fraction of Desmoglein 3 Encompassing its Immunodominant Domain is Present in Human Serum: Implications for Pemphigus Vulgaris Autoimmunity
Authors: Lanza A. , Femiano F. , De Rosa A. , Cammarota M. , Lanza M. , Cirillo N.
Published: January 2017

Pemphigus vulgaris (PV) is considered as an autoimmune disease against a tissue-restricted antigen, desmoglein 3, a 130 kDa glycoprotein expressed by keratinocytes of skin and mucous membranes. Therefore, a breakdown of peripheral tolerance is generally invoked to explain this horror autotoxicus. The availability of a self-antigen and the strength of antigenic stimulation represent critical points in the regulation of immune system homeostasis. Our study shows for the first time that the immunodominant fraction of the PV self-antigen is present in sera of healthy individuals and patients as a circulating 30 kDa fragment (sDsg3). These findings provide a good explanation for the N-terminal specificity of antibody production and peptide recognition in PV patients by B and T cell, respectively. Moreover, the presence of the sDsg3 in human sera could allow to reconsider pemphigus as a disease against a circulating antigen; once produced, PV-autoantibodies also recognize the 130 kDa epidermal antigen desmoglein 3 on keratinocyte surface (kDsg3), thus triggering the acantholysis and the clinical manifestations of pemphigus.
The Role of Terlipressin in Pediatric Septic Shock: A Review of the Literature and Personal Experience
Authors: Papoff P. , Mancuso M. , Barbara C.S. , Moretti C.
Published: January 2017

Vasopressin and its synthetic analog terlipressin are potent vasopressors that could be useful in vasodilatory septic shock. In septic adults, vasopressin/terlipressin have been shown to increase mean arterial pressure and to decrease the necessity for catecholamines. Moreover, low doses of vasopressin (or terlipressin) increase urine output and ameliorate oxygenation. Although pediatric septic shock is more often hypodynamic, both vasopressin and terlipressin have proved to be effective in restoring blood pressure or increasing the diuresis in this setting. The purpose of this review is to summarize the physiology of vasopressin and to report the available evidence for the use of vasopressin or terlipressin in pediatric septic shock in order to make best use in this population. We also report our experience with the continuous infusion of terlipressin in two pediatric patients who developed catecholamine refractory septic shock.
Human Monocytoid THP-1 Cell Line versus Monocyte-Derived Human Immature Dendritic Cells as in Vitro Models for Predicting the Sensitising Potential of Chemicals
Authors: Bocchietto E. , Paolucci C. , Breda D. , Sabbioni E. , Burastero S.E.
Published: January 2017

Immature dendritic cells (DCs) modulate differentiation markers following in vitro exposure to chemicals generating contact allergies. THP-1 is a monocytoid cell line maintaining some differentiating plasticity. In this study, human DCs and THP-1 cells were compared as in vitro models to predict contact sensitisation of chemicals with different sensitising potential. Expression of CD80 and CD86 was assessed by flow cytometry after exposure to subtoxic concentrations of potent (2,4-dinitrochlorobenzene, DNCB and p-phenylendiamine, PPD), strong (thimerosal, TMS), moderate (sodium tetrachloroplatinate, Na2PtCl4) sensitising compounds as well as of non-sensitising, irritating sodium dodecyl sulphate (SDS) as compared to a vehicle of sensitising substances (dimethyl sulphoxide, DMSO). Up-regulation of CD86 following in vitro incubation of DCs and THP-1 cells with DNCB, PPD, TMS and Na2PtCl4 but not with SDS, was observed. The CD80 membrane marker was up-regulated on DCs following in vitro incubation with DNCB and PPD, but not with TMS, Na2PtCl4 and SDS. On THP-1 cells, only DNCB up-regulated CD80 expression. In conclusion, both the cell line THP-1 and DCs are promising in vitro models for assays aiming at predicting the sensitisation potential of chemicals. THP-1 cell line is by far easier to handle and offers relevant advantages from the practical point of view.
A New Sensitive Enzyme-Linked Immunosorbent Assay (ELISA) for Alemtuzumab Determination: Development, Validation and Application
Authors: Montagna M. , Avanzini M.A. , Visai L. , Locatelli F. , Montillo M. , Morra E. , Regazzi M.B.
Published: January 2017

Alemtuzumab is a humanized (IgG,) rat monoclonal antibody to CD52 antigen and is currently used in the treatment of chronic lymphocytic leukemia (CLL) and other CD52-positive lymphoproliferative disorders. Various techniques have been developed to measure Alemtuzumab levels in human serum/plasma. The authors report on the validation of a very sensitive enzyme-linked immunosorbent assay (ELISA) to measure serum concentrations of the humanized IgG, using a rabbit polyclonal antibody specifically produced against the rat sequence of Alemtuzumab after papain digestion. The assay was successfully applied to test the serum samples of patients with B-lymphocyte CLL who received Alemtuzumab subcutaneously. This ELISA assay could be easily used to determine human serum levels of Alemtuzumab pre- and post-treatment to optimize dosing and scheduling and to study the relationship between dose and clinical response.
Pulp-Dissolving Ability of Several Endodontic Irrigants: A Spectro-Photometry Evaluation
Authors: D'Arcangelo C. , Di Maio F. Di Nardo , Stracci N. , Spoto G. , Malagnino V.A. , Caputi S.
Published: January 2017

The aim of this study is to test the dissolving action of different concentrations of NaOCl (0.5%, 2.5% and 5%) and EDTA 17% on bovine pulp tissue, testing solutions at three different times (1, 5, 10 minutes). 100 mg. of dental pulp placed into a becher with 20 ml of solution was evaluated using a spectrophotometer. A solution of NaOCl 5% showed the highest solubility value. Samples treated with 2.5% NaOCl showed solubility values of 0.98 in one minute, 29.1 in five minutes and 57 in ten minutes. Groups treated with NaOCl 0.5% showed small dissolving modifications. 17% EDTA showed the lowest values of solubility. 5% NaOCl solution showed highest pulp dissolving ability, even a 2.5% solution showed high dissolving ability but in longer times.
Bovine Lactoferrin Inhibits the Efficiency of Invasion of Respiratory A549 Cells of Different Iron-Regulated Morphological Forms of Pseudomonas Aeruginosa and Burkholderia Cenocepacia
Authors: Berlutti F. , Superti F. , Nicoletti M. , Morea C. , Frioni A. , Ammendolia M.G. , Battistoni A. , Valenti P.
Published: January 2017

Pseudomonas aeruginosa and Burkholderia cenocepacia are two important opportunistic respiratory pathogens of cystic fibrosis (CF) patients. Infections caused by these microorganisms are particularly difficult to eradicate because they are usually highly resistant to several currently available broad-spectrum antibiotics. Lactoferrin (Lf), a glycoprotein found in physiological fluids of mammals and present at high concentrations in infected and inflamed tissues, plays an important role in the natural defence mechanism against pathogens and in immune regulation. In the present study, we evaluate the ability of bovine lactoferrin (bLf) to influence P. aeruginosa PAO1 and B. cenocepacia PV1 adhesiveness and invasiveness, using the A549 human bronchial cell line. Three different iron-induced morphological forms of bacteria (free-living, aggregates and biofilm) were assayed. The addition of bLf to cells just before infection had little influence on adhesion efficiency for all three of the morphological forms of B. cenocepacia PV1, while a slight increase in adhesion efficiency by P. aeruginosa PAO1 was noticed. Conversely, invasion of all three morphological forms of both P. aeruginosa and B. cenocepacia was strongly inhibited by the presence of bLf, independently of its degree of iron-binding activity. This is the first report demonstrating an anti-invasive property of bLf for strains of P. aeruginosa and B. cenocepacia.
Periodate Oxidized ATP (oATP) Reduces Hyperalgesia in Mice: Involvement of P2X7 Receptors and Implications for Therapy
Authors: Fulgenzi A. , Ticozzi P. , Gabel C.A. , Dell'Antonio G. , Quattrini A. , Franzone J.S. , Ferrero M.E.
Published: January 2017

Some inflammatory mediators play an important role not only in the pathogenesis of the inflammatory pain, but also in that of neuropathic and visceral pain. We previously showed the antihyperalgesic effect of oATP, the inhibitor of the P2X7 receptors for the pro-nociceptive ATP, in experimental inflammation. Here we show the antihyperalgesic effect of oATP in mouse models of neuropathic and visceral pain, other than in a model of arthritic pain mimicking rheumatoid arthritis in humans. We also show that mice lacking P2X7 receptors (KO) are resistant to hyperalgesic thermal stimuli following the induction of arthritic, neuropathic and visceral pain. Local (injection into the right hind paw) pre-treatment with oATP is able to prevent the successive induction of ATP-dependent hyperalgesia in wild type mice. In addition, KO mice are not insensitive to intraplantar treatment with ATP. Our data suggest that, even if oATP is able to inhibit purinoceptors different from P2X7, the latter are the more important involved in pain transmission.
Modified Arabinoxylan Rice Bran (Mgn-3/Biobran) Enhances Intracellular Killing of Microbes by Human Phagocytic Cells in Vitro
Authors: Ghoneum M. , Matsuura M. , Gollapudp S.
Published: January 2017

Phagocytic cells, comprised of neutrophils and moncytyes/macrophages, play a key role in the innate immune response to infection. Our earlier study demonstrated that arabinoxylan rice bran (MGN-3/Biobran) activates murine peritoneal macrophage and macrophage cell lines. In this study, we investigated whether MGN-3 can upregulate the phagocytic activity of human phagocytes in peripheral blood to phagocytize Escherichia coli (E. coli), trigger the oxidative burst and produce cytokines. Phagocytic cells were pre-labeled with dichlorofluorescin diacetate dye and were incubated with phycoerythrin-labeled E. coli in the presence or absence of MGN-3. Phagocytosis and oxidative burst were assessed by flow cytometry. Results showed that treatment with MGN-3 enhanced the phagocytosis of E. coli by neutrophils and moncytes. This was associated with an increased oxidative burst. In addition, it caused a significant induction of cytokines (TNF-α, IL-6, IL-8 and IL-10); the effect was detected at 1 μg/ml and increased in a dose-dependent manner (P≤ 0.01). Notably, MGN-3 alone had no effect on the growth of 31 strains of bacteria suggesting that MGN-3 modulates phagocytic cellular function. These findings may have applications in the treatment of infections in the elderly and in immunocompromised patients.
Bronchiectasis in Children with Recurrent Pneumonia: An Immunopathological Damage Associated with Secondary Ciliary Dysmotility
Authors: Pifferi M. , Caramella D. , Ragazzo V. , Cangiotti A.M. , Macchia P. , Boner A.L.
Published: January 2017

The aim of this study is to assess ciliary motion patterns in children with bronchiectasis unrelated to cystic fibrosis or primary ciliary dyskinesia. In 51 children with recurrent pneumonia, high resolution computed tomography (HRCT) was carried out to detect and score bronchiectasis. Moreover, ciliary ultrastructure, beat frequency and motion pattern were evaluated and compared to those observed in 30 healthy children. Bronchiectasis at HRCT was found in 31/51 children. Ciliary dysmotility was found in 20/31 children with bronchiectasis (64.5%). Overall, ciliary dysmotility was found in 39/51 patients (76.5%). Ciliary dysmotility showed a significant correlation with the HRCT score (p=0.02). Absent motion in some fields was found in 44/51 patients (86.3%) and this also showed significant correlation with the HRCT score (p=0.005). The specificity and sensitivity of ciliary dysmotility as an indicator of bronchiectasis was 74.3% and 83.3% respectively. The positive predictive value was 93.5%, and negative predictive value was 50%. Ciliary dysmotility, in children with recurrent airways infections, correlates with the presence and severity of bronchiectasis. Whether ciliary dysmotility is a cause or a consequence of anatomical lesion is a matter of speculation. Very likely there is an amplification and self-maintaining mechanism between the two events which may lead to more serious disease.
Effects of the Hormones of the Thyroid Axis on the Vitamin K-Dependent Plasma Factors of Blood Coagulation (II, VII, IX and X)
Authors: Negrev N.N. , Radev R.Z. , Velikova M.S. , Anogeianaki A.
Published: January 2017

The hormonal regulation of haemostasis is a problem which has not received much attention. The data concerning the influence of hormones from the hypothalamic-pituitary-thyroid axis are scarce, contradictory and based mainly on clinical observations. The objective of the current research is to study the influence of the Thyrotropin releasing hormone (TRH), Thyroid stimulating hormone (TSH), Trijodthyronin (T3) and Thyroxin (T4) on the activity level of the vitamin K-dependent plasma factors of blood coagulation – factor II (F II), factor VII (F VII), factor IX (F IX) and factor X (F X). This study was carried out on 40 male Wistar rats. The necessary quantity of blood was obtained by cardiac puncture under ether narcosis. The indicators studied were activated partial thromboplastin time (aPTT), protothrombin time (PT), F II, F VII, F IX and F X, and were determined by means of Diagnostica Stago tests and with the help of an automatic coagulometer. The hormones studied were: TRH (0.06 mg/kg b.w.), TSH (1 MU/kg b.w.), T3 (0.08 mg/kg b.w.) T4 (0.08 mg/kg b.w.) prolonged aPTT (p < 0.001) and PT (p < 0.001). TRH and T3 significantly reduced the activity level of factors II, VII, IX and X; T4 only reduced the level of F II (p < 0.05), and TSH did not induce significant changes in the haemocoagulation factors studied. The TRH, TSH, T3 and T4 hormones, although elements of one and the same axis, have an ambiguous effect on the vitamin K-dependent factors of blood coagulation. The results obtained show that the determined changes in the activity levels of the vitamin K-dependent plasma factors of blood coagulation are undoubtedly related to the hypocoagulation observed in the intrinsic and extrinsic pathways under the influence of the hormones of the thyroid axis.
Recurrent Venous Thromboembolism Complicated by Heparin-Induced Thrombocytopenia as a First Manifestation of an Occult Cancer: A Case Report
Authors: Pinto A. , Tuttolomondo A. , Fernandez P. , Siragusa S. , Di Raimondo D. , Malato A. , Di Sciacca R. , La Placa S. , Miceli S. , Licata G.
Published: January 2017

Heparin-Induced Trombocytopenia (HIT) is a serious and potentially fatal complication of patients on heparins. Its management is difficult and it can be more complicated in patients with cancer because of the hemorrhagic risk carried out by direct inhibitor of thrombin, the currently approved drug for HIT. At present, it is not clear whether cancer patients also have an increased risk of HIT. We describe the case of a patient with occult cancer at the moment of the index venous thrombosis, who developed Deep Vein Thrombosis (DVT) and concomitant HIT with thrombotic complications (recurrent contralateral venous thrombosis). The management of HIT was efficaciously based on the combined use of alternative antithrombotic regimens (Dermatan-Sulphate and Defibrotide), without an increased risk of bleeding. This case highlights the potential relationship between DVT, as first episode of an occult cancer, and the risk of developing HIT. The use of alternative antithrombotic therapy seems to be efficacious even in this high-risk cancer patient.
Decrease in Phosphorylation of ERK following Decreased Expression of NK Cell-Activating Receptors in Human NK Cell Line Exposed to Asbestos
Authors: Nishimura Y. , Maeda M. , Kumagai N. , Hayashi H. , Miura Y. , Otsuki T.
Published: January 2017

YT-CB5, which had been continuously cultured with chrysotile B (CB) asbestos, showed impaired cytotoxicity with decreased expression of NKG2D and 2B4 NK cell-activating receptors. In the present study, the phosphorylation of extracellular signal-regulated kinase (ERK), which is known to induce degranulation downstream of many NK cell-activating receptors, was examined in YT-CB5 by flow cytometry and compared with the control line YT-Org. YT-CB5 exhibited impaired phosphorylation of ERK1/2 induced by the recognition of K562 cells, downstream of a process mediated by Src family kinase and phosphoinositide 3-kinase. YT-CB5 also exhibited impaired phosphorylation of ERK1/2 following incubation with K562 cells in the presence of anti-2B4 antibodies, where co-stimulation by 2B4 augmented the phosphorylation of ERK1/2 in YT-CB5 to a similar degree as in YT-Org. The phosphorylation of ERK1/2 induced by an inhibitor against phosphatase (PP) 1 and PP2A was also lower in YT-CB5 compared with YT-Org. Moreover, bead-bound antibodies to NKG2D, which contribute to cytotoxicity against K562 cells, induced negligible phosphorylation of ERK1/2 in YT-CB5, although antibodies to 2B4. induced a comparatively greater level of phosphorylation. Additionally, peripheral blood (PB-) NK cells with low expression of NKG2D showed lower phosphorylation of ERK1/2 mediated by anti-NKG2D antibodies compared with PB-NK cells with high expression of NKG2D. These results indicate that signal transduction events leading to the phosphorylation of ERK is impaired in YT-CB5 due to decreased expression of NKG2D. Further studies are required to clarify whether this suppressive effect of asbestos exposure on NK cells might promote lung cancer and mesothelioma in people who have inhaled asbestos.
Beta Glycosphingolipids Suppress Rank Expression and Inhibit Natural Killer T Cell and CD8+ Accumulation in Alleviating Aortic Valve Calcification
Authors: Shuvy M. , Ya'Acov A. Ben , Zolotarov L. , Lotan C. , Ilan Y.
Published: January 2017

CD8 lymphocytes play a role in aortic valve inflammation leading to aortic valve calcification (AVC). RANK is a transmembrane protein that is important in osteoclast differentiation and calcification. β-glucosylceramide (β-GC) together with β-lactosylceramide (β-LC), the 1:1 combination of β-glucosylceramide and β-lactosylceramide, designated “IGL,” exerts an immune modulatory effect in various inflammatory disorders in a CD8- and NKT (natural killer T cell)-dependent manner. We hypothesized that IGL may affect the inflammatory condition associated with AVC. AVC was induced in rats by oral administration of a high-adenine, high-phosphorus diet and was assessed by multislice computer tomography. Administration of this diet was associated with a marked increase in CD8 and NKT lymphocyte accumulation in the aortic valve. Administration of IGL led to marked suppression of RANK expression, associated with inhibition of both NKT and CD8 lymphocyte accumulation in the aortic valve. These effects were associated with a significant improvement in the degree of AVC in IGL-treated animals (25 and 53 by Agatston Score, in IGL-treated and controls, respectively). CD8 and NKT lymphocytes play a role in the pathogenesis of AVC, and RANK-mediated NKT inhibition by β-glycosphingolipids can alleviate AVC.
Acute Rejection Features in Dual Kidney Transplant Recipients from Elderly Donors: Comparison of Calcineurin Inhibitor-Based and Calcineurin Inhibitor-Free Immunosuppressive Protocols
Authors: Aiello F.B. , Furian L. , Marino S. , Marchini F. , Cardillo M. , De Fazio N. , Rigotti P. , Valente M.
Published: January 2017

Features of acute rejection in dual kidney transplant have not been studied. The aim of this study is to compare acute rejections in dual kidney transplant recipients from elderly donors on different immunosuppressive protocols. Sixty-nine patients were evaluated: 28 received calcineurin inhibitor-based (group 1) and 41 received calcineurin inhibitor-free immunosuppression (group 2). Histology of all donor kidneys was evaluated before implantation. All rejections showed tubulitis in both groups, and were classified as T cell-mediated acute rejections. Incidence and Banff grade of rejections in the two groups were not significantly different. Late rejections however, were observed in group 1 ( P < 0.01) whereas steroid-resistant rejections occurred in group 2 ( P < 0.03). C4d deposition was only observed in group 2. Occurrence of acute rejection was significantly associated with graft loss due to interstitial fibrosis/tubular atrophy in both groups. In group 1 mean serum creatinine levels of patients with rejections at six months and one year were higher than those of patients without rejections ( P < 0.03 and P < 0.009, respectively). In group 2 they were higher at six months ( P < 0.01) but not at one year. In addition, graft loss due to interstitial fibrosis/tubular atrophy occurred in 3/28 patients in group 1 (10.7%, OR= 1.95, 95%CI 1.02–3.71), and in 1/41 patients in group 2 (2.4%, OR= 0.41, 95%CI 0.07–2.24). Taken together these results suggest better renal function in patients on calcineurin inhibitor-free immunosuppression. In conclusion, acute rejections were detrimental irrespective of the type of immunosuppression, but different features were observed with each therapy. A tailored approach should be advantageous for prevention and treatment of acute rejections.
Microbiological and Biochemical Effectiveness of an Antiseptic Gel on the Bacterial Contamination of the Inner Space of Dental Implants: A 3-Month Human Longitudinal Study
Authors: D'Ercole S. , Tetè S. , Catamo G. , Sammartino G. , Femminella B. , Tripodi D. , Spoto G. , Paolantonio M.
Published: January 2017

Microbial penetration inside the implant's internal cavity produces a bacterial reservoir that is associated with an area of inflamed connective tissue facing the fixture-abutment junction. The aim of this clinical trial is to evaluate the effectiveness of a 1% chlorhexidine gel on the internal bacterial contamination of implants with screw-retained abutments and on the level of AST secreted in peri-implant crevicular fluid. Twenty-five patients (aged 29 to 58 years) each received one implant. Three months after the end of the restorative treatment, and immediately after a clinical and radiographic examination and the abutment removal, microbiological samples were obtained from the internal part of each fixture and biochemical samples were collected by peri-implant sulci. The patients were then divided into two groups: the control (CG; n=10) and test (TG; n=15) groups. The CG had the abutment screwed into place and the crown cemented without any further intervention. In contrast, before the abutment placement and screw tightening, the TG had the internal part of the fixture filled with a 1% chlorhexidine gel. Three months later, the same clinical, microbiological and biochemical procedures were repeated in both groups. Total bacterial count, specific pathogens and AST activity were detected. The clinical parameters remained stable throughout the study. From baseline to the 3-month examination, the total bacterial counts underwent a significant reduction only in the TG. In contrast, the AST activity showed a significant increase in the CG. The administration of a 1% chlorhexidine gel appears to be an effective method for the reduction of bacterial colonization of the implant cavity and for safeguarding the health status of peri-implant tissue over a 3-month administration period.
T Cell Response in Acute Motor Axonal Neuropathy
Authors: Cencioni M.T. , Notturno F. , Caporale C.M. , Creati B. , Prencipe V. , Battistini L. , Uncini A.
Published: January 2017

There is evidence that in the acute axonal motor neuropathy (AMAN) subtype of Guillain-Barré syndrome antibodies to gangliosides, produced through molecular mimicry by antecedent Campylobacter jejuni ( C. jejuni) infection, attack gangliosides expressed in human peripheral nerve axolemma, inducing a primary axonal damage. The aim of this study is to investigate whether the T cell response has a role in AMAN pathogenesis. We isolated monocytes from 4 healthy subjects and 5 AMAN patients with antecedent C. jejuni infection and antibodies to GM1 and/or GDla gangliosides. Immature dendritic cells expressing CD1 molecules cultured with autologous T cells were stimulated with 2 lipopolysaccharides (LPSs) extracted from C. jejuni strains containing GM1 and GDla-like structures and with GM1 and GDla. The T cell response to LPSs and to gangliosides was determined by measuring the release of IFN-γ and TNF-α. We observed a T cell response to both LPSs in controls and AMAN patients, whereas only AMAN patients showed T cell reactivity to gangliosides GM1 and GD1a with a tight correlation between T cell reactivity to the ganglioside and individual antibody responses to the same ganglioside. T cells responding to gangliosides were CD1c-restricted CD8 positive and CD27 negative. These findings indicate a contribution of cellular immunity in the pathogenesis of AMAN. A possible role for ganglioside-reactive T cells might be to facilitate the production of antibodies against gangliosides.
Idiopathic Recurrent Pericarditis Refractory to Colchicine Treatment Can Reveal Tumor Necrosis Factor Receptor-Associated Periodic Syndrome
Authors: Cantarini L. , Lucherini O.M. , Cimaz R. , Baldari C.T. , Bellisai F. , Paccani S. Rossi , Pasini F. Laghi , Capecchi P.L. , Sebastiani G.D. , Galeazzi M.
Published: January 2017

Recurrences develop in up to 20–50% of patients with acute pericarditis. Although different causes of recurrent pericarditis have been identified, the etiology remains obscure in most cases which are therefore labelled as idiopathic. Autoinflammatory syndromes include familial Mediterranean fever (FMF), due to mutations in the MEFV gene, and tumor necrosis factor receptor-associated periodic syndrome (TRAPS), due to mutations in the TNFRSF1A gene. Recurrent pericarditis is a common feature of both conditions, but it rarely occurs alone. Colchicine is the standard treatment for FMF, while patients with TRAPS do not respond to colchicine therapy, but are responsive to corticosteroids. Based on the proven efficacy of colchicine in preventing polyserositis in FMF, colchicine has been proposed for the treatment of recurrent pericarditis and is able to decrease the recurrence rate. Our aim was to investigate the possible involvement of TNFRSF1A mutations in a group of patients with idiopathic recurrent pericarditis who were refractory to colchicine treatment. Thirty consecutive patients (17 males, 13 females) diagnosed with idiopathic recurrent pericarditis, who were characterized by a poor response to colchicine treatment, were enrolled in the study. Mutations of the TNFRSF1A gene were searched for by amplifying, using polymerase chain reaction (PCR), genomic DNA, and direct sequencing. TNFRSF1A mutations were found in 4 of the 30 patients. None of these 4 patients had a family history of recurrent inflammatory syndromes or history of pericarditis. One of the 4 patients had a novel heterozygous deletion (ΔY103-R104) and three patients carried a heterozygous low-penetrance R92Q mutation. Our data suggest that TRAPS should be kept in mind in the differential diagnosis of recurrent pericarditis, and mutation analysis of the TNFRSF1A gene should be considered, in addition to MEFV analysis, in patients of Mediterranean origin. A poor response to colchicine treatment and/or a steroid-dependence may be the clue to investigate TNFRSF1A mutations in patients with idiopathic recurrent pericarditis.
Clinical Importance of Eosinophil Count in Nasal Fluid in Patients with Allergic and Non-Allergic Rhinitis
Authors: Di Lorenzo G. , Mansueto P. , Pacor M.L. , Martinelli N. , Rizzo M. , Ditta V. , Leto-Barone M.S. , D'Alcamo A. , Politi D. , Pepe I. , Rotolo G. , Di Fede G. , Caruso C. , Rini G.B. , Corrocher R.
Published: January 2017

Eosinophil count in nasal fluid (ECNF) was used to differentiate nasal pathologies. Receiver Operating Characteristic (ROC) curve analysis and the area under the curve (AUC) were performed to evaluate the ECNF's accuracy in distinguishing allergic rhinitis (AR) from non-allergic rhinitis (NAR). We also evaluated the accuracy of ECNF in recognizing patients with mild and severe symptoms of rhinitis and patients with ineffective and effective clinical responses to antihistamines. 1,170 consecutive adult patients with a clinical history of rhinitis were studied. ECNF's median in AR was 6.0 and 2.0 in NAR and the best cut-off value was > 3.0, AUC = 0.75. ECNF's median in AR with mild nasal symptoms was 3.0 and 7.0 with severe symptoms, and the best cut-off value was 4.0, AUC = 0.90. ECNF's median in NAR with mild nasal symptoms was 2.0 and 8.5 with severe symptoms, and the best cut-off value was > 4.0, AUC = 0.86. ECNF's median in AR with effective clinical response to antihistamines was 4.0 and 8.0 with ineffective response, the best cut-off value was ≤ 5.0, AUC = 0.94. ECNF's median in NAR with an effective clinical response to antihistamines was 1.0 and 2.0 with ineffective response, and the best cut-off value was ≤ 3.0, AUC = 0.64. Our results suggest an interesting practical use of ECNF data as evaluator of the clinical severity both AR and NAR. As predictor of the clinical response to antihistamines, ECNF is accurate only in patients with AR. The ECNF's performance was moderately accurate in distinguish patients with AR and NAR.
Tunel and Growth Factor Expression in the Prefrontal Cortex of Alzheimer Patients over 80 Years Old
Authors: Lorke D.E. , Wai M.S.M. , Liang Y. , Yew D.T.
Published: January 2017

To elucidate factors underlying the increased risk of developing Alzheimer's disease (AD) in older individuals, the prefrontal cortices of younger (58–79 years) and of older (over 80 years) AD patients were examined by silver impregnation, TUNEL assay and immunohistochemistry for hyperphosphorylated tau, LDH and two growth factors (BDNF, NGF). Quantitative data were compared with those of age-matched controls. TUNEL-positive cells were mainly located in superficial cortical layers of younger and in deeper layers of older AD patients. Their density was more than 5 times higher in older AD than in younger AD (p≤ .05), but apoptotic cell morphology was rarely seen. Significantly more neuronal somas were contacted by degenerating fibers both in younger and older AD cortices. Density of tauimmunoreactive cells, which were virtually absent in controls, was twice as high in older AD patients as in younger AD individuals (p≤ .05). In younger AD, TUNEL positive cells generally lacked tau immunoreaction, whereas in older AD, most cells were double-labeled for hyperphosphorylated tau and TUNEL (p≤ .05). Numerical density of BDNF-immunoreactive cells was significantly reduced by 20% in older AD patients, compared to both control individuals and younger AD patients, whereas density of NGF-positive cells was the same in all patient groups examined. The distinct differences between younger and older AD patients suggest a faster progression of AD in older patients.
Serum and Gene Expression Profile of Tumor Necrosis Factor-α and Interleukin-6 in Hypertensive Diabetic Patients: Effect of Amlodipine Administration
Authors: Navarro-González J. , Mora-Fernández C. , Gómez-Chinchón M. , Muros M. , Herrera H. , García J.
Published: January 2017

Pro-inflammatory cytokines are critical factors in type 2 diabetes-associated atherosclerosis. We aim to analyze in hypertensive type 2 diabetic patients the serum concentrations and the mRNA expression levels in peripheral blood mononuclear cells (PBMC) of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), as well as to evaluate the effect of amlodipine administration. Twenty-one hypertensive diabetic patients and 10 healthy non-diabetic controls were included in the study. Serum levels of cytokines were measured by chemiluminescent immunometric assay, and mRNA expression levels by RT-PCR. The mean serum concentrations of TNF-α and IL-6 in diabetic patients showed a 6.1-fold and 2.9-fold increase with respect to non-diabetic control subjects, respectively (p<0.0001). Likewise, there was a 3.3- and a 4-fold increase in the PBMC mRNA expression level of TNF-α and IL-6 (p<0.0001) in diabetic subjects. After amlodipine administration, a significant decrease (p<0.01) was observed in the serum TNF-α and IL-6 levels. In addition, pre-treatment mRNA expression of TNF-α and IL-6 also decreased, with a mean percent reduction of 26% (p<0.01) and 25% (p<0.001), respectively. In conclusion, serum concentrations and PBMC mRNA expression levels of TNF-α and IL-6 are significantly elevated in hypertensive type 2 diabetic patients. Administration of amlodipine is associated with a significant reduction of the increased levels of these inflammatory parameters, both at the protein as well as at the transcriptional level. These modulatory effects of amlodipine on proinflammatory cytokine level and expression may be related to its suggested anti-atherosclerotic actions.
1,5-Anhydroglucitol Attenuates Cytokine Release and Protects Mice with Type 2 Diabetes from Inflammatory Reactions
Authors: Meng X. , Tancharoen S. , Kawahara K-I. , Nawa Y. , Taniguchi S. , Hashiguchi T. , Maruyama I.
Published: January 2017

1,5-anhydroglucitol (1,5-AG) decreases in diabetic patients and is used as a marker of glycemic control. Type 2 diabetic patients are susceptibile to lipopolysaccharides (LPS), which stimulate macrophages to release large quantities of tumor necrosis factor (TNF)-α and interleukin (IL)-6. This study examines the effects of 1,5-AG on lung inflammation induced by LPS and consequent systemic inflammation to determine whether the decrease of 1,5-AG concentration induces susceptibility to LPS. Before the challenge with LPS (1 mg/kg in vivo and 500 ng/ml in vitro), we pretreated db/db mice and RAW264.7 cells with 1,5-AG at 38.5 mg/kg and 500 μg/ml, respectively. The levels of IL-6, TNF-α, macrophage chemoattractant protein (MCP)-1 and IL-1β in the serum and in the cell supernatants were measured. We also measured macrophage recruitment and the expression of inducible nitric oxide synthase (iNOS) in pulmonary tissues. We found that 1,5-AG attenuated serum cytokine release and protected db/db mice from LPS-induced pulmonary inflammation. In addition, 1,5-AG suppressed cytokine release and iNOS expression by suppressing Akt/NF-κB activity in RAW264.7 cells. These results suggest that 1,5-AG may be a mediator in, as well as marker for diabetes, and 1,5-AG intake may confer tolerance to LPS in patients with type 2 diabetes.
Oral Hyposensitization to Nickel Induces Clinical Improvement and a Decrease in TH1 and TH2 Cytokines in Patients with Systemic Nickel Allergy Syndrome
Authors: Minelli M. , Schiavino D. , Musca F. , Bruno M.E. , Falagiani P. , Mistrello G. , Riva G. , Braga M. , Turi M.C. , Di Rienzo V. , Petrarca C. , Schiavone C. , Di Gioacchino M.
Published: January 2017

Some patients with nickel (Ni) allergic contact dermatitis suffer from systemic (intestinal or cutaneous) symptoms after ingestion of Ni-rich foods and experience symptoms reduction with low-Ni diet, a condition termed “systemic Ni allergy syndrome” (SNAS). We aimed at evaluating whether oral administration of low nickel doses improved clinical conditions and modulated immunological aspects of SNAS, without significant side effects. Thirty-six SNAS patients were enrolled. Treatment started after 1-month of low-Ni diet and consisted in an incremental oral NiOH dose phase (0.3ng to 1.5 μg/week) followed by a 12-months maintenance phase (1.5 μg/week). Randomly, twenty-four patients added Ni therapy to low-Ni diet and 12 remained with diet alone. All patients were allowed rescue medications (antihistamines and topical steroids). After 4 months, Ni-rich foods were gradually reintroduced. In vitro allergen-driven IL13, IL5 and IFNγ release by peripheral blood mononuclear cells was evaluated before and after treatment. Twenty-three patients receiving NiOH and the 12 control patients completed the study. Evaluation of SNAS clinical severity (by VAS and drug consumption) showed a significant difference in favor of NiOH-treated patients compared to controls. Twenty of 23 patients in the NiOH group and none in the control group tolerated Ni-rich food reintroduction. Release of all studied cytokines in culture supernatants was significantly lower after NiOH treatment. In conclusion NiOH is effective in reducing symptoms and drug consumption in SNAS and is able to modulate inflammatory parameters.
Circulating Plasma Antioxidants, Inflammatory Markers and Asymptomatic Carotid Atherosclerosis in End-Stage Renal Disease Patients: A Case Control Study
Authors: Riccioni G. , D'Orazio N. , Scotti L. , Petruzzelli R. , Latino A. , Bucciarelli V. , Pennelli A. , Cicolini G. , Di Ilio E. , Bucciarelli T.
Published: January 2017

Few studies have been conducted on the relationship between antioxidant plasma vitamin concentrations, inflammatory markers and carotid atherosclerosis with inconclusive results in end-stage renal disease (ESRD) patients. A case-control study was performed to investigate the relationship between plasma antioxidant concentrations, inflammatory markers, and carotid intima-media thickness (CIMT) in healthy subjects and in patients undergoing hemodialysis (HD). We enrolled 40 subjects (20 healthy, 20 with ESRD) asymptomatic for carotid atherosclerosis. After carotid ultrasound investigation (CUI), medical history data, physical examination, venous blood samples were collected. These were analyzed for concentrations of antioxidant vitamins (A, E), carotenoids (lycopene, β-carotene), inflammatory markers (C-reactive protein, fibrinogen), and lipid profile. Low concentrations of vitamin A, vitamin E, lycopene, and β-carotene were significantly associated with carotid atherosclerosis in patients with ESRD (p<0.001). In addition, high concentration of low density lipoprotein cholesterol and total cholesterol (p<0.01), C-reactive protein and fibrinogen (p<0.001) were also associated with carotid atherosclerosis, while other laboratory parameters considered (high density lipoprotein cholesterol and triglycerides) were not significantly associated with carotid atherosclerosis. A regular intake of foods rich in antioxidant vitamins with low fat concentrations may slow the progression of atherosclerotic process in this group of patients.
Electrochemical Behaviour of Titanium in Ammine and Stannous Fluoride and Chlorexidine 0.2% Mouthwashes
Authors: Quaranta A. , Ronconi L.F. , Di Carlo F. , Vozza I. , Quaranta M.
Published: January 2017

Titanium (Ti) is widely used in dentistry. Fluorides at acid pH could destabilize Ti oxide and make it susceptible to corrosion. The behaviour of IV grade machined Ti disks in 5 electrolytic solutions: Fusayama artificial saliva (Fas), ammine fluoride-stannous fluoride (Am-SnF2), 0.2% Chlorexidine (CHX) 0.20%, Fas with 20% Am-SnF2 and Fas with 20% CHX, was evaluated. Open circuit potential E was determined by immersing Ti disks for 24 hours in an electrochemical cell containing the solutions, potential changes were measured until a stable value was obtained. Examination by Scanning Electronic Microscope and Energy Dispersive X-ray Analysis were then performed. One way ANOVA analysis showed a significant difference of Ecorr values regarding the 5 solutions (p<0.001). The highest values were observed for Fas (−37.6 mV), intermediate for Am-SnF2 (−81mV) and lowest for CHX (−87.6mV). SEM analysis of disks after polarization curve in CHX showed a marked localized corrosion, while the other solutions showed no considerable corrosive action on Ti surface. When considering corrosive potential range in oral cavity, Ti had an excellent behaviour on both antiseptics evaluated. The results obtained in this study will enable us to recommend the use of Am-SnF2 mouthwash for patients with dental implants.
Peripheral TH-17 Cells in Children with Allergic Rhinitis: Preliminary Report
Authors: Ciprandi G. , Castellazzi A.M. , Fenoglio D. , Battaglia F. , Marseglia G.
Published: January 2017

Th17 is a subset of T helper lymphocytes and exerts pro-inflammatory activities. Recently, it has been reported that serum IL-17 levels are high in the most severe patients with birch allergy studied both outside and during the pollen season. This study aims to compare the frequency of peripheral IL-17-producing T cells in children with allergic rhinitis and in healthy controls. Ten children with allergic rhinitis and 5 healthy non-allergic subjects were evaluated. Th17 were evaluated by intracellular staining in ex-vivo T cell compartment. Ex- vivo PBMNC evaluation showed that allergic patients had higher frequencies of IL-17 producing T cells, both concerning CD4+ and CD8+ cells. In particular, there is a subset co-expressing IL-17 and IFN-γ both for CD4+ and CD8+ cells. In conclusion, this preliminary study suggests a possible role of Th-17 cells in the response to allergens in children.
Helicobacter Pylori Therapy in Children: Overview and Challenges
Authors: Chiesa C. , Pacifico L. , Anania C. , Poggiogalle E. , Chiarelli F. , Osborn J.F.
Published: January 2017

Helicobacter pylori is one of the most common infections found in humans. It was first identified in 1982 and by 1989 had been associated with gastric inflammation and ulcers in adults and children. During the 1990's evidence emerged of its etiologic role in stomach cancers in adults. That the infection is common and may have serious consequences, has led to an avalanche of research during the last twenty years. During this time, there have been many studies on children which have sought an effective and safe treatment to eradicate the infection, but as yet, no therapy regimen has been found which is always effective and safe. This article provides information, from a pediatric point of view, on the major developments in the therapeutics and therapy of H. pylori infection. It examines first-line treatment regimens, evaluates the efficacy of the main drugs used in the management of (primary) H. pylori infection in children, assesses the potential for the use of probiotics and sequential therapy, examines therapeutic options after failure of initial treatment, and discusses factors affecting eradication rate, including antibiotic resistance, adherence to therapy, and bacterial factors.
The Effect of Newer Serotonin-Noradrenalin Antidepressants on Cytokine Production: A Review of the Current Literature
Authors: De Berardis D. , Conti C.M.V. , Serroni N. , Moschetta F.S. , Olivieri L. , Carano A. , Salerno R.M. , Cavuto M. , Farina B. , Alessandrini M. , Janiri L. , Pozzi G. , Di Giannantonio M.
Published: January 2017

Cytokines may influence brain activities especially during stressful conditions, and elevated levels of IL-6 and C-reactive protein have been pointed out in subjects with Major Depression. If pro-inflammatory cytokines play a causative role in major depressive disorders, one would expect that antidepressants may down-regulate these cytokines or interfere with their actions, leading to improvement of depressive symptoms. Accumulating evidence has been published that antidepressants modulate cytokine production and this is particularly true for Tricyclics and Selective serotonin reuptake inhibitors (SSRIs), but the influence of newer antidepressants acting on both serotonin (5-HT) and norepinephrine (NE) such as venlafaxine, duloxetine and mirtazapine on cytokine levels has not been extensively studied. However, both pre-clinical and clinical studies examined in this review have demonstrated that newer serotonin-noradrenalin antidepressants can inhibit the production and/or release of pro-inflammatory cytokines and stimulate the production of anti-inflammatory cytokines, suggesting that reductions in inflammation might contribute to treatment response. Moreover, the results of the present review support the notion that the serotonin-noradrenalin antidepressants venlafaxine and mirtazapine may influence cytokine secretion in patients affected by MD, restoring the equilibrium between their physiological and pathological levels and leading to recovery. To date, no studies have evaluated the effect of duloxetine, the newest serotonin-noradrenalin antidepressant, on cytokine levels and therefore this should be evaluated in future studies.