bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibacterial Activity and Anti-Biofilm Effect of Chitosan against Strains of Streptococcus Mutans Isolated in Dental Plaque
Authors: Pasquantonio G. , Greco C. , Prenna M. , Ripa C. , Vitali L.A. , Petrelli D. , Di Luca M.C. , Ripa S.
Published: January 2017

Streptococcus mutans is the major cause of dental plaque and is often associated with biofilm formation. The aim of this study is to evaluate the activity of a hydrosoluble derivative of chitosan against S. mutans biofilms in vitro and in vivo. Strains of S. mutans were isolated from the dental plaque of 84 patients enrolled in the study. The antibacterial activity of chitosan was determined by broth microdilutions. The effect of chitosan at different concentrations and exposure times on S. mutans biofilms at different phases of development was assessed by a clinical study using the classical “4-day plaque regrowth” experiment in adult volunteers. The MIC values of chitosan were between 0.5 and 2 g/L. Compared to distilled water, the chitosan solution significantly decreased the vitality of plaque microflora (p≤0.05). Chlorhexidine, used as a positive control, reduced vitality even further. The results showed that S. mutans in the adhesion phase (4 h) was completely inhibited by chitosan at any concentration (0.1, 0.2, 0.5XMIC) or exposure time investigated (1, 15, 30, 60 min), while S. mutans at successive stages of accumulation (12–24 h) was inhibited only by higher concentrations and longer exposure times. These data confirm the effective action of chitosan against S. mutans biofilms.
Chlamydia Pneumoniae and Chronic Diseases with a Great Impact on Public Health
Authors: Sessa R. , Cipriani P. , Di Pietro M. , Schiavoni G. , Santino I. , Del Piano M.
Published: January 2017

Chlamydia pneumoniae is recognised as a common cause of respiratory tract infections and has recently been implicated in several extrapulmonary chronic diseases, with great impact on public health, such as atherosclerosis, multiple sclerosis and Alzheimer's disease. The involvement of C. pneumoniae in such diseases may be correlated to characteristic features of this pathogen, including intracellular growth and ability to induce persistent forms. C. pneumoniae persistent forms are inherently more suited to evade the host immune response and are more difficult to eradicate by antibiotics. Our preliminary experimental findings show that interaction of C. pneumoniae with macrophages and/or T cells characterized by interference with TNF-α production, and redox state, culminates in the induction of T cell apoptosis and survival of infected macrophages. Based on our evidence, the poor cooperation between T cells and macrophages could lead to an inappropriate immune response against C. pneumoniae that may therefore promote the development of extrapulmonary chronic diseases.
Holly's Story: Illustration of an Attention Deficit Hyperactivity Disorder Case
Authors: Aureli A. , Piancatelli D. , Del Beato T. , Sebastiani P. , Melillo V. , Marimpietri A. , Sechi E. , Di Loreto S.
Published: January 2017

During the last 10 years a significant increase of childhood neuropsychiatric disorders, such as attention deficit hyperactivity disorder (ADHD), has been reported. ADHD is believed to have a multifactorial etiology including multiple genetic and prenatal environmental factors. For this reason, there has been a recent revival regarding the role of autoimmunity in this pathology. An ADHD combined-type patient born from a drug-addicted mother was studied. Neuropsychological tests according to the criteria of the 4th edition of the Diagnostic and Statistical Manual (DSM4) permitted us to make the ADHD-diagnosis. The HLA-A, -B, and -DRB1 alleles of the child were determined by sequence-based typing (SBT) after DNA extraction. Although no autistic behavioral features were observed in the patient, a double genetic association between ADHD and autism was reported. In fact, HLA class I alleles (A*02 and B*44) associated to autism and the HLA class II allele (DRB1*04) associated both to autism and ADHD were identified.
Immunological Treatments for Occupational Allergy
Authors: Crivellaro M. , Senna G. , Marcer G. , Passalacqua G.
Published: January 2017

Although avoidance of occupational triggers remains the primary step in the management of work-related allergies, immunological treatments (including biological agents and specific immunotherapy) can be regarded as potential therapeutic options for IgE-mediated diseases; for example, many studies with allergen-specific immunotherapy have been carried out on latex allergy, showing overall favorable results, at least with sublingual immunotherapy. On the other hand, only few case reports have suggested the efficacy of immunotherapy in baker's asthma as well as in laboratory animal-induced asthma. The new technologies, including component-resolved diagnosis and recombinant allergens, are expected to improve the quality and efficacy of specific immunotherapy in the future. Also the use of omalizumab may represent a suitable therapeutic choice in very selected cases of occupational allergy, as well as an approach to reduce side effects of venom immunotherapy in subjects with previous severe reactions to the treatment.
Use of Oral Chroma™ in the Assessment of Volatile Sulfur Compounds in Patients with Fixed Prostheses
Authors: Sinjari B. , Murmura G. , Caputi S. , Ricci L. , Varvara G. , Scarano A.
Published: January 2017

Prosthetic rehabilitation improves the patient's quality of life and oral health. The purpose of the present study was to assess the production of volatile sulfur compounds (VSCs) using Oral Chroma™ in patients wearing provisional and permanent fixed prosthesis, who were treated or not, with supportive non-surgical periodontal therapy. A total of 10 healthy patients not affected by periodontal disease and who needed the restoration of at least two edentulous single sites were included in the present study. Registrations of VSCs were carried out with a Gas Chromatograph OralChroma™ (Oral Chroma™, Abimedical, Abilit Corp., Osaka, Japan) one month after placement of the provisional restoration (group 1) and one month after placement of the final restoration (group 3). After each measurement, professional oral hygiene was carried out both on patients with provisional (group 2) and permanent prostheses (group 4) and VSC values were registered. The results showed that there were no statistical significant differences in the VSC quantity between groups with temporary or permanent prostheses. Meanwhile, statistically significant differences were found in VCS values between groups before and after the professional health care session (p < 0.05). Also it was observed that dimethyl sulphide (CH3)2S was present in all the study groups. The present preliminary study suggests that OralChroma™ produce a comprehensive assessment of VSC in the clinical diagnosis of halitosis and that professional oral hygiene seems to influence VSC production. However, further clinical long-term studies with a larger sample size are necessary for a better understanding of halitosis manifestation in patients wearing provisional and permanent fixed prosthesis.
Systemic Nickel Allergy Syndrome: Nosologic Framework and Usefulness of Diet Regimen for Diagnosis
Authors: Braga M. , Quecchia C. , Perotta C. , Timpini A. , Maccarinelli K. , Di Tommaso L. , Di Gioacchino M.
Published: January 2017

Systemic (gastrointestinal and skin) reactions to ingestion of nickel rich foods in patients with nickel allergic contact dermatitis characterize Systemic Nickel Allergy Syndrome (SNAS). The objective of the study was to describe the nosologic framework of the syndrome and to compare sensibility and specificity for SNAS diagnosis between two different low nickel diets - BraMa-Ni and the usually prescribed list of forbidden foods - along with patient adherence to diet. One hundred forty-five patients with suspected SNAS (by history and benefit from nickel dietary restrictions) were selected and orally challenged with nickel for a definite diagnosis. Specificity and sensibility of the diets were calculated in relation to the results of nickel challenges. The nosologic framework of SNAS was deduced from the clinical pictures of 98 patients with positive nickel challenge and characterized essentially by skin and gastrointestinal symptoms, whereas all other symptoms (dizziness, headache etc.) were never elicited by the oral nickel challenge. The specificity and sensibility of BraMa-Ni in detecting SNAS were significantly higher than the forbidden food list diet, with an excellent patient adherence. Therefore, BraMa-Ni diet can be prescribed for the treatment of the syndrome other than for the diagnosis, the gold standard of which remains the oral nickel challenge.
The Role of Transforming Growth Factor-β1 in Airway Inflammation of Childhood Asthma
Authors: Gagliardo R. , Chanez P. , Gjomarkaj M. , La Grutta S. , Bonanno A. , Montalbano A.M. , Di Sano C. , Albano G.D. , Gras D. , Anzalone G. , Riccobono L. , Profita M.
Published: January 2017

TGF-β-targeting structural and inflammatory cells has been implicated in the mechanisms leading to the inflammatory and restructuring processes in asthma, suggesting an impact of TGF-β1 signaling on the development and persistency of this disease. We investigated the potential early involvement of TGF-β1 activity in the immunological and molecular mechanisms underlying progression of inflammation in childhood asthma. We evaluated the levels of TGF-β1 in induced sputum supernatants (ISSs) and the expression of small mother cell against decapentaplegic (Smad) 2 and Smad7 proteins in induced sputum cells (ISCs) from children with intermittent asthma (IA), moderate asthma (MA) and control subjects (C). Furthermore, we investigated the regulatory role of TGF-β1 activity on eosinophil and neutrophil adhesion to epithelial cells using adhesion assay, and on the granulocyte expression of adhesion molecule CD11b/CD18 Macrophage-1 antigen (MAC-1), by flow cytometry. We found that the levels of TGF-β1 are increased in ISSs of IA and MA in comparison to C, concomitantly to the activation of intracellular signaling TGFβ/Smads pathway in ISCs. In MA, TGF-β1 levels correlated with the number of sputum eosinophils and neutrophils. Furthermore, we showed the ability of sputum TGF-β1 to promote eosinophil and neutrophil adhesion to epithelial cells, and to increase the expression of MAC-1 on the granulocyte surface. This study shows the activation of TGFβ/Smad signaling pathway in the airways of children with IA and, despite the regular ICS treatment, in children with MA, and provides evidence for the contribution of TGF-β1 in the regulation of granulocyte activation and trafficking.
Huperzine A Inhibits CCL2 Production in Experimental Autoimmune Encephalomyelitis Mice and in Cultured Astrocyte
Authors: Tian G.X. , Zhu X.Q. , Chen Y. , Wu G.C. , Wang J.
Published: January 2017

The active role of chemokines and inflammatory cytokines in the central nervous system (CNS) during the pathogenesis of experimental autoimmune encephalomyelitis (EAE) has been clearly established. Recent studies from our laboratory reported that Huperzine A (HupA) can attenuate the disease process in EAE by the inhibition of inflammation, demyelination, and axonal injury in the spinal cord as well as encephalomyelitic T-cell proliferation. In this study, the effects of low dose HupA on CCL2, TNF-α, IL-6, and IL-1β expression were evaluated in EAE. The effect of HupA on lipopolysachharide (LPS)-induced inflammatory molecule secretion was investigated in cultured-astrocytes in vitro. In MOG35-55-induced EAE mice, intraperitoneal injections of HupA (0.1 mg/kg·d−1) significantly suppressed the expression of CCL2, IL-6, TNF-alpha, and IL-1beta in the spinal cord. HupA also repressed LPS-induced CCL2 production, but with little influence on pro-inflammatory cytokines in primary cultured astrocytes. The inhibition effect of HupA on CCL2 is PPARγ-dependent and nicotine receptor-independent. Conditioned culture media from HupA-treated astrocyte decreased PBMC migration in vitro. Collectively, these results suggest that HupA can ameliorate EAE by inhibiting CCL2 production in astrocyte, which may consequently decrease inflammatory cell infiltration in the spinal cord. HupA may have a potential therapeutic value for the treatment of MS and other neuroinflammatory diseases.
Remission of Psoriatic Arthritis after Etanercept Discontinuation: Analysis of Patients' Clinical Characteristics Leading to Disease Relapse
Authors: Chimenti M.S. , Esposito M. , Giunta A. , Graceffa D. , Babino G. , Teoli M. , Mazzotta A. , Perricone R. , Chimenti S.
Published: January 2017

Psoriatic arthritis is a chronic, inflammatory, disabling arthritis affecting up to 30% of psoriatic patients. Recently, it has been demonstrated that tumor necrosis factor alpha (TNF-α) plays a pivotal role in inducing and maintaining joint damage and that molecules that block this cytokine are effective in the treatment of psoriatic arthritis. Etanercept is a recombinant fusion protein acting as a competitive inhibitor of TNF-α, and numerous clinical trials have demonstrated its efficacy in determining psoriatic arthritis remission. However, specific criteria defining psoriatic arthritis remission have not been delineated and few data describing the length of the remission after etanercept discontinuation are available. The aim of this observational, retrospective study was to assess post-remission efficacy maintenance and relapse characteristics after etanercept interruption in patients with moderate-to-severe peripheral psoriatic arthritis (PsA) and cutaneous involvement.
Natalizumab Treatment in Multiple Sclerosis Patients: A Multicenter Experience in Clinical Practice in Italy
Authors: Totaro R. , Lugaresi A. , Bellantonio P. , Danni M. , Costantino G. , Gasperini C. , Florio C. , Pucci E. , Maddestra M. , Spitaleri D. , Lus G. , Ardito B. , Farina D. , Rossi M. , Di Carmine C. , Altobelli E. , Maccarone B. , Casalena A. , De Luca G. , Travaglini D. , Di Ioia M. , Di Tommaso V. , Fantozzi R. , Ruggieri S. , Provinciali L. , De Riso S. , Mundi C. , Fuiani A. , Galgani S. , Ruggieri S. , Maniscalco G.T. , Giuliani G. , Cartechini E. , Petretta V. , Fratta M. , Alfieri G. , Gatto M. , Carolei A. ,   on behalf of Natalizumab Long-Term Treatment Study group (NALTET)
Published: January 2017

We evaluated efficacy of natalizumab in relapsing-remitting multiple sclerosis patients in a clinical practice setting. We report data on the first consecutive 343 patients receiving natalizumab in 12 multiple sclerosis (MS) Italian centers enrolled between April 2007 and November 2010. The main efficacy endpoints were the proportion of patients free from relapses, disease progression, combined clinical activity, defined as presence of relapse or disease progression, from MRI activity, and from any disease activity defined as the absence of any single or combined activity. At the end of follow-up, the cumulative proportion of patients free from relapses was 68%; the proportion of patients free from Expanded Disability Status Scale (EDSS) progression was 93%; the proportion of patients free from combined clinical activity was 65%; the proportion of patients free from MRI activity was 77%; and the proportion of patients free from any disease activity was 53%. Natalizumab was effective in reducing clinical and neuroradiological disease activity. Its effectiveness in clinical practice is higher than that reported in pivotal trials and was maintained over time.
Risk Factors Affecting Quality of Life in a Group of Italian Children with Asthma
Authors: Indinnimeo L. , Chiarotti F. , De Vittori V. , Baldini L. , De Castro G. , Zicari A.M. , Tancredi G. , Leonardi L. , Duse M.
Published: January 2017

The measure of Quality of Life (QoL) has become one of the most important criteria used to assess the impact of chronic illness, such as asthma, on the patient's daily life, in adults and children alike. The objective of our open observational study was to measure the QoL and analyze several factors that potentially affect QoL, such as symptoms and functional respiratory parameters, in a cohort of children with asthma. One hundred and twenty-seven children with asthma, 6 to 14 years of age, living in the city of Rome, were enrolled as outpatients. They were subjected to Skin Prick Tests (SPT), underwent spirometry and filled out the Pediatric Asthma Quality of Life Questionnaire (PAQLQ). One hundred and eleven children were diagnosed with intermittent asthma, 12 (10%) with mild asthma, and four with moderate persistent asthma. Ninety-six children had a positive SPT. The mean total score of QoL, obtained from the questionnaire, was 5.4 (±1.2 SD). Two QoL groups were created. Children with total QoL score <5.5 were included in the “Lower QoL” score group while children with total QoL score ≥ 5.5 were included in the “Higher QoL” score group. Children in the Higher group and their mothers had a higher mean age, suffered from fewer asthma exacerbations during the year preceding the study, and showed a higher mean value of forced expiratory volume (FEV1) compared to the children in the Lower category. Using Logistic regression we identified the main factors that may affect QoL as FEV1, symptoms in the previous year and mother's age. QoL is correlated with the frequency of asthma exacerbations and FEV1 values. Furthermore, our research shows that a significant impairment of QoL may also occur in patients with normal lung function, pointing out the importance of evaluating QoL in all children with asthma.
Local rhBMP-2 Injection after Drill-Hole Injury in Rats: Does it Have Systemic Effects?
Authors: Demirkan N. , Demirkan F. , Aksoy A. , Özdemir M. , Akman A.
Published: January 2017

The aim of this study is to investigate the histopathological findings of drill hole healing and interactions of parathyroid hormone (PTH), β-catenin and transcription factor-4 (TCF7L2/Tcf-4) after local application of recombinant human bone morphogenic protein-2 (rhBMP-2). Sprague Dawley rats were used in two groups of ‘femoral cortex hole model’. In the non-treated group, a hole was opened with a 3 mm K-wire in the distal and mid third junction of the right femur. In the treated group, local rhBMP-2 protein was injected into the similar femoral hole. Sterile 18M H2O was injected into the femoral hole at contralateral femur. There was more subperiosteal membranous bone reaction in the group treated with rhBMP-2 injection compared to the non-treated group. This was also proven immunohistochemically in both ipsilateral and contralateral femur with increased anti bone morphogenic protein-2 (anti BMP-2) expression. Moreover, there was an increased subperiosteal reaction at the contralateral femur. Also, in the treated group, PTH expression was increased in cells that form callus, and nuclear beta-catenin expression was increased in chondrocytes of periosteal ossification. Future studies should try to find whether the effects of rhBMP-2 on PTH and Wnt signaling pathway changes with different fracture models, also the systemic effects of local rhBMP-2 application should be investigated.
Modulation of MMP-2 and MMP-9 in Churg-Strauss Syndrome Respiratory Mucosa: Potential Monitoring Parameters
Authors: Leone A. , Uzzo M.L. , Gerbino A. , Tortorici S. , Tralongo P. , Cappello F. , Incandela S. , Spatola G.F. , Jurjus A.R.
Published: January 2017

Churg-Strauss (CSS) syndrome is rare and of unknown etiology. It is associated with vasculitis, blood eosinophilia and granulomatosis, and affects multiple organs and systems at various stages of the disease. Specific diagnostic and monitoring tests are not yet available. This study aims to assess the changes in MMP-2 and MMP-9 along with the histopathological alterations in two cases of CSS, as possible potential diagnostic and monitoring criteria. Two adult male patients were diagnosed with CSS in the otorhinolaryngology clinic in the University of Palermo, based on multiple clinical and histopathologic criteria. Biopsies of respiratory mucosa were taken after the consent of the patients, processed for routine histopathology and immunohistochemistry as well as quantitative polymerase chain reaction (qPCR). Similar biopsies were also taken from a non-CSS patient. The Assessment of MMP-2 and MMP-9 was performed using both immunohistochemistry and qPCR techniques. Histopathological alterations in the respiratory mucosa were consistent with vasculitis and granulomatous tissue formation, in addition to inflammatory cell infiltration with abundance of eosinophils. Immunohistochemistry assay performed on the samples derived from the two CSS patients showed a relative and remarkable increase of both MMP-2 and MMP-9 compared to controls. Such an increase was consistent with the qPCR results which depicted a significant increase between 20 and 30% for both MMP-2 and MMP-9, respectively. Since the secretion of MMPs is an essential step in angiogenesis, could these enzymatic factors be used as parameters to diagnose or monitor the evolution of CSS? The small number of samples analyzed in this study does not allow us to suggest a general statement correlating the increase in expression of MMP-2 and MMP-9 to the appearance or evolution of vasculitis; it is only speculative.
Review on Medicinal Uses, Pharmacological, Phytochemistry and Immunomodulatory Activity of Plants
Authors: Akram M. , Hamid A. , Khalil A. , Ghaffar A. , Tayyaba N. , Saeed A. , Ali M. , Naveed A.
Published: January 2017

Since ancient times, plants have been an exemplary source of medicine. Researchers have discovered some important compounds from plants. The present work constitutes a review of the medicinal plants whose immunomodulant activity has been proven. We performed PUBMED, EMBASE, Google scholar searches for research papers of medicinal plants having immunomodulant activity. Medicinal plants used by traditional physicians or reported as having immunomodulant activity include Acacia concocinna, Camellia sinensis, Lawsonia inermis Linn, Piper longum Linn, Gelidium amansii, Petroselinum crispum, Plantago major and Allium sativum. Immunomodulant activities of some of these medicinal plants have been investigated. The medicinal plants documented have immunomodulant activity and should be further investigated via clinical trial.
Evaluation of CD44 Variant Expression in Oral, Head and Neck Squamous Cell Carcinomas Using a Triple Approach and its Clinical Significance
Authors: Athanassiou-Papaefthymiou M. , Shkeir O. , Kim D. , Divi V. , Matossian M. , Owen J.H. , Czerwinski M.J. , Papagerakis P. , McHugh J. , Bradford C.R. , Carey T.E. , Wolf G.T. , Prince M.E. , Papagerakis S.
Published: January 2017

Cancer stem cells possess the qualities of self-renewal, tumorigenesis and the ability to recapitulate a heterogeneous tumor. Our group was the first to isolate head and neck squamous cell carcinoma (HNSCC) stem cells using the cell surface marker CD44. CD44 is a trans-membrane glycoprotein with a multitude of key-functions that regulate cancer cell proliferation and metastasis. The variety of CD44 functions is due to tissue-specific patterns of glycosylation of the extracellular portion, and to the multiple protein isoforms (CD44 variants, CD44v) generated by alternative splicing. This study investigates the expression pattern of CD44 variants in HNSCC. Ten cell lines from the most common HNSCC locations and representative of various clinical outcomes were assayed by quantitative real-time PCR, flow cytometry and immunofluorescence comparatively with normal oral keratinocytes. The CD44 v4 and v6 were exclusively abundant in HNSCC while the isoform v1,2 was expressed in normal oral keratinocytes. Of interest, the highest level of CD44v6 expression was detected in advanced metastatic HNSCC, suggesting a link between CD44v6 expression and HNSCC metastasis, while the highest CD44v4 was detected in a stage IV HNSCC refractory to chemotherapy which developed recurrence. Oral-derived HNSCC expressed the highest CD44v4 and v6, and levels corresponded with staging, showing also an increasing tendency with recurrence and metastasis. CD44v were detected predominantly in smaller cells (a characteristic that has been associated with stem cell properties) or cells with mesenchymal morphology (a characteristic that has been associated with the migratory and invasive potential of epithelial tumor cells), suggesting that CD44v differential expression in HNSCC may be representative of the morphological changes inherent during tumor progression towards a more aggressive potential, and thus contributing to the individual tumor biology. The mechanism of CD44 variant involvement in HNSCC progression and metastasis is under investigation.
Ozone Autohemotherapy Induces Long-Term Cerebral Metabolic Changes in Multiple Sclerosis Patients
Authors: Molinari F. , Simonetti V. , Franzini M. , Pandolfi S. , Vaiano F. , Valdenassi L. , Liboni W.
Published: January 2017

Ozone autohemotherapy is an emerging therapeutic technique that is gaining increasing importance in treating neurological disorders. A validated and standard methodology to assess the effect of such therapy on brain metabolism and circulation is however still lacking. We used a near-infrared spectroscopy (NIRS) system to monitor the cerebral metabolism and a transcranial Doppler (TCD) to monitor the blood flow velocity in the middle cerebral arteries. Fifty-four subjects (32 neurological patients and 22 controls) were tested before, during, and after ozone autohemotherapy. We monitored the concentration changes in the level of oxygenated and deoxygenated haemoglobin, and in the level of the Cytochrome-c-oxidase (CYT-c). As a primary endpoint of the work, we showed the changes in the brain metabolism and circulation of the entire population. The concentration of oxygenated hemoglobin increased after the reinjection of the ozoned blood and remained higher than the beginning for another 1.5 hours. The concentration of the deoxygenated haemoglobin decreased during the therapy and the CYT-c concentration markedly increased about 1 hour after the reinjection. No significant changes were observed on the blood flow velocity. As secondary endpoint, we compared the NIRS metabolic pattern of 20 remitting-relapsing multiple sclerosis (MS) patients against 20 controls. We showed that by using only 7 NIRS variables it was possible to characterize the metabolic brain pattern of the two groups of subjects. The MS subjects showed a marked increase of the CYT-c activity and concentration about 40 minutes after the end of the autohemotherapy, possibly revealing a reduction of the chronic oxidative stress level typical of MS sufferers. From a technical point of view, this preliminary study showed that NIRS could be useful to show the effects of ozone autohemotherapy at cerebral level, in a long-term monitoring. The clinical result of this study is the quantitative measurement of the CYT-c level changes in MS induced by ozone autohemotherapy.
Recurrent Miscarriages in Women Not Fulfilling Classification Criteria for Antiphospholipid Antibody Syndrome
Authors: Proietta M. , Ferrero S. , Ferri L. , Cifani N. , Bruno G. , Del Porto F.
Published: January 2017

Obstetric antiphospholipid antibody syndrome (APS), is well defined by classification criteria. It is well known that women with APS should receive prophylactic anticoagulation therapy with subcutaneous low weight heparin all throughout pregnancy and in the first 6 weeks postpartum. However, the optimal treatment for pregnant women having positive anti-phospholipid antibodies, but not fullfilling classification criteria for APS is still unclear. In this retrospective study we report pregnancy outcomes of 10 patients affected by recurrent miscarriages and positive anti-cardiolipin or aβ2GP1 antibodies with titers ranging from 10 to 20 GPL/MPL demonstrated at least twice before pregnancy.
Novel Hydroxyapatite Biomaterial Covalently Linked to Raloxifene
Authors: Memè L. , Santarelli A. , Marzo G. , Emanuelli M. , Nocini P.F. , Bertossi D. , Putignano A. , Dioguardi M. , Muzio L. Lo , Bambini F.
Published: January 2017

Since raloxifene, a drug used in osteoporosis therapy, inhibits osteoclast, but not osteoblast functions, it has been suggested to improve recovery during implant surgery. The present paper describes an effective method to link raloxifene, through a covalent bond, to a nano-Hydroxyapatite-based biomaterial by interfacing with (3-aminopropyl)-Triethoxysilane as assessed by Infra Red-Fourier Transformed (IR-FT) spectroscopy and Scanning Electron Microscope (SEM). To evaluate the safety of this modified new material, the vitality of osteoblast-like cells cultured with the new biomaterial was then investigated. Raloxifene-conjugated HA-biomaterial has been shown to be a safe material easy to obtain which could be an interesting starting point for the use of a new functional biomaterial suitable in bone regeneration procedures.
Retrospective Observational Study to Investigate Sinerga, a Multifactorial Nutritional Product, and Bacterial Extracts in the Prevention of Recurrent Respiratory Infections in Children
Authors: Nigro A. , Nicastro A. , Trodella R.
Published: January 2017

In this retrospective observational clinical study, 167 children, aged 3 to 7 years, of both sexes, with a clinical history of recurrent respiratory infections, administered with bacterial extracts of first and second generation or Sinerga a nutritional product containing palmitoylethanolamide, bovine colostrum, phenylethylamine and the new generation of probiotic kluyveromyces FM B0399, were observed. The goal of the study was to compare the supplementation with Sinerga with the supplementation with bacterial extracts, for the effect on the frequency of episodes of respiratory infection that had resulted in a prescription for antibiotics. The study focused retrospectively on the months from March 2013 to November 2012. The results showed a greater reduction in the frequency of respiratory infections with antibiotic therapy in the group of children supplemented with Sinerga than in the group treated with bacterial extracts. In particular, it was observed that 49.3% of the children supplemented with Sinerga, against 5% of those supplemented with extracts, had no infectious episodes requiring the administration of an antibiotic. 100% of subjects supplemented with Sinerga have had no more than two episodes of respiratory infection, while this condition, in the cohort treated with bacterial extracts, was observed in only 51 % of cases.
Pathology of Upper Tract Urothelial Carcinoma with Emphasis on Staging
Authors: Mazzucchelli R. , Scarpelli M. , Galosi A.B. , Di Primio R. , Lopez-Beltran A. , Cheng L. , Montironi R.
Published: January 2017

The first two authors contributed equally to this work Classification of upper tract urothelial preneoplastic and neoplastic lesions mirrors that of the urinary bladder, with all lesions of the bladder urothelium being possible in the upper tract and vice versa. There are three major groups of non-invasive urothelial neoplasms: flat, papillary, and inverted. These three groups share a similar morphological spectrum of intraurothelial changes, ranging from hyperplasia to dysplasia to carcinoma in situ. However, they differ in terms of architectural growth pattern compared to the surrounding non-neoplastic mucosal surface. Infiltrating urothelial carcinoma is defined as a urothelial tumor that invades beyond the basement membrane. Unlike in non-invasive papillary urothelial neoplasms (pTa), the role of histologic grade in pT1 and higher stage tumors has been suggested to be of only relative importance. The vast majority of tumors of the upper urinary tract are urothelial carcinoma. More commonly seen, however, are foci of squamous differentiation and, less frequently, glandular differentiation. Pure urothelial carcinomas also display a wide range of variant morphologies, and recognition of these morphologies is important for diagnosis, classification, and prognosis.
Clinical Significance of HMGB1 Expression in Human Gastric Cancer
Authors: Zhang J. , Zhang R. , Lu W.W. , Zhu J.S. , Xia L.Q. , Lu Y.M. , Chen N.W.
Published: January 2017

High mobility group box 1 (HMGB1) has been proved to be implicated in a variety of cell physiological and pathological behaviors including immune response, inflammation and cancer. Accumulating evidence suggests that HMGB1 plays a critical role in the development and progression of multiple malignancies. However, the clinical significance and prognosis of HMGB1 expression in some cancers remain controversial. The present study aimed to investigate whether overexpression of HMGB1 is an independent prognostic factor in patients with gastric cancer. The correlation of HMGB1 expression with clinicopathologic characteristics and prognosis was assessed by immunohistochemical assay through tissue microarray procedure in 50 primary gastric cancer cases. Our results indicated that the positive expression of HMGB1 was significantly increased in the nucleus of gastric cancer tissues compared with the adjacent non-cancerous tissues (ANCT) (64.0% vs 44.0%, P=0.025), but was not linked to the clinicopathologic features, including the TNM stage ( P=0.533) and metastatic lymph node ( P=0.771), in patients with gastric cancer. Kapalan-Meier and log-rank analysis demonstrated that overexpression of HMGB1 did not exert significant impact on the overall survival of patients with gastric cancer ( P=0.805). Furthermore, Cox regression analysis showed that high HMGB1 protein expression did not represent an independent risk factor for patients with gastric cancer ( P=0.677). Taken together, our findings suggest that high expression of HMGB1 is not correlated with the clinicopathologic characteristics of gastric cancer, and can not serve as an independent prognostic biomarker for patients with gastric cancer.
In vitro Action of Sho-Seiryu-to on Allergen-Exposed Mononuclear Cells
Authors: Tanaka M. , Inoue K. , Kitamura Y. , Shimada A. , Takano H.
Published: January 2017

Although Sho-seiryu-to (SST), used as a traditional herbal (Kampo) medicine mainly in China and Korea, is shown to have immunomodulating potential, such as an anti-allergic one, its underlying mechanism has not been completely clarified. To partially address the issue, we explored its effects on allergen-exposed mononuclear cells. Male balb/c mice were intraperitoneally administered ovalbumin (OVA: 20 μg) plus alum or vehicle twice (Day 0 and Day 14). At Day 21, mice were sacrificed and splenocytes (mononuclear cells) were isolated and cultured in the presence or absence of OVA with or without SST. Thereafter, helper T-related cytokines in the culture supernatants were evaluated by means of ELISA. Protein level of interferon-γ was lower than 5.0 pg/mL in the supernatants from OVA-non-exposed or -exposed mononuclear cells in the presence or absence of OVA stimulation. On the other hand, SST induced the cytokine from both types of mononuclear cells in the presence (P < 0.05) or absence of OVA stimulation as compared to corresponding control. By contrast, interleukin (IL)-4 level tended to be decreased by SST in OVA-non-exposed mononuclear cells as did IL-13 in both non-exposed and exposed mononuclear cells as compared to vehicle. In conclusion, immunoregulating efficacy by SST on allergy-prone subjects may include, at least in part, restoring helper T balance mainly through hyperproduction of IFN-γ against mononuclear cells such as lymphocytes.
Effect of Betamethasone in Combination with Antibiotics on Gram Positive and Gram Negative Bacteria
Authors: Artini M. , Papa R. , Cellini A. , Tilotta M. , Barbato G. , Koverech A. , Selan L.
Published: January 2017

Betamethasone is an anti-inflammatory steroid drug used in cases of anaphylactic and allergic reactions, of Alzheimer and Addison diseases and in soft tissue injuries. It modulates gene expression for anti-inflammatory activity suppressing the immune system response. This latter effect might decrease the effectiveness of immune system response against microbial infections. Corticosteroids, in fact, mask some symptoms of infection and during their use superimposed infections may occur. Thus, the use of glucocorticoids in patients with sepsis remains extremely controversial. In this study we analyzed the in vitro effect of a commercial formulation of betamethasone (Bentelan) on several Gram positive and Gram negative bacteria of clinical relevance. It was found to be an inhibitor of the growth of most of the strains examined. Also the effect of betamethasone in combination with some classes of antibiotics was evaluated. Antibiotic-steroid combination therapy is, in such cases, superior to antibiotic-alone treatment to impair bacterial growths. Such effect was essentially not at all observable on Staphylococcus aureus or Coagulase Negative Staphylococci (CoNS).
The Role of Tumour Necrosis Factor in the Pathogenesis of Immune-Mediated Diseases
Authors: Blandizzi C. , Gionchetti P. , Armuzzi A. , Caporali R. , Chimenti S. , Cimaz R. , Cimino L. , Lapadula G. , Lionetti P. , Marchesoni A. , Marcellusi A. , Mennini F.S. , Salvarani C. , Girolomoni G.
Published: January 2017

Immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthropathies, Crohn's disease, ulcerative colitis and juvenile idiopathic arthritis, comprise a group of chronic disorders characterized by an immune-mediated pathogenesis. Although at clinical presentation these diseases appear unrelated, they have been recognized to share similar pathogenic mechanisms. Data from epidemiological and genetic studies further support the concept that IMIDs are interrelated, as they can co-occur in the same patient and share a similar genetic susceptibility. The specific aetiologies of IMIDs remain unknown, but all are known to involve dysregulation of the immune system, including an over-expression of the pro-inflammatory cytokine tumour necrosis factor (TNF). The pivotal role played by TNF in the pathogenesis and pathophysiology of IMIDs has been documented by extensive preclinical and clinical investigations, and confirmed by the efficacy of anti-TNF biotechnological drugs, such as etanercept, infliximab and adalimumab, in the therapeutic management of these disorders. In this narrative review, we discuss the available data on the TNF-dependent pathogenesis of IMIDs and associations among the different disorders. Although much remains to be discovered about the pathogenesis and aetiology of IMIDs, their common inflammatory pathological features may explain why they can be successfully targeted by anti-TNF drugs. Among these, adalimumab, a fully human monoclonal antibody, has been approved for treatment ofnine distinct IMID indications and it is likely to become a valuable therapeutic tool for this complex cluster of chronic inflammatory disorders.
Dibutyryl Cytidine and Adenosine 3':5'-Cyclic Monophosphates Inhibit A23187-Stimulated Rat Peritoneal Macrophage Leukotriene B4 Synthesis
Authors: Elliott G. R. , Lauwen A. P. M. , Bonta I. L.
Published: January 2017

Dibutyryl cytidine and adenosine 3':5'-cyclic monophosphates (db-cCMP and db-cAMP respectively) inhibited the synthesis of thromboxane (TX) B2, the stable product of TXA2, and leukotriene (LT) B4 by 4-day carrageenin-elicited rat peritoneal macrophages stimulated by the calcium ionophore A23187. Incubation of macrophages with dbcAMP, at concentrations inhibiting eicosanoid release, was associated with an increase in intracellular cAMP concentrations. No such increase was seen when db-cCMP was used.
The Immunohistochemical Investigation of Epidermal Growth Factor (EGF) Receptors in Various Gynecological Tumors
Authors: Wittmaack F. M. , Schwörer D. , Wintzer H. O. , Von Kleist S. , Pfleidere A. , Bauknecht T.
Published: January 2017

Monoclonal antibodies to the extracellular domain of the EGF-receptor were used for immunohistochemical staining.

Nine of 10 squamous cell carcinomas of the cervix, vagina, and vulva showed strong staining for EGF-receptors. Of 12 endometrial carcinomas and 19 ovarian tumors approximately 50% revealed moderate staining. Cells with immunohistochemically identifiable EGF-receptors and those without coexist in EGF-receptor positive tumors. The percentage of positive cells in endometrial carcinomas was higher than in ovarian carcinomas, 80% and 25%, respectively.

There was good correlation between the immunohistochemical detection of EGF-receptors and the amount of EGF-receptors quantitated by biochemical methods, although immunohistochemistry appeared to be somewhat less sensitive (especially in breast carcinomas).
Trichinella Spiralis-Ab3 (IgG, IgM, IgA), IL-6 and Tnf Levels in Murine Trichinellosis
Authors: Haralabidis S. , Frydas S. , Karagouni E. , Himonas C.
Published: January 2017

The syngeneic anti-anti-idiotypic antibodies (Ab3) IgG, -IgM, and -IgA induced by polyclonal mouse anti-idiotypic antibodies (Ab2) against the rabbit F(ab) T. spiralis-Ab1, was studied. IL-6 level and cytotoxic activity (TNFα and LT) in the serum of mice infected with L1- T. spiralis or immunized with T. spiralis-Ab2 antibodies were also determined. The Ab1 antibody response was found to reflect the life cycle of the parasite. High IgA-, IgM-, and IgG-Ab1 levels, as well as corresponding levels of cytotoxic activity (62.3, 88.8 and 107.8 5/ml) and IL-6 (216, 447 and 789 U/ml) on days 10, 20 and 28 after the infection, respectivelly, were detected. The Ab3 antibody response against the polyclonal T. spiralis-Ab2, followed the classical pattern of antibody level after initial infection with an immunogen. IgM was first detected 10 days p.i., while IgA and IgG were detected 20 days p.i. Cytotoxic activity of 93.2, 245.9, and 326.7 U/ml, and IL-6 levels of 237, 304, and 487 U/ml, were detected on 10, 20, and 28 days p.i., respectivelly. Although Ab3 bound to T. spiralis-Ab2 antibodies or to L1 -T-spiralis antigen and cytotoxic activity in mice immunized with T. spiralis-Ab2 antibodies was increased, there was no protection against the parasitic infection.
Histological Study of Murine Fibrosarcoma Treated with Prostaglandin Inhibitors
Authors: Valdez J.C. , Mercau G.T. , Vitalone H. , Perdigon G.
Published: January 2017

In a previous work we reported that treatment with indomethacin, aspirin and piroxicam in inbred BALB/c mice bearing a transplantable fibrosarcoma induced by methylcholanthrene produced tumor regressions in 45, 32 and 30 per cent of the animals, respectively. In the remaining mice, in which there was no tumor regression, tumor volumes varied (small 0.05<0,5 cm3 medium 0,5<1,35 cm3 and large > 1,35 cm3).

In this histological study we observed that the antitumoral effect of these nonsteroidal antiinflammatory drugs occurred together with a remarkable tumor encapsulation and a decrease in the physical characteristics of malignancy of the tumor cells. The tumor-associated macrophages, which can be detected only by the iron-dextran phagocytosis but not by that of colloidal carbon or trypan blue, were found in the peritumoral area in all cases under study. Their numbers and/or phagocytic capacity were slightly increased in both regressing and small tumors with respect to large, medium and control tumors. These findings suggest that the action of these prostaglandin synthesis inhibiting drugs would permit tumor encapsulation by an improvement in the macrophage-fibroblast relationship together with a decrease in the malignancy of the tumor cells.
Peripheral Nerve Myelin Modulates the Effect of Antidepressants on Major Histocompatibility Complex Expression on Macrophages in Experimental Allergic Neuritis
Authors: Zhu J. , Bengtsson B.-O. , Mix E. , Thorell L.-H. , Olsson T. , Link H.
Published: January 2017

The effect of bovine peripheral nerve myelin (BPM) used for induction of experimental allergic neuritis (EAN) in Lewis rats, on antidepressants' modulation of interferon-gamma (IFN-γ)-induced major histocompatibility complex (MHC) class I and II antigen expression on peritoneal macrophages in EAN rats was studied. Antidepressants with different profiles concerning inhibition of the neuronal reuptake of the monoamines serotonin (5-HT) and noradrenalin (NA), respectively, in concentrations of 10−4 to 10−8 M were used. At the concentration of 1.0 U/ml IFN-γ, most antidepressants significantly enhanced both MHC class I and class II expression, except maprotiline, a selective NA reuptake inhibiting antidepressant that suppressed MHC class I expression. Zimeldine, a selective 5-HT reuptake inhibitor did not affect MHC class II expression. BPM in general had an enhancing effect on modulation of both MHC class I and class II expression by antidepressants. By itself BPM enhanced MHC class I expression, but did not affect class II expression at IFN-γ 1.0 U/ml. The modulating effect of BPM on regulation of MHC expression by antidepressants could be the result of contaminating T cells and release of IFN-γ into cultures. The modulatory effect of antidepressants on MHC expression may to some extent be exerted by the action on 5-HT and/or NA regulation, but also by direct effects of antidepressants on macrophages. They probably play a role in zimeldine-induced Guillain-Barré syndrome in some patients and in the suppression of clinical signs of EAN in Lewis rats reported for some antidepressants.
IL-1α, IL-6 and TNF-α in Cutaneous Lesions of Lupus Erythematosus are Inhibited by Topical Application of Calcipotriol
Authors: Feliciani C. , Amerio P. , Pour S. Mohammad , Allegretti T. , Proietto G. , Coviello C. , Amerio P. , Vena G.A.
Published: January 2017

Lupus Erythematosus (LE) is an autoimmune disorder with an unknown etiology and pathogenesis. Skin lesions of LE express several cytokines which correlate to histological findings such as IL-1 and IL-6 which are mediators of epidermal growth and proliferation. Skin lesions of LE are generally treated with immunosuppressive agents such as oral or topically applied corticosteroids. Recently a new drug, calcipotriol, a vitamin D3 analogue has been useful in treatment of psoriasis with no ad verse effect on calcium metabolism. This drug shares immunomodulatory effects with vit. D3 by inhibiting several cytokines produced by keratinocytes.

In order to test the clinical effectiveness of calcipotriol in cutaneous lesions of LE we have investigated several proinflammatory cytokines such as: IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-8, MCP-1, TNF-α. Using an avidin-biotin immunoperoxidase system we have found IL-1 in both forms, IL-6 and TNF-α in basal keratinocytes in patients affected with LE, after treatment they were reverted to normal. This inhibition is induced at a molecular level as demostrated by reduced IL-1, IL-6 and TNFα mRNA expression. This is the first report showing that calcipotriol is effective in cutaneous lesions of LE and suggesting that this action is due to an inhibition of protein synthesis and mRNA expression for IL-1α, IL-6 and TNFα.
Current Status of Kidney Graft in 6 Recipients after Pregnancy
Authors: Mazzarella V. , Tozzo C. , Pisani F. , Tisone G. , Splendiani G. , Casciani C.U.
Published: January 2017

To determine whether pregnancy has an adverse influence on survival or graft function, a retrospective study was conducted. A total of 321 renal transplant(rTx) patients were followed on a day hospital basis of Tor Vergata University of Rome between January 1981 and April 1996. Out of 90 female subjects, 74 of childbearing age (less than 45 years) underwent the study. Six women had 7 pregnancies which resulted in 5 live births and two first trimester abortions. In one case the pregnancy occurred at 4 months after rTx: spontaneous abortion and acute rejection with graft loss occurred, for the four successful pregnancies the preconception serum creatinine (sCr) was 1.34 mg/dl (range: 1.3–1.4) and remained stable at the end of follow-up. The woman with two successful pregnancies had a sCr increase after second pregnancy, but it has remained stable at 4 yrs after rTx. The pt receiving rTx at 1981 with successful pregnancy after two yrs, reached ESRD 7 yrs after delivery because chronic rejection. Our data are consistent with other studies demonstrating no contraindication to pregnancy in women with stable renal transplant and controlled blood pressure. However, careful interdisciplinary monitoring is needed to reduce maternal and fetal risks.