bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro and in Vivo Therapeutics of β-Thujaplicin on Lps-Induced Inflammation in Macrophages and Septic Shock in Mice
Authors: Shih M-F. , Chen L-Y. , Tsai P-J. , Cherng J-Y.
Published: January 2017

β-thujaplicin, an active constituent from Chamaecyparis obtusa, has been shown to have acaricidal and antimicrobial effects. Very few studies have focused on the potential of the anti-inflammatory effect of β-thujaplicin. Moreover, its capability of inhibiting inflammatory mediators e.g. TNF-α gene transcription, nitric oxide (NO) and prostaglandin E2, remains unknown. Besides those molecular mechanisms behind the anti-inflammatory effect of β-thujaplicin, solid proof of its effectiveness in vivo has not yet been studied. In our study, in vitro effects of β-thujaplicin were verified on RAW 264.7 macrophages which were stimulated by LPS. Indomethacin was used as a positive control. The inducible NO production after stimulation was measured by Griess reagent. PGE2, IL-6 and TNF-α were measured by ELISA methods. Protein expressions of iNOS, COX2, and NF-κB were evaluated by Western blotting. Septic ICR mice were administered 20 mg/kg of LPS and then the mortality rate was monitored. Within the concentration range which was devoid of cytotoxicty, β-thujaplicin exhibited a clear dose-dependent inhibition on LPS-induced NO production. Furthermore, β-thujaplicin inhibited LPS-induced PGE2, IL-6, and TNF-α production as well as iNOS, COX2, and NF-κB protein expression more substantially potent than indomethacin. In agreement with the in vitro study, β-thujaplicin was shown to be effective in vivo for inhibiting LPS-induced NO and TNF-α production and a significant decrease in mortality rate of mice suffering from septic shock was observed. This study demonstrates the potential of β-thujaplicin in treatment of inflammation and sepsis. These effects occur through an efficient blockage of TNF-α and iNOS production, β-thujaplicin efficacy is comparable to that of indomethacin thus it can be a substitution but bear less depletion of PGE2, making this compound very promising in clinical applications.
Increased Percentages of Tumor Necrosis Factor-α+/Interferon-T+Lymphocytes and Calprotectin+/Tumor Necrosis Factor-A+ Monocytes in Patients with Acute Kawasaki Disease
Authors: Guggino G. , Cimaz R. , Accomando S. , Pagnini I. , Simonini G. , Di Liberto D. , De Martino M. , Dieli F. , Sireci G.
Published: January 2017

In vivo exposure to microorganisms resident in the oral cavity is considered as a possible cause of Kawasaki disease (KD), and some epitopes derived from streptococci display homology with Factor H of Complement. Additionally, calprotectin, a major calcium binding protein released by neutrophils and activated monocytes, could be directly involved in endothelial damage occurring in KD. The aim of our study is to evaluate the percentages of IFN-γ+ and/or TNF-α+ lymphocytes and double positive calprotectin/TNF-α monocytes (CD14+) after in vitro stimulation with streptococcal- and/or Factor H-derived peptides, in patients with acute KD. Peripheral Blood Mononuclear Cells (PBMCs) obtained from KD patients and febrile controls were stimulated in vitro with peptides. After culture, cells were collected, stained with fluorochrome-labelled monoclonal antibodies against CD3, CD14, calprotectin, IFN-γ and TNF-α, and cytofluorimetric analyses were performed. Our results showed increased percentages of TNF-α+/IFN-γ+ lymphocytes in KD patients in respect to controls when PBMCs were stimulated with streptococcal or Factor H-derived epitopes. In addition, also calprotectin+/TNF-α+ monocytes from KD patients were activated after PBMC in vitro stimulation. These findings lead us to speculate that some peptides, derived from oral streptococci and cross-reactive with the human Factor H of Complement, could induce lymphocyte and monocyte activation potentially involved in the pathogenesis of KD. Our results should be confirmed by further studies enrolling more patients and controls than those analyzed in our study.
Expression of Gelatinases (MMP-2, MMP-9) and Cyclooxygenases (COX-1, COX-2) in Some Benign Salivary Gland Tumors
Authors: Lipari L. , Mauro A. , Gallina S. , Tortorici S. , Buscemi M. , Tetè S. , Gerbino A.
Published: January 2017

Salivary gland tumors, most of which are rare benign tumors, represent a histologically heterogenous group with the greatest diversity of morphological and cellular features. The aim of this study is to analyse the expression and possible interactions between gelatinases (MMP-2, MMP-9) and cyclooxygenases (COX-1, COX-2) in some benign salivary gland tumors. We investigated the expression of gelatinases and cyclooxigenases in control salivary gland, Pleomorphic adenoma and Warthin's tumor through immunohistochemistry and Reverse Transcription – Polymerase Chain Reaction (PCR). We identified the expression of both classes of enzyme in normal samples and in the two types of pathological samples without any quantitative differences. From the present data no significant differences emerge in the expression of these enzymes among the different pathologies examined. Nevertheless, due to the small number of samples included in this study, general statements regarding correlation between the degree of severity of the tumoral pathology and the quantitative expression of these potential tumoral markers can not be made.
Prostaglandin E2 to Diagnose between Reversible and Irreversible Pulpitis
Authors: Petrini M. , Ferrante M. , Ciavarelli L. , Ceccarini A. , Brunetti L. , Vacca M. , Spoto G.
Published: January 2017

The aim of this work is to verify a correlation between the grade of inflammation and the concentration of PGE2 in human dental pulp. A total of 25 human dental pulps were examined by histological analysis and radioimmunologic dosage of PGE2. The pulps used in this experiment were from healthy and symptomatic teeth; the first ones were collected from teeth destined to be extracted for orthodontic reasons. An increase was observed of PGE2 in reversible pulpitis compared with healthy pulps and with the irreversible pulpitis and the clear decrease of these when NSAIDs are taken. This study demonstrates that PGE2 level is correlated to histological analysis thus allowing to distinguish symptomatic teeth in reversible and irreversible pulpitis.
Occurrence of Salivary Gland Tumours in Two Patients Treated with Biological Agents
Authors: Carlesimo M. , Mart E. , La Pietra M. , Orsini D. , Pranteda G. , Pranteda G. , Grimaldi M. , Arcese A.
Published: January 2017

We report two cases of salivary gland tumors arising in two psoriatic patients treated with an anti-TNF-alpha agent. A clear causal relationship could not be established, but the exceptional onset of a bilateral Warthin's tumor in one of these patients should be emphasized.
A Case Series of a Luteolin Formulation (Neuroprotek®) in Children with Autism Spectrum Disorders
Authors: Theoharides T.C. , Asadi S. , Panagiotidou S.
Published: January 2017

There has been an impressive, little understood increase in cases of Autism Spectrum Disorders (ASD). The lack of any distinctive pathogenetic mechanism has hampered the development of any effective treatments. Increasing evidence indicates oxidative stress, brain inflammation, gastrointestinal (GI) dysfunction and allergic symptoms may be present in ASD patients. The flavone luteolin has antioxidant, anti-flammatory, anti-allergy and neuroprotective properties. Given these findings, a dietary supplement was developed with a unique mixture of luteolin with the related flavonoids quercetin and rutin in a liposomal formulation of olive kernel oil (OKO), which increases their absorption. Results are presented for children with ASD (n=37, 4–14 years old) who had not obtained any benefit from multiple other regimens and who used this formulation for at least 4 months. GI and allergy symptoms improved in about 75% of children, eye contact and attention in 50%, social interaction in 25% and resumption of speech in about 10%. There were no adverse effects. Even though these results represent an uncontrolled open case series, they are encouraging because they suggest good tolerability and potential effectiveness.
Endothelial Cells, Cholesterol, Cytokines, and Aging
Authors: Teté S. , Tripodi D. , Rosati M. , Conti F. , Maccauro G. , Saggini A. , Salini V. , Cianchetti E. , Caraffa A. , Antinolfi P. , Toniato E. , Castellani M.L. , Pandolfi F. , Frydas S. , Conti P. , Theoharides T.C.
Published: January 2017

It has been reported that high levels of cholesterol and triglycerides are associated with increased risk of developing atherosclerosis and shorter life. In fact, vascular endothelial dysfunction occurs during the human aging process. Accumulation of lipids in vascular endothelium activates leukocytes to produce cytokines and chemokines which recruit macrophages. On the other hand, macrophages augment inflammatory response and secrete vascular endothelial growth factor, a key cytokine that mediates angiogenesis and inflammatory response. In addition, hyperlipidaemia is one of the main risk factors for aging, hypertension and diabetes. Here, we review the interrelationship between endothelial cells, high level of cholesterol, and aging.
A Validated HPLC Method for the Monitoring of Thiopurine Metabolites in Whole Blood in Paediatric Patients with Inflammatory Bowel Disease
Authors: Cangemi G. , Barabino A. , Barco S. , Parodi A. , Arrigo S. , Melioli G.
Published: January 2017

Therapeutic drug monitoring (TDM) of major metabolites of thiopurine drugs is a widely used tool for assessing treatment efficacy and toxicity in patients with inflammatory bowel disease (IBD). We report the laboratory and clinical validation of a simple and reliable high performance liquid chromatography (HPLC) method for the measurement of 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP) on paediatric patients with IBD. The aim of this paper is to develop and validate a method for the measurement of 6-TGN and 6-MMP applicable to routine practice and to evaluate the usefulness of the TDM of thiopurine drugs in children with IBD attending our Gastroenterology Unit. The HPLC method was validated following international guidelines starting from red blood cells (RBC) and whole blood (WB). A comparison between RBC and WB was assessed. The usefulness of TDM was then evaluated using the new method from WB in 47 paediatric patients with IBD treated with thiopurine drugs. WB and RBC resulted in interchangeable matrices. The majority of patients had the metabolite levels inside the therapeutic ranges. A moderate correlation was found between 6-MMP concentration and the dose of thiopurines. A higher percentage of non responders was found among patients with lower levels of 6-TGN. Toxicity was found in eight patients and was evaluated in respect to the metabolite concentration. The described HPLC method is applicable to routine practice and it is suitable for its use in multicentric studies. Our results of TDM on paediatric IBD patients can contribute to clarify its role in their therapeutic management.
Omalizumab Modulates Bronchial Reticular Basement Membrane Thickness and Eosinophil Infiltration in Severe Persistent Allergic Asthma Patients
Authors: Riccio A.M. , Dal Negro R.W. , Micheletto C. , De Ferrari L. , Folli C. , Chiappori A. , Canonica G.W.
Published: January 2017

Severe persistent asthma causes a substantial morbidity and mortality burden and is frequently not well controlled, despite intensive guideline-based therapy. The unique monoclonal antibody approved for patients with severe allergic asthma is omalizumab: a recombinant humanised murine against IgE antibodies. The aim of the present study is to investigate the effect of long-term anti-IgE on the thickening of the reticular basement membrane (RBM) and eosinophil infiltration in bronchial biopsies from patients with severe persistent allergic asthma. Biopsies were obtained from 11 patients with severe persistent allergic asthma before and after (12 months) treatment with omalizumab. RBM thickness and eosinophils were measured by using light microscope image analysis. A significant mean reduction in RBM thickness and eosinophil infiltration were measured after one-year omalizumab treatment. No correlation between eosinophil reduction and RBM thickness reduction was found. No correlation between each of the previous two parameters and clinical parameters was detected. In conclusion, our study showed that a substantial proportion of severe asthmatics reduced the original bronchial RBM thickness and eosinophil infiltration after one-year treatment with anti-IgE, thus emphasizing the possible role of omalizumab in affecting airway remodeling in severe persistent allergic asthma.
Effectiveness of Nebulized Hypertonic Saline and Epinephrine in Hospitalized Infants with Bronchiolitis
Authors: Del Giudice M. Miraglia , Saitta F. , Leonardi S. , Capasso M. , Niglio B. , Chinellato I. , Decimo F. , Maiello N. , Capristo C. , Perrone L. , Peroni D.
Published: January 2017

The objective of the study is to verify effects of nebulized 3% saline hypertonic solution (HS) in comparison to normal saline (NS) in addition to epinephrine in hospitalized children with bronchiolitis. Infants were randomly assigned either to receive every 6 hours nebulized NS (group I) or 3% HS (group II) in addition to epinephrine (1.5 mg) and to conventional treatment. The main endpoints of this study were the length of stay (LOS) in hospital and the clinical response score (CSS). Patients presented a significant decrease in CSS from the first through the third day of treatment, present in the first group but even more evident in the second group (p=0.0001). Comparison between group I and II data shows significant decrease in CSS in the 3% HS-treated patients both at the second (p<0.005) and at the third day of treatment (p<0.005). Infants in the NS control group had a mean LOS of 5.6±1.6 days, whereas children treated with 3% HS were discharged with a LOS of 4.9±1.3 days, reaching a significant decrease in stay (p<0.05). In hospitalized patients bronchiolitis nebulized 3% HS and epinephrine significantly decreased symptoms and LOS as compared to 0.9% NS and epinephrine.
Skewed T-Cell Receptor Variable Beta Repertoire and Massive T-Cell Activation in Idiopathic Orofacial Granulomatosis
Authors: Giovannetti A. , Mazzetta F. , Cavani A. , Pennino D. , Caprini E. , Ortona E. , Donato G. , Rosato E. , Salsano F. , Pierdominici M.
Published: January 2017

Orofacial granulomatosis (OFG) is a clinicopathologic entity describing oral lesions with noncaseating granulomas including a spectrum of diseases such as the Melkersson-Rosenthal syndrome. The involvement of abnormal T-cell responses has been suggested in the pathogenesis of OFG although few and contrasting data are currently available on this issue. In a patient with OFG, we observed virtually complete CD4 and CD8 T-cell receptor (TCR) β-chain variable region (BV) repertoires at the lesion level and in circulation. However, oligoclonal profiles were found in CD4 and, to a greater extent, in CD8 subsets. These findings were seen in association with a massive peripheral T-cell activation, decreased naive T cells, reduced thymic output, altered cytokine production, and increased apoptosis. Our data, pointing to a random influx of T cells at the site of inflammation, argue against the hypothesis of a main allergen acting at the level of oral mucosa. The profound dysregulation of the peripheral T-cell compartment suggests that OFG should be regarded as a systemic disorder with localized manifestations.
Profilin Desensitization in Two Patients with Plant-Derived Food Allergy
Authors: Nucera E. , Aruanno A. , Rizzi A. , Buonomo A. , Pecora V. , Colagiovanni A. , Pascolini L. , Ricci A.G. , Schiavino D.
Published: January 2017

Profiling are “panallergens”, responsible for many cross-reactivities between inhalant, latex and plant-derived food allergens. We evaluated the effectiveness and the safety of sublingual desensitization treatment (SLIT) in two patients with allergic respiratory and food diseases. Skin prick tests, IgE and IgG4 assays to pollens, some plant-derived foods, profilin, non-lipid specific transfer protein and PR 10 proteins were performed. The patients also underwent double-blind placebo-controlled challenge (DBPCFC) with the culprit foods and profilin and then a SLIT with it. Both the patients had positive SPT, specific IgE and DBPCFCs with profilin and some vegetables referred in anamnesis. They therefore underwent SLIT with profilin extract. At the end of treatment, the patients had negative DBPCFCs with culprit foods and a decrease of specific IgE levels for profilin and vegetable foods. Profilin desensitization allowed our patients to manage their diet without restriction, eating several foods previously not tolerated.
Laser Removal of Tattoos
Authors: Tammaro A. , Fatuzzo G. , Narcisi A. , Abruzzese C. , Caperchi C. , Gamba A. , Parisella F.R. , Persechino S.
Published: January 2017

In Western countries the phenomenon of “tattooing” is expanding and tattoos are considered a new fashion among young people. In this paper we briefly trace the history of tattooing, the techniques used, the analysis of pigments used, and their possible adverse reactions. We also carried out a review of the international literature on the use of Q-switched laser in tattoo removal and its complications, and we describe our experience in the use of this technique.
Salbutamol: How Does it Enter Smooth Muscle Cells?
Authors: Chiappori A. , Folli C. , Riccio A.M. , Caci E. , Descalzi D. , De Ferrari L. , Ingrassia E. , Nicolini G. , Canonica G.W.
Published: January 2017

Polyspecific organic cation transporters (OCTs) in human cell membranes are involved in the uptake, distribution and excretion of cationic compounds. Although their relevance to drug disposition in the liver, small intestine and kidney has been investigated previously, less is known about the influence of these transporters on the pharmacokinetics and pharmacodynamics of inhaled drugs. Drugs that are commonly administered by inhalation for the treatment of respiratory diseases, such as glucocorticoids and cationic β2-agonists, might interact with several of these transporters, which are strongly expressed on the surfaces of airway epithelial cells. We evaluated the expression of OCT3 and measured the in vitro uptake of the short-acting β2-agonist salbutamol (SALB), alone or in combination with corticosterone (CS) and beclomethasone dipropionate (BDP), by bronchial smooth muscle cells. Our results showed that these cells express the OCT3 transporter and that SALB enters the cell in a transporter-independent fashion. Moreover, CS and BDP have different activities on SALB transport inside the cell. CS increases SALB transport and BDP decreases SALB transport, although neither of these effects are statistically significant. A better understanding of these mechanisms might lead to the improved treatment of airway diseases.
Thyroid Hormone Analogue Stimulates Keratinocyte Proliferation but Inhibits Cell Differentiation in Epidermis
Authors: Zhang B. , Zhang A. , Zhou X. , Webb P. , He W. , Xia X.
Published: January 2017

Gross clinical manifestations of thyroid hormone (TH) imbalance are often first seen in the skin where TH plays an integral role in sustaining natural function. Although mounting evidence suggests that TH plays an important role in epidermal proliferation and wound healing, the physiologic role of thyroid hormone in skin is not well understood. In the current study, we investigated the effect of a natural thyroid hormone analogue-3, 3', 5-triiodo-thyroacetic acid (TRIAC) on regulating proliferation and differentiation and its possible molecular mechanism in normal human epidermal keratinocytes and C57BL/6 mice. We determined that TRIAC could stimulate epidermal thickening in mice and promote human keratinocyte proliferation by activating Cyclin D1 expression and promoting entrance into S phase. Moreover, TRIAC might inhibit cell differentiation through repressing the expression of Casein Kinase 1 (CK1), which is a key regulatory protein involved in the control of cell differentiation. Taken together, our data explored the physiologic effect of TRIAC on skin and the possible molecular mechanism of TRIAC, which might be an interesting compound for the treatment of hyperkeratotic skin disorders.
Microrna-149 Inhibits Proliferation and Invasion of Glioma Cells via Blockade of Akt1 Signaling
Authors: Pan S-J. , Zhan S-K. , Pei B-G. , Sun Q-F. , Bian L-G. , Sun B-M.
Published: January 2017

MicroRNAs (miRNAs) play important roles in the regulation of gene expressions. Aberrant expression of miRNAs is implicated in a variety of biological and pathological processes, including the tumorigenesis of glioma (GM). Though the molecular mechanisms of protein kinase B (AKT) survival signal have been comprehensively explored, the role of miR-149 in glioblastoma (GBM) and its regulation on AKT signaling have not yet been ascertained. The present study aimed to elucidate the role and molecular mechanisms of miR-149 in U251 GM cells. Using a gain-of-function approach, we investigated the effects of lentivirus-mediated overexpression of miR-149 on the expression of phosphated-AKT1 (p-AKT1), proliferating cell nuclear antigen (PCNA), matrix metallopeptidase-2 (MMP-2) and CyclinD1 in U251 cells and nude mice subcutaneous xenograft tumors by Real-time PCR, Western blot and immunohistochemical assays. Proliferative activities indicated by MTT assay, invasive potential by Transwell and cycle distribution by flow cytometry were carried out for functional analysis of U251 cells after infection with miR-149 mimic. As a consequence, miR-149 inhibited the expression of p-AKT1, PCNA, CyclinD1 and MMP-2, reduced the proliferative activities and invasive potential, and induced cycle arrest in G0/G1 phase in U251 cells. In conclusion, our findings show that miR-149 as tumor suppressor may be involved in the proliferation and invasion of GM cells via blockade of the AKT1 signaling, and be considered as a candidate target for the treatment of cancer.
Ikaros Family Transcription Factors Expression in Rat Thymus: Detection and Impaired Development
Authors: Paradzik M. , Novak S. , Mokrovic G. , Niksic T. Bordukalo , Heckel D. , Stipic J. , Baldani D. Pavicic , Cicin-Sain L. , Antica M.
Published: January 2017

The expression of Ikaros family transcription factors and consequently their signalling pathway is limiting for hematopoietic and lymphocyte development in mice and human. Due to their importance, these transcription factors are highly homologous between species. As an initial approach to examining the possible involvement of Ikaros transcription factors in pathogenesis of rat lymphoid development, we analyzed the expression of all known Ikaros family members, Ikaros, Aiolos, Helios, Eos and Pegasus in the rat thymus. We established a semi-quantitative RT-PCR to detect mRNA of each transcription factor. For the first time we give evidence of the expression of Ikaros family transcription factors in the rat thymus. Further, we evaluated whether their mRNA expression was succumbed to changes when the rats were exposed to ethanol, as a known debilitating agent during development. Therefore we analyzed the thymus of adult rats whose mothers were forced to drink ethanol during gestation, to detect possible changes in thymus mRNA expression levels of Ikaros, Aiolos, Helios, Eos and Pegasus. We found that rats prenatally exposed to ethanol show a slightly higher expression of Ikaros family transcription factors in the adult thymus when compared to control rats, but these differences were not statistically significant. We further studied the distribution of the major lymphocyte subpopulations in the rat thymus according to CD3, CD4 and CD8 expression by four color flow cytometry. We found a higher incidence of CD3 positive cells in the double positive, CD4+CD8+ thymic subpopulation of rats prenatally exposed to ethanol when compared to non-exposed animals. Our findings indicate that ethanol exposure of pregnant rats might influence the development of CD3 positive cells in the thymus of the offspring but this result should be further tackled at the level of transcription factor expression.
Optimization and Culture Conditions to Improve Helicobacter Pylori Growth in HAM's F-12 Medium by Response Surface Methodology
Authors: Bessa L.J. , Correia D.M. , Cellini L. , Azevedo N.F. , Rocha I.
Published: January 2017

Helicobacter pylori is a gastroduodenal pathogen that colonizes the human stomach and is the causal agent of gastric diseases. From the clinical and epidemiological point of view, enhancing and improving the growth of this bacterium in liquid media is an important goal to achieve in order to allow the performance of accurate physiological studies. The aim of this work was to optimize three culture conditions that influence the growth of H. pylori in the defined medium Ham's F-12 supplemented with 5% fetal bovine serum by using response surface methodology as a statistical technique to obtain the optimal conditions. The factors studied in this experimental design (Box-Behnken design) were the pH of the medium, the shaking speed (rpm) and the percentage of atmospheric oxygen, in a total of 17 experiments. The biomass specific growth rate (μ) was the response measured. The model was validated for pH and shaking speed. The percentage of atmospheric oxygen did not influence the growth for the range of values studied. At the optimal values found for pH and shaking speed, 8 and 130 rpm, respectively, a specific growth rate value of 0.164 h−1, corresponding to a maximal concentration of approximately 1.5xl08 CFU/ml, was reached after 8 h. The experimental design strategy allowed, for the first time, the optimization of H. pylori growth in a semi-synthetic medium, which may be important to improve physiological and metabolic studies of this “fastidious” bacterium.
Polydatin Protects against Lipopolysaccharide-Induced Fulminant Hepatic Failure in D-Galactosamine-Sensitized Mice
Authors: Wu M.J. , Gong X. , Jiang R. , Zhang L. , Li X.H. , Wan J.Y.
Published: January 2017

Fulminant hepatic failure (FHF) is a devastating clinical syndrome with extremely poor prognosis and high mortality. Therefore, better treatment is urgently needed. Polydatin (PD), a traditional anti-inflammatory drug, has been described to protect against liver injury induced by certain hepatotoxins. The present study investigated the protective effect of PD against lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced FHF in mice and the underlying mechanism. Mice were pretreated with an increasing dose of PD (10, 30, and 100 mg/kg), following LPS/D-GalN challenge. The liver injury was assessed biochemically and histologically. We found that PD exerted a protective effect on LPS/D-GalN-induced FHF as evidenced by reducing sera alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, diminishing liver histopathological injury, and lowering mortality in a dose-dependent manner. In addition, pretreatment mice with PD dose-dependently suppressed tumor necrosis factor-α (TNF-α) production, myeloperoxidase (MPO) activity, intercellular adhesion molecule-1 (ICAM-1) and endothelial cell adhesion molecule-1 (ECAM-1) expression, caspase-3 activation, and transcription factor nuclear factor-kappa B(NF-kB) activity induced by LPS. These results suggested that PD could effectively protect from LPS/D-GalN-induced FHF and the protective effect afforded by PD probably contributed to reduce TNF-α production via inhibiting NF-kB activation.
Adenovirus Mediated Knockdown and Bone Morphogenetic Protein 2 Inhibits Human Lung Cancer Growth and Invasion In Vitro and in Vivo
Authors: Ye X-Y , Niu X-M. , Tang N-W. , Xu Y-H. , Li Z-M. , Yu Y-F. , Lu S. , Chen Z-W.
Published: January 2017

Bone morphogenetic protein 2 (BMP-2) is a member of the TGF-β superfamily of signaling molecules, and has been shown to function as a tumor suppressor involved in development and progression of many malignancies. BMP-2 has previously been reported to be closely correlated with lung cancer. But, the role and molecular mechanisms of BMP-2 in lung cancer have not yet been comprehensively explained. The present study aims to elucidate the role of BMP-2 in growth and invasion of human lung adenocarcinoma (LAC) in vitro and in vivo. Adenovirus vector-mediated BMP-2 small hairpin RNA (shBMP-2) was used to transfect into A549 LAC cells to determine the functional relevance of BMP-2 and tumor growth and invasion in vitro and in vivo, and further investigate the expression levels of BMP-2, vascular endothelial growth factor (VEGF), matrix metallopeptidase-9 (MMP-9), phosphatidylinositol 3-kinase p85a (P13Kp85α) and phosphorylated AKT (p-AKT). As a result, LAC cell proliferation and invasion were significantly diminished by knockdown of BMP-2 indicated by MTT and Transwell assays, and cell apoptosis and cycle arrest were markedly induced indicated by flow cytometry. When BMP-2 expression was knocked down, the expression of PI3Kp85α, p-AKT, VEGF and MMP-9 was also down-regulated in LAC cells. In addition, the tumor volumes in LAC subcutaneous nude mouse model treated with shBMP-2 were significantly smaller than those in control and ad-GFP groups. Taken together, our findings indicate that knockdown of BMP-2 inhibits growth and invasion of LAC cells possibly via blockade of the PI3K/AKT signaling pathway, and BMP-2 may be a potential therapeutic target for lung cancer.
Primary Headaches in Children: Clinical Findings and the Association with other Conditions
Authors: Pavone P. , Rizzo R. , Conti I. , Verrotti A. , Mistretta A. , Falsaperla R. , Praticò A.D. , Grosso G. , Pavone L.
Published: January 2017

The aim of the present study is to report on the frequency of some comorbidities in primary headaches in childhood. Two hundred and eighty children (175 males and 105 females; ratio 1.7:1), aged 4 to 14 years, affected by primary headaches were consecutively enrolled in this study. In direct interviews, parents and children gave information about the association of their headaches with different conditions including asthma and allergic disorders, convulsive episodes, sleep disorders and increased body weight, affections some time associated in the literature to headache as comorbidities. In addition, anxiety and depression, attention deficit/hyperactivity disorder, tics, learning disabilities and obsessive-compulsive disorders, using psycho-diagnostic scales were evaluated. Two hundred and eighty children matched for age, sex, race and socio-economic status, were used as controls. No significant association of primary headaches was found with asthma and allergic disorders, convulsive episodes, sleep disorders and increased body weight. Overall behavioral disorders were more common in children who experienced headache than in controls. A significant association of primary headache was found with anxiety and depression (p value <0.001), but not with the other psychiatric disorders. Primary headaches in children are not associated with most of the psychiatric and systemic conditions herein investigated. On the contrary, there was a significant association with anxiety and depression, as frequently reported in adults.
Ocular Clinical Pictures Disclosed by PCR Molecular Diagnosis and Chlamydia Trachomatis Infection Performed following the Appropriate Sampling Modality in Ocular Ecosystem
Authors: Gallenga P.E. , Del Boccio M. , Rapinese L. , Lobefalo M. , Pennelli A. , Martinotti S.
Published: January 2017

Four clinical cases regarding the correct diagnosis of early ocular Chlamydia trachomatis (Ct) inflammation, performed by two different modalities on the ocular ecosystem, are discussed. The present study was carried out in parallel using a cotton flock ocular swab and the scraping of upper lid conjunctiva. The ocular samplings were carried out by a first ocular swab from inner canthus and fornix, while the second by a conjunctival scraping from upper the conjunctiva of four patients. In the first case, by ocular swab, all samples resulted negative to Ct-DNA research by PCR, while the cultural analyses showed a growth of saprophytic and opportunist germs in all patients. No growth micetes resulted. On the contrary, in the second case, by conjunctival scraping, three of four samples were positive to Ct-DNA research. No fungal growth was observed, while only the 3rd patient, negative to Ct-DNA research, showed microbial growth. Our study, carried out with two different modalities of sampling on different areas of the same ecosystem, showed different results, demonstrating the importance of sampling accuracy for chlamydial research by molecular analysis in PCR, during the slight phase of inflammation. These initial data indicate that laboratory diagnosis by PCR for precocious Ct infection, not revealed clinically, could represent the first step for a correct diagnostic procedure, eliminating one of the critical points, allowing an accurate, effective and precocious antibiotic therapy. We hypothesize that only by following these correct procedures of sampling during the early phase of chlamydial inflammation, in the future, will it be possible to reduce a pejorative evolution of this worsening disease in people genetically susceptible, building a more efficacious Public Health program of prevention against chronic conjunctivitis and to favour a major prevention of trachoma in endemic areas.
Vascular Endothelial Growth Factor (VEGF), Mast Cells and Inflammation
Authors: Shaik-Dasthagirisaheb Y.B. , Varvara G. , Murmura G. , Saggini A. , Potalivo G. , Caraffa A. , Antinolfi P. , Tetè S. , Tripodi D. , Conti F. , Cianchetti E. , Toniato E. , Rosati M. , Conti P. , Speranza L. , Pantalone A. , Saggini R. , Theoharides T.C. , Pandolfi F.
Published: January 2017

Vascular endothelial growth factor (VEGF) is one of the most important inducers of angiogenesis, therefore blocking angiogenesis has led to great promise in the treatment of various cancers and inflammatory diseases. VEGF, expressed in response to soluble mediators such as cytokines and growth factors, is important in the physiological development of blood vessels as well as development of vessels in tumors. In cancer patients VEGF levels are increased, and the expression of VEGF is associated with poor prognosis in diseases. VEGF is a mediator of angiogenesis and inflammation which are closely integrated processes in a number of physiological and pathological conditions including obesity, psoriasis, autoimmune diseases and tumor. Mast cells can be activated by anti-IgE to release potent mediators of inflammation and can also respond to bacterial or viral antigens, cytokines, growth factors and hormones, leading to differential release of distinct mediators without degranulation. Substance P strongly induces VEGF in mast cells, and IL-33 contributes to the stimulation and release of VEGF in human mast cells in a dose-dependent manner and acts synergistically in combination with Substance P. Here we report a strong link between VEGF and mast cells and we depict their role in inflammation and immunity.
Knockdown of MMP11 Inhibits Proliferation and Invasion of Gastric Cancer Cells
Authors: Kou Y-B. , Zhang S-Y. , Zhao B-L , Ding R. , Liu H. , Li S.
Published: January 2017

Matrix metalloproteinase 11 (MMP11 or stromelysin-3) has recently been reported to play a crucial role in the development and progression of multiple malignancies. The aim of this study was to investigate the function of MMP11 expression in human gastric adenocarcinoma (GAC). Using immunohistochemistry assay, we studied the expression level of MMP11 in GAC and adjacent non-cancerous tissues (ANCT). The association between MMP11 expression and tumor size and pathological grade, as well as metastatic potential was analyzed. Through small hairpin RNA (shRNA)-mediated MMP11 knockdown in SGC-7901 GAC cells, we observed the changes of the biological behaviors of GAC cells. Our results indicated that the rate of positive expression of MMP11 was higher in GAC tissues than in ANCT (55.0% vs 30.0%, P=0.025). MMP11 expression had no association with the factors of age or gender of the GAC patients, or the size, pathological staging and lymph node metastases of the tumors (each P>0.05). Furthermore, MMP11 knockdown inhibited the proliferative activities and invasive potential of SGC-7901 GAC cells with decreased expression of IGF-1, PCNA and VEGF. Taken together, our findings demonstrated that MMP11 expression was increased in GAC tissues, but did not correlate with the clinicopathologic features. Knockdown of MMP11 expression could inhibit the proliferation and invasion of GAC cells probably through down-regulation of the IGF-1 signaling pathway, suggesting that MMP11 might be a potential therapeutic target for the treatment of gastric cancer.
In Vitro Adhesion of Commensal and Pathogenic Bacteria to Commercial Titanium Implants with Different Surfaces
Authors: Passariello C. , Pera F. , Gigola P.
Published: January 2017

Although dental implants have undergone impressive evolution in recent years, periimplantitis still remains a relevant problem and information on the susceptibility of commercial implants to bacterial colonization is insufficient. This work evaluated the susceptibility of different commercial implants to bacterial colonization, to identify key features for good performances. Twenty-four implants, produced with different technologies, were colonized with 9 bacterial strains following pre-conditioning with culture medium, or saliva or serum proteins and adherent bacteria were enumerated by Real Time quantitative PCR. The studied implants differed significantly for susceptibility to bacterial adhesion. Pre-conditioning of surfaces affected adhesion assays in a species specific manner. Although surface topography influenced bacterial adhesiveness, implants produced by different manufacturers with comparable technologies showed great variability of results. These data demonstrate that susceptibility of implants to bacterial colonization is influenced by productive technologies (in a surface topography proportional manner) and by the productive environment. In choosing an implant the clinician should rely upon specific experimental studies, because surface characteristics alone cannot predict susceptibility to colonization by pathogenic bacteria. Tests should include assays performed in the medium of culture and in the presence of serum proteins.
New Insights into Chlamydiae Persistence: An Energy Metabolism Strategy?
Authors: Di Pietro M. , Filardo S. , De Santis F. , Sessa R.
Published: January 2017

Chlamydiaceae is a family of obligate intracellular bacteria generally considered energy parasites. Several studies have suggested that Chlamydiae are capable of independently producing energy and, more importantly, several genes involved in the energy metabolism are up-regulated during the persistent state. Thus, it has been suggested that chlamydial persistence could be a complex and flexible metabolic strategy designed to favor a lengthy survival in the host cell by evading the immune response. In conclusion, more detailed studies on the shift in the chlamydial energy metabolism, from the active to the persistent form, may be helpful in future to determine whether chlamydial persistence observed in vitro does occur in vivo and whether chronic sequelae of chlamydial diseases may be related to the persistence.
Macrophage Activation Syndrome in a Child Affected by Malaria: The Choice of Steroid
Authors: Trapani S. , Canessa C. , Fedi A. , Giusti G. , Barni S. , Montagnani C. , Galli L. , Resti M. , De Martino M.
Published: January 2017

Macrophage activation syndrome is a potentially fatal clinical syndrome caused by an excessive activation and proliferation of macrophages and T cells, leading to an exaggerated inflammatory reaction. It is well known that it can complicate the course of different conditions, especially autoimmune, lympho-proliferative, infectious diseases and drugs. Many infective pathogens can trigger the syndrome but the association with malaria has rarely been described, especially in children. We report a child with severe malaria complicated by MAS, in whom the clinical appearance of this syndrome could be considered as worsening of malaria itself. Furthermore, the use of steroids as first choice drugs in this complication, but arguable in malaria, has been highlighted. Clinicians should be aware of this syndrome when malaria does not respond to conventional therapy, since early diagnosis and prompt treatment may dramatically reduce the mortality associated with this condition.
IGG4: Not Only for Allergists
Authors: Lombardi C. , Belli D. , Facchetti F. , Passalacqua G.
Published: January 2017

We describe herein a case of IgG4-related disease with the isolated clinical presentation of malabsorption due to pancreatic failure. Histology of an abdominal lymph node was critical for diagnosis. IgG4-related disease is increasingly recognized as an immunological disorder that can mimic various clinical entities.
Hospitalization Rates of Complicated Pneumococcal Community-Acquired Pneumonia is Increasing in Tuscan Children
Authors: Bonsignori F. , Chiappini E. , Orlandini E. , Parretti A. , Sollai S. , Resti M. , Galli L. , Azzari C. , De Martino M.
Published: January 2017

To provide epidemiological data on community-acquired pneumonia (CAP) and complicated CAP, a retrospective study was conducted on a partially vaccinated paediatric population. Data from children hospitalized for CAP in Tuscan hospitals between January 1st, 1999 and December 31st, 2009 were analysed. A total of 5,450 children with CAP were hospitalized. Annual hospitalization rates for CAP did not change significantly over the study period (χ2 for trend= 0.652; p=0.419). The total annual hospitalization rate for pneumococcal CAP varied according to age (28.04 per 100,000 children aged ≤ 5 years, 10.06 per 100,000 children aged 6–12 years and 0.98 per 100,000 children aged ≥ 13years). Hospitalization rates for pneumococcal CAP increased from 12.84 (95% CI:7.35–18.34) in 2001 to 45.4 (95%CI:35.93–54.90) per 100,000 children aged ≤ 5 years in 2009 (p<0.0001). In addition, a significant increase of hospitalization rates for complicated CAP (from 6.07 in 1999 to 13.66 in 2009 per 100,000 children; P<0.0001) and pneumococcal complicated CAP (from 0.19 in 1999 to 3.41 in 2009 per 100,000 children) over the study period were highlighted. Our epidemiological data confirm the decision to introduce the PCV13 vaccine, to satisfy the need to prevent a wider group of pneumococcal serotypes.
Nerve Growth Factor Interactions with Mast Cells
Authors: Kritas S.K. , Caraffa A. , Antinolfi P. , Saggini A. , Pantalone A. , Rosati M. , Tei M. , Speziali A. , Saggini R. , Pandolfi F. , Cerulli G. , Conti P.
Published: January 2017

Neuropeptides are involved in neurogenic inflammation where there is vasodilation and plasma protein extravasion in response to this stimulus. Nerve growth factor (NGF), identified by Rita Levi Montalcini, is a neurotrophin family compound which is important for survival of nociceptive neurons during their development. Therefore, NGF is an important neuropeptide which mediates the development and functions of the central and peripheral nervous system. It also exerts its proinflammatory action, not only on mast cells but also in B and T cells, neutrophils and eosinophils. Human mast cells can be activated by neuropeptides to release potent mediators of inflammation, and they are found throughout the body, especially near blood vessels, epithelial tissue and nerves. Mast cells generate and release NGF after degranulation and they are involved in iperalgesia, neuroimmune interactions and tissue inflammation. NGF is also a potent degranulation factor for mast cells in vitro and in vivo, promoting differentiation and maturation of these cells and their precursor, acting as a co-factor with interleukin-3. In conclusion, these studies are focused on cross-talk between neuropeptide NGF and inflammatory mast cells.
Suppression of CD4+ T Lymphocyte Activation in Vitro and Experimental Encephalomyelitis in Vivo by the Phosphatidyl Inositol 3-Kinase Inhibitor PIK-75
Authors: Acosta Y.Y. , Montes-Casado M. , Aragoneses-Fenoll L. , Dianzani U. , Portolés P. , Rojo J.M.
Published: January 2017

Class IA phosphatidyl inositol-3 kinases (PI3-K) are important targets in cancer therapy and are essential to immune responses, particularly through costimulation by CD28 and ICOS. Thus, small PI3-K inhibitors are likely candidates to immune intervention. PIK-75 is an efficient inhibitor of the PI3-K p110α catalytic subunits that suppresses tumor growth, and its effects on immune and autoimmune responses should be studied. Here, we describe the effect of PIK-75 on different immune parameters in vitro and in vivo. PIK-75 at concentrations commonly used in vitro (≥0.1 μM) inhibited T and B cell activation by Concanavalin A and LPS, respectively, and survival of non-stimulated spleen cells. In naive CD4+ T lymphocytes, PIK-75 induced apoptosis of resting or activated cells that was prevented by caspase inhibitors. At low nanomolar concentrations (≤10 nM), PIK-75 inhibited naive CD4+ T cell proliferation, and IL-2 and IFN-γ production induced by anti-CD3 plus anti-CD28. In activated CD4+ T blasts costimulated by ICOS, PIK-75 (≤10 nM) inhibited IFN-γ, IL-17A, or IL-21 secretion. Furthermore, PIK-75 (20 mg/kg p.o.) suppressed clinical symptoms in ongoing experimental autoimmune encephalomyelitis (EAE) and inhibited MOG-specific responses in vitro. Thus, PIK-75 is an efficient suppressor of EAE, modulating lymphocyte function and survival.
Saccharomyces Cerevisiae Fungemia, a Possible Consequence of the Treatment of Clostridium Difficile Colitis with a Probioticum
Authors: Santino I. , Alari A. , Bono S. , Teti E. , Marangi M. , Bernardini A. , Magrini L. , Di Somma S. , Teggi A.
Published: January 2017

The yeast Saccharomyces boulardii is a biotherapeutic agent used for the prevention and treatment of several gastrointestinal diseases, such as diarrhoea caused by Clostridium difficile, in addition to the antibiotic therapy. In this study we report a case of Saccharomyces cerevisiae fungemia in a patient with Clostridium difficile-associated diarrhoea (CDAD) treated orally with S. boulardii in association with vancomycin. The identification of the S. cerevisiae was confirmed by molecular technique. Fungemia is a rare, but a serious complication to treatment with probiotics. We believe it is important to remind the clinicians of this risk when prescribing probiotics, especially to immunocompromised patients.
Dysplastic Collagen Fibrils in Idiopathic Carpal Tunnel Syndrome
Authors: Stransky G. , Weis S. , Wenger E. , Dimitrov L.
Published: January 2017

Surgical biopsies of dissected transverse carpal ligaments of patients with idiopathic carpal tunnel syndrome were examined with an electron microscope revealing collagen fibrils with extremely varying diameters. Morphometric analysis was performed on photomicrographs exhibiting fibrils with a small diameter comparable to that in control tissue as well as fibrils with a far bigger diameter that could not be observed in control tissue. Morphometric parameters were evaluated in order to analyse the relation between number and covered area of collagen fibrils in control and in carpal tunnel syndrome tissue. In control tissue twice as many collagen fibrils as in pathological tissue occupied an equal area.
Effectes of Low-Power I.R. Laser on Cultured Fibroblasts
Authors: Continenza M. A. , Ricciardi G. , Rizzo F. M.
Published: January 2017

The Infrared laser effects (λ = 904 nm) on in vitro cultured fibroblasts were tested. It was found that, changing the frequency and the intensity of radiation, it was possible to have opposite results. At low frequency (0,4 KHz) the cellular growth was inhibited; at 1,6 KHz frequency and 3W/cm2/min intensity the proliferation was increased; at higher frequencies the cellular differentiation was stimulated and an increased fibrosynthetic activity was found.